CHAPTER 1.

BACTERIAL TAXONOMY

G R AM-POSITIVE C E L LS GRAM-NEGATIVE C E L LS

2 Layers:
1 . I n ner cy1oplasmic membrane
2. Outer thick peptidoglycan layer
(60-1 00% peptidoglycan)
3 Layers:
1 . Inner cy1oplasmic membrane
2 . Thin peptidoglycan layer
(5- 1 0% peptidoglycan)
3. Outer membrane with
lipopolysaccharide (LPS)

Low lipid content High lipid content

NO endotoxi n Endotoxin (LPS) - l ipid A

NO periplasmic space Periplasmic space

NO porin channel Porin channel

Vulnerable to lysozyme and Resistant to lysozyme and

penicil l i n attack penicillin attack

Figure 1-7 DIFFERENCES BETWEEN GRAM-POSITIVE

AND GRAM-NEGATIVE ORGANISMS

from one organism to another and are antigenic determi
nants. This part is called the 0-specific side chain or the
0-antigen. Think of 0 for Outer to help remember this.
2 ) The center part is a water soluble core polysac
charide.
3) Interior to the core polysaccharide is the third
component, lipid A, which is a disaccharide with mul
tiple fatty acid tails reaching into the membrane. Lipid
A is toxic to humans and is known as the gram-negative
endotoxin. When bacterial cells are lysed by our
efficiently working immune system, fragments of mem
brane containing lipid A are released into the circula
tion, causing fever, diarrhea, and possibly fatal
endotoxic shock ( also called septic shock).
Embedded in the gram-negative outer membrane are
porin proteins, which allow passage of nutrients. These
are also unique to gram-negative organisms.
What does this mean clinically?
The differences between gram-positive and gram
negative organisms result in varied interactions with
the environment. The gram-positive thickly meshed
peptidoglycan layer does not block diffusion of low mol
ecular weight compounds, so substances that damage
the cytoplasmic membrane (such as antibiotics, dyes,
and detergents) can pass through. However, the gram
negative outer lipopolysaccharide-containing cell mem
brane blocks the passage of these substances to the
peptidoglycan layer and sensitive inner cytoplasmic
membrane. Therefore , antibiotics and chemicals that
attempt to attack the peptidoglycan cell wall (such as
penicillins and lysozyme) are unable to pass through.
Interestingly, the crystal violet stain used for Gram
staining is a large dye complex that is trapped in the
thick, cross-linked gram-positive cell wall , resulting in
the gram-positive blue stain. The outer lipid-contain
ing cell membrane of the gram-negative organisms is
partially dissolved by alcohol, thus washing out the
crystal violet and allowing the safranin counterstain to
take.
Fig. 1-7. Summary of differences between gram
positive and gram-negative bacteria.
BACTERIAL MORPHOLOGY
Bacteria have 4 major shapes :
1 ) Cocci: spherical.
2) Bacilli: rods. Short bacilli are called coccobacilli.
3) Spiral forms: comma-shaped, S-shaped, or spiral
shaped.
4) Pleomorphic: lacking a distinct shape (like j ello).
The different shaped creatures organize together into
more complex patterns, such as pairs (diplococci), clus
ters, strips, and single bacteria with flagella.
Fig. 1-8. Bacterial morphology.
SO, WHAT ARE THE NAMES?!!!!
Gram-Positive
Start by remembering that there are 7 classic gram
positive bugs that cause disease in humans, and basically
every other organism is gram-negative.

4
 CHAPTER 1. BACTERIAL TAXONOMY

M ORPHOLOGY GRAM-POSITIVE G RA M-NEGATIVE

Circular (Coccus) Streptococcus Neisseria

Enterococcus Moraxella
Staphylococcus

Rod ( Bacill us) Corynebacterium E NTE RICS (live i n the G I tract) :

Listeria Escherichia coli
Bacillus Shigella
Clostridium Salmonella
Yersinia
Klebsiella
Proteus
Enterobacter
Mycobacterium (acid-fast) Serratia
Vibrio
Campylobacter
Helicobacter

Pseudomonas
Bacteroides (anaerobic)
Haemophilus
Bordetella
Legionella
Yersinia
Francisella
Bruce/la
Pasteurella
Gardnerella

Spiral Spirochetes:
Treponema
Borrelia
Leptospira

Branch ing filamentous growth Actinomyces (anaerobic)

(like fungi) Nocardia (partially acid-fast)

Pleomorphic Chlamydia
Rickettsiae

No cell wall Mycoplasma

Figure 1-9 MORPHOLOGICAL DIFFERENCES AMONG THE BACTERIA

CYTOPLASMIC STRUCTURES
Bacterial DNA usually consists of a single circle of
double-stranded DNA Smaller adj acent circles of
double-stranded DNA are called plasmids; they often
contain antibiotic resistance genes. Ribosomes are
composed of protein and RNA and are involved in the
translation process, during the synthesis of proteins.
Bacteria, which are procaryotes, have smaller ribo
somes ( 70S) than animals (80S), which are eucaryotes.
Bacterial ribosomes consist of 2 subunits, a large
subunit (50S) and a small subunit (30S). These numbers
relate to the rate of sedimentation. Antibiotics, such as
erythromycin and tetracycline, have been developed
that attack like magic bullets. They inhibit protein syn
thesis preferentially at the bacterial ribosomal subunits
while leaving the animal ribosomes alone. Erythromycin
works at the 50S subunit, while tetracycline blocks
protein synthesis at the 30S subunit.
METABOLIC CHARACTERISTICS
Bacteria can be divided into groups based on their
metabolic properties. Two important properties include :
1) how the organism deals with oxygen, and 2 ) what the
organism uses as a carbon and energy source. Other
properties include the different metabolic end-products
that bacteria produce such as acid and gas.

6
 CHAPTER 1. BACTERIAL TAXONOMY

OBLIGATE FAC U LTATIVE MICROAE ROPHI LIC OBLIGATE

AEROBES ANAEROBES ANA E R O B E S

G ram-positive Nocardia Staphylococcus Enterococcus Clostridium

(weakly acid-fast) Bacillus anthracis Streptococcus
Bacillus cereus Corynebacterium Some species of
Listeria streptococci are
Actinomyces facultative
anaerobes

G ram-negative Neisseria Most other gram- Spirochetes Bacteroides

Pseudomonas negative rods Treponema
Bordetella Borrelia
Legionella Leptospira
Bruce/la Campylobacter

Acid-fast Mycobacterium
Nocardia

No cell wall Mycoplasma

Chlamydia and Rickettsia do not have the metabolic machinery to uti l ize oxygen . They are energy paras ites, and must steal the i r host's ATP.

Figure 1- 10 OXYGEN SPECTRUM

Oxygen
How bacteria deal with oxygen is a major factor in their
classification. Molecular oxygen is very reactive, and
when it snatches up electrons, it can form hydrogen per
oxide m202), superoxide radicals (02-), and a hydroxyl
radical (OH). All of these are toxic unless broken down.
In fact, our very own macrophages produce these oxygen
radicals to pour over bacteria. There are 3 enzymes
that some bacteria possess to break down these oxygen
products :
1 ) Catalase breaks down hydrogen peroxide in the
following reaction :
2H202 -+ 2H20 + 02
2) Peroxidase also breaks down hydrogen peroxide.
Superoxide dismutase breaks down the super
3)
oxide radical in the following reaction:
Bacteria are classified on a continuum. At one end are
those that love oxygen, have all the preceding protective
enzymes, and cannot live without oxygen. On the oppo
site end are bacteria which have no enzymes and pretty
much kick the bucket in the presence of oxygen:
1 ) Obligate aerobes : These critters are just like
us in that they use glycolysis, the Krebs TCA cycle ,
a n d the electron transport chain with oxygen as the
final electron acceptor. These guys have all the above
enzymes .
2 ) Facultative anaerobes : Don't l e t this name
fool you! These bacteria are aerobic. They use oxygen
as an electron acceptor in their electron transfer chain
and have catalase and superoxide dismutase. The
only difference is that they can grow in the absence of
oxygen by using fermentation for energy. Thus they
have the faculty to be anaerobic but prefer aerobic
conditions. This is similar to the switch to anaerobic
glycolysis that human muscle cells undergo during
sprinting.
3) Microaerophilic bacteria (also called aerotol
erant anaerobes): These bacteria use fermentation
and have no electron transport system. They can toler
ate low amounts of oxygen because they have superoxide
dismutase (but they have no catalase).
4) Obligate anaerobes: These guys hate oxygen
and have no enzymes to defend against it. When you are
working on the hospital ward, you will often draw blood
for culture. You will put the blood into 2 bottles for
growth. One of these is an anaerobic growth media with
no oxygen in it!
Fig. 1-10. The oxygen spectrum of the major bacterial
groups.
Carbon and Energy Source
Some organisms use light as an energy source (pho
totrophs), and some use chemical compounds as

7
 CHAPTER 2. CELL STRUCTURES, VIR ULENCE FACTORS AND TOXINS

O R GA N I S M TOX I N M E C HANISM

NEU ROTOXINS

Clostridium tetani
Tetanospasmin (tetanus toxin)
1 . H (Hea vy) subunit: binds to neuronal
gangliosides
2 . L (L ight) subunit blocks release of
inhibitory neurotransmitters (glycine,
GABA) from Renshaw inhibitory
interneurons

Clostridium Botulinum toxi n I n h ibits acetylcholine release

botulinum from motor neuron endplates
at neuromuscular junctions

ENTEROTOXINS A. I nfectious Diarrhea

Vibrio cholerae Choleragen 1 . Five B subunits: binds to G M 1 gangliosides

on intestinal cell membranes
2. Two A subunits: carry out the ADP-
ribosylation of the GTP-binding p rotein.
This activates membrane associated
adenylate cyclase, which converts ATP to
cAM P . Elevated levels of cAM P induces
the secretion of NaCl and inhibits
reabsorption of NaCl

1 . E. coli E. coli heat labile toxin ( LT)

2. Campylobacter jejuni Structurally similar to
3. Bacillus cereus choleragen

1 . E. coli E. coli heat stable toxin (ST) No effect on concentration of cAM P . Rather,
2 . Y. enterocolitica it binds to a receptor on the i ntestinal brush
border and activates guanylate cyclase to
produce GM P . This results i n inhibition of
resorption of NaCl

1 . Shigella dysenteriae 1 . Shiga toxin 1 . Five B subunits: bind to intestinal epithelial

2. Enterohemorrhagic 2 . Shiga-like toxin (When cells
E. coli "shiga-toxin" is released by 2 . A subunit inhibits protein synthesis by
3. Enteroinvasive E. coli bacteria other than Shigella) inactivating the 608 ribosomal subunit.
This kills intestinal epithelial cells

ENTEROTOXINS B. Food Poisoning

Staphylococcus Staphylococcal heat

aureus stable toxin

Bacillus cereus Heat stable toxin

Figure 2-8 EXOTOXINS

14
 CHAPTER 2. CELL STRUCTURES, VIRULENCE FACTORS AND TOXINS

R E S U LTS NOTES
-

Tetanus: continuous motor neuron activity. 1 . Vaccine: formalin i nactivated tetanus toxin (Part
U ncontrolled muscle contractions with lockjaw of DTaP vaccine):
and tetanic paralysis of respiratory m uscles 1 . Diphtheria
2 . Tetanus
3. a cellular Pertussis
2. Toxin gene carried on plasmid

Botulism: Flaccid paralysis with respi ratory muscle 1 . Most potent exotoxi n
paralysis 2. Toxin obtained by lysogenic conversion

Cholera: Increasing cyclic AMP levels result in Death by dehydration

increased i ntral uminal NaCl, which osmotically
pulls fluid and electrolytes i nto the intestinal tract.
This causes diarrhea and dehydration

I ncreasing cyclic G M P levels inhibit NaCl resorption

by i ntestinal epithelial cells. This results in increased
osmotic pull of fluid and electrolytes into the
intestinal tract, causing diarrhea

Shiga toxin kills absorptive intestinal epithelial cells, 1 . Bloody diarrhea

resulting i n sloughing off of dead cells and poor 2. May be responsible for hemolytic u remic syndrome
absorption of fluid and electrolytes from the intestinal 3. I n h i bits protei n synthesis in a manner analogous to
tract the antiribosomal antibiotics (eryth romycin,
tetracycline, etc.)

Diarrhea and vomiti ng that lasts for less than 24 hours Toxins are deposited on food colonized with
toxi n-producing Staphylococcus

1 . Vomiting that lasts for less than 24 hours . 1. 8 . cereus endospores survive l o w temperatu re
2. Limited diarrhea cooking. Then, this bacteri um g rows and deposits
this toxi n on food
2. B. cereus can also produce food poisoning by
secretion of a heat labile enterotoxin (similar to
that of E. coli)

15
 CHAPTER 2. CELL STRUCTURES, VIRULENCE FACTORS AND TOXINS

ORGANISM TOXIN MECHANISM

PYROG ENIC TOXINS

Streptococcus pyogenes Streptococcus pyrogenic toxi n Activates t h e endogenous mediators of

G roup A streptococci sepsis, such as the cytokine i nterleukin-1

Staphylococc us Toxic shock syndrome toxin Activates the endogenous mediators of

a ure us (TSST- 1 ) sepsis, such as the cytokine i nterleukin- 1

TISSUE INVASIVE TOXINS

Streptococcus 1 . Hemolysi ns/Streptolysin 1. Lyses red blood cells

pyogenes O and S 2. Activates plasminogen to lyse fibrin clots
2. Streptokinase 3. Hydrolyzes DNA
3 . DNAases 4. B reaks down proteoglycans
4 . Hyaluronidase 5. Hyd rolyzes NAO
5. NADase

Staphylococcus Many of the above, and: 1 . Hydrolyzes l ipids

1 . Lipases 2. Destroys penici llins
2 . Penicillinase
aureus
3. Activates plasminogen to lyse fibrin clots
3. Staphylokinase 4 . Lyses white blood cells
4 . Leukocidin 5 . Epithelial cell lyses
5. Exfoliatin 6. Cripples host complement defense
6. Factors that bind complement

Clostridium More than 1 2 lethal toxins, Alpha toxin : lecithinase hydrolyzes lecithin
perfringens named by Greek letters: Alpha i n cel l membranes, resulting i n cell death
toxin (lecithi n ase) is the most
important (and most lethal)

MISCELLANEOUS EXOTOXINS

Bacillus anthracis
Anth rax toxin (th ree components):
1 . Edema Factor (EF):
2 . Lethal Factor ( LF)
3 . P rotective Antigen (PA)
1 . Protective Antigen (PA) : binding (B)subunit,
which allows entry of E F i nto the target cel l
2 . Edema Factor (EF): (A subunit)
Calmodulin-dependent adenylate cyclase ,
increases cAM P , which i mpairs neutrophil
function & causes massive edema (disrupts
water hemostasis)
3 . Lethal Factor (LF): is a zinc metalloprotease
that i nactivates protein kinase. This toxin
stimulates the macrophage to release tumor
necrosis factor alpha and interleukin-1 Beta,
which contributes to death in anthrax.

Corynebacterium Diphtheria toxi n 1 . B subunit b i n d s t o h e a rt a n d neural tissue

diphtheriae 2 . A subunit ADP ribosylates elongation factor
( E F2), thereby inhibiting translation of human
mRNA into proteins

Figure 2-8 (continued)

16
 CHAPTER 2. CELL STRUCTURES, VIRULENCE FACTORS AND TOXINS

RES U LTS N OTES

Scarlet fever Obtains exotoxi n from a temperate bacteriophage

by lysogenic conversion

Toxic shock syndrome: Streptococcus pyogenes can

1 . Fever also cause toxic shock
2. Rash syndrome
3 . Desquamation
4 . Diarrhea
5. Hypotension (shock)

Tissue destruction:
1 . Abscesses
2. Skin i nfections
3 . Systemic infection

1 . Tissue destruction :
A. Abscesses
B. Skin i nfections
C. Systemic infection
2. Exfoliatin is responsible for scalded skin syndrome
in i nfants

Tissue destruction and gas gangrene

Anth rax 1 . All 3 components are req uired for activity of

Edema factor: an extracellular adenylate cyclase this toxin
which gets i nternalized by "defensive" phagocytic 2. PA is the B (action) subunit and EF is the
cells. Adenylate cyclase is activated by calmodulin, A (binding) subunit of the anthrax toxin
increasing the concentration of cAM P withi n
neutrophils a n d macrophages. This inhibits their
ability to phagocytose bacteria

Diphtheria: 1 . This exotoxin can be considered a human antibiotic,

1 . Myocarditis (heart) as it inhibits protein synthesis, just as tetracycline
2 . Peripheral nerve palsies and erythromycin inhibit protein synthesis
3. Central nervous system effects in bacteria

17
 CHAPTER 2. CELL STRUCTURES, VIR ULENCE FACTORS AND TOXINS

O R GANISM TOXIN M E CHANISM

Corynebacterium
diphtheriae
(contin ued)

Borde tel/a Four toxins: 1 . Pertussis toxi n

pertussis 1 . Pertussis toxin
B Subunit: binds to target cel ls
A Subunit: inhibits phagocytosis
2 . Extracytoplasmic adenylate
cyclase
3. Filamentous hemagglutin i n :
allows binding t o ciliated
epithelial cells
4 . Tracheal cytotoxin
B S ubunit b i n d s t o target cells
A Subunit activates membrane G p roteins
to activate membrane bound adenylate
cyclase (th us increasing cAM P levels) . This
inhibits macrophage & neutrophil
phagocytosis
2 . Extracytoplasmic adenylate cyclase: Similar
to Bacillus anthracis edema factor, which
impairs chemotaxis and phagocytosis
3 . Filamentous hemagglutinin: allows binding
to ciliated epithelial cells
4. Tracheal cytotoxin: damages respi ratory
epithelial cells

Clostridium difficile 1 . Toxin A 1 . Toxin A: causes fluid secretion and mucosal

2. Toxin B inflammation, leading to diarrhea
2. Toxin B: cytotoxic to colonic epithelial cells

Pseudomonas Pseudomonas exotoxin A Inhibits protei n synthesis by inhibiting

aeruginosa Elongation Factor 2 ( E F2) : same mechanism
as the diphtheria toxin

Figure 2-8 (continued)

A or L B or H

Figure 2-9

18
 CHAPTER 2. CELL S TR UCTURES, VIR ULENCE FACTORS AND TOXINS
R E S U LTS
Whooping cough
Pseudomembranous enterocolitis: colonic
i nflammation, with pseudo-membrane formation .
Clinically: diarrhea (often bloody) , fever, &
abdom inal pain
M . Gladwin, W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple MedMaster
and fungi can also trigger this adverse immune
response, the term septic shock is more appropriate
and inclusive.
The chain of events that lead to sepsis and often
death begins with a localized site of infection of gram
negative or gram-positive bacteria or fungi . From this
site or from the blood (bacteremia), the organisms
release structural components ( such as endotoxin
and/or exotoxin) that circulate in the bloodstream and
stimulate immune cells such as macrophages and
neutrophils . These cells , in response to the stimulus,
release a host of proteins that are referred to as
endogenous mediators of sepsis.
The most famous endogenous mediator of sepsis is
tumor necrosis factor (TNF). TNF is also called
cachectin because it is released from tumors, produc
ing a wasting (weight loss) syndrome , called cachexia,
in cancer patients . Injecting TNF into experimental
19
NOTES
2 . Vaccine: formalin i nactivated tetanus toxin (Part
of DTaP vaccine) :
A. Diphtheria
B. Tetanus
C . acellular Pertussis
3. Obtains exotoxi n from a temperate bacteriophage
by lysogenic conversion
Vaccine: formalin inactivated tetanus toxin (Part
of DTaP vaccine):
1 . Diphtheria
2 . Tetanus
3 . acellular Pertussis
1 . Antibiotic-associated diarrhea
2 . Hypervirulent strain NAP1 /Bl/027
produces additional "binary toxin"
Note that diphtheria toxin has the same action as
Pseudomonas exotoxi n A, but they have different
targets
1 . Exotoxin A: liver
2 . Diphtheria toxin: heart
animals produces hypotension and death ( shock).
In sepsis, TNF triggers the release of the cytokine
interleukin-I from macrophages and endothelial cells,
which in turn triggers the release of other cytokines and
prostaglandins. This churning maelstrom of mediators
at first defends the body against the offending microor
ganisms, but ultimately turns against the body. The
mediators act on the blood vessels and organs to pro
duce vasodilatation, hypotension, and organ system
dysfunction .
The mortality rate for septic shock is high : up to 40%
of patients will die , even with intensive care and
antibiotic therapy. For every organ system that fails
the mortality rises. Usually two organs are involved
(vascular system with hypotension and lungs with
hypoxia) and the mortality rate is about 40%. For each
additional organ failure ( renal failure , etc. ) add
15-20% mortality!
 CHAPTER 4. STREPTOCOCCI

GRAM-POSITIVE M ETABOLISM VIRULE.NCE TOXINS

COCCI

Lancefield g roup A: 1 . Catalase-negative 1 . M-protein (70 types) Erythrogenic or Pyrogenic

Streptococcus 2. Microaerophilic a. Adherence factor Toxin (produced only by
pyogenes 3. Beta-hemolytic, b. Anti-phagocytic lysogenized G roup A
due to enzymes c. Antigenic: Induces Streptococci ) : responsible
that destroy antibodies which for scarlet fever
red and white can lead to 2 . Toxic shock syndrome
blood cells phagocytosis toxi n (similar to, but
A. Streptolysin 0: 2 . Lipoteichoic acid: different from the staph
a. Oxygen labile adherence factor exotoxi n TSST- 1 )
b. Antigenic 3. Streptokinase
B . Streptolysin-S 4. Hyalu ronidase
a. Oxygen stable 5. DNAase
b. Non-antigenic 6. Anti-C5a peptidase

Lancefield group B: 1 . Catalase-negative

Streptococcus 2. Facultative anaerobe
agalactiae 3. Beta-hemolytic

Figure 4- 1 1 STREPTOCOCCI

36
 CHAPTER 4. STREPTOCOCCI

PATHOLOGY TR EATM ENT DIAGNOSTICS MISCELLANEOUS

DIRECT INVASION/TOXIN 1 . Penicillin G 1. G ram stain : g ram 1. Dick Test: once

1. Pharyngitis: 2. Penicillin V positive cocci commonly used to
A. Red , swollen 3. E rythromycin in chains confirm Scarlet Fever
tonsils and 4 . Penicillinase-resistant 2. Culture on standard diagnosis
pharynx penici l l i n : in skin laboratory media. 2 . C-Carbohydrate:
B. Purulent exudate infections, where G rowth is inhibited used for Lancefield
on tonsils staphylococci could be by bacitracin groupings
C. Fever the responsible organism ( S. Pyogenes is
D. Swollen lymph nodes Followi ng rheumatic the only beta-hemolytic
2. Skin I nfections: fever: streptococcus which
A. Follicul itis A. Patients are placed is sensitive to bacitracin)
B. Cel lulitis on continuous 3. Pharyngitis: Th roat swab
C. Impetigo prophylactic rapid antigen detection
D . Necrotizing fasci itis antibiotics to test ( RADT) is specific for
3. Scarlet fever: prevent repeat strep Streptococcus pyogenes
fever and scarlet th roat infections and immunologically
red rash on body that could potentially detects group A carbo
4. Toxic shock lead to a repeat hydrate antige n .
syndrome case of rheumatic
fever
ANTIBOD Y MEDIA TED For invasive streptococcus
1 . Rheumatic fever pyogenes infections, such
(may follow as necrotizing fasciitis or
streptococcal pharyngitis) : streptococcal toxic shock
A. Fever syndrome, consider
B. Myocarditis: heart adding clindamycin
inflammation
C. Arth ritis : migratory
polyarth ritis
D. Chorea
E. Rash: erythema
margi natum
F. Subcutaneous
nodules
1 0-20 years after
infection , may develop
permanent heart valve
damage
2. Acute post-streptococcal
glomeruloneph ritis:
tea-colored urine,
following streptococcal
skin or pharynx infection

1. Neonatal meningitis Penicillin G 1. G ram stain of Part of normal flora

2. Neonatal pneumonia cerebrospinal fluid (CSF) (25% of pregnant
3. Neonatal sepsis or urine women carry G roup B
4. Sepsis in pregnant women 2 . Culture of CSF, streptococci in their
(with secondary infection u rine or blood vagina)
of fetus)
5. I ncreasing incidence of
infections in elderly > 65
years of age and patients
with diabetes or neu ro
logical disease : causes
sepsis and pneumonia.

37
 CHAPTER 4. STREPTOCOCCI

GRA M-POSITIVE M ETABOLISM VIRU LENCE TOXINS

COCCI

Lancefield group D : 1 . Catalase-negative Extracellular dextran

2 sub-types: 2. Facultative anaerobe helps them bind to
1 . Enterococci: 3. Usually gamma-hemolytic, heart valves
Streptococcus but may be alpha-hemolytic
faecalis
Streptococcus
faecium
2. Non-enterococci
Streptococcus
bovis
Streptococcus
equinus

Streptococcus 1 Catalase-negative
. Extracellular dextran
viridans 2. Facultative anaerobe helps them bind to
3. Alpha-hemolytic heart valves

Streptococcus 1 . Catalase-negative Capsule Pneumolysin : binds to

pneumoniae 2. Facultative (83 serotypes) cholesterol in host-cel l
(pneumococci) anaerobe membranes (but its actual
3. Alpha-hemolytic effect is u nknown)

Figure 4- 1 1 (continued)

38
 CHAPTER 4. STREPTOCOCCI

PATH OLOGY TREATMENT DIAGNOSTICS M I SCELLANEOUS

1 . Subacute bacterial 1 . Ampici llin, sometimes 1 . G ram stain S. Bovis associated

endocarditis combined with an 2 . Culture : with colonic
2 . Biliary tract I nfections aminoglycoside A. Enterococci c a n b e malignancies
3 . U rinary tract I nfections 2 . Resistant to penici l l i n G
1 . 40% bile
cultu red i n :
(especially the 3. Emerging resistance
enterococci) to vancomycin 2 . 6.5% sod i u m
4. For vancomycin resistant chloride
organisms (VRE) consider B. Nonenterococci
li nezol id, daptomycin, and can only grow in bil e
nitrofurantoin.

1 . Subacute bacterial Penicillin G 1 . G ram stai n Part of the normal

endocarditis 2 . C u lture oral flora (found in
2 . Dental caries 3. Resistant to optochin the nasopharynx and
(cavities) : caused by gingival crevices)
Streptococcus mutans and GI tract
3. B rai n or liver
abscesses: caused by
Streptococcus
intermedius group

1 Pneumonia
. 1 . Penici llin G ( I M ) A. G ram stain : reveals Quellung reaction :
2 . Meni ngitis 2 . Erythromycin gram-positive diplococci technique used
3. Sepsis 3. Ceftriaxone B . Culture: does not to detect
4. Otitis media (in children) 4 . Vaccine: made against grow in presence of: encapsulated
the 23 most common 1 . Optochin b acte r ia ( s uc h as
capsular antigens. 2 . Bile S. pneumoniae
Vaccinate individuals C . Positive Quellung test: and H. influenzae)
who are susceptible, swelling when tested
such as elderly folk or against antiserum
asplenic individuals containing anti-capsular
(including being antibodies
functionally asplenic due
to sickle cell anemia)
5. Heptavalent and the newer
13 valent conjugated
vaccines are effective at
preventi ng otitis media
and pneumonia.

M. G l adwi n , W. Trattler, and S. Maha n , Clinical Microbiology Made Ridiculously Simple Med Master

39
 CHAPTER 5. STAPHYLOCOCCI

G R AM-POSITIVE COCCI M ETABOLISM VIRU LENCE TOXINS

Staphylococcus aureus 1 . Catalase Protective Proteins: Assault Weaponry

positive 1 . Protein A: binds lgG, preventing 1 . Exfoliatin : scalded skin
2. Coagulase opsonization and phagocytosis syndrome
positive 2 . Coagulase : allows fibrin 2 . Enterotoxi n : food
3. Facu ltative formation around organism poisoning
anaerobe 3. Hemolysins 3. Toxic shock syndrome
4. Leukocidins toxin (TSST- 1 )
5 . Penicilli nase

Tissue-Destroying Proteins:
1 . Hyal u ronidase: breaks down
connective tissue
2 . Staphylokinase: lyses formed
clots
3. Lipase

Staphylococcus 1 . Catalase 1 . Polysaccharide capsule:

epidermidis adheres to a variety of
2.
positive
Coagulase
negative
prosthetic devices. Forms
a biofi lm.
3. Facu ltative 2 . Highly resistant to antibiotics!
anaerobe

Staphylococcus 1 . Catalase
saprophyticus positive
2 . Coagulase
negative
3. Facu ltative
anaerobe

Figure 5- 1 1 STAPHYLOCOCCI

For more information about the myriad mechanisms of
Staphylococcus aureus resistance to antibiotics, please
refer to Chapter 34.
Staphylococcus epidermidis
This organism is part of our normal bacterial flora
and is widely found on the body. Unlike Staphylococcus
aureus , it is coagulase-negative.
This organism normally lives peacefully on our skin
without causing disease. However, compromised hospi
tal patients with Foley urine catheters or intravenous
lines can become infected when this organism migrates
from the skin along the tubing.
Staphylococcus epidermidis is a frequent skin cont
aminant of blood cultures. Contamination occurs when
the needle used to draw the blood passes through skin
covered with Staphylococcus epidermidis . Drawing
blood from 2 sites will help determine if growth of
Staphylococcus epidermidis represents a real bac-
46
teremic infection or is merely a contamination. If only
one of the samples grows Staphylococcus epidermidis,
you can suspect that this is merely a skin contaminant.
However, if 2 cultures are positive, the likelihood of
bacteremia with Staphylococcus epidermidis is high.
Staphylococcus epidermidis also causes infections of
prosthetic devices in the body, such as prosthetic joints,
prosthetic heart valves, and peritoneal dialysis catheters.
In fact, Staphylococcus epidermidis is the most frequent
organism isolated from infected indwelling prosthetic
devices. The organisms have a polysaccharide capsule
that allows adherence to these prosthetic materials.
Staphylococcus epidermidis often forms biofilms on
intravascular catheters and leaches out to cause bac
teremia and catheter related sepsis. A biofilm is an extra
cellular polysaccharide network, similar to the capsule
polysaccharides, that forms a mechanical scaffold around
bacteria. The biofilm allows bacteria to bind to prosthetic
devices, like intravenous catheters, and protects them
 CHAPTER 5. STAPHYLOCOCCI

CLINICAL TR EATM ENT DIAGNOSTI CS

A. Exotoxin Dependent 1 . Penicillinase-resistant 1 . G ram stain: reveals gram

1 . Gastroenteritis (food poisoning) : Rapid onset penicillins: nafcillin ( I V) positive cocci in clusters
of vomiting & diarrhea, with rapid recovery and dicloxacillin (oral). 2. Culture:
2 . Toxic shock synd rome: 2. 1 st generation A. Beta-hemolytic
A. High fever cephalosporins: 8 . Produces a golden yellow
B. Nausea and vom iting cefazolin (IV), pigment.
C . Watery diarrhea cephalexin (oral) 3. Metabolic
D. Erythematous rash treat with i ntravenous A. Catalase-positive
E. Hypotension 3. Clindamycin (IV and oral) B. Coagulase-positive
F. Desquamation of palms and soles 4 . Polymerase chain reaction (PCR)
3. Scalded skin syndrome detection of ribosomal RNA.
B . Direct Invasion If M RSA:
1 . Pneumonia 1 . Vancomycin (IV)
2. Meningitis 2. Daptomycin (IV)
3 . Osteomyelitis (in chi ldren) 3. Clindamycin ( I V and oral)
4 . Acute bacterial endocarditis 4. Trimethapri m
5 . Septic arth ritis sulfamethoxazole
6. Skin infection (IV and oral)
7. Bacteremia/sepsis 5. Linezolid (IV and oral)
8. U rinary tract i nfection

A. Nosocomial infections: Vancomycin 1 . G ram stain ; reveals gram

1 . Prosthetic joints (since resistant positive cocci i n clusters
2. Prosthetic heart valves to multiple 2. Culture
3. Sepsis from intravenous lines antibiotics) 3. Metabolic
4. U rinary tract i nfections A. Catalase-positive
B. Frequent skin contaminant in blood 8. Coagulase-negative
cultures!

U ri nary tract infections in sexually Penici llin 1 . G ram stain: reveals gram
active women positive cocci i n clusters
2. C ulture: gamma-hemolytic
3. Metabolic
A. Catalase-positive
B. Coagulase-negative

M. Gladwin, W. Trattler, and S . Mahan , Clinical Microbiology Made Ridiculously Simple Med Master

from attack by antibiotics and the immune system. Imag
ine bacteria secreting their polysaccharide concrete
around themselves to form a biological bunker.
Staphylococcus saprophyticus
This organism is a leading cause ( second only to E.
coli ) of urinary tract infections in sexually active young
women. It is most commonly acquired by females (95%)
in the community (NOT in the hospital ). This organism
is coagulase-negative.
Fig. 5-1 1. Summary chart of staphylococci.
Recommended Review Articles:
Bamberger DM and Boyd SE. Management of Staphylococcus
aureus infections. Am Fam Physician 2005;72:2474-8 1 .
Boucher H, Miller LG, Razonable RR. Serious infections
caused by methicillin-resistant Staphylococcus aureus.
Clin Infect Dis. 2010;5 1 Suppl 2:S183-97.
Davis SL, et al. Epidemiology and outcomes of community
associated methicillin-resistant Staphylococcus aureus in
fection. J Clin Microb 2007 ;45( 6): 1705-17 1 1 .
Eckmann C, Dryden M. Treatment o f complicated skin and
soft-tissue infections caused by resistant bacteria: value of
linezolid, tigecycline, daptomycin and vancomycin. Eur J
Med Res. 2010; 15( 12):554-63.
Henderson DK. Managing methicillin-resistant staphylococci :
a paradigm for preventing nosocomial transmission of re
sistant organisms. Am J Med 2006 ; 1 19:S45-52.
Jeyaratnam D, Reid C, Kearns A and Klein J. Community ac
quired MRSA: an alert to paediatricians. Arch Dis Child
2006;91:51 1-2.
Liu C, Bayer A, et al. Clinical practice guidelines by the In
fectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus Aureus infections in
adults and children. Clin Infect Dis 20 1 1 ;52: 1-38.
Mehnert-Kay SA. Diagnosis and management ofuncomplicated
urinary tract infections. Am Fam Physician 2005;72:45 1-6.
Moran GJ, et al. Methicillin-resistant S. aureus infections
among patients in the emergency department. NEJM 2006;
355(7):666-674.

47
 CHAPTER 6. BACILLUS AND CLOSTRIDIUM (SPORE-FORMING RODS)

into the bloodstream and is carried to the site of infection References

via the colonic blood vessels, so that it can be given orally
or IV. see Chapter 1 8 , Fig. 18-6).
Unfortunately relapse due to C. difficile is increas
ingly common ( 10-25%) and with each relapse further
recurrences may occur. A new agent, fidaxomicin, was
approved in 20 1 1 and has been shown to be superior to
vancomycin in treating recurrences of C. difficile infec
tion. For those with an adventurous spirit . . . fecal trans
plantation has been shown to be highly effective at
preventing recurrent disease in persons who have had
multiple relapses of C. difficile infection.
Fig. 6-6. Summary of the Gram-positive spore-forming
rods
Arnon SS, Schechter R, Maslanka SE, Jewell, NP, Hatheway
CL. Human botulism immune globulin for the treatment of
infant botulism. New Eng J Med 2006;354:462-4 7 1 .
Bartlett J G , Gerding D N . Clinical recognition a n d diagnosis
of Clostridium difficile infection. Clin Infect Dis 2008;46:
S 12-8.
Gerding DN, Johnson S. Management of Clostridium diffi
cile infection: Thinking inside and outside the Box. Clin
Infect Dis 2010;5 1 : 1306-13.
Jernigan DB, et al. Investigation of bioterrorism-related
anthrax, United States, 2001 : epidemiologic findings. Emerg
Infect Dis 2002;10: 1019-1028.
Louie TJ , Miller MA, et al . Fidaxomicin versus Vancomycin for
Clostridium difficile infection. NEJM 201 1;364:422-3 1 .

ORGANISM R E S E RVOIR TRANSMISSION METABOLISM VIRULENCE

Bacillus Herbivores Endospores Aerobic (but 1 . Unique protein capsule (polymer of

anthracis (zoonotic) 1 . Cutaneous since it can gamma-D-gl utamic acid) : antiphagocytic
A. Sheep 2 . I nhalation grow without 2. Non-motile
B . Goats 3. Ingestion oxygen, it is 3. Vi rulence depends on acq u i ring
C. Cattle classified as 2 plasmids. One carries the gene for
a facultative the protei n capsule; the other carries the
anaerobe) gene for its exotoxin

Bacillus E ndospores Aerobic 1 . No Capsule

cereus 2. Motile

Clostridium 1 . Soil Endospores Anaerobic Motile: flagella (so H-antigen positive)

botulinum 2. Stored ( heat resistant)
vegetables:
Home-canned
Zip-lock
storage bags
3. Smoked fish
4 . Fresh honey:
associated
with i nfant
botulism

Figure 6-6 GRAM-POSITIVE SPORE-FORMING RODS

54
 CHAPTER 6. BACILLUS AND CLOSTRIDIUM (SPORE-FORMING RODS)

McDonald LC , et al. An epidemic, toxin gene-variant stain of Recommended Review Articles:

Clostridium difficile . New Eng J Med 2005 ;353 :2433-244 1 .
Machem CC, Walter F G . Woun d botulism. Vet Hum Toxicol
1994;36:233-237 .
van Nood E, Vrienze A , e t a l . Duodenal infusion o f donor
feces for recurrent Clostridium difficile. NEJM 2013 ;368:
407-15.
Update: Investigation of bioterrorism-related anthrax and
interim guidelines for the exposure management and
antimicrobial theraphy, October 200 1 . MMWR Weekly
2001;50:909-9 19.
Warny M, et al. Toxin production by an emerging strain of
Clostridium difficile associated with outbreaks of severe
disease in North America and Europe. Lancet 2005;366:
1079-1084.
TV, O'Toole T, Henderson DA, et al. Anthrax as a
Inglesby
biological weapon, 2002 : updated recommendations for
management. JAMA. 2002;287( 17):2236-52
Kelly CP, LaMont JT. Clostridium difficile-more difficult
than ever. N Engl J Med. 2008;359( 1 8 ) : 1 932-40.
Pellizzari R, et al. Tetanus and Botulism Neurotoxins:
mechanisms of action and therapeutic uses. Philosophical
Transactions of the Royal Society of London 1999;354:
259-268.
Salkind AR Clostridium difficile : an update for the primary
care clinician. South Med J. 2010; 103(9):896-902.
Swartz MN. Recognition and management of anthrax-an
u pd ate. N Engl J Med. 200 1 ;345(22): 162 1-6. Ep u b 200 1
6.
Nov

TOXINS C L I N ICAL TR EATM ENT DIAGNOSTICS

Exotoxin: 3 proteins Anthrax 1 . Ciprofloxacin 1. G ram stain

a. Protective antigen ( PA)
b. Edema factor ( E F)
c. Lethal factor (LF)
1 . Cutaneous (95%) :
pain less black vesicles;
Can be fatal if untreated
2. Pulmonary (woolsorter's
disease)
3. G I : abdominal pai n ,
vomiting a n d bloody
diarrhea
I nfection results in
permanent immunity (if
the patient su rvives)
2 . Doxycycline 2. Culture
3. Raxibacumab (monoclonal antibody 3. Serology
for use in inhalational anthrax) 4. PCR of
4. Vaccine: for high-risk individuals nasal swab
A. Vaccine is composed of the
protective antigen ( PA)
B. Animal vaccine is composed
of a live strain, attenuated
by loss of its protein capsule

Enterotoxins Food poisoning: 1 . Vancomycin Cu ltu re

A. Heat labile: similar nausea, vomiting and 2. Clindamycin specimen from
to enterotoxin of cholera diarrhea 3. Resistant to beta-lactam suspected
and E. coli. antibiotics food source
B. Heat stable: produces 4. No treatment for food
syndrome similar to that poisoning ("Be serious,
of Staphylococcus Dr. Goofball : food poisoning
aureus food poisoning, is caused by the pre-formed
but with limited diarrhea enterotoxin)

1 . Neu rotoxin: i n hibits
release of acetylcholine
from peripheral nerves
2. Toxin is not secreted .
Rather it is released
upon the death of the
bacteri um
Food-borne botulism: 1 . Antitoxin (for food-borne and 1 . G ram stain
1 . Cranial nerve palsies wound botulism) 2. Culture :
2. M uscle weakness 2 . H u man botulism immunoglobulin requ i res
3. Respi ratory paralysis (for infant botulism) anaerobic
Infant botulism: 3. Penicillin conditions
1 . Constipation 4. Hyperbaric oxygen 3. Patient's
2 . Flaccid paralysis 5 . Supportive therapy: serum injected
Wound botulism: including incubation and i nto mice
1 . Similar to Food-borne ventilatory assistance results in
except absence of G I death
prodromal symptoms

55
 CHAPTER 6. BACILLUS AND CLOSTRIDIUM (SPORE-FORMING RODS)

ORGANISM RESERVOIR TRANS M I SS I O N M ETABOLI S M VIRULENCE

C/ostridium Soi l Endospores: Anaerobic Motile: flagella (so H-antigen positive)

tetani introduced
through wound

Clostridium Ubiquitous: Endospores Anaerobic NON-motile

perfringens 1 . Soil
2 . GI tract of
h u mans &
mammals

Clostridium 1 . I ntestinal Fecal-oral : Anaerobic Motile: flagella (so H-antigen positive)

difficile tract ingestion of
2. Endospores endospores
found in
hospitals
and nursing
homes

Figure 6-6 (continued)

56
 CHAPTER 6. BACILL US AND CLOSTRIDIUM (SPORE-FORMING RODS)

TOXI NS CLINICAL TR EATM E NT DIAGNOSTICS

Tetanospasm i n : inhibits Tetanus 1 . Tetanus toxoid: vaccination 1 . G ram stain:
release of GABA and 1. Muscle spasms with formalin-i nactivated toxin g ram-positive
glycine (both inhibitory 2. Lockjaw (trismus) (toxoid). Part of the D PT vaccine rods, often with
neurotransmitters) from 3. Risus sardonicus 2. Antitoxin: human tetanus an endospore
nerve cells, resulting in 4. Respi ratory m uscle immune globulin (preformed at one end,
sustained muscle paralysis anti-tetanus antibodies) giving
contraction 3. Clean the wound them the
4. Metronidazole or penici llin appearance of
5. Supportive therapy: may requ i re a drumstick
venti latory assistance 2 . Culture:
Vaccine: DTap requires
1 . Diphtheria anaerobic
2 . Tetanus conditions
3. acellular Pertussis

1 . Alpha toxin: lecithi nase Gaseous Gangrene 1 . Radical su rge ry (may require 1 . G ram stain
(splits lecithin into A. Cellulitis/wound amputation) 2 . Culture:
phosphochol ine infection 2. Penicillin requires
and diglyceride) B . Clostridial myonecrosis: 3. Hyperbaric oxygen anaerobic
2 . 1 1 other tissue fatal if untreated conditions
destructive enzymes C. Watery diarrhea:
associated with food-borne
ingestion

1 . Toxin A: diarrhea Pseudomembranous 1. Metronidazole 1 . I m m unoassay

2. Toxin B: cytotoxic to enterocolitis: 2. Oral vancomycin for C. difficile
colonic epithelial cells antibiotic-associated 3. Fidaxomicin toxin
diarrhea 4. Fecal transplant 2 . PCR for toxin
5. Discontinue unnecessary A and B
antibiotics genes

M . Gladwi n , W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple Med Master

57
 CHAPTER 7. CORYNEBACTERIUM AND LISTERIA (NON-SPORE-FORMING RODS)

NAME M O R P H O LO G Y TRANSMISSION M ETA B O LISM VIRULENCE

Corynebac 1 . G ram-positive Respi ratory 1 . Facultative Pseudomembrane forms

terium rods (very droplets from anaerobe i n the pharynx, which
diphtheriae pleomorphic and a carrier 2. Catalase-positive serves as a base from
club-shaped) where it secretes its
2 . Non-spore-forming toxin
3. Non-motile

Listeria 1 . G ram-positive 1 . I ngestionof 1 . Facultative 1 . M ot i le (via flagel la) :

monocytogenes rods contam inated anaerobe so has H-antigen
2. Non-spore-form ing raw milk or 2. Catalase-positive 2 . Hemolysi n : (like
3. Moti le: tumbling cheese from 3. Beta-hemolytic streptolysin 0)
moti l ity is seen infected cows on blood agar a. Heat labile
when grown 2. Vaginally b. Antigenic
at 25 C. (during birth)
3. Transplacental
infection of
fetus from bac
teremic mother

Figure 7-3 NON SPORE-FORMING GRAM-POSITIVE RODS

62
 CHAPTER 7. CORYNEBACTERIUM AND LISTERIA (NON-SPORE-FORMING RODS)

TOXI N S C L I N ICAL TREATM ENT DIAGNOSTICS MISC ELLANEOUS

Exotoxin (coded Diphtheria 1 . Antitoxin 1 . G ram stain: 1 . Obtains exotoxin

by a bacteriophage) : 1 . Mild sore th roat 2. Penicillin or gram-positive from a temperate
A subunit: blocks with fever erythromycin pleomorphic bacteriophage by
protei n synthesis initially 3. Vaccine: D PT rods (sometimes lysogenic
by i nactivating E F2 2. Pseudomem- Diphtheria: described as conversion
B subunit: provides brane forms on formalin looki ng l i ke 2. Schick test:
entry into cardiac pharynx Inactivated Chinese letters) i njection of
and neural tissue 3. Myocarditis causing exotoxin, as 2. Culture : diphtheria exotoxi n
A-V conduction antibodies A. Potassium into the skin , to
This exotoxi n block and to the tellu rite: get determine whether a
is like an anti-human dysrhythmia B-subunit dark black person is susceptible
antibiotic, as it 4. Neural are colonies to i nfection by
inhibits eucaryotic involvement protective B. Loeffler's mediu m : C . diphtheriae
protein synthesis, a. Peripheral Pertussis after 1 2 hours of
just as tetracycline nerve palsies Tetanus growth, stain
inhibits protein b. Guillain with methylene
synthesis in Barre-l i ke blue. Reddish
bacteria syndrome (Babes-Ernst)
c. Palatal paralysis granu les can
and cranial be seen
neuropathies

Listeriolysin 0 and 1 . Neonatal 1 . Ampicillin 1 . G ram stain : Facultative

phospholi pases: meningitis 2. Trimethoprim/ g ram-positive intracellular parasite
allows escape from 2. Meningitis sulfamethoxazole rods Cell-mediated
the phagolysosomes in immuno- 2. Culture : immunity i s
o f macrophages suppressed can grow at protective
patients and the temperatu res
elderly ( > 50) as low as 0 C.
3. Septicemia in So use cold
pregnant women en richment
tech nique to
isolate from
mixed flora

M. Gladwi n , W. Trattler, and S. Mahan , Clinical Microbiology Made Ridiculously Simple MedMaster

63
 CHAPTER 8. NEISSERIA

type beta-lactamase (penicillinase) encoding plasmid
(called the Per determinant). There is a plasmid with the
tetM gene sequence that encodes a protein that protects
ribosomes from the effects of tetracycline.
2) Chromosomally mediated antibiotic resis
tance to beta-lactams, tetracycline and now the fluoro
quinolones is a big problem. The mtr gene locus encodes
an effiux pump that prevents accumulation of antibi
otics in cells. The penA locus represents a mutation that
alters penicillin binding protein 2 (the transpeptidase
required to synthesize peptidoglycan) to reduce its affin
ity for penicillin. Multiple mutations in the chromoso
mal gyrA and gyrB genes that encode the DNA gyrases
confer resistance to ciprofloxacin.
We may be fast approaching the day of untreatable gon
orrhea! The recommended treatment of choice is currently
ceftriaxone, a third generation cephalosporin (see page
181) combined with a 1 gram single dose of azithromycin.
Until 2012, ceftriaxone alone was considered sufficient,
but reduced susceptibility to cephalosporins as a result of
several gene mutations has led to increased resistance.
The azithromycin will also cover Chlamydia trachomatis,
because up to 50% of patients will be concurrently infected
with this beta-lactam-resistant (ceftriaxone included)
bacteria.
MORAXELLA (BRANHAMELLA)
CATARRHALIS
The greater family of Neisseriaceae is composed of
five genera: Ne isse ria, Moraxella (subgenera Bran
hamella ) , Kingella, Acinetobacter, and Oligella . We will
only discuss Moraxella and Kingella as they are impor
tant human pathogens you will need to know about.
Moraxella (Branhamella) catarrhalis causes
two major diseases: otitis media and upper respiratory
infection in patients with chronic obstructive pul
monary disease (COPD or emphysema) or in the elderly:
Otitis media: this middle ear infection occurs in
about 80% of all children by 3 years of age. It is caused
by three main bacteria, Streptococcus pneumoniae
( = 30% of cases) , Haemophilus infiuenzae ( = 25%) and
Moraxella catarrhalis ( = 15-20%).

G RAM-NEGATIVE R ES E R V O I R M O R P H O LOGY & VIRULENCE TOXI N S

D I P LOCOCCI M ETABO L I S M

Neisseria 1 . Nasopharynx 1 . Kidney bean shaped 1 . Capsule: 1 . Endotoxin:

meningitidis of humans only. with concave sides a. 1 3 serotypes Lipopoly
I m m u n ity can facing each other, based on antigeni saccharide (LPS)
develop to forming the appearance city of capsule 2 . No exotoxins
particular of a doughnut polysaccharides
strains 2. G ram-negative b. Serotypes
Strict human diplococci A, B, & C are
parasite 3. Facultative-anaerobe associated with
2. Spread by 4. G rows best in high epidemics of
respi ratory C02 environment meningitis (usually
transmission 5. Ferments maltose type B)
and glucose - easy 2 . lgA1 protease
to remember, since 3. Have unique p roteins
there is both an "m" that can extract i ron
and "g" in meningitidis from transferri n ,
lactoferrin and
hemoglobin
4 . Pili: for adherence

Figure 8-2 NEISSERIA

68
 CHAPTER S. NEISSERIA

COPD exacerbations : worsening of wheezing, Fig. 8-2. Summary of Neisseria.

shortness of breath and cough . These exacerbations are
often associated with an acquisition of a new strain of
nontypeable Haemophilus influenzae or infection with
Moraxella catarrhalis (30% of cases). Moraxella catar
rhalis also causes pneumonia in the elderly.
Kingella kingae is the most frequent human
pathogen of the Kingella genera. It frequently colonizes
the throats of young children and can cause septic
arthritis and osteomyelitis in children. In children and
adults it can cause endocarditis of native and prosthetic
valves.
Clinical Pearl: Kingella kingae is commonly grouped
with several slow growing gram negative pathogens
known to cause endocarditis called the HACEK group of
bacteria :
Haemophilus species
Actinobacillus species
Cardiobacterium species
Eikenella species
Kingella species
Recommended Review Articles:
Bolan GA, Sparling, et al. The emerging threat of untreatable
Gonococcal infection. NEJM 2012;366:485-7.
Cook RL, Hutchison SL, Ostergaard L, et al. Sy stematic
review: noninvasive testing for Chlamy dia trachomatis and
Neisseria gonorrhoeae. Ann Intern Med 2005; 142:9 14-25.
Crossman SH. The challenge of pelvic inflammatory disease.
Am Fam Physician 2006;73:859-64.
Deeks ED. Meningococcal quadrivalent (serogroups A, C,
w l35, and y) conjugate vaccine (Menveo): in adolescents
and adults. BioDrugs. 2010;24(5):287-97
Gottlieb SL, Berman SM, Low N. Screening and treatment to
prevent sequelae in women with Chlamydia trachomatis
genital infection: how much do we know? J Infect Dis.
2010;201 Suppl 2:Sl56-67.
Pathan N, Faust SN, and Levin M. Pathophysiology of
meningococcal meningitis and septicaemia. Arch Dis Child
2003;88:60 1-7 .

C L I N ICAL TREATM ENT DIAGNOSTICS MISCE LLANEOUS

1 . Asymptomatic carriage 1 . Vaccine against capsular 1 . G ram-stain 1 . Neonates are

in the nasopharynx antigens: A, C , Y & W- 1 35 2 . Culture very susceptible
2 . Meni ngitis: only not B (as antibodies
- A. Culture speci men on from 6 to 24 months,
A. Fever don't form against B) blood agar that has when protective
B. Stiff neck (nuchal rigidity) 2. Antibiotics: been heated to 80 C. anti meningococcal
C. Vomiting A. Penicillin G for 15 min utes (called lgG is low
D. Lethargy or altered B. Ceftriaxone (or other third chocolate agar) 2 . Army recruits are
mental status generation cephalosporins) B . Selective media: also at high risk
E. Petechial rash C . R ifampin and ciprofloxacin prevents g rowth of (with carriage rates
3. Septicemia are used for prophylaxis bacteria of greater than 40%)
(meningococcemia) : of close contacts of Thayer Martin VCN
A. Fever infected persons. V Vancomycin
=

B. Petechial rash C Colistin

=

C. Hypotension N = Nystati n
D . Fulmi nant C . Cell wall contains
meningococcemia cytoch rome oxidase
(Waterhouse-Friderichsen which oxidizes dye
Syndrome) : hemorrhage tetramethylphenylene
of the adrenal glands along diamine from colorless
with hypotension and the to deep pink. Used to I D
petechial rash colonies
D. PCR of bacteria DNA i n
clinical specimens

69
 CHAPTER 8. NEISSERIA

GRAM-NEGATIVE R ES E RVO I R M O R P H O LOGY & VIRULENCE TOXINS

D I P LOCOCCI M ETABOLISM

Neisseria 1 . Humans only 1 . Kidney bean shaped 1 . Pili: 1 . Endotoxin :

gonorrhoeae (no immunity to with concave sides A. Adherence Lipopoly
repeated facing each other, to epithelial cells saccharide (LPS)
i nfections) forming the B. Antigenic variation 2. No exotoxins
2 . Sexually appearance of C . Antiphagocytic:
transm itted a doughnut binds bacteria
2. G ram-negative tightly to host
diplococci cell , protecting
3. Facultative-anaerobe it from
4. G rows best in phagocytosis
high C02 environment 2 . l gA1 protease
5. Ferments only glucose 3. Outer membrane
(not maltose) - easy proteins: Protei n I :
to remember, since porin P rotei n I I
there is only a "g" (opacity protein):
(no "m") in gonorrhoeae presence associated
with dark, opaque
colonies
for adherence
4 . H ave unique proteins
that can extract i ron
from transferri n ,
lactoferrin and
hemoglobin

Moraxella Part of the normal

(Branhamella) respi ratory flora
catarrhalis

Figure 8-2 (continued)

70

C L I N ICAL
1 . Asymptomatic (but still
infectious)
2 . Men: ureth ritis
3 . Women: cervical
gonorrhea, which can
progress to pelvic
inflammatory disease {P I O )
Complications o f PIO
A. Steril ity
8. Ectopic pregnancy
C. Abscess
D. Peritonitis
E . Perihepatitis
4 . Both men and women :
A. Gonococcal bacteremia
8. Septic arth ritis:
gonococcal arthritis is
the most common cause
of septic arthritis in
sexually active
individuals
5 . Neonates: Ophthalmia
neonatorum conj unctivitis
in newborns .
N . gonorrhoeae
is acquired d u ring passage
through an i nfected b i rth
canal. Conj u nctivitis
usually erupts within
the first 5 days
1 . Otitis media in children
2 . Can cause other
respi ratory tract
i nfections, such as
sin usitis, bronchitis, &
pneumonia
3. COPD exacerbations
CHAPTER 8. NEISSERIA
TREATM E NT DIAG N OSTICS MISCELLANEOUS
1 . Antibiotic of choice: 1 . G ram-stain of No immunity
Ceftriaxone 250 mg u reth ral pus reveals the fol lowing infection:
I M and Azith romycin tiny gram-negative a person can be
1 gm orally x 1 doughn ut-shaped reinfected
2. Second line: diplococci within wh ite numerous times
A. Cefixime + azithromycin blood cells
or doxycycline 2 . Culture
B. Spectinomycin A. Culture specimen
(not available in the U . S . ) on chocolate agar
3. For ophthalmia 8 . Selective media:
neonatoru m : prevents growth of
E rythromycin eye drops other bacteria
should be given Thayer Martin VCN
immediately following birth , V Vancomycin
=
for prophylaxis agai nst C Col isti n
=
both N. gonorrhoeae and N = Nystatin
Chlamydia trachomatis C. Cell wall contains
conjunctivitis cytochrome oxidase
I nfants with ophthalmia which oxidizes dye
neonatorum require tetramethylphenylene
systemic treatment with diamine from colorless
ceftriaxone. Eryth romycin to deep pink. Used to I D
syrup should also be colonies
provided to cover for D . PCR of bacterial DNA in
possible concu rrent clinical specimens
Chlamydia! disease (Th is
is important, as fail u re
to treat neonatal Chlamydia
conjunctivitis can lead to
Chlamydia! pneumonia)
1 . Azithromycin or Resistant to
clarithromycin penicillin
2 . Amoxicillin with clavulanate
3. Oral second or third
generation cephalosporin
4. Trimethopri m/
sulfamethoxazole
M . Gladw i n , W. Trattler, a n d S . Maha n , Clinical Microbiology Made Ridiculously Simple M e d Master
71
 CHAPTER 9. THE ENTER/CS

G R AM-NEGATIVE RESERVOI R TRA N S M I SSION M ETABOLISM VIRUL E N C E

RODS

E N T E R O B A CT E R I A C E A E

Enterobacteriaceae All are G ram 1 . Fecal-oral 1. Catalase-positive Many of these

generalities negative rods 2 . Migration u p the 2. Oxidase-negative organisms can
u reth ra 3. Ferments glucose acqu i re antibiotic
3. Colonization of 4. Facultative resistance
catheters in anaerobic
hospitalized
patients ( Foley
catheters,
central lines, etc.)

Escherichia coli Humans: 1 . Fecal-oral 1 . l ndole-positive 1 . Fimbriae (pili):

G I and 2. Migration up (makes indole colonization factor
u rinary tract the u rethra from tryptophan) 2. Siderophore
3. Colonization of 2 . Beta-hemolytic 3. Adhesins
catheters i n 3 . Ferments lactose 4. Capsule
hospitalized (K-antigen)
patients (Foley 5. Flagella
catheters, (H-antigen)
central lines, etc.)
4 . Aspi ration of
oral E. coli

Klebsiella l ndole-negative 1 . Capsule

pneumoniae Ferments lactose 2. Non-motile

Figure 9- 1 1 ENTERIC BACTERIA

82
 CHAPTER 9. THE ENTER/CS

TOXI N S C L I N ICAL TR EATM E N T DIAGNOSTICS M I S C ELLANEOUS

1 . Many have 1. Many organisms 1 . Eosi ne methylene A ntigenic

enterotoxins cause diarrhea blue agar ( E M B) : Classification
2 . All have 2. Various other inhibitory t o gram 1 . 0-antigen:
endotoxin: infections i ncluding positive bacteria Outer portion
lipopolysac u rinary tract infections, 2 . MacConkey agar: of LPS.
charide (LPS) pneumonia and Contains bile salts 2. K-antigen:
sepsis especially in the media that Kapsule
(in debil itated inh ibit gram-positive 3. H-antigen:
hospitalized patients) bacteria Flagella

Enterotoxins 1 . Newborn meningitis 1 . Cephalosporins 1 . Gram stain I ndex organ

1 . LT (Heat 2. U rinary tract infection 2. Aminoglycosides 2. Culture (specimen ism for fecal
labile) : 3. Hospital acqui red 3. Trimethoprim & may be urine, contami nation
increases sepsis su lfamethoxazole sputum , CSF or of water
cAMP (same 4 . Hospital acqui red 4 . Fluoroq ui nolones blood ) . Can grow
as cholera pneumonia at 45.5 C.
toxi n) 5. Diarrhea 3. Pathogenic strains
2 . ST (heat A. Noninvasive strain may be isolated
stable) : ( Enterotoxigenic) : from stool
increases releases LT and ST E. coli ferments
cGMP toxins, causing lactose. Its colonies
3. Shiga-like traveler's diarrhea produce a green
toxin B . Enterohemorrhagic: metallic sheen on
(verotoxi n ) : bloody diarrhea; no EMB agar and are
inh ibits fever, no pus i n pink-pu rple on
protein stool; secretes MacConkey agar.
synthesis by Shiga-li ke toxin:
i nactivating causes hemor
the 60S rhagic colitis and
ribosomal hemolytic uremic
subunit syndrome ( E. coli
strain 0 1 57: H7)
C. Enteroinvasive:
bloody diarrhea
(with pus in stool)
and fever. Also
secretes small
amounts of
Shiga-like toxin.

1 . Pneumonia, with 1 . Third

significant lung generation
necrosis and bloody cephalospori n
sputum , commonly in 2. Ciprofloxaci n
alcoholics, or those
with underlying lung
disease
2. Hospital acq ui red
urinary tract infections
and sepsis

83
 CHAPTER 9. THE ENTER/CS

GRAM-NEGATIVE RESERVOIR TRANSM ISSION M ETABOLISM VIRU L E N C E

RODS

Proteus 1 . U rease: splits Motile (swarming)

mirabilis u rea into N H 3 &
C02
2. l n dole
negative
3. Does not
ferment
lactose.

Shigella H umans Fecal-oral 1 . No H2S 1 . I nvades

dysenteriae transmission production submucosa of
2. Does not intestinal tract,
ferment but not the lamina
l acto se . propria
2. NON-motile: No
H-antigen (since
no flagella)

Salmonella typhi S. typhi is S. typhi is 1 . Produces H2S 1 . Mot il e (H-antigen)

found only transmitted 2. Does not 2. Capsule (called
in humans via fecal-oral route ferment lactose. the VI antigen):
prote cts from
Non-typhi groups Zoonotic: i ntracellular killing
of Salmonella 1 . Pet tu rt I es 3. Siderophore
2. Chickens
3. U ncooked
eggs

Yersinia Zoonotic: can 1 . I ngestion of 1 . Non-lactose 1 V and W antigens

.

enterocolitica be found in contaminated food fermenter 2. Motile

pigs or water 2 . Virulence
2. U npasteu rized milk factors are
temperature
sensitive;
expressed
at 37 C

Figure 9- 1 1 (continued)

84
 CHAPTER 9. THE ENTER/CS

TOXIN S C LI N I CA L TREATMENT DIAGNOSTICS MISCELLANEOUS

No toxin 1 . U rinary tract infection: 1 . Ampicillin 1. Culture: colonies Weil-Felix test:

urine has a high pH 2. Trimethoprim & swarm over entire a test that uses
due to urease. May get sulfamethoxazole culture plate antibodies
stones in the bladder 2. Exami nation of against certain
2 . Sepsis urine shows a strains of
high pH (from proteus to
spl itting u rine into diagnose
NH3 and C0 2 ) rickettsial
diseases (as
certain rick-
ettsiae share
similar antigens)

Shiga toxin: BLOODY 1 . Fluoro- Stool culture: never l gA is best

I nactivates diarrhea with q u inolones part of the normal for immunity
the 60S mucus and 2. Azithromycin intestinal flora
ribosome , p u s (similar 3. Trimethoprim &
inhibiting to enteroin- su lfamethoxazole
p rotein vasive E. coli)
synthesis
and killing
i ntestinal
epithelial
cells

1 . Enteric Fever 1 . Ciprofloxacin Culture: blood , A. Facultative

A. Typhoid fever: 2. Ceftriaxone stool or urine may intracellular
1 . Fever 3. Trimethoprim & contain S. typhi. parasite:
2. Abdominal pain sulfamethoxazole never part of the 1 . Lives
3. Liver or spleen 4. Azithromycin normal i ntestinal within
enlargement *Salmonella flora macrophages
4 . Rose spots gastroenteritis : i n lymph
on abdomen there is l ittle nodes
B. Paratyphoid benefit from 2 . Can live in
fever (similar to antibiotic treatment- gallbladder for
typhoid fever, but can prolong carrier years (carriers
caused by state secrete S. typhi
non-typhoid i n stools)
Salmonella) B. Persons who are
2. Chronic carrier state asplenic or have
3. Gastroenteritis nonfunctioning
4 . Sepsis spleens (sickle
5. Osteomyelitis: cell anemia) are
especially in sickle at i ncreased risk
cell patients of i nfection by
this organism

Enterotoxi n Acute enterocolitis, Antibiotics do 1 . Stool or blood 1 . Can su rvive

similar to the with fever, diarrhea not alter the cultures may be refrigeration .
heat stable and abdominal pain . course o f the positive 2. Closely related
toxin of diarrhea. 2. Examination to Yersinia
E. coli: However, patients of the terminal pestis, which is
increases with positive ilium with the cause of
cG M P levels blood culture colonoscopy bubonic plague
should be treated wil l reveal m ucosa!
with antibiotics ulceration

85
 CHAPTER 9. THE ENTER/CS

G RAM-NEGATIVE RESERVOI R TRANSMISSION M ETABOLISM VIRU LENCE

RODS

VIBRIONACEAE

Vibrio cholerae 1 . Fecal-oral 1 Oxidase-positive

. 1 . Motile (H-antigen)
transmission 2 . Ferments 2. M ucinase:
2 . Morphology: sugars (except digests mucous
short comma lactose) layer so
shaped, gram- V. cholerae can
negative rod , attach to cells.
with a single 3. Fimbriae: helps
polar flagellum with attachment
to cells.
4. Non-invasive ! !

Vibrio Fish 1 . Consumption of Halophi l ic (likes 1 . Motile (H-antigen)

parahaemolyticus raw fish salt) 2 . Capsule
2 . Morphology:
short comma
shaped, with a
single polar flagellum

Campylobacter Zoonotic: 1 . Uncooked 1 . Microaerophilic 1 . Motile (H-antigen)

jejuni wild and meat (especially 2. Oxidase positive 2. I nvasive
domestic poultry) 3. Optimum
animals, 2 . U n pasteurized milk temperatu re
and poultry 3. Fecal-oral is 42 C
4 . Morphology: curved
gram-negative
rods, with a single
polar flagel l u m

Helicobacter pylori Morphology: cu rved 1 . Microaerophilic

g ram-negative rods, 2 . U rease-positive
with a tuft of polar
flagellum

BACTEROIDACEAE

Bacteroides fragilis Part of the 1 . Anaerobic

normal flora 2. G ram-negative
of the intestine rod

Figure 9-1 1 (continued)

86
 CHAPTER 9. THE ENTER/CS

TOX I N S CLIN ICAL T R E ATM E N T DIAG N OSTICS M ISCELLAN EOUS

Choleragen Cholera: severe 1 . Replace flu ids 1 . Dark field Death by

(enterotoxin) : diarrhea with rice 2. Doxycycline microscopy of dehydration ;
l i ke LT of water stools. No 3. Fl uoroqu inolone stool reveals children affected in
coli; pus i n stools motile endemic areas
1 99 1 : Latin America
E.
increases organisms that
levels of cAMP, are immobilized epidemic
causing with antiseru m 1 993: Epidemic in
secretion of 2. G rows as flat Bangladesh and
electrolytes yellow colonies I ndia
from the on selective
i ntestinal media: thiosu lfate-
epithelium. citrate-bile
This results in salts-sucrose
secretion of (TCBS) agar
fluid i nto the
intestinal tract.

Hemolytic Cause of 25% 1 . Doxycycline Req u i res

cytotoxin of food poisoning 2 . Fluoroq ui nolone thiosulfate &
in Japan (diarrhea * (unclear if bile salts
for 3 days) antibiotics change
clinical course)

1 . Enterotoxi n : Secretory o r 1 . Fluoroqui nolone 1 . Microscopic exam One of the th ree

similar to bloody diarrhea 2 . E ryth romycin of stool reveals most common
cholera toxin moti le, curved causes of
and the LT gram-negative rods diarrhea in the
of E. coli 2. Selective media world
2. Cytotoxin : with antibiotics
destroys at 42 C.
mucosal cells

No toxin 1 . D uodenal ulcers 1 . Bismuth ,

2. Chronic gastritis ampici l l i n ,
metronidazole
and tetracycline
2 . Clarithromycin
and omeprazole
Both regimens
reduce duodenal
ulcer relapse

Does not Abscesses in the 1 . Metronidazole 1 . G ram-stain I nfection occurs

contain lipid gastrointestinal 2 . Clindamycin 2. Anaerobic when the
A (so NO tract, pelvis and 3 . Chloramphen icol culture organism

87
 CHAPTER 9. THE ENTER/CS

G RAM-NEGATIVE RESE RVOIR TRANSMISSIO N VIRULENCE

R O DS

3. Non-spore
former
4. Polysaccharide
capsule

Bacteroides Part of the 1 Anaerobic

.

melaninogenicus normal flora of 2 . G ram-negative

the i ntestine rod
3. Non-spore
former
4. Polysaccharide
capsule

Fusobacterium 1 Anaerobic
.

2. G ram-negative
rod
3. Non-spore
former

Figure 9- 1 1 (continued)

88
 CHAPTER 9. THE ENTER/CS

TOX I N S CLINICAL TR EATM ENT DIAGN OSTICS M I S C E LLAN EOUS

Endotoxin) lungs 4. Surgically enters i nto the

d rain peritoneal cavity
abscesses

Does not 1 . Necrotizing 1 Metronidazole

. Produce a black
contain lipid anaerobic 2. Clindamycin pigment when
A (so NO pneumonia g rown on blood
E ndotoxin) 2 . Periodontal agar
disease

1 . Necrotizing Penicillin G 1 . G ram-stai n

anaerobic 2. Anaerobic
pneumonia culture
2 . Periodontal
disease
3. Abdominal and
pelvic abscess
4. Otitis media

M . G ladwi n , W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple MedMaster

89
 CHAPTER 10. HOSPITAL-ACQ UIRED GRAM-NEGATNES

persons . Infections include pneumonia (isolated in 3% of
hospitalized persons with pneumonia) and line-related
bacteremia. Due to its very narrow range of antibiotic
susceptibility, it is often selected for and has a chance to
thrive in persons placed on broad antibiotic coverage for
other pathogens. Trimethoprim-sulfamethoxazole is
the treatment of choice for this pathogen.
Acinetobacter
Acinetobacter species are very similar to Pseudo
monas. They are aerobic gram-negative b act eria
found in the soil and water and cause a wide range of
infections in the hospital environment. Acinetobacter
b auman nii is the species most commonly isolated. A.
baumannii can survive for extended periods on
environmental surfaces, increasing its transmission
in healthcare settings . Much like Pseudomonas,
Acinetobacter is a frequent cause of hos pita l -a cq uire d
pneumonia, line related bacteremias, burn infections ,
and foley catheter-associated urinary tract infections .
These guys can fool the lab technicians . At times they
may appear gram-positive, and at other times th ey may
even be misidentified as Neisseria species. This is be
cause they can be coccobacillary (short rods) or coccal in
appearance, and on solid media they often form diplo
cocci similar to Neisseria.
A. baumannii can be a real challenge to treat. It has
acquired multiple mechanisms of antibiotic resistance,
making the choice of appropriate antibiotics difficult.
Acinetobacter strains may be susceptible to aminoglyco
sides (such as gentamicin, tobramycin, and amikacin),
carbapenems, polymixins (colistin, polymyxin E , and
polymyxin B), tigecyline, and sulbactam (the B-lactamase

GRAM-N E GATIVE R E S E RVOIR TRANSMISSION M ETABOLISM VIR U L E N C E

RODS

Pseudomonas - Soil - Medical 1 . Obligate 1 . Moti le (polar

aeruginosa - Water devices aerob e flagella)
- Plants - Hands of 2. Non-lactose 2. Hemolysin
- Animals healthcare fermenter 3. Collagenase
- I ntestinal flora workers 3. Oxidase- 4. Elastase
- Skin positive 5. Fibrinolysin
6. Phospholi pase C
7. D NAse
8. Antiphagocytic
capsule (som e strains)

Burkholderia - Soil - Medical 1 . Oxidase-positive Extremely antibiotic

cepacia - Water devices 2 . Non-lactose and disinfectant
- Plants - Hands of fermenter resistant
- Ani mals healthcare
- Lungs of cystic workers
fibrosis patients - Between cystic
fibrosis patients?

Stenotrophomonas - Soil - Medical 1 . Oxidase Extremely antibiotic

maltophilia - Water devices negative and disinfectant
- Plants - Hands of 2. Non-lactose resistant
- Animals healthcare fermenter
- Normal workers
respi ratory flora

Acinetobacter - Soil - Medical 1 . Obligate Multiple acq u i red

baumannii - Water devices aerobe mechanisms of
- Skin - Hands of 2. Oxidase antibiotic resistance
- Secretions healthcare negative
workers 3. Non-lactose
fermenter

Figure 10-3
94
 CHAPTER 10. HOSPITAL-ACQUIRED GRAM-NEGATNES

inhibitor). Sometimes Acinetobacter strains are resistant
or only intermediately sensitive to all available antibi
otics. It is in these cases that creativity comes into play
and one must try unusual antibiotic combinations for
synergy as well as prolonged infusions. This difficult task
often falls on the Infectious Disease specialist.
Prevention
The best bet to limit morbidity and mortality from
hospital-acquired infections is to prevent them from
occurring in the first place . Probably the three most
important factors in preventing these infections are
good hand-hygiene by all healthcare practioners, lim
iting the use of invasive devices (ventilators , foley
catheters , and intravenous lines), and j udicious use of
antibiotics.
Fig. 10-3. Summary of hospital-acquired gram
negative bacteria.
References
Fishbain, J, Peleg, AY. Treatment of Acinetobacter Infections.
Clin Infect Dis 2010;5 1( 1 ):79-84.
Garnacho-Montero J, Amaya-Villar R. Multiresistant Aci ne
tobacter baumannii infections: epidemiology and manage
m e n t. Curr Opin Infect Dis. 2010;23(4):332-9.
Guidelines for the Management of Adults with Hospital
acquired, Ventilator-associated, and Healthcare-associated
Pneumonia. Am J Respir Crit Care Med 2005 ; 1 7 1 : 388-4 16.
Jones RN. Microbial Etiologies of Hospital-acquiredBacterial
Pneumonia and Ventilator-associated Bacterial Pneumo
nia. Clin Infect Dis 2010;5 1(Sl):S81-S87.
Peleg AY, Hopper DC. Hospital-Acquired Infections Due to
Gram-negative Bacteria. N Engl J Med 2010;362: 1804-13.

TOXI N S C L I N I CAL TREATMENT DIAGNOSTICS M I S C E LLAN EOUS

1. Exotoxi n A 1. Burns 1. Timentin 1. Culture: greenish 1. Common etiology

(similar to 2. Endocarditis 2. Piperacillin metallic appearing for infection in
diphtheria toxin): 3. Pneumonia 3. l mipenem colonies on blood neutropenic patients
inhibits protein 4. Sepsis 4. Doripenem agar, which have 2. Produces pigments
synthesis by 5. External malignant 5. Aminoglycosides fruity (grape) smell when cultured :
blocking E F2 otitis media 6. Aztreonam a. pyocyanin
6. UTI 7. Ciprofloxacin (blue pigment)
7 . Diabetic 8. Ceftazidime b. pyoverdin
osteomyelitis 9 . Cefepime (green pigment)
1 0. Polym ixins

1 . Pneumonia in 1 . Trimethoprim- 1 . May use selective

Cystic fibrosis sulfamethoxazole media with colistin
patients. 2. Timentin to select for growth.
2 . I nfections in 3 . Ciprofloxacin
patients with 4 . Ceftazidime
chronic 5. Carbapenems
g ranulomatous
disease

1 . Pneumonia i n 1 . Trimethoprim 1 . Often a non

ventilated patients sulfamethoxazole pathogenic colonizer
on b road antibiotics of respi ratory flora
2. Line-related
bacteremia

1 . Bacteriocin 1 . Pneumonia 1. Aminoglycosides 1 . May be mistaken

production 2 . Line-related 2. Carbapenems for Neisseria
2 . Protective capsule bacteremia 3. Polymixins 2. G u ide therapy
(inhibits 3 . UTI 4. Tigecyl ine with antibiotic
phagocytosis) 4 . Bu rn/wound 5. Sulbactam susceptibilities
infections
5. Eye infections

95
 CHAPTER 1 1 . HAEMOPHILUS, BORDETELLA, AND LEGIONELLA

Legionella is responsible for diseases ranging from
asymptomatic infection and a flulike illness called Pon
tiac fever to a severe pneumonia called Legionnaires'
disease:
1 ) Pontiac fever: Like influenza, this disease involves
headache, muscle aches, and fatigue, followed by fever
and chills. Pontiac fever strikes suddenly and completely
resolves in less than one week. Pontiac fever was so
named for the illness that struck 95% of the employees of
the Pontiac, Michigan, County Health Department. The
causative agent was identified as Legionella pneumophila
carried by the air conditioning system.
2) Legionnaires' disease: Patients develop very
high fevers and a severe pneumonia.
Legionella pneumophila is a common cause of commu
nity acquired pneumonia, accounting for an estimated
0.5-10% of all admitted pneumonia cases (2% is likely,
the most accurate estimate). While it causes a classic
lobar consolidative pneumonia that can be impossible to
distinguish from pneumococcal pneumonia there are a
few unusual clinical elements, such as a fever with pulse
temperature dissociation (high fever, low heart rate),
severe headache, confusion, myalgia (muscle aches)
sometimes associated with rhabdomyolysis (muscle
breakdown with increased levels of serum CPK and
myoglobinuria), cough (only half of the time productive of
purulent sputum), hyponatremia, hypophosphatemia
and elevated liver enzymes (AST, ALT, alkaline phos
phatase, LDH). Diarrhea and abdominal pain also occur.
Sometimes the systemic symptoms like fever, myalgias,
confusion, abdominal pain and diarrhea precede the lung
symptoms, leading to misdiagnosis of influenza or acute
abdomen.

G RAM-N E GATIVE RESERVOIR V I R U L E NCE TOXI N S

RODS

Haemophilus Man only (obligate 1 . Capsule: 6 types, a-f Cytolethal

influenzae human parasite) (b is most virulent) distending
Transm itted 2 . Attachment pili toxin (C DT)
via respi ratory 3. lgA1 protease Hemolysin
route

Haemophilus Sexually transmitted No exotoxins

ducreyi disease

Figure 1 1 - 1 HAEMOPHILUS, BORDETELLA AND LEGIONELLA

1 00
 CHAPTER 11. HAEMOPHIL US, BORDETELLA, AND LEGIONELLA

To kill this bug the antibiotic has to be concentrated Recommended Review articles:
inside a cell, the macrophage, where the Legionella is
Carratala J, Garcia-Vidal C. An update on Legionella. Curr
hiding. Beta-lactams and aminoglycosides do not do
Opin Infect Dis. 2010;23(2): 152-7 .
Cornia P B , Hersh AL, et a l . Does this coughing adolescent or
this well so the mainstays of treatment for Legionella
pneumophila are the macrolides (erythromycin, adult patient have pertussis? JAMA. 2010;304(8):890-6.
azithromycin, clarithromycin), tetracyclines (doxycy Mandell LA, Wunderink RG, et al. ; Infectious Diseases Society
cline) and quinolones (ciprofloxacin, levofloxacin, moxi of America; American Thoracic Society. Infectious Diseases
floxacin). We call these drugs "atypical coverage" since Society of America/American Thoracic Society consensus
they cover the atypical bacteria Mycoplasma, Legionella, guidelines on the management of community-acquired pneu
and Chlamydia, which-in addition to viral pneumonia monia in adults. Clin Infect Dis. 2007;44 Suppl 2 :S27-72.
all cause atypical pneumonia (atypical pneumonia was
so named because the penicillins did not work for these
pneumonias). Then attempt to determine the source of
Legionella. Is the air conditioning system contaminated?
Fig. 1 1- 1 . Summary o f Haemophilus, Bordetella and
Legionella .

C L I N ICAL TR EATM ENT DIAG NOSTICS MISC E LLANEOUS

ENCA PSULA TED 1 . Second or third generation 1 . G ram stain 1 . Haemophilus

H. influenzae
(usually type B capsu le)
1 . Meningitis: Haemophilus
influenzae type b is the
primary cause of
meningitis in infants
from 3 to 36 months of
age. Complications
include mental
retardation, seizures,
deafness, and death
2. Acute epiglottitis
3. Septic arthritis in i nfants
4 . Sepsis: especially in
patients without
functioning spleens
5 . Pneumonia
NONENCAPSULA TED
H . influenzae
1 . Otitis media
2. Sin usitis
3 . COPO exacerbation
and pneumonia
cephalosporins (since
H. influenzae can acquire
ampicillin resistance
by plasmids)
2 . Hib vaccine: H. influenzae
polysaccharide capsule
of type b strain ( H ib) is
conj ugated to diphtheria
toxoid and given to
ch ildren at 2 , 4 , 6, and
1 5 months ( OTaP and oral
pol io are g iven at the same
time) . This has resulted
in solid i m m unity d u ring
the critical 3 month to 3 year
age, and has dramatically
reduced the incidence of
Hib infection (acute
epiglottitis, meningitis, etc.)
in the U . S .
3 . Passive immunization :
mother is immunized
during 8th month of
pregnancy to increase
passive antibody transfer
in breast milk
2 . Cultu re specimen on inf/uenzae requ i res
blood agar that has two factors for
been heated to 80 C. growth (both found
for 15 minutes (now in blood):
called chocolate X factor: Hematin
agar) . This high V factor: NAO +
temperatu re lyses the 2 . Note :
red blood cells, Haemophi/us
releasing both hematin stands for "blood
(called X factor) and loving"
NAO+ (called V factor) .
Like the Neisseria,
H. influenzae organisms
g row best when the
chocolate agar is
placed in a high C02
environment at 37 C.
3. Fluorescently labeled
antibodies ( E LISA and
latex particle
aggluti nation)
4 . Positive Quellung test:
due to its capsule U ust
like Streptococcus
pneumoniae)

Chancroid: pai nful 1 . Azithromycin G ram stain and culture 1 . A sexually

gen ital ulcer, often
associated with
uni lateral swollen lymph
nodes that can ruptu re ,
releasing pus
or eryth romycin of ulcer exudate and transmitted disease
2. Ceftriaxone ( I M ) p u s released from 2. Requires X factor
3. Ciprofloxacin swollen lymph node (hematin ) only.

101
 CHAPTER 1 1. HAEMOPHILUS, BORDETELLA, AND LEGIONELLA

G RA M - N EGATIVE R E S E RVO I R VIRULENCE TOXIN S

RODS

Gardnerella Sexual ly transm itted N o capsule No exotoxins

vagina/is disease

Bordetel/a Man : highly contagious 1 . Capsule 1 . Pertussis

pertussis Transmitted via 2 . Beta-lactamase toxin: activates
respi ratory route 3. Filamentous hemagglutinin G proteins that
(FHA) : A pili rod that i ncrease cAM P,
extends from the su rface resulting i n :
of B. pertussis, enabling A. I ncreased
the bacteria to bind to sensitivity to
ciliated epithelial cells of histamine
the bronchi B. I ncreased insulin
release
C. I ncreased n umber
of lymphocytes
in blood
2 . Extracytoplasmic
adenylate cyclase:
"weakens"
neutrophils,
lymphocytes and
monocytes
3. Filamentous
hemagglutin i n :
allows b i n d i n g to
ciliated epithelial
cells
4 . Tracheal cytotoxi n :
kills ciliated
epithelial cells

Legionella Ubiquitous in man 1 . Facultative i ntracel l u lar Cytotoxi n : kills

pneumophila and natural water parasite: Dot/lcm type IV hamster ovary
environments secretion system i n hibits cells
1 . Air conditioning macrophage phagosome/
systems endo/lysosome fusions
2. Cool ing towers 2 . Cu-Zn superoxide dismutase
and catalase-peroxidase
protects bacteria from
macrophage superoxide
and hydrogen peroxide
oxidative bu rst
3. Pili and flagella promote
attach ment and i nvasion
4. Secretion of protei n toxins
l i ke R N Aase, phospholipase A
and phospholipase C .

Figure 1 1 - 1 (continued)

102
 CHAPTER 1 1 . HAEMOPHILUS, BORDETELLA, AND LEGIONELLA

C L I N ICAL TREAT M E N T DIAG NOSTICS M ISCE LLAN EOUS

Bacterial vag i n itis:fou l Metronidazole vaginal

C l u e cel l s : Does not require
smelling vaginal epithelial cells that X factor or V factor
discharge (with fishy contain tiny for g rowth
odor) , vaginal pru ritus, pleomorphic g ram
and often dysuria negative bacilli withi n
t h e cytoplasm

Wh oo p in g Cough 1 . Erythromyci n (most effective 1 . Bordet-Gengou media: High risk g roups:

1 . Catarrhal phase: patient
is highly contagious ( 1 -2
weeks)
A. Low g rade fever, runny
nose & mild cough
B . Anti biotic susceptible
during this stage
2. Paroxysmal phase (2-1 0
weeks)
A. Whoop (bu rsts of
non-productive coughs)
B. I ncreased number of
lymphocytes in blood
smear
C . Antibiotics ineffective
during this stage
3. Convalescent stage
if given in catarrhal stage)
2 . Vaccine: DaPT
1 . Diptheria
2 . acellular Pertussis
3 . Tetanus
(G iven routinely at ages
2, 4, 6 , 1 5 months and
between 4-6 years.)
3 . Treat household contacts
with e ryth romycin.
potatoes, blood 1 . I nfants less than
and glycerol agar, one year old
with penicillin 2. Adults (as immunity
added acquired from
2. Rapid serologic tests vaccine wears off)
(ELISA)
Collect speci men from
posterior pharynx on a
calci um alginate swab
since 8. pertussis will
not g row on cotton
3. Di rect fluorescein
labeled antibodies
applied to
nasopharyngeal
specimens for
rapid diagnosis.
4 . PCR detection of
bacterial DNA in
respi ratory secretions

1 . Ponti ac fever: headache, 1 . Azith romycin 1 . Cu lture on buffered 1 . Facultative

fever, muscle aches and
fatigue, Self-limiting;
recovery i n a week
is com mon .
2. Legionnaires' Disease:
pneumonia: fever and
non-productive cough
2 . Levofloxacin charcoal yeast extract intracellular
3. Doxycycline agar ( L-cysteine is a parasite: i nside
critical ingredient) alveolar
2 . Serology ( I FA and macrophages
ELISA) 2. Persons with
3 . U rinary antigen can be compromised
detected by radioim i m m u ne systems
munoassay with high are especially
sensitivity and specificity susceptible
and will remain positive
for months after i nfection .
U rine antigen test only
detects L. pneumophi/a
serogrou p 1 , but this
accou nts for 90%
of cases.

M . Gladwi n , W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple MedMaster

1 03
 CHAPTER 12. YERSINIA, FRANC/SELLA, BR UCELLA, AND PASTEURELLA

O RGANISM RESERVOI R TRAN S M ISSION METABOLISM VIRULENCE TOXI N S

Yersinia 1 . W i l d rodents 1 . Flea bite 1 . Facultative 1 . Fraction 1 { F 1 ): this 1 . Pesticin: kills

pestis 2. City rats 2. Contact with anaerobe capsular antigen other bacteria
3. Squi rrels i nfected animal 2. Virulence factors is antiphagocytic (including
and prairie tissue are temperatu re 2. V and W p roteins E. coli)
dogs in the 3. I n haled aerosolized sensitive: only 3. Non-motile 2. I ntracellular
SW U . S. organ isms: h u man expressed at 4. Req u i res calcium murine toxin:
to human trans 37 C. (tempera at 37 C. If insuffi lethal to mice
mission occurs ture inside cient calciu m ,
during epidemics macrophages) Y. pestis alters its
3. Virulence metabolism and
is plasmid protei n p roduc
mediated tion . This trait
assists with its
intracellular state

Yersinia Wild & U npasteu rized milk 1 . Facultative 1 . I nvasive Enterotoxin

enterocolitica domestic anaerobe 2. V & W proteins (like ST toxi n
animals 2 . Virulence factors 3. Motile at 25 c o f E. coli) :
are temperature increase
sensitive: only cG M P levels
expressed at
37 C.

Francise/la 1 . Rabbits and 1 . Bite of tick, deerfly 1 . Obligate aerobe 1 . Capsule:

tularensis squ irrels or infected animals 2. Req u i res antiphagocytic
2. Ticks can 2. Di rect contact with cysteine 2. Non-motile
serve as a i nfected animal
reservoir tissue (usually
rabbit)
3. I n haled aerosolized
organ isms
4 . Ingestion of conta-
minated meat
or water
5. Easily transmitted
to lab personnel

Bruce/la 1 . Di rect contact with Obligate aerobe 1 . Capsule

contaminated l ive- 2 . Non-motile
Bruce/la Goats stock or aborted 3. Tropism for
melitensis: placentas eryth ritol, a sugar
Bruce/la abortus. Cattle 2. I n gestion of found i n animal
Bruce/la suis: Pigs infected milk placentas
Bruce/la canis: Dogs products
3. Aerosolization
i n laboratory or
possibly due to
bioterrorism

Pasteurella Part of the Bite from dog or cat Facultative 1 . Capsule

multocida normal flora anaerobe 2 . Non-moti le
of domestic &
wild animals

Figure 12-6 ZOONOTIC GRAM-NEGATIVE RODS

1 08
 CHAPTER 12.
C L I N I CAL
1 . Bubonic plague:
A. regional lymph nodes (usually
groin) swell, and become red ,
hot a n d tender (called a bubo)
B. High fever
C. Conju nctivitis
2 . Sepsis: bacteria survive in
macrophages, and spread to
blood and organs. Death occurs
in 75% if u ntreated
3. Pneumonic plague: during
epidemics, pneumonia occurs,
as bacteria are spread from
person to person by aerosolized
respi ratory secretions: 1 00%
fatal if untreated
1 . Enterocol itis: focal ulcerations in
ileum & mesenteric lymph nodes
2 . Arth ritis
3. Rash
Tularemia
1 . Ulceroglandular: at the site of
tick bite or di rect contact with
contaminated rabbit, an ulcer
develops, with swelling of local
lymph nodes
2 . Pneumonia: i nhalation , or through
the blood
3. Oculoglandular: di rect i noculation
into eyes
4. Typhoidal: ingestion results in
gastroi ntestinal symptoms
(abdominal pain) and fever
1 . Brucellosis:
U ndulati ng fever (fever peaks
in the evening, and retu rns to
normal by morning)
Weakness
Loss of appetite
2. Induces abortions in animals.
Wound infections (following dog
or cat bites) : may prog ress to
infection of nearby bones and
joints
YERSINIA, FRANCISELLA, BR UCELLA, AND PASTEURELLA
TR EATM ENT
1 . Streptomyci n or
gentamicin
2. Doxycycline
3. Killed vaccine is
effective only for a
few months (attenu
ated vaccine is more
effective but also has
more side effects)
1 . Fluoroqu inolone
2 . Trimethopri m I
sulfamethoxazole
Cephalosporin
resistant!
1 . Gentamicin or
streptomycin
2 . Doxycycline
3. Attenuated vaccine:
only for high risk
individuals
1 . Pasteurization of
milk
2 . Treat with
combination of
doxycycline and one
othe r drug (genta
micin, streptomycin,
or rifampi n ) .
3. A l l cattle are immu
nized with a living
attenuated strain of
Bruce/la abortus
1 . Penicil l i n G
2. Doxycycline
3. Third generation
cephalosporin
M . G ladwi n , W. Trattler, a n d S . Maha n , Clinical Microbiology Made Ridiculously Simple M e d Master
1 09
DIAGNOSTICS
1 . G ram stain will reveal
g ram-negative rods
with bipolar stai ning: the 2 . Yersinia can accept
ends of these rod shaped
bacteria take up stai n
more than t h e center
2 . Blood culture
3. Culture of bubo
aspi rate
4. Serology
5. Rapid diagnostic test:
antibody against F 1
(capsular antigen)
Cold enrichment of stool
with saline selects for
Yersinia
1 . Culture (but very
dangerous due to its
high infectivity) : requ i res
addition of cysteine to
blood agar media
2 . Skin test
3. Measure rise in lgG
antibody titer ( l g M is
not very good)
1 . Cultu re of blood , bone
marrow (best yield),
liver, or lymph nodes
2 . Serologic tests
3. Skin test: indicates
exposure only
Culture specimen on
standard laboratory
media
M I S C E LLANEOUS
1 . Facultative i ntracellular
parasite
plasmids from E. coli,
and shares many
antigens with enteric
bacteria
3. Subcutaneous
hemorrhage results in
a blackish skin discol
oration, giving the
name "Black Death"
1 . Facultative i ntracellular
parasite
2. Bipolar staining
Facultative intracellular
parasite
Facultative i ntracellular
parasite
Not a facultative
i ntracellular organism!
 CHAPTER 13. CHLAMYDIA, RICKETTS/A, AND FRIENDS

ORGANISM RESERVOIR TRANSMISSION METABOLISM

Chlamydia H u mans 1 . Di rect personal contact LIFE C YCLE

trachomatis Morphologic note: 2. Primarily affects the: 1 . Elementary body (EB):
gram-negative, A. Eyes dense spherule that
but lacks B. Genitals infects cells
peptidoglycan C . Lungs 2. I n itial (reticulate) body:
layer and m u ramic 3. Note that trachoma is After E B enters cell ,
acid found in underdeveloped it transforms i nto
countries, and transmission an i n itial body
occurs due to poor hygiene A. Larger & osmotically fragile
B . Can reproduce via binary fission
C . Req u i res ATP from the host
D. The i nitial body transforms
back i nto EB, which leaves
the cell to infect other cells

Note: Chlamydia are obligate

I ntracellular parasites -
steal ATP from host
with ATP/ADP translocator

Chlamydophila Birds & poultry 1 . Bird feces dry out Life cycle is similar to
psittaci 2 . Fecal particles are Chlamydia trachomatis
inhaled, i nfecting
the lungs

Figure 1 3- 1 7 GRAM-NEGATIVE OBLIGATE INTRACELLULAR PARASITES:

CHLAMYDIA AND RICKETTSIA

122
 CHAPTER 13. CHLAMYDIA, RICKETI'SIA, AND FRIENDS

VIRULENCE C L I N ICAL TR EATM E NT DIAGNOSTICS

1 . Resistant to Serotypes A, B, & C Genital and eye 1 . Can NOT be g rown on

lysozyme (since Trachoma: causes i nfections: artificial media. Can
their cell wall lacks scarri ng of the inside of 1 . Doxycycline (use only classically be grown in
m u ramic acid) the eyel id, resulting in for adu lts) chick yolk sacs. More
2. Prevents redi rection of the 2 . E ryth romycin (especially commonly, Chlamydia
phagosome - eyelashes onto the for infants and pregnant is cultu red i n certain cell
lysosome fusion corneal surface . woman) li nes (McCoy cells,
3. Non-moti le This resu lts in corneal 3 . Azith romycin for example)
4. No pili scarring and blindness Note: systemic treatment 2. For inclusion conjunctivitis
5. No exotoxins is required for any (ophthalmia neonatorum):
Serotypes D through K: chlamydia! Scrapings from the surface
1 . I ncl usion conj unctivitis eye infection ! ! This is of the conjunctiva will show
(ophthalmia neonatorum) especially true for i nfants, intracytoplasmic incl usion
2 . I nfant pneumonia who can develop bodies withi n conju nctiva!
3. U reth ritis, cervicitis and chlamydia! pneumonia epithelial cells. The i nclusion
pelvic i nflammatory following ch lamydia! bodies contain glycogen,
disease (PIO) in women conjunctivitis and thus stain with iodine
4. Nongonococcal or giemsa
urethritis, 3. G ram stain of genital
epididymitis and secretions will NOT
prostatitis in men show g ram-negative
intracellular diplococci
Complications of 4. U reth ritis: most commonly
chlamydia/ genital diagnosed by polymerase
tract infections chain reaction of u rethral
1 . Sterility, ectopic preg swab or u rine sample.
nancy and chronic pain 5. l mmunofl uorescent slide test:
may occur after pelvic place infected genital or
inflammatory disease ocular secretions on a
2. Reiter's syndrome: triad slide and stain with
of conjunctivitis, u reth ritis, fluorescein-conj ugated anti
and arth ritis chlamydial antibody
3. Fitz-H ugh-Curtis 6. Serologic: Examine blood for
Syndrome: perihepatitis elevated titers of anti
Serotypes L 1, L2, & b chlamydial antibodies with
Lymphogran uloma complement fixation and
venereum immunofl uorescence tests
7. Lymphogranu/oma venereum:
A. Serologic tests
B. Frei test, which is rarely
used , is similar to the PPD
skin test for tuberculosis

same Psittacosis: a viral-like 1 . Doxycycline 1 . Serologic: Exam ine blood for

atypical pneumonia, 2. E rythromycin elevated titers of antibodies
with fever and d ry , with complement fixation and
non productive cough
- immunofl uorescence tests
(similar to a Mycoplasma 2. l ntracytoplasmic inclusion
pneumonia) bodies do not stain with iodine

123
 CHAPTER 13. CHLAMYDIA, RICKETTSIA, AND FRIENDS

ORGANISM RESERVOI R TRANSMISSION METABOLISM

Chlamydophila Humans (spread Respiratory route Life cycle is similar to

pneumoniae from human to Chlamydia trachomatis
(strain TWAR) h uman)

Rickettsia Arthropod vector 1 . Rickettsiae are obligate

generalities (except Q fever) intracellular parasites:
They can not make their
own ATP
2. G row in cytoplasm
(in contrast to Chlamydia,
which replicates in endosomes)

Rickettsia rickettsii Dogs, rabbits & 1 . Wood tick: I n Western

wild rodents U . S . Dermacentor
andersoni
2. Dog tick: I n Eastern
U . S . Dermacentor
variabilis

Rickettsia akari House m ice M ites (which live on the

house m ice)

Rickettsia 1 . H umans H u man body louse

prowazekii 2 . Flying squi rrels ( Pediculus corporis)

Rickettsia typhi 1 . Rats Rat flea (Xenopsyl/a

2 . Small rodents cheopis)

Rickettsia 1. Rats Mite larvae (chiggers)

tsutsugamushi 2. Shrew
3. Mongooses
4. Birds

Figure 13-1 7 (continued)

124
 CHAPTER 13. CHLAMYDIA, RICKETTS/A, AND FRIENDS
VIRULENCE CLINICAL
Atypical pneumonia: viral-
l i ke atypical pneumonia
(similar to a Mycoplasma
pneumonia) in young
adu lts
1 . Non-moti le Damages ENOOthelial
2. No exotoxins cells lining blood vessels
Rocky Mountain
Spotted Fever.
1 . Fever
2. Conj u nctival i njection
(redness)
3. Severe headache
4. Rash on wrists, ankles,
soles & palms i n itially,
becomes more gener-
alized later
Rickettsial Pox:
vesicular rash similar
to chicken pox. It
resolves over 2 weeks
1 . Epidemic Louse-borne
Typhus
A. Abrupt onset of fever
and headache
B. Rash, which spares
the palms, soles and face
C. Delirium/stupor
D . Gangrene of hands or feet
2. Brill-Zinsser Disease:
A. Reactivation of Rickettsia
prowazekii
B. Mild symptoms
C. NO rash
Endemic (or M u rine)
Typhus: fever, headache
and rash
Scrub Typhus:
1 . Fever and headache
2 . Eschar (scab) at
bite site
3. Followed by a rash
TR EATM E N T DIAG N O STICS
1 . Doxycycline 1 . Serologic: Examine blood for
2. Erythromycin elevated titers of antibodies
with complement fixation and
immunofl uorescence tests
2. l ntracytoplasmic inclusion
bodies do not stain with iodine
1 . Doxycycline 1 . Culture: chick yolk sac
2. Chloramphenicol Can NOT be g rown on
artificial media (except
for Bartone/la species)
2 . Serology: identify antibodies
against the rickettsial
organ ism
3 . Weil-Felix reaction
1 . Doxycycline 1 . Cli nical exam
2. Chloramphen icol 2. Di rect immu nofluorescent
exam of skin biopsy from
rash site
3. Serology
4 . Weil-Felix reaction:
A. Positive OX- 1 9
8 . Positive OX-2
1 . Doxycycline Weil-Felix reaction negative
2. Chloramphenicol
1 . Doxycycline 1 . Weil-Felix reaction : positive
2. Chloramphenicol OX- 1 9
3. Eradicate h u man lice 2. Serology
1 . Doxycycline Weil-Felix reaction: positive
2. Chloramphenicol OX-1 9
1 . Doxycycline Weil-Felix reaction : positive
2. Chloramphenicol OX-K
125
 CHAPTER 13. CHLAMYDIA, RICKETTS/A, AND FRIENDS

ORGANISM RESERVOIR TRANSMISSION METABOLISM

Bartone/la H umans Body louse Not an obligate

quintana intracellular parasite

Bartone/la Not an obligate

henselae intracellular parasite

Coxiella burnetii Cattle, sheep, & EXCEPTION: EXCEPTION:

goats No arthropod vector 1 . Can grow at a pH of
required. Di rect airborne 4.5 within phagolysosomes
transmission of endospore 2. Has an endospore form
from cow hide or d ried
placenta, or via
consumption of
endospore-contaminated
u npasteu rized cow milk

Ehrlichia Deer, dogs, coyotes Ticks

chaffeensis ( H M E)
Anap/asma
phogocytophilum Deer, white-footed
(HGA) mouse
Ehrlichia ewingii

Figure 13- 1 7 (continued)

126
 CHAPTER 13. CHLAMYDIA, RICKETTS/A, AND FRIENDS

V I R U LE N C E C L I N ICAL TR EATM ENT DIAGNOSTICS

1 . Trench Fever. fever, 1 . Doxycycline 1 . Serology

headache and back pai n . 2. Chloramphenicol 2. PCR
It lasts f o r 5 days and 3. Azithromycin
recu rs at 5 day i ntervals
2. Bacteremia, endocarditis,
and bacillary angiomatosis

1 . Cat-scratch disease 1 . Azith romycin 1 . Serology

2. Bacillary angiomatosis 2. Doxycycline 2. PCR
3 . Bacteremia
4 . E ndocarditis
("culture negative")

1 . Q Fever. fever, 1 . Doxycycline 1 . Complement fixation test

headache & viral-like 2. Erythromycin demonstrating a rise in antibody
pneumonia. No Rash ! ! ! Pasteu rize m i l k to 60 C 2. PCR
(This i s the only
rickettsial disease without
a skin rash ! ! )
2 . Complications:
1 . Hepatitis
2. Endocarditis

Human Ehrlichiosis: 1 . Doxycycline 1 . Rise in acute and conva

similar to Rocky 2. Rifampin lescent antibody titers
Mountain spotted fever, Resistant to 2. Characteristic ehrtichial
but rash is rare chloramphenicol inclusion bodies are some
times seen in leukocytes
on blood smears
3. PCR

M . G ladwi n , W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple MedM aster

127
 CHAPTER 14. SPIROCHETES

S P I R O C H ETES RESE RVOI R TRA N S M I S S I O N M ETABOLISM & VIRULENCE

G RAM-N EGATIVE M O R P HOLOGY

Spirochete 1 . Multiply by transverse No exotoxins! ! !

general ities fission
2. Motile: six axial filaments
wind around the organism
between the peptidoglycan
layer and the outer cell
membrane. Contraction of
axial filaments conveys
spinning motion

Treponema pal/idum Humans only Sexual 1 . Microaerophilic Motile

2. Morphology: thick rigid
spirals
3. H ighly sensitive to elevated
temperatu res

Treponema pallidum Desert zones Sharing of Morphologically and sero- Motile

subspecies of Africa drinking and logically i n d ist inguishab le
endemicum and the eating utensils from T. pallidum
Middle East

Treponema pertenue Moist tropical Person-to- Morphologically, geneti- Motile

regions person contact cally and serologically
or via flies indistinguishable from
T. Pallidum

Treponema carateum Latin America Person-to- Morphologically and sero Motile

person contact logically indistinguishable
from T. pa/lidum

Figure 14-13 SPIROCHETES

138
 CHAPTER 14. SPIROCHETES

C L I N ICAL TR EATM ENT DIAGNOSTICS

Can not culture on artificial

media (except for Leptospira)

S YPHILIS 1 . Penici llin G 1 . Cutaneous lesions examined by

A. Primary stage: painless chancre (skin ulcer) 2. Erythromycin dark field microscopy, im m uno
B. Secondary stage: 3. Doxycycline fluorescence , ELISA, or silver
1 . Rash on palms and soles Jarisch-Herxheimer stain
2 . Condyloma latu m : painless, wartlike lesion which reaction : acute wors 2 . Non-specific treponemal test:
occu rs in warm , moist places (vulva or scrotum) ening of symptoms VDRL; R P R
3. CNS, eyes , bones , kidneys and/or joi nts can be after antibiotics are 3 . Specific treponemal test:
i nvolved started FTA-ABS, MHA-TP
C. Latent stage: 25% may relapse back to the All pregnant women should be
secondary stage screened with VDRL because
D. Tertiary stage (33%) : antibiotic treatment prior to
1 . Gummas of skin and bone 4 months of gestation prevents
2 . Cardiovascular syph ilis congenital syphilis
3. Neurosyphilis: may get the Argyll-Robertson pupil 4 . Polymerase chain reaction
E . Congenital syphilis: contracted in-utero (PCR) detection of bacterial
DNA is available

BEJEL Penicillin VDRL and FTA-ABS are

A. Primary & secondary lesions: occur in oral mucosa positive
B. Tertiary lesions: gum mas of skin & bone

YA WS 1 . Azith romycin VDRL and FTA-ABS are positive

A. Primary and secondary lesions: ulcerative skin 2. Penici llin
lesions near initial site of infection - often looks 3. Plastic surgery to correct
like condyloma lata facial disfigurement
B. Tertiary lesions: gum mas of skin and bone
(resulting in severe facial disfigurement)

PINTA Penici llin VDRL and FTA-ABS are positive

Flat red or blue lesions which do NOT ulcerate

139
 CHAPTER 14. SPIROCHETES

SPIROCH ETES RE SE RVOIR T RA NS MIS S ION M ETABOLISM & VIRULENCE

G RAM-NEGATIVE MORPHOLOGY

Borrelia burgdorferi 1. White-footed Vector = lxodes Microaerophilic

mouse ticks
2 . White-tailed 1 . lxodes scapu-
deer /aris : East &
Midwest
2 . lxodes
pacificus:
West coast

1 8 other species Wild rodents Vectors Microaerophilic 1 . Antigenic variation:

of Borrelia in remote 1 . Borrelia variable expression
undisturbed recurrentis: of outer membrane
areas in the louse Vmp lipoproteins
Western U . S . 2. The other allows Borrelia
species of to escape
Borrelia: ticks opsonization and
phagocytosis
2. No toxins! ! !

Leptospira interrogans Zoonotic Di rect contact with 1 . AEROB I C

23 serog roups (dogs, cats, infected u rine 2. Spiral shaped , with hooks
250 serovars l ivestock, or animal tissue. on both ends ("ice tongs")
and wild Organisms pene 3. Two axial flagella wrap
animals) trate broken skin around and run along
(i.e. on feet) and the length of the
m ucous mem organism u nder the
branes (swallow outer membrane
ing u rine (periplasmic flagella)
contaminated
water)

Figure 14-13 (continued)

140
 CHAPTER 14. SPIROCHETES

C L I N ICAL TREATM ENT DIAGNOSTICS

L YME DISEASE 1 . Doxycycline 1. Elevated levels of antibodies

A. Early localized stage (stage 1 ) : Erythema 2 . Amoxicillin against Borrelia burgdorferi
chronicum migrans (ECM) 3. Cettriaxone for can be detected by ELISA
B . Early disseminated stage (stage 2) neurologic disease 2. Western immunoblotti ng
1 . Multiple smaller ECM
2. Neurologic: aseptic meningitis, cranial nerve
palsies (Bell's palsy) , and peripheral neuropathy
3. Cardiac: transient heart block or myocarditis
4. Brief attacks of arth ritis of large joints (knee)
C . Late stage (stage 3)
1 . Chronic arth ritis
2 . Encephalopathy

RELAPSING FEVER 1 . Doxycycline 1 . Blood culture during febrile

A. Recu rring fever about every 8 days 2 . E rythromycin periods
B. Fevers break with drenching sweats 3. Penicillin G 2 . Dark field examination of blood
C. Rash & splenomegaly drawn during febrile periods
D. Occasionally meningeal i nvolvement 3. Wright's or giemsa - stained
peripheral blood smear reveals
organism 70% of the time
4. Serologic

1. Fi rst phase (leptospirem ic) : organisms in blood and 1 . Penicillin G 1. Fi rst week: culture blood or
CSF causes high spiking temperatures, headache 2. Doxycycline cerebral spinal fluid (on lab
and severe muscle aches (thighs and lower back) media, or by i noculation i nto
2. Second phase (immune): correlates with animals)
emergence of l g M and i nvolves recu rrence of the 2. Second week to months: culture
above symptoms, often with meningismus u rine
(neck pai n) 3. Rarely, dark field microscopy is
3. WEIL ' S DISEASE: severe case of leptospi rosis successful (not recommended)
with renal fai l u re , hepatitis (and jaundice) , mental 4. Antibody based ELISA to detect
status changes, and hemorrhage in many organs Leptospira antigens in the urine
5. Polymerase Chain Reaction
(PCR) to detect bacterial DNA
in seru m , CSF and u rine

M . Gladwi n , W. Trattler, a n d S . Mahan , Clinical Microbiology Made Ridiculously Simple M e d Master

141
 CHAPTER 15. MYCOBACTERIUM

ACID FAST RODS M O R P H O LOGY M ETA BOLISM VIRULENCE TOX I N S

Mycobacterium 1 . 40% of total 1 . Aerobic 1 Mycosides

. N o exotoxin nor
tuberculosis cell dry weight 2 . Catalase-positive A. Cord factor: only endotoxin. (It has
is lipid 3. Slow growth rate found in virulent lipopolysac
2 . Composed of strains (May be charide, but no
mycolic acids responsible for release Lipid A)
3 . Thin rods of tumor necrosis
4 . Non-motile factor (cachecti n ) ,
causing weight loss)
8 . Sulfatides: inhibit
* Remember, phagosome-lysosome
mycolic acids are fusion
also found in C . Wax D: acts as an
Nocardia (which adjuvant
also is acid fast) 2 . I ron siderophore
(Mycobactin)
3. Facultative intracellular
growt h : M . tuberculosis
can su rvive and m u ltiply
i n macrophages

Notice! ! !
Non-motile
No capsule
No attachment pili

Figure 1 5- 1 1 ACID FAST BACTERIA

150
 CHAPTER 15. MYCOBACTERIUM

C L I N ICAL TREATM ENT DIAGN OSTICS M ISCE LLANEOUS

Tuberculosis First line drugs: 1 . Acid-fast stai n of Purified Protein

A. Primary tuberculosis: 1 . lsoniazid ( I N H ) specimen Derivative (PPD) Test
1 . Asymptomatic 2 . R ifampin 2. RAP I D C U LTU R E : 1 . Measure zone of
2. Overt disease, involving the 3 . Pyrazinamide Bactec radiometric induration :
lungs or other organs 4 . Ethambutol culture, a liquid broth Positive reaction:

B . Reactivation or secondary 5. Streptomyci n in a bottle, with 1 . ?. 5 m m

tuberculosis: radioactive palmitate as (immuno
1 . Pulmonary a carbon source. compromised
2. Pleural or pericardia! Mycobacteria g row and host)
3. Lymph node i nfection use the carbon, allowing 2. ?. 1 0 mm (have
4. Kidney early detection (in 1 -2 chronic disease
5 . Skeletal weeks) even before or risk factors for
6. Joints colon ies can be see n . exposure to TB)
7. Central nervous system 3. PPD skin test 3. ?. 1 5 mm
8. Miliary tuberculosis 4. I G RA ( I nterferon gamma (all others)
release assay) 2 . A positive reaction
5. Chest X-ray does not mean
6. Gene Xpert MTB/Rif active disease.
(and similar PCR 3. Can get false
based studies) negatives in patients
with AIDS or
malnourished
individuals

151
 CHAPTER 15. MYCOBACTERIUM

ACID FAST RODS MORPHOLOGY M ETAB O LISM VIRULl:NCE TOXINS

Mycobacterium 1 . Catalase-positive 1 . Non-motile

leprae 2 . G rows best at low 2 . Facultative i ntracellular
temperatu re growth
3. Phenolase-positive:
converts Dopa into a
pigmented product
(used for diagnosis)

NONTUBERCULOUS MYCOBACTERIA

NAME COMMON CLINICAL PRESENTATIONS

M. a vium complex (i ncludes M. a vium and 1 . I n AI DS patients: disseminated infection

M. intracellulare) with fever, weight loss, hepatitis, and diarrhea.
2 . l m munocompetent hosts:
a. upper lung cavitary disease in elderly smokers.
b . M iddle and lower lung nodular and bronchiectatic
disease i n middle-aged female non-smokers.
3. Lymphadenitis-most commonly in children.
M. kansasii 1 . Pulmonary: upper lung cavitary disease.
(Appears similar to tuberculosis.)
2 . Disseminated disease (immunocomprom ised)
M. abscessus 1 . Pulmonary disease
2. Ski n , soft tissue, and bone disease

M. fortuitum 1. Ski n , soft tissue, and bone disease

Figure 1 5- 1 1 (continued)

1 52
 CHAPTER 15. MYCOBACTERIUM

C L I N I CAL TREATM ENT DIAGNOSTICS MISCELLANEOUS

Leprosy 1 . Rifampin 1 Can NOT be g rown

. Lepromin Skin Test
A. Lepromatous leprosy (LL) : 2. Dapsone on artificial lab media; Although not useful
1 . Low cell-mediated immunity 3. Clofazimine Can only be cultured for diagnosis, it
2 . Organisms found everywhe re in certain animals, allows positioning
(organs and blood) Leprosy reactions such as m ice foot of patients on the
3. Skin, nerves, eyes and testes (type 1 & type 2) pads, armadillos or immunologic
i nvolved bilaterally: m ultiple skin Can occur with monkeys spectrum
lumps and bumps, leonine facies, treatment (see 2. Skin or nerve biopsy:
saddle nose, peripheral leprosy drug text will reveal acid-fast
neuropathy, for details) bacilli (lepromatous) or
digit absorption , blindness and granulomas (tuberculoid)
infertility in men (from testicular
damage)
B . I ntermediate forms: BL, BB, BT
C. Tuberculoid leprosy (TL) :
1 . I ntact cell-mediated i m m u n ity
2. Difficult to isolate M. leprae from
skin or blood
3. Skin and nerves involved : 1 or 2
superficial unilateral lesions

TREATM E NT (general overview) MISCELLANEOUS

1 . Disseminated disease in A I D S patients: 1 . Common cause of Fever of

clarithromycin, rifampin or rifabutin , and U nknown Origin (FUO) in
ethambutol A I D S patients
2 . Pulmonary: clarithromycin , rifampin, 2 . Most common cause of NTM lung
ethambutol disease.
3. Lymphadenitis: excisional surgery

l soniazid, Rifampin, Ethambutol Second most common cause of NTM

pulmonary disease in the U . S .

1 . Pulmonary disease: usually requ i res - Rapid grower: usually g rows i n culture
surgery combined with antibiotics for in <7 days.
cure (need susceptibilities to guide
therapy) .
2. Macrolides (clarith romycin, azith romycin),
combined with intravenous agents (amikacin ,
cefoxitin , o r imipenem) .
Two agents with in vitro activity: amikacin, 1 . Rapid grower
ciprofloxacin , sulfonamides, clarith romycin, 2. Common laboratory contaminant
etc. 3. Associated with contaminated foot
baths .

153
 CHAPTER 15.
ATYPICAL MYCOBACTERIA
NAME
M. chelonae
M. marinum
M. ulcerans
Figure 15-11 (continued)
The 3 remaining categories represent a continuum
between LL and TL. They are called borderline
lepromatous (BL), borderline (BB), and border
line tuberculoid (BT) . The skin lesions of BL will be
more numerous and have a greater diversity of shape
than those of BT.
The lepromin skin test is similar to the PPD used in
tuberculosis. It measures the ability of the host to mount
a delayed hypersensitivity reaction against antigens of
Mycobacterium leprae. This test is more prognostic than
diagnostic and is used to place patients on the immuno
logic spectrum. It makes sense that TL patients would
have a positive cell-mediated immune response and thus
a positive lepromin skin test, while LL patients, who
cannot mount a cell-mediated immune response, have a
negative response to lepromin.
See Chapter 1 9 for information about the treatment
of leprosy.
Fig. 15-10. The spectrum of leprosy.
NONTUBERCULOUS MYCOBACTERIA
Nontuberculous mycobacteria (NTM) are an ex
pansive group of organisms that are ubiquitous in the
soil and water. Healthy immunocompetent persons
rarely develop disease despite continued, likely daily,
exposure. The incidence of disease due to these organ
isms has been increasing, likely due to increased aware
ness and improved laboratory diagnosis. NTM can
cause a broad range of disease from asymptomatic colo
nization to a chronic disabling pneumonia.
A clinician's first exposure to NTM is likely to be car
ing for AIDS patients with disseminated Mycobac
terium avium-complex (MAC) disease. This is a very
common opportunistic infection in persons with AIDS
and CD4 T cell counts <50 cells/mm3. These patients
often present with unexplained fevers, weight loss,
diarrhea, and general malaise, with an elevation of
alkaline phosphatase on their routine labs. Diagnosis is
154
MYCOBACTERIUM
CLINtCAL
1 . Ski n , soft tissue, and bone dise as e
2 . Disseminated disease (immunocompromised)
3. Keratitis - associated with contact use
Ski n , soft tissue, and bone disease ("Fish
Tank G ranuloma")
"Buruli ulcers": progressive necrotic skin
ulcerations
confirmed by showing growth in mycobacterial blood
cultures. These patients generally respond well to
appropriate antibiotic therapy and by starting anti
retroviral therapy (ART) for HIV.
MAC is also the most common cause of NTM lung dis
ease. It usually presents in one of two ways : 1) as upper
lung cavitary disease, predominantly in male smokers,
or 2 ) as lower and middle lung involvement with
bronchiectasis and nodular infiltrates in middle aged
non-smoking women. In this group it is felt that these
women have some as yet undefined underlying predis
position. Treatment of pulmonary MAC disease is long
and arduous, requiring an average of 18 months of ther
apy with a macrolide (clarithromycin, azithromycin)
based regimen.
NTM can cause pulmonary disease, lymphadenitis,
skin lesions , bone and joint infections, and more. See
Figure 15- 1 1 for a broad overview of the most com
monly observed NTM organisms.
Fig. 15- 1 1 . Summary of Mycobacteria.
References
Britton WJ, Lockwood DNJ. Leprosy. The Lancet. 2004; 363 :
1209-12 19.
Boehme CC, Nabeta P, Hillemann D , et al. Rapid molecular detection
of tuberculosis and rifampin resistance. NEJM 2 0 10;363: 1005-15.
Recommended Review Articles:
Diagnosis and Treatment of Disease Caused by Nontuberculous
Mycobacteria: The Official Statement of the American Thoracic
Society. American Journal of Critical Care Medicine 2007; 17 5 : 1-50.
Ma Z, Lienhardt C, et al. Global tuberculosis drug development pipe
line: the need and the reality. Lancet. 2010;375(97 3 1 ):2 100-9.
Maartens G, Wilkinson RJ. Tuberculosis. Lancet. 2007 ;370(9604 ) :
2030-43.
Schluger NW, Burzynski J. Recent advances in testing for latent TB.
Chest. 2 0 10 Dec;138(6): 1456-63.
 CHAPTER 15. MYCOBACTERIUM

T R EATM ENT MISCELLANEOUS

Two agents with in vitro activity : Usually responds well t o treatment.

tobramycin , clarith romycin, l inezolid,
imipenem, amikacin .
Usually with two agents: clarithromycin, Common in fresh and salt water.
ethambutol, rifampin.
Surgical debridement often combined with Found i n tropical rai n forests
clarithromycin and rifampi n .

M . Gladw i n , W. Trattler, and S . Mahan, Clinical Microbiology Made Ridiculously Simple MedMaster

155
 CHAPTER 1 6. MYCOPLASMA

CELL WALL M O R P HOLOGY M ETA BOLISM VIRU LENCE TOXINS

LESS BACTE R I A

Mycoplasma 1 . NO Cel l Wall 1 . Req u i res Protei n P 1 : adheres NONE

pneumoniae 2. Pleomorphic: can CHOLESTEROL to epithelial cells of
( Eaton's Agent) appear round to for membrane the respiratory tract
oblong shaped. formation
3. Smallest bacteria 2. Facultative
capable of growth anaerobe
& reproduction
outside a living cell
(smaller than
some vi ruses:
. 1 -.2 microns)
4 . Motile (glides)

Ureaplasma 1 . NO Cell Wall 1 . Requires NONE

urealyticum 2 . Pleomorphic cholesterol
2. U rease:
metabolizes u rea
i nto ammonia
and C02 )

Figure 16-2 MYCOPLASMA

Mycoplasma , as it produces Tiny colonies when Fig. 16-2. Summary of the Mycoplasmataceae.
cultured.
Ureaplasma urealyticum is part of the normal flora Recommended Review Articles:
in 60% of healthy sexually active women and commonly
infects the lower urinary tract, causing urethritis. Burstein GR, Zenilman JM. Nongonococcal urethritis-a new para
digm. Clin Infect Dis. 1999;28 Suppl 1 :866-73 .
Urethritis is characterized by burning on urination
Loens K, Goossens H, Ieven M . Acute respiratory infection due to
(dysuria) and sometimes a yellow mucoid discharge
Mycoplasma pneumoniae: current status of diagnostic methods.
from the urethra. Neisseria gonorrhoeae and Chlamydia Eur J Clin Microbiol Infect Dis. 2010;29( 9 ) : 1055-69.
trachomatis are the other 2 bacteria that cause urethri
tis (see Chapter 13, page 1 14).
Ureaplasma urealyticum can be identified by its
ability to metabolize urea into ammonia and carbon
dioxide.

158

C L I N ICAL
1 . Tracheobronchitis
2 . Walki ng pneumonia
(also called atypical
pneumonia) : fever with
a d ry, non-productive
hacking cough
Non-gonococcal u reth ritis:
burning on u ri nation, with a
yellow mucoid discharge
from the ureth ra
CHAPTER 1 6. MYCOPLASMA
TR EATMENT DIAG N O STICS MISCELLANEOUS
1 . M ac rolides 1 . Cold agglutinins 1 . Chest X-ray will show
( azith romyci n , 2 . Complement fixation test patchy i nfiltrates that
clarithromycin) 3. Culture: Takes 2-3 weeks look worse than
2 . Tetracycl i nes A. Req u i res cholesterol and physical exam and
(doxycycline) nucleic acids. clinical symptoms
3. Quinolones B. Add penicillin to inh ibit g rowth suggest
(ciprofloxacin, of contaminating bacteria 2. Disease usually
levofloxacin) C . Dome-shaped colonies with occu rs in children ,
''fried egg" appearance or adolescents, and
Penicillin and "mulberry" appearance ( in young adults
cephalosporins the case of Mycoplasma
do NOT work, pneumoniae)
as Mycoplasma 4. Rapid identification tests:
does not have a sputum can be tested with DNA
cell wall probes (nucleic acid
hybridization). PCR of sputum
samples.
1 . E ryth romycin 1 . Requires cholesterol and T-Form Mycoplasma
2. Tetracycline u rea for g rowth (T = Tiny)
2. Colonies are extremely tiny
(thus called T-strai n )
159
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS

Figure 17-14

1 . Antipseudomonal penicillins
A. Ticarci llin
B . Timentin (ticarcillin & clavulanate)
C . Piperacillin
D. Zosyn (piperacillin & tazobactam)
E . Carbenicillin (no longer produced in U . S . ) 1 . Penicillins with beta-lactamase inhibitor
A. Augmentin (Amoxicillin & clavulanate)
2. Thi rd generation cephalosporins B. Timentin (Ticarcillin & clavulanate)
A. Ceftazidime C. Unasyn (Ampicillin & sulbactam)
B. Cefoperazone (no longer produced i n U . S . ) D . Zosyn (Pipericillin & tazobactam)
3. Fourth generation cephalosporins 2 . Second generation cephalosporins
A. Cefepime A. Cefoxitin
4.
B. Cefotetan
Carbapenems
C. Cefmetazole
A. l m i penem
B. Meropenem 3. l mipenem, Meropenem, Doripenem , and Ertapenem
C . Doripenem
4. Chloramphenicol
5. Aztreonam
5 . Clindamycin
6. Ciprofloxacin

7. Aminoglycosides 6. Metronidazole
A. Amikacin
B. Gentamicin 7 . Moxifloxacin
C . Tobramycin
8 . Tigecycline
8. Polymixins
Figure 1 7-16 ANTIBIOTICS THAT
Figure 1 7-15 ANTIBIOTICS THAT COVER THE ANAEROBES (INCLUDING
COVER PSEUDOMONAS AERUGINOSA BACTEROIDES FRAGILIS)
1 68
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS
Meth icil I i n-resistant
Staphylococcus aureus ( M R SA)
Meth i c i l l i n -resistant
Staphylococcus epidermidis
Vancomyci n-resistant
Enterococci (VRE)
Figure 1 7- 1 7 ANTIBIOTICS THAT COVER THE
DIFFICULT-TO-KILL GRAM-POSITIVE BACTERIA
Data suggest there is little cross-reactivity with the
bicyclic beta-lactams, so we can use this in penicillin
allergic patients !
Clinical notes: Because this antibiotic only kill s
gram-negative bugs, i t is used (much like the aminogly
cosides) along with an antibiotic that covers gram
positives. The resulting combinations give powerful
broad-spectrum coverage:
vancomycin + aztreonam
clindamycin + aztreonam
Fig. 17-15. Antibiotics that cover Pseudomonas
aeruginosa .
Fig. 17-16. Antibiotics that cover anaerobic bacteria,
including Bacteroides fragilis.
Fig. 17-17. Antibiotics that cover the difficult-to
kill gram-positive bacteria: methicil l in -resistant
Staphylococcus aureus ( MRSA), methicillin-resistant
Staphylococcus epidermidis and Vancomycin
Resistant Enterococci (VRE ) .
Fig. 17-18. Summary o f the penicillin (beta-lactam)
family antibiotics.
1 . Vancomycin
2. Llnezolid
3. Daptomycin
4. Quinupristin /dalfopristin
5 . Tigecyc l i ne
6. Ceftarol i ne
1 . Linezolid
2 . Daptomycin
3. Tigecyc l i ne
References
Fish DN, Singletary TJ. Meropenem, a new carbapenem an
tibiotic. Pharmacotherapy 1997; 17:644-669.
Fraser KL, Grossman RF. What new antibiotics to offer in the
outpatient setting. Sem Resp Infect 1998; 13:24-35.
Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA. The
Sanford Guide to Antimicrobial Therapy 2008. 38th edi
tion. Antimicrobial Therapy Inc. Sperryville VA, 2008.
Mandell GL, Bennett JE, Dollin R, eds. Principles and Prac
tice of lnfectious Diseases; 4th edition. New York: Living
stone 1995.
Owens RC, Nightingale CH, et al. Ceftibuten: An overview.
Pharmacotherapy 1997; 17:707-720.
Rockefeller University Workshop. Special report: multiple-an
tibiotic-resistant pathogenic bacteria. N Engl J Med 1994;
330:124 7-125 1 .
Recommended Review Articles:
Bush K, Macielag MJ. New B-lactam antibiotics and B-lactamase
inhibitors. Expert Opin Ther Pat. 2010;20( 10):1277-93.
1 69
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS

NAME M ECHANISM O F ACTION PHARMOKIN ETICS

P E N ICILLINS

Penicillin G Competitive inhibitor of the Can not survive passage

Aqueous (crystall i ne) penicillin G transpeptidase enzyme; through the stomach
Procaine penicillin G I n hibits bacterial cell Aqueous penicillin G:
Benzathine penicillin G wall synthesis i ntravenous ( I V)
P rocaine and benzathine
penicillin G:
i ntramuscular ( I M )
PO penicillin G .

Penicillin V Same Oral

Amino penicillins Same 1 . Ampicillin: IV or oral

Ampicillin 2 . Amoxicil l i n : Oral (better oral
Amoxicillin absorption than ampicillin)

Penici llinase-resistant penicillins ( I V) Same IV

Methicillin
Nafcillin
Oxacillin

Pen ici II i nase-resistant Same Oral

penicillins (Oral)
Cloxaci llin
Dicloxaci llin

Antipseudomonal penicillins Same 1 . IV-Ticarcillin and Piperacillin

Carbenicillin 2. PO-Carbenicillin (rarely used)
Ticarcillin
Piperacillin

Combi nation of penici l l i n with Same 1 . Augmentin : oral

beta-lactamase i n h ibitors: 2 . U nasyn, Timenti n , and
Amoxicillin + clavulanate (Augmentin) Zosyn: IV.
Ticarcillin + clavulanate (Timentin)
Ampicillin + sulfbactam ( U nasyn)
Piperacillin + tazobactam (Zosyn)

CEPHALOSPORINS

Fi rst Generation Competitive inh ibitor of the 1 . O ral

1 . Cephalothin transpeptidase enzyme; a. Cephalexin
2 . Cephapirin I n h ibits bacterial cell wall b. Cefadroxil
3. Cephradine synthesis 2 . IV
4 . Cephalexin a. Cephalothi n
5 . Cefazolin b. Cephapirin
6. Cefadroxi l c. Cefazol i n
3. O ral or IV: Ceph radine

Figure 1 7- 1 8 PENICILLIN FAMILY ANTIBIOTICS (chart continued o n page 1 72)

1 70
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS

ADVER S E E F F E CTS TH E RAPEUTIC USES M ISCELLANEOUS

1 . Allergy (due to presence of 1 . Streptococci pneumoniae Bacteria "cidal"

preformed lgE)
A. Anaphylactic shock
B. U rticaria ( H ives)
C. Rash
2. Delayed rash 1 -2 weeks later
3. Superi nfections: Clostridium difficile
can overrun the colon , causing
pseudomembranous en te roc ol i t is
2 . G roup A beta-hemolytic
streptococci ( Streptococcus
pyogenes)
3. Neisseria meningitidis
4. Treponema pallidum (syphilis)
5 . Pasteurella multocida
6. Listeria monocytogenes
7 . Actinomyces israelii
Strategies of bacteria resistance:
1 . Prevent entrance of penicillin
2 . Enzymatically cleave the beta
lactam ring (with a beta
lactamase enzyme)
3. Alter the structu re of the
transpeptidase enzyme

1 . Strep th roat caused by g roup

A beta-hemolytic streptococci
( Streptococcus pyogenes)
2. Covers all organisms that
penicillin G does

1 . Broader g ram-negative coverage

than the above penicillins
2 . Covers the enterococci
(group D streptococci)

Used for skin infections when M ET a NAsty OX

penicillinase-producing
Staphylococcus aureus is
a possible pathogen

Used for skin infections when The clocks (clox) were ticking
penici llinase-producing
Staphylococcus aureus is
a possible pathogen

1 . Use when Pseudomonas James Bond's weapons:

aeruginosa is a possible 1 . Car
pathogen 2 . Tick
2. Anaerobic coverage 3. Pipe bomb

1 . Very broad coverage ; can be

used with hospital-acqu i red
pneumon ias
2. Anaerobic coverage
3 . Timentin and Zosyn cover
Pseudomonas

1 . Allergy (due to presence of 1 . Excellent g ram-positive 1 . Strategies of bacteria resistance:

preformed lgE)
A. Anaphylactic shock
B. U rticaria (Hives)
C. Rash
2. Delayed rash 1 -2 weeks later
Note: 5-1 0% of patients
with allergy to penicillin will also
bacteria coverage cleavi ng the beta lactam ring
2 . Excellent for skin i nfections (with a beta lactamase enzyme)
2. The fi rst generation
cephalosporins are th e on ly
ones with a PH in their name

1 71
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS

NAME MECHANISM OF ACTION PHARMOKINETICS

First Generation (contin ued) 4. Renal excretion

Second Generation Same 1 . Oral: Cefaclor, Cefprozil

1 . Cefamandole 2 . Oral or IV: Cefuroxime
2 . Cefaclor 3. IV: the rest
3. Cefuroxime 4. Renal excretion
4. Cefoxitin
5 . Cefotetan
6. Cefmetazole
7. Cefonicid
8. Cefprozil

Third Generation Same 1. Oral :

1 . Cettriaxone a. Cefixime
2 . Ceftazidime b. Cefpodoxime
3. Cefotaxime c. Ceftibuten
4. Ceftizoxime d . Cefdinir
5 . Cefixime e. Cefditoren
6. Cefoperazone 2 . IV: the rest
7. Cefpodoxime 3. Renal excretion
8 . Ceftibuten
9. Cefepime
(a fou rth-generation)

Fourth Generation Same 1 . I ntravenous

Cefepime 2 . Renal excretion

Fifth Generation Same 1 . I ntravenous

Ceftaroline 2 . Renal excretion

Carbapenems 1 . l mipenem: inhi bits bacterial 1 . I V or IM

l mipenem (co-formulated cell wall synthesis 2 . Renal excretion
with cilastatin) 2 . Cilastatin:
Meropenem A. I n h ibits an enzyme i n the
Doripenem kidneys that metabolizes
E rtapenem i mipenem (thus i ncreasing
its half l ife)
B. Protects the kidney from
toxicity caused by i mipenem

Aztreonam (a monobactam) I n h ibits bacterial cell 1 . I V or IM

wall synthesis 2 . Renal excretion

Figure 1 7- 1 8 (continued)

1 72
 CHAPTER 1 7. PENICILLIN-FAMILY ANTIBIOTICS

ADVERSE EFFECTS T H E RAPEUTIC USES MISCELLANEOUS

have a reaction to
cephalosporins
3. S u perinfections: Clostridium difficile
can overrun the colon , causing
pseudomembranous enterocolitis

1 . Allergy 1 . Covers more gram-negatives The FAMily is gathered , some

2 . Superinfection than the first generation wearing FUR coats, and your
3. Cephalosporins with the methyl- 2 . Cefotetan , cefoxitin and cefmeta- FOXy cousin is drinking TEA i n
thio-tetrazole (MTI) side chain zole: anaerobic coverage a toast to you r achievement
(incl udes cefamandole,
cefmetazole, & cefotetan ) :
A. I nterferes with t h e synthesis of
vitamin K dependent clotting factors,
resulting in poor coagulation
B. May i nterfere with the metabolism
of alcohol, resulting i n the
accumulation of acetaldehyde,
which causes nausea and vomiting

1 . Allergy 1 . Ceftazidime, cefoperazone, and Most of the third generation

2 . Superinfection
3. Cephalosporins with the methyl-
thio-tetrazole (MTI) side chain
(as mentioned above)
cefepime have antipseudomonal cephalosporins have a 'T' (for tri)
activity in their names
2 . Ceftriaxone has excellent penetration
into the cerebrospinal fluid. So
excellent choice for meningitis

1 . Allergy 1 . H ealth care associated pneumonia Poor anaerobic coverage

2. Superinfection 2 . Neutropenic fever
3. Pseudomonal i nfections

1 . Allergy 1 . M RSA The newest kid on the block

2 . Superi nfection 2 . Skin and soft tissue infection
3. Pneumonia

1 . Nausea/vomiting (when Broad spectrum I ' m a pen crossing out all bacteria
i nfused rapidly) 1 . G ram-positives "decerebrate antibiotic"
2. I ndividuals allergic to penicillin 2 . G ram-negatives
are at high risk to be ( E rtapenem does not cover
Pseudomonas)
allergic to imipenem 3. Anaerobes
3. Seizures 4. Does not cover methicillin-
resistant Staphylococcus
aureus (MRSA)

Minimal cross-reactivity G ram-negative organisms only Magic bullet for g ram-negatives

with penicillins

M . Gladwin, W. Trattler, a n d S . Mahan, Clinical Microbiology Made Ridiculously Simple MedMaste r

1 73
 CHAPTER 18. ANTI-RIBOSOMAL ANTIBIOTICS

NAME M ECHANISM O F P H A R M O K I N ETICS ADVERSE EFFECTS

ACTION

Chloramphenicol Binds to 50S 1 . Oral or IV 1 . Bone marrow depression :

ribosomal 2 . Metabolized & A. Dose related anemia
subunit, & completely inactivated B . Aplastic anemia (rare , but
inhibits p rotein in the liver often fatal)
synthesis 3. Metabol ites excreted 2 . Gray Baby Syndrome (40% fatal) :
in u rine cyanosis, vomiting, green stools &
vasomotor col lapse (This is caused
by the accumulation of unmetabolized
chloramphenicol , since the neonatal
liver has yet to synthesize sufficient
metabolic enzymes)

Clindamycin Binds to SOS 1 . O ral or IV Pseudomembranous colitis: destroys

(derivative of ribosomal 2 . Excreted from bile the normal intestinal flora, which allows
lincomyci n) subunit, & and urine Clostridium difficile to grow and secrete
inhibits p rotein its toxin, causing a bloody diarrhea.
synthesis Treat with oral vancomycin or
metronidazole
Pseudomembranous colitis can also be
caused by other antibiotics , such as
the penicillins (ampicillin)

Linezolid Binds to 508 1 . Oral or IV 1 . Bone marrow suppression

ribosomal 2 . Metabolized partially (thrombocytopenia, anemia, and
subunit, & i n the liver neutropen ia)
inhibits protein 3. Metabolites and 2 . Headache
synthesis u nchanged drug 3. GI i rritation: nausea, diarrhea
excreted i n u rine

Macrolides Binds to 50S Well absorbed oral ly. 1 . GI u pset due to stimulation of
E ryth romycin, ribosomal ( E ryth ro and Azith ro gastric motil ity
Azith romycin, subunit & also in IV) 2. Rare cholestatic jaundice
Clarithromycin inhibits protein 3. P rolonged QT syndrome
synthesis

Tel ith romyci n Binds to 50S 1 . Oral formulation 1 . GI upset.

(a ketolide) ribosomal 2 . QT prolongation-don't
subunit & inhibits g ive i n patients with
protein synthesis arrythmias or on
anti-arrhythmics

Tetracycline Binds to 3JS 1 . Oral absorption from 1 . GI i rritation : nausea, vomiting and
Doxycycline ribosomal the stomach and small diarrhea
M inocycline subunit, & intestine (however, 2. Phototoxic Dermatitis (often get
Demeclocycline inhibits protein absorption is severely a skin rash)
synthesis impaired by food , milk, 3. Renal & hepatic toxicity (with high
Ca + + & Mg + + salts) doses)

Figure 18-14 ANTI-RIBOSOMAL DRUGS (chart continued on page 184)

182
 CHAPTER 18. ANTI-RIBOSOMAL ANTIBIOTICS

TH ERAPEUTIC USES MISCELLANEOUS

Wide spectrum of activity : kills Think "chlorine": wide spectrum , but toxic
gram-positives, g ram-negatives and anaerobes
(but its toxicity can be lethal)
Generally, it is only used for:
1 . Bacterial meningitis i n infants who are known to have
severe allergies to penicillin and cephalosporin
2 . Rickettsial infections in children and pregnant women
(si nce tetracycline should be avoided i n children)

1 . Anaerobes:
A. For wounds which penetrate the abdomen
B. For anaerobic i nfections of the female genital tract
2. G ram-positive organisms, if the patient has severe
allergies to penicillin and cephalosporin
3. Toxoplasma gondii: use clindamycin in combination
with pyrimethamine
4 . Toxic shock syndrome : due to G roup A
Streptococcus and Staphylococcus aureus

1. Healthcare associated pneumonia Avoid with antidepressants

2. Complicated skin and soft tissue i nfections
3. Staph aureus pneumonia
4. I nfections due to: Methicillin Resistant Staphylococcus
Aureus (M RSA) and Vancomycin Resistant
Enterococcus (VRE)

1 . Outpatient treatment of upper and lower tract Metabolized by Cytochrome P450

respi ratory i nfections
2 . Atypical organisms L egionella, Mycoplasma,
-

Chlamydia

Community acqui red pneumonia 1 . Primarily metabolized by CYP450

2. Do not use in patients with myasthenia gravis!

1 . Rickettsia Democlocycline: used p rimarily i n the US

2 . Chlamydia (erythromycin is equally for the treatment of the Syndrome of
effective) I nappropriate ADH secretion (SIADH)
3. Mycoplasma pneumoniae rather than for its antibacterial effect.
4. Entamoeba histolytica
5 . Spi rochetes:

183
 CHAPTER 18. ANTI-RIBOSOMAL ANTIBIOTICS

NAME MECHANISM Of PHARMOKIN ETICS ADVERSE Eff'.ECTS

ACTION

Tetracycline 2 . I V formulations available 4 . Fanconi Syndrome: occurs with

Doxycycline 3 . Concentrates in l iver ingestion of outdated drug; Results in
M inocycline and undergoes renal tubular dysfunction, which can
Demeclocycline extrahepatic circulation lead to renal failure
(Continued) 4 . Excretion: 5 . Superinfections (like Clostridium
A. U rine: tetracycline difficile induced pseudomembranous
B . Stool: doxycycline colitis)
6. Teratogenic: depresses bone growth
in fetus, by chelating Ca+ + and
therefore decreasing Ca+ + serum
levels
7. Discolors teeth and stains bone at
site of bone calcification!

Tigecycline Binds 3:ls 1 . IV only 1 . GI i rritation-nausea, vomiting,

(a glycycline) ribosomal diarrhea- (very common ! )
subun it 2. Other side effects similar
to tetracyclines

Aminoglycosides Binds to 3:JS 1 . I V or IM (Not oral) 1 . Vestibular and auditory ototoxicity

ribosomal 2 . Diffuses across cell (due to cranial nerve 8 damage)
subunit, & wall of microbes, so 2. Neph rotoxicity
inhibits p rotein synergistic with 3. Neuromuscular blockade: m uscle
synthesis penicillin (since paralysis and apnea
penicillin breaks down
cell walls, so that the
aminoglycoside works
better)
3. Crosses CNS only if
meninges are inflamed !
4. Not metabolized
5. Excreted renally

Quinupristin/ Inhibits SOS 1 . I V only Common:

dalfopristin ribosomal 1 . Hyperbilirubinemia
(streptogramin) subunit 2 . I nfusion site pain and i nflammation
3. Myalgia/arthralgia

Spectinomycin Binds to 3:JS 1 . IM NO serious toxicity

ribosomal subunit, 2. Excreted in u rine
& inhibits protei n unmetabol ized
synthesis

Figure 18-14 (continued)

Fig. 18-14. Summary of anti-ribosomal antibiotics.
References and Recommended Reading
Eckmann C , Dryden M. Treatment of complicated skin and soft
tissue infections caused by resistant bacteria: value of line
zolid, tigecycline, daptomycin and vancomycin. Eur J Med
Res. 2010; 15(12):554--63 .
Gilbert, DN. Aminoglycosides. In: Principles and Practice of
Infectious Diseases, 6th ed, Mandell, GL, Bennett, JE, Dolin,
R (Eds), Churchill Livingstone, New York 2005. p. 328.
McDonald, LC, Killgore, GE, Thompson, A, et al. An epidemic,
toxin gene-variant strain of Clostridium difficile. N Engl J
Med 2005; 353:2433.

184
 CHAPTER 18. ANTI-RIBOSOMAL ANTIBIOTICS

THERAPEUTIC USES MISCELLANEOUS

A. Borrelia and Leptospira

B. Treponema pallidum (second choice behind penicillin)
6. Brucella (second choice behind Bactrim)
7. Nocardia (second or third choice)
8 . Facial acne

1 . Complicated skin and soft tissue infections 1 . Use associated with increased mortality
2. I ntra-abdomi nal i nfections 2 . Similar in structure to tetracyclines
3. Covers Methicillin Resistant
Staphylococcus A ureus (M RSA) and
Vancomycin Resistant Enterococcus (VRE)

1 . Aminoglycosides are effective against g ram-negative 1 . Streptomycin: oldest member of family;

enteric organisms many bugs are resistant!
2. Also effective against: 2. Gentamicin: most commonly used of all
A. Tularemia ami noglycosides
B . Yersinia pestis 3. Tobramycin: good against Pseudomonas aeruginosa
C. Brucellosis 4. Amikacin: has the broadest spectrum
D . Mycobacterium tuberculosis 5 . Neomycin: used topically, as it is very toxic. Also very
broad spectrum
6. Netilmicin

1 . Complicated skin infections with A "nasty" medication

G roup A strep and S . aureus
2. Life-threatening bacteremia with Vancomycin
Resistant Enterococcus (VRE) ( Enterococcus
faecium only)

Gonorrhea (as an alternative to penicillin)

Not effective against Treponema pallidum (syphilis) or
Chlamydia

M . Gladw i n , W. Trattler, and S . Mahan , Clinical Microbiology Made Ridiculously Simple Med Master

Severe Clostridium difficile -associated disease in populations Zuckerman, JM. Macrolides and ketolides: azithromycin, clar
previously at low risk-four states, 2005. MMWR Morb ithromycin, telithromycin. Infect Dis Clin North Am 2004;
Mortal Wkly Rep 2005; 54: 120 1 . 18:62 1
Tigecycline (tygacil). Med Lett Drugs Ther 2005; 4 7:73
Warny, M, Pepin, J, Fang, A, et al. Toxin production by an
emerging strain of Clostridium difficile associated with
outbreaks of severe disease in North America and Europe.
Lancet 2005; 366: 1079.

1 85
 CHAPTER 19. ANTI- TB AND ANTI-LEPROSY ANTIBIOTICS

There's only one thing to help your dancin,

Time to reach for the drug, rifampin.
Their peelin' clown faces look really lean.
They're healing faster than can be seen,
As long as they stay close to clofazimine.
Severe cases ofleprosy should be treated with rifampin,
dapsone, and clofazimine for a minimum of 2 years and
until patients are acid-fast bacilli negative.
Less severe cases are treated with rifampin and
dapsone for 6 months.
See anti-tuberculosis medications (page 188), for
more on rifampin. See the sulfa drugs (Chapter 20) for
more on dapsone.

Clofazimine
Fig. 19-3. A clown-faced clown climbs a DNA double
helix stairway. His outfit is colored red and black:
1 ) Clofazimine works by binding to the DNA of
Mycobacterium leprae. It also has anti-inflammatory
actions that are helpful in treating the leprosy reactions.
2) Clofazimine is a red-colored compound, and when
it deposits in the skin and conjunctiva, it colors these
tissues red. Any place on the body where there is a lep
rosy lesion, the skin will appear tan to black. Note the
clown's red and black outfit.

Leprosy Reactions
Fifty percent of patients treated for leprosy develop
a leprosy reaction . There are 2 types ( 1 and 2) Figure 19-3

NAME M E C H A N I S M O F ACTI O N P H A R M O KI N ETICS

ANTI-TUBERCULOSIS DRUGS

lsoniazid ( I N H) I nterferes with the biosynthesis of 1 . Oral , IM, or I V

the mycolic acid component of
the cell wal l of Mycobacteri um
2 . Penetrates into all fluids & tissues
3 . Metabolized in liver by acetylation
(a small population in U . S . are "slow
acetylators")
4. Excreted via urine
5 . Increases u rinary excretion of
pyridoxine (vitamin 85)

Figure 19-4 ANTIBIOTICS FOR MYCOBACTERIA

1 90
 CHAPTER 19. ANTI-TB AND ANTI-LEPROSY ANTIBIOTICS

and both are immune-mediated, possibly in response
to the increase in dead organisms with treatment.
The reactions involve inflammation of the nerves ,
testicles, eyes, joints, and skin (erythematous nodules).
Type 1 reactions occur only in borderline patients
(BT, BB, BL), and almost always occur during the first
year of treatment. The skin lesions of leprosy typically
swell, becoming more edematous, and occasionally
ulcerate . Neuritis can also occur, leading to sensory or
motor nerve loss. The type 1 reaction is thought to be a
delayed hypersensitivity reaction to the dead bacilli.
When this reaction occurs, patients can be treated with
prednisone . It is important that you do NOT withdraw
the anti-leprosy drugs if a leprosy reaction occurs.
Type 2 reaction (called Erythema Nodosum Lep
rosum) is associated with borderline lepromatous (BL)
and lepromatous leprosy (LL). Commonly, a painful
nodular rash erupts in a previously normal-appearing
area of skin, along with a high fever. Neuritis, orchitis,
arthritis, iritis, and lymphadenopathy can occur as
well . The type 2 reaction is thought to be an immune
complex-mediated reaction involving the deposition of
the immune complexes in tissues followed by comple
ment activation. These patients can also be treated
with prednisone or clofazimine. However, the treat
ment of choice is thalidomide. This is one of the few
uses of thalidomide that is condoned in the U.S.
because it is a potent teratogen (also used in the treat
ment of multiple myeloma). Again, the anti-leprosy
antibiotics are NOT to be withdrawn!
Fig. 19-4. Summary of antibiotics for
Mycobacteria.
References
American Thoracic Society, CDC, and IDSA. Treatment of
Tuberculosis. MMWR. 2003; 52(RR 1 1 ) : 1-77.
Hopewell PC, Bloom BR. Tuberculosis and other Mycobacter
ial Diseases. In: Murray JF, Nadel JA, eds. Textbook of
Respiratory Medicine. 2nd ed. Phil adelphia : W.B. Saunders
Co. 1994: 1094-1 160.
U.S. Department of Health and Human Services, Division of
Tuberculosis Elimination, Centers for Disease Control and
Prevention, American Thoracic Society. Core Curriculum
on Tuberculosis: What the Clinician Should Know. 4th Edi
tion. Atlanta, Georgia, 2000.
Recommended Reading:
Daley CL. Update in tuberculosis 2009. Am J Respir Crit Care
Med. 2010; 181(6):550-5.
Forno C, Hausermann P, et al. The difficulty in diagnosis and
treatment of leprosy. J Travel Med. 2010; 17(4):281-3.
LoBue PA, Enarson DA, Thoen TC . Tuberculosis in humans
and its epidemio logy , diagnosis and treatment in the
United State. Int J Tuberc Lung Dis. 2010; 14( 10): 1226-32.
Ma Z, Lienhardt C , et al. Global tuberculosis drug develop
ment pipeline: the need and the reality. Lancet. 2010; 375
(973 1):2 100-9.
Sterling T, Villarino M, et al. Three months of rifapentine and
isoniazid for latent tuberculosis infection. NEJM. 20 1 1 ;
365(23):2155-66.

ADVERSE EFFECTS THERAPEUTIC USES MISCELLA N E O U S

1 . Hepatotoxicity: 1 . Prophylaxis for 1 . No beer, wine or liquor, as

A. Risk of hepatitis i ncreases with age
B . Increase risk of hepatitis when
alcohol is consumed
2 . Can induce pyridoxine (vitamin Bs)
deficiency, resulting in pellagra
(which is manifested as peripheral
neuritis, rash and anemia)
tuberculosis {used alone)
2 . For active tuberculosis
(use in combo with
other drugs)
alcohol increases the risk of
developing hepatitis
2 . Vitamin Bs (pyridoxine)
supplements are often given to
avoid deficiency of pyridoxine
3. Monitor hepatic enzyme level
4. Combo drugs:
A. Rifamate : l soniazid & rifampin
8. Rifater: l soniazid, rifampin, &
pyrazinamide

191
 CHAPTER 19. ANTI-TB AND ANTI-LEPROSY ANTIBIOTICS

NAME M EC H A N I S M O F ACTION P H A R M OK I N ETICS

Rifampin I n h ibits DNA dependent RNA 1 . Oral

polymerase 2. Penetrates into all fluids & tissues
3. Metabol ized via microsomal oxidase
system (MOS) : induces MOS, thereby
increasing its own metabolism as well
as the metabolism of other drugs
4. Excreted via l iver

Pyrazinamide 1 . U n known mechanism 1 . Oral

2. This drug is an analog of 2. Renal excretion
nicoti namide

Ethambutol 1 . U nknown mechanism 1 . Oral

2 . Metal chelator 2 . Can cross blood brain barrier
3. Excreted u nchanged i n urine & feces

Rifabutin Rifabutin inhibits DNA-dependent 1 . Oral

RNA polymerase in susceptible 2 . I nduces Cytoch rome P450 and may
strains of Escherichia coli and alter blood levels of other medications
Bacillus subtilis but not in mammalian (such as antiretroviral drugs)
cells. It is not known whether rifabutin
inhibits DNA-dependent RNA
polymerase in MAC

Rifapentine I n h ibits DNA dependent RNA 1 . Oral

polymerase 2. Hepatic metabolism
3. Long half l ife

Streptomycin Binds to 30S ribosomal subunit and Streptomycin can be administered

(an aminoglycoside) inhibits protein synthesis IM or IV

ANTI-LEPROSY DRUGS

Sulfones PABA antagonist (similar mechanism 1 . Oral

1 . Dapsone as sulfonamides) . Results in blockage
2. Sulfoxone of di hydrofolic acid ( D H F) synthesis,
a precu rsor to tetrahydrofolic acid (TH4) ,
which is crucial to the synthesis of
purines. This results i n inhibition of
bacterial DNA synthesis
2 . Absorbed from GI tract via enterohe-
patic circulation.
3. Metabol ized in l iver - via acetylation
4. Excreted in urine

Clofazimine 1 . Binds to DNA Oral

2 . Anti-inflam matory actions are helpful for
treati ng the leprosy reactions.

Rifampin: see above

Figure 19-4 (continued)

192
 CHAPTER 19. ANTI-TB AND ANTI-LEPROSY ANTIBIOTICS

A D V E R S E E F F ECTS TH E RA P E UTIC U S E S M I S C ELLAN E O U S

1 . Asymptomatic jaundice, elevated 1 . This drug is used for both I ncreases metabolism of (and
liver enzymes tuberculosis and leprosy thus decreases half-life) of:
2 . U rine, sweat & tears become 2 . Also used prophylactically for 1. Coumadin
R E D-ORAN G E color persons exposed to patients i l l 2. Corticosteroids
with N. meningitidis 3. Oral contraceptives - careful ! ! !
3. Sometimes used for: 4. Oral hypoglycemics
A. Legionella pneumophila 5. Digoxin
8. Staph. aureus endocarditis 6. Methadone

1 . Hepatotoxic! ! Mycobacteri um tuberculosis Do not use in pregnancy

2 . Gout (inhibits uric acid secretion,
thus increasing u ric acid levels)
(Go put out the pyre)

1 . Dose related , bilateral, ocular Mycobacteri um tuberculosis Only fi rst line drug that is
toxicity that is usually reversible bacteriostatic
A. Decreased visual acuity
8. Color vision loss
C. Loss of central vision
(central scotoma)

1 . Possible kidney and liver effects Rifabutin is used in combination 1 . MAC is related to tuberculosis
2 . Bone marrow suppression with other drugs for p revention (TB), but no one anti-TB drug
3. Rash, fever and treatment of Mycobacterium works against MAC
4. Uveitis (inflammation avium or in M. intracellulare 2. Care must be taken when
of the eye ) . which comprise M . avi um rifabutin is used with other
5 . Orange discoloration of urine, complex (MAC) medications that are metabolized
sweat, tears and even soft by the cytochrome P450 system
contact lenses

1 . Hepatitis Mycobacterium tuberculosis Induces P450

2. Hypersensitivity reaction

Vestibular & ototoxic Mycobacteri um tuberculosis Do not use in pregnancy

1 . Skin rash, drug fever Mycobacterium leprae Mycobacteri um leprae develops

2 . Bone marrow suppression resistance rapidly
causi ng agranulocytosis
(low neutrophils)
3 . Leprosy reactions may occur
with treatment (see text)

Red and black skin discolorations 1 . Mycobacteri um leprae Resistance develops slowly!
2 . Leprosy reaction

M . G ladwi n , W. Trattler, and S . Maha n , Clinical Microbiology Made Ridiculously Simple MedMaster

193
 CHAPTER 20. MISCELLANEOUS ANTIBIOTICS

NAME MECHANISM OF ACTION PHARMOKINETICS

Fluoroquinolones I n h ibits the enzyme DNA Gyrase. 1 . Oral or IV

First generation This results in the breakage of the 2 . Enterohepatic circulation results in
Nalidixic acid bacterial DNA structu re, and high concentration withi n stool)
inhibition of DNA synthesis 3. Excellent tissue penetration
Second generation 4. Renal excretion ( results i n high
Norfloxacin u rinary levels)
Ciprofloxacin
Enoxacin
Lomefloxacin
Ofloxacin
Levofloxacin

Third generation
Gatifloxacin

Fourth generation
Moxifloxacin
Gemifloxacin

Glycopeptides I n h i bits biosynthesis of the gram 1 . If administered IV: excreted renally

Vancomycin positive peptidoglycan a step 2 . If administered orally:
earlier than penici l l i n . Specifically: A. Not absorbed from GI tract
inhibits transpeptidation of B. Attains high concentration
D-alanine. i n stool
Telavancin Telavancin also disrupts cell membrane
potential and changes cell permeability
due to its lipophilic side chain .

Daptomycin (CU B I C I N ) 1. Binds t o t h e g ram-positive bacterial 1 . IV administration

cel l membrane in a calcium (Ca2 +) 2 . 92% protein bound
dependent manner without penetrating 3. Not extensively metabolized
the cytoplas m , leading to rapid 4. Renal excretion :
depolarization of membrane potential. Adjust dose in renal disease
2 . Depolarization causes rapid inhibition
of bacterial DNA, RNA & p rotein
synthesis, which results i n bacterial
cell death .

Figure 20-5 MISCELLANEOUS ANTIBIOTICS (chart continued on page 200)

198

ADVERSE EFFECTS
1 . Gastroi ntestinal symptoms
2 . Damage to cartilage in
animals. So it is not used in
children or pregnant women
3. Achilles Tendonitis
4 . CNS: headache, insomnia,
restlessness
5 . Disruption of bowel flora
and increased risk of
Clostridium difficile diarrhea
When administered IV:
1 . Hearing loss is rare
2. "Red man syndrome":
Get red , pruritic rash on
torso. This occu rs with
rapid IV i nfusion of
vancomycin, which
stimulates histamine
release; simply slow
down infusion to prevent
1 . Potential for myopathy:
mon itor baseline CPK
enzyme levels and
weekly thereafter
2 . Eosi nophilic pneumonia
CHAPTER 20. MISCELLANEOUS ANTIBIOTICS
THERAPEUTIC USES MISCELLANEOUS
Covers the gram-negative bacteria exceptionally well Resistance develops by
1 . Ciprofloxacin is indicated for the coverage of point m utations of the
Pseudomonas aeruginosa (although resistance DNA gyrase enzyme.
is increasing ! )
2. Diarrhea caused by enteric organisms ( Salmonella,
Shigella, Campylobacter or E. coli) as high levels are
attai ned in stool
3. U rinary tract i nfections: High renal and prostate
concentrations
4. Chronic bone i nfections (osteomyelitis): covers
Pseudomonas, Staphylococcus aureus or
Enterobacteriaceae
5. Covers g ram-negative facultative intracellular
organisms, i ncluding Legionella, Bruce/la,
Salmonella, and atypical Mycobacteria
6 . Newer generation fluoroquinolones: Expanded
gram-positive coverage ( Streptococcus pneumoniae,
Staphylococcus aureus, and Enterococcus faecalis)
and atypical bacteria coverage ( Legionella,
Mycoplasma, and Chlamydia) make them good
choices for community acq u i red pneumonia
7 . Moxifloxacin is indicated for the empi ric
coverage of i ntra-abdominal i nfections due to its
broad spectru m of activity, including anaerobes.
1 . Covers all g ram-positive organ isms, including 1 . There is increasing
exceptionally resistant organ isms such as: resistance to
A. M RSA (methicillin-resistant Staphylococcus aureus) vancomycin .
B. Enterococcus 2 . Telavancin retains
C . M u ltidrug resistant Staphylococcus epidermidis. activity against
2. Pseudomembranous colitis caused by S. aureus with
Clostridium difficile (administer oral ly) intermediate
3. Useful for the treatment of gram-positive susceptibility
organisms in patients who are allergic to penicillin to vancomycin.
and cephalosporin
Broad g ram-positive coverage , including organisms 1 New antibiotic class:
.
resistant to methicillin & vancomycin cyclic lipopeptide
Complicated skin and skin structure i nfections due 2. Not indicated for the
to S. aureus (including methicillin-resistant strains) , treatment of pneumonia
Streptococcus pyogenes, Streptococcus agalactiae, due to low lung
Streptococcus dysgalactiae, and Enterococcus penetration and
faecalis (vancomyci n susceptible strains only) decreased activity in the
presence of pulmonary
su rfactant.
1 99
 CHAPTER 20. MISCELLANEOUS ANTIBIOTICS

NAME MECHANISM OF ACTION PHARMOKINETICS

Tri methoprim/ Together, these two drugs inhibit 1. Good oral absorption
su lfamethoxazole the synthesis of tetrahydrofolate 2. Can also be given i ntravenously
(TM P/SMX): called (TH4) , which is a crucial cofactor 3. Metabolized in the liver
Bactrim for the synthesis of puri nes 4. Renal excretion
(nucleic acids ) . I n h ibition of TH4
production will therefore block
DNA synthesis
1 . Sulfamethoxazole looks like PABA.
It competitively inhibits conversion of
PABA to dihydrofolate (DHF)
2 . T ri met h o prim inhibits the enzyme
DHF reductase, blocking conversion
of D H F to TH4
Animal cells do not synthesize TH4. They
require folate i n their diet since
they can not synthesize TH4.
Therefore, TMP/SMX does not block
mammalian DNA synthesis

Figure 20-5 (continued)

References Recommended Review Articles:

Khaliq Y, Zhanel GG. Fluoroquinolone-associated ten
dionopathy: A critical review of the literature. Clin Infect
Dis. 2003;36: 1404-1410.
Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA. The
Sanford Guide to Antimicrobial Therapy 2005. 35th Edition.
Antimicrobial Therapy Inc., Hyde Park VT 2005.
Pepin J, Saheb N, Coulombe M, et al. Emergence of fluoro
quinolones as the predominant risk factor for Clostridium
difficile-associated diarrhea: A cohort study during an epi
demic in Quebec. Clin Infect Dis. 2005;4 1 : 1254-1260.
Tedesco KL, Rybak MJ. Daptomycin. Pharmacotherapy 2004;
24:4 1.
Nailor MD, Sobel JD. Antibiotics for gram-positive bacterial in
fections: vancomycin, teicoplanin, quinupristin/dalfopristin,
oxazolidinones, daptomycin, dalbavancin, and telavancin.
Infect Dis Clin North Am. 2009; 23(4):965-82.
Pappas G, Athanasoulia AP, Matthaiou DK, Falagas ME.
Trimethoprim-sulfamethoxazole for methicillin-resistant
Staphylococcus aureus: a forgotten alternative? J Chemo
ther. 2009; 2 1(2 ) : 1 15-26.

200

ADVERSE E FFECTS
1 . G I : nausea, vomiting and
diarrhea
2. Skin rashes
3. Bone marrow suppression;
primarily i n patients infected
with A I DS
4. Do not use in pregnancy, as
it causes increased bilirubin
levels in the fetus and
reduces TH4
Folate deficiency: can
increase neural tube
defects in fi rst trimester
5. Patients with low folate
levels can get macrocytic
anemia. Coadministering
folinic acid will prevent the
anemia without affecting its
antibacterial effect
CHAPTER 20. MISCELLANEOUS ANTIBIOTICS
TH E R A P E UTIC USES MISCELLANEOUS
Wide g ram-positive and g ram-negative coverage Other anti-folate drugs:
(but no anaerobic coverage) 1 . Dapsone
Uses: TMP SMX 2 . Sulfadiazine
1 . T ( Tree): Respiratory tree. TM P/SMX covers
Streptococcus pneumoniae and Haemophilus
influenzae. It is good for otitis media, sin usitis,
b ronchitis, and pneumonia, which are frequently
caused by these bugs
2 . M (Mouth): Gastroi ntestional tract TM P/SMX covers
g ram-negatives that cause diarrhea such as Shigel/a,
Salmonella, and E. coli
3. P (PEE): Genitourinary tract. TM P/SMX covers
urinary tract infections,prostatitis and urethritis caused
by the E nterics, N. gonorrhoeae and Chlamydia
4 . SMX (Syndrome) : A I D S . TMP/SMX covers
Pneumocystis carinii pneumonia (PC P ) . It is given to
prevent PCP when CD4+ T-cell counts drop
below 200-250. More than 60% of PCP i nfections are
being prevented with this prophylactic i ntervention!
It is also given intravenously i n high doses for
active pneumonia
5 . In addition to Pneumocystis carinii, other protozoans
covered by TMP/SMX are Toxoplasma gondii and
lsospora be/Ii
6. Nocardia
M . G ladwi n , W. Trattler, and S . M a h a n , Clinical Microbiology Made Ridiculously Simple M e d Master
201
 CHAPTER 21. THE FUNGI

NA M E RESERVOIR M O R P H OLOGY CLIN ICAL

1 . Phialophora verrucosa These copper-colored Sclerotic bodies: Chromoblastomycosis

2 . C/adosporium carrionii soil saprophytes can copper colored cells Following a punctu re wound, a small ,
3. Fonsecaea species be found on rotting violet wart-like lesion develops. With
wood time, cl usters of these skin lesions
can develop (resembling cauliflower)

Coccidioides immitis 1 . Desert areas of the Dimorphic. Coccidioidomycosis

southwestern 1. Mycelial forms with 1 . Asymptomatic (in most persons)
U nited States spores at 25 C 2. Pneumonia
and northern 2. Yeast forms at 3. Disseminated: can affect the l u ngs,
Mexico 37 C skin , bones, and meninges
2 . Respi ratory Note: A small percentage of indi
transmission viduals with this i nfection will
develop painful erythematous
nodular lesions called erythema
nodosum

Histoplasma capsulatum 1 . Mississippi valley Dimorphic: Histop/asmosis

2 . Present in bird and 1 . Mycelial forms with 1 . Asymptomatic (in most persons)
bat droppings spores at 25 C 2 . Pneumonia: lesions calcify , which
3. Respiratory 2. Yeast forms at can be seen on chest X-ray (may
transmission 37 C look similar to tuberculosis)
3. No capsule (despite 3. Disseminated: can occur in almost
its name) any organ, especially in the lung,
spleen, or liver

Blastomyces dermatitidis 1 . Mississippi R iver Dimorphic Blastomycosis

valley extending North 1 . Mycelial forms with 1 . Asymptomatic (uncommon)
to the G reat Lakes spores at 25C 2 . Pneumonia: lesions rarely calcify
2. Resides in soi l or 2. Yeast forms at 3. Disseminated (most common): pre
rotten wood 37C sent with weight loss, night sweats,
3. Respi ratory lung i nvolvement, and skin ulcers
transmission 4. Cutaneous: skin u lcers

Cryptococcus 1 . Found in pigeon 1 . Polysaccharide Cryptococcosis

neoformans droppings capsule 1 . Subacute or chronic meningitis
2 . Respiratory trans 2. Yeast form only A. Headache
mission (Not dimorphic!) B. Fever
C. Vomiting
D . Neurologic or mental status
changes
Cryptococcus gattii 1 . Found in soil 2 . Pneumonia: usually self-limited
3. Skin lesions: look like acne

Candida albicans 1. Normal inhabitant of Pseudohyphae and Candidiasis in a normal host

the ski n , mouth and yeast 1 . Oral thrush
gastrointestinal tract 2 . Vulvovaginal candidiasis
2. Not found in blood ! 3. Cutaneous
A. Diaper rash
B. Rash in the skin folds of obese
individuals

Figure 2 1 - 1 1 (continued) (chart continued o n page 2 14)

212

TREATMENT
1 . ltraconazole
2. Local excision
1 . Amphotericin B
2. ltraconazole
3 . Fluconazole
1. ltraconazole
2 . Amphotericin B
(in imm unocompro
mised patients)
1 . ltraconazole
2 . Ketoconazole
3. Amphotericin B
1 . Amphotericin B and
flucytosine (is superior
to amphoterici n
B alone)
2 . Fl uconazole
The choice of antifun 1.
gal agent depends on
on the area involved
and its severity. Pos
sible choices i nclude:
1 . Thrush- oral
fluconazole, nystatin
swish and spit, and
clotrimazole candies
2 . Cutaneous i nfec
tion: topical imidazole
or oral fluconazole.
CHAPTER 21. THE FUNGI
DIAGNOSIS IUSCELLAHEWS: . LOCATION
Skin scrapings with KOH prep S U BCUTAN EOUS
reveal copper-colored cells, called
sclerotic bodies
1. Biopsy of affected tissue: lung Common opportunistic SYSTEM I C
biopsy, skin biopsy, etc. i nfection i n AIDS patients
A. Silver stain or KOH prep from the southwest U nited
B. Cultu re on Sabouraud's agar States
2. Serology
3. Skin test (tests for exposure only)
1. Lung biopsy Can su rvive i ntracellularly SYSTEM I C
A. Silver stain specimen within macrophages
B . Culture on Sabouraud's agar
will reveal hyphae at 25 C,
and yeast at 37 C.
2 . Serology
3. Skin test (tests for exposure only)
4. U rine antigen test.
1. Biopsy of affected tissue: lung 1 . bLAST to get SYSTE M I C
biopsy, skin biopsy, etc. 2. No B LAST to have
A. Silver stain specimen
B . Cultu re on Sabouraud's agar
2 . Serology
3. Skin test (tests for exposure only)
1 . India-ink stain of cerebrospinal Most cases occur i n SYSTEM I C
fluid (CSF) : observe encapsu immunocompromised
lated yeast persons
2. Cryptococcal antigen test of CSF:
detects polysaccharide antigens
3. Fungal culture
KOH stai n of specimen CUTANEOUS or
2 . Silver stain of specimen SYSTEM I C
3. Blood culture : g rowth m ust be (Normal host, o r
respected opportunistic)
4. Blood assay for beta-D-glucan.
213
 CHAPTER 21. THE FUNGI

NAME RESERVOIR MORPHOLOGY CLINICAL

Candida a/bicans Candidiasis in an immunocompro

(continued) mised host
Thrush , vaginitis and/or cutaneous,
plus:
1 . Esophageal:
A. Retrosternal chest pain
B. Dysphagia
C . Fever
2 . Disseminated candidiasis:
acqu i red by very sick hospi
tal ized patients, resulting in
multi-organ system fail u re
3. C h ronic mucocutaneous
candidiasis

1 . Aspergillus fumigatus 1. Everywhere (frequent Branching septated Aspergillosis

2 . Aspergillus flavus
3. Aspergillus niger 2. Aspiration of
lab contaminant) hyphae 1 . Allergic bronchopulmonary
asperg i llosis (lgE mediated): asthma
Aspergillus asthma
= type reaction with shortness of
breath and high fever
2. Aspergilloma (fungus bal l ) :
associated with hemoptysis
(bloody cough)
3. Invasive aspergillosis: necrotizing
pneumonia. May disseminate to
other organs in immunocompro
mised patients
4 . Aflatoxin consumption (produced by
Aspergil/us f/avus) can cause liver
damage a n d l i ve r can ce r

1 . Rhizopus Saprophytic molds B road , non-septated , Mucormycosis

2 . Rhizomucor b ranching hyphae 1 . Rhinocerebral (associated with
3. Mucor diabetes): starts on nasal mucosa
and invades the sinus and orbit
2. Pulmonary m ucormycosis

TH E FUNGI-LIKE BACTERIA

Actinomyces israelii Part of the normal flora 1 . G ram-positive rods Eroding abscesses of the mouth ,
of the mouth and 2. A naerobic bacteria lung or gastrointestinal tract,
gastrointestinal tract 3. G row as branching classified as:
chains o r beaded 1 . Cervicofacial actinomycosis
filaments 2. Thoracic actinomycosis
3. Abdom inal actinomycosis

Nocardia asteroides 1 Never part of the

. 1 . G ram-positive rods 1 . Pneumonia
normal flora 2. Partially acid-fast: 2 . Formation of abscesses i n the lung,
2 . Respi ratory due to mycolic acids kidney, and central nervous system
transmission in the cell wall
3. Aerobic
4. G row as branching
chains or beaded
filaments

Figure 2 1 - 1 1 (continued)
214
 CHAPTER 21. THE FUNGI

TR EATM ENT DIAGNOSIS M ISCELLANEOUS LOCATION

3. Esophageal
candidiasis
(most common
in HIV): fl uconazole
or caspofungin .
4. Systemic candidiasis:
i ntravenous
amphotericin B,
fluconazole, or
caspofung i n .
5 . Chronic
mucocutaneous
candidiasis:
ketoconazole or
fluconazole

1 . Allergic bronchopul A. Allergic bronchopulmonary Aflatoxins contaminate

monary aspergillosis: aspergillosis: peanuts, grains and rice
treat with cortico 1 . High level of lge and lgG
steroids against aspergillis
2. Aspergilloma: 2. Sputum cultu re
removal via su rgery 3. Wheezing patient and chest
3. invasive aspergillosis: X-ray with fleeting infiltrates
treat with voriconazole, 4. I ncreased level of eosinophils
amphotericin B, or 5 . Skin test: immediate hypersen
possibly caspofungin. sitivity reaction
(very high mortality) B . Aspergilloma: diagnose with chest
X-ray or CT scan
C. I nvasive aspergillosis: sputum
examination and culture

1 . Aggressive surgical 1 . Biopsy This disease is rapidly fatal

debridement 2. Black nasal discharge
2. IV Amphotericin or
posaconazole as an
oral alternative

1 . Penicillin G 1 . Examine tissue or pus from Yellow "sulfu r granules":

2. Surgery infection site , and look for "su lfur microcolonies of Actino
granules" myces and cellular debris
2. Anaerobic culture

Trimethopri m/ 1 . G ram stain Nocardia i nfections usually

sulfamethoxazole 2 . Modified acid fast stain: occur in immunocompro
Decolorize with 1 % sulfu ric acid m ised patients
instead of acid alcohol.
3. Aerobic culture

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 CHAPTER 22. ANT/FUNGAL ANTIBIOTICS

GREASY FULCRUM

DERMATOPHVTE
INFECTION

Figure 22-3

NAME M ECHANISM O F ACTION PHARMOKIN ETICS

Amphotericin-B Punches holes in ergosterol: This 1 . N o oral absorption: so give it IV

(a polyene antibiotic)
increases membrane permeability,
resulting in cell death
2 . Does N OT cross blood brain barrier:
so must give intrathecally to reach the
cerebrospinal fluid (CSF)
3. Excreted via biliary tract and kidney
(clearance is not affected by kidney
dysfunction)

Flucytosine Converted to 5-fluorou racil , which 1 . Oral absorption

inhibits fungal DNA & RNA synthesis 2. Excreted i n u rine
3. Penetrates CSF wel l ! ! !

Ketoconazole Blocks ergosterol synthesis by inhibiting 1 . Oral absorption

(an l midazole) the cytochrome P4so enzymes. This 2 . Absorbed better at low pH - so worse
causes depletion of ergosterol, absorption when taken with antacids or
resulting in disru ption of the H2 blockers
permeability of the cell membrane 3. Extensive hepatic metabolism

Figure 22-4 ANTI-FUNGAL DRUGS

220
 CHAPTER 22. ANTIFUNGAL ANTIBIOTICS

These antifungals are great against all species of can Griseofulvin

dida and also as an option for salvage of patients with
invasive aspergillosis failing conventional therapy.
Other Antifungal Drugs
Nystatin
Nystatin , like amphotericin B, binds to ergosterol ,
increasing the permeability of the cell membrane and
causing cell lysis.
Think "Nasty Nystatin" because this drug is too
toxic to take parenterally (intravenously). It is only
used topically on the skin and mucous membranes.
Also, since it is not absorbed from the gastrointestinal
tract, oral nystatin can be used to treat oral and
esophageal infections with yeast or fungi. You will
order nystatin on the wards as Nystatin, Swish and
Swallow for treatment of oral , esophageal, and gas
tric candidiasis. It is also given topically for vaginal
candidiasis.
Fig. 22-2. Nasty Nystatin cruises down the esopha
gus killing fungi on the wall of the esophagus. In one
end and out the other!
Fig. 22-3. Visualize griseofulvin as a greasy ful.
crum used to lever the dermatophyte plaques off the
skin. It inhibits fungal growth by disrupting spindle
formation, thus preventing mitosis. Note the worker
peeling fungus off your "toe,"sis.
Griseofulvin deposits in keratin precursor cells in
the skin, hair, and nails, where it inhibits the growth of
fungi in those cells. Note that it does not kill the fungi;
it just inhibits their growth (static rather than cidal).
The uninfected drug-infiltrated keratin precursor
cells mature and move outward toward the keratinized
layer. As the older, infected cells fall off with normal
cell turnover, this translates into a slow cure of skin
fungus.
Adverse effects of griseofulvin are uncommon. They
include headache, nausea, vomiting, photosensitivity,
and mental confusion, in addition to bone marrow sup
pression (leukopenia and neutropenia).
Potassium Iodide
Potassium iodide is used to treat sporotrichosis.
Remember that you get sporotrichosis from pricking

ADVERSE E F FECTS T H ER A P EUTIC USES MISCELLANEOUS

1. Nephrotoxic (reversible) Severe systemic fungal i nfections: 1 . Monitor BUN and creatinine
2. Acute febrile reaction 1 . Systemic Candida i nfections levels daily to follow
3. Anemia 2 . Cryptococcal meningitis kidney dysfunction
4. Phlebitis at IV site 3. Excellent for blastomycosis, 2 . Newer lipid and l iposomal
histoplasmosis and preparations are less
coccidioides neph rotoxic
4. Invasive aspergillosis
5 . Invasive sporotrichosis
6. Mucormycosis

1 Bone marrow suppression

. 1 . Cryptococcal meningitis (in The reason for these adverse effects
A. leukopenia combi nation with amphotericin B) is that flucytosine inhibits DNA
B. thrombocytopenia 2 . Candida! endocarditis (in synthesis, which occurs i n rapidly
2 . Nausea, vomiting and diarrhea combo with amphotericin B) dividing cells such as bone marrow
cells & GI epithelial cells

1 . Nausea, vomiting and anorexia Chronic mucocutaneous

2 . Hepatotoxic candidiasis
3. I nhibits CYP4so system , resulting
i n decreased androgen &
testosterone synthesis:
A. Gynecomastia
B. I mpotence
C. Decreased sex drive
D. Decreased sperm production
4. Rash/pruritus

221
 CHAPTER 22. ANTIFUNGAL ANTIBIOTICS

NAME M E C H A N I S M OF ACTI ON PHARMOl(INETICS

M iconazole and Blocks ergosterol synthesis by inhibiting 1 . Topical usage

clotrimazole the cytoch rome P4so enzymes 2. Oral (not absorbed systemically)
(these are
imidazoles)

Fluconazole Blocks ergosterol synthesis by inhibiting 1 . Oral absorption

(a triazole) the cytoch rome P4so enzymes 2 . Can also be administered IV

ltraconazole Blocks ergosterol synthesis by inhibiting 1 . Oral absorption

(a triazole) the cytochrome P4so enzymes 2 . Metabolized and excreted via l iver
3. Available IV

Voriconazole Blocks ergosterol synthesis by inhibiting 1 . Oral absorption

the cytochrome P4so enzymes 2 . Can also be administered IV

Posaconazole 1. Blocks ergosterol synthesis by inhibiting 1. Oral

the cytoch rome P450 enzymes

Echinocandins 1 . I n hibit fungal cell wall synthesis by 1 . I ntravenous

(caspofungin, m icafungin, i n h i biting 1 ,3 D-glucan synthase
and anidulafungin)

Terbinafi ne Blocks ergosterol synthesis by 1. Oral

i n h i biting squalene epoxide 2 . Topical

Figure 22-4 (continued)

222
 CHAPTER 22. ANT/FUNGAL ANTIBIOTICS

ADVERSE EFFECTS THERAPEUTIC USES MISCELLANEOUS

Low toxicity when used topically A. Topical fungal infections

1 . Tinea versicolor
2 . Cutaneous candidiasis
3. Dermatophytosis
B. Oral troches for th rush
(oral candidiasis)
C . Vaginal suppositories for
candida vaginitis

Less toxic than ketoconazole 1 . Oral, vagi nal and

No interference with esophageal Candida
testosterone synthesis 2 . Alternative to amphotericin B
1 . Nausea for treatment of:
2. Skin rash A. Systemic candidiasis
3. Headache B. Cryptococcal meningitis
C. Pulmonary & extrapulmonary
coccidioidomycosis (but
fl uconazole is not used to treat
coccidioides meningitis)

Less toxic than ketoconazole A therapeutic option for the Absorption enhanced by taking with
No i nterference with testosterone following fungal infections: acid drinks (such as O.J. or colas)
synthesis 1 . Blastomycosis
1 . Nausea 2. Histoplasmosis
2 . Skin rash 3. Coccidioidomycosis
3. Headache 4. Sporotrichosis
5 . Ch romomycosis
6 . Invasive aspergillosis

1 . Photophobia Broad activity against multiple fungi. Do not use IV formulation in

2 . Rash Its primary use at this time is for patients with decreased renal
3. Liver enzyme increases infections with : function (creatinine clearance < 50)
1 . Aspergillus
2. Fluconazole resistant candida
3. Antifungal prophylaxis in bone
marrow transplant recipients

Few side-effects in initial trials Broad antifungal activity

including Rhizipus sp.

1 . Well tolerated 1. A good candida d rug (including

2 . I nfusion may cause flushing fluconazole resistant species)
due to histamine release 2. I n dicated for salvage of
aspergillus infections

1 . Rare gastrointestinal side effects 1. Primarily used for dermatophyte

2. Rare rash infections - has largely replaced
3. Rare reversible agranulocytosis g riseofulvin in treatment of
onychomycosis (fungal nail
infections)

223
 CHAPTER 22.
NAME MECHANISM OF ACTION
Nystatin Punches holes i n ergosterol: This
increases membrane permeability,
resulting in cell death
G riseofulvin I n h ibits mitosis of cells, by disru pting
spindle formation
Potassium Iodide
Figure 22-4 (continued)
your finger in the garden. "You get Sporotrichosis while
Potting plants." If the infection becomes systemic,
amphotericin B or itraconazole is better.
Terbinafine
Terbinafine is a newer oral fungicidal agent that
blocks fungal cell wall synthesis. It blocks ergosterol
synthesis by inhibiting the formation of squalene epox
ide from squalene. Terbinafine tends to accumulate in
nails, and is therefore useful for tinea unguium (ony
chomycosis). It also appears useful in the treatment of
tinea pedis, tinea capitis, and tinea corporis. Since it is
not metabolized by the cytochrome p450 system (as are
the azole antifungals), there is little potential for drug
drug interactions.
Fig. 22-4. Summary of the anti-fungal drugs.
Reference
Andriole VT. Current and future antifungal therapy: new tar
gets for antifungal therapy. International Journal of
Antimicrobial Agents 2000;16:317-2 1 .
ANT/FUNGAL ANTIBIOTICS
PHARMOKINETICS
1. Not absorbed from GI tract. Oral
administration results i n "topical"
treatment along the GI tract
2. Apply topically to skin and vaginal
i nfections
3 . Too toxic to give IV
1 . Oral absorption
2. Absorbed better with fatty foods.
3. Deposits in keratin
4 . Excreted in feces unchanged
Bennett JE. Antifungal Agents. In: Mandell GL. Bennett JE,
Dolin R, eds. Principles and Practice of Infectious Diseases.
4th edition. New York: Churchill Livingstone 1995; 401-410.
Gupta AK, Tomas E . New antifungal agents. Dennatologic
Clinics 2003; 21(3).
Jackson CA, et al. Drug therapy: Oral azole drugs as systemic
antifungal therapy. N Engl J Med 1994;330:263-272.
Sanford JP, Gilbert DN, et al. Guide to antimicrobial therapy
1994. Antimicrobial Therapy, Inc, Dallas Texas; 1994.
www. doctorfungus.org
Recommended Review Articles:
Chen SC, Playford EG, Sorrell TC. Antifungal therapy in in
vasive fungal infections. Curr Opin Phannacol. 2010;10(5):
522-30.
Bennett JE. Echinocandins for candidemia in adults without
neutropenia. N Engl J Med. 2006;355( 1 1 ) : 1 154-9.
224
 CHAPTER 22. ANTIFUNGAL ANTIBIOTICS

ADVERSE E FFECTS THERAPEUTIC USES MISCELLANEOUS

Highly toxic if given IV 1. Oral, esophageal or gastric Order as "nystatin, swish and
candidiasis (oral administration) swallow"
2 . Vaginal candidiasis
(apply topically)

1. Headache, nausea, vomiting, Dermatophytosis of the skin , Works very slowly! ! !

photosensitivity and mental hair and nails
confusion
2 . Bone marrow suppression

Skin rash Cutaneous sporotrichosis "You get Sporotrichosis while

Potting plants"

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 CHAPTER 23. VIRAL REPLICATION AND TAXONOMY

N U C LEIC ACID SYMMETRY PRESENCE OR PHYSICAL STATE

ABSENCE (NAKED) OF NUCLEIC ACI D
OF ENVELOPE

SS NONsegmented

NAKED

SS NONsegmented

ICOSAH E D RAL
OS S E G M E NTED ( 1 1 )

SS NONsegmented

ENVELOPED SS NONsegmented

SS NONsegmented
RNA
SS S E G M E NTED (3)

SS SEGM ENTED (8)

SS NONsegmented
H ELICAL ENVELO P E D

S S NONsegmented

SS NONsegmented

SS S E G M E NTED (2)

SS D I PLO I D
COMPLEX COM PLEX COAT (2 identical copies of + stranded RNA)

Figure 23-19 VIRAL MORPHOLOGY

236
 CHAPTER 23. VIRAL REPLICATION AND TAXONOMY

POSITIVE ( +) O R FA M I LY S P E C I F I C PATHOG E N I C V I R U S E S
N EGATIVE ( - ) (OR DIS EASES C A U S E D )
STRAN D E D

+ PICORNA vi ridae Polio virus

Coxsackie A & B virus
ECHO virus
Hepatitis A vi rus
Rhino virus
New enterovi ruses

+ CALC/ vi ridae Norwalk virus

Hepevi ridae Hepatitis E vi rus

Double stranded REO vi ridae Rota virus

+ TOGA vi ridae Mosquito borne encephalitis (WE E , E E E , VEE)
Rubivirus ( rubel la)

+ FLA VI viridae Yellow fever virus

Dengue virus
St. Louis encephalitis
Japanese encephalitis
Hepatitis C virus

+ CORONA vi ridae Respi ratory ill ness (cold)

-
BUNYA vi ridae California encephalitis vi rus
Rift Valley fever virus
Sandfly fever virus
Hantavirus
-
ORTHOMYXO vi ridae I nfluenza vi rus (types A, B & C)
-
PARAMYXO vi ridae Para-influenza vi rus
Respi ratory syncytial vi rus
Mumps
Measles
Metapneumovirus
-
RHABDO vi ridae Rabies virus
-
FILO vi ridae Marburg virus (acute hemorrhagic fever)
Ebola vi rus (acute hemorrhagic fever)
-
ARENA vi ridae Lymphocytic choriomen ingitis virus
Lassa vi rus

+ RETRO vi ridae H u man immunodeficiency virus (H IV)

Note: RNA reverse transcribed to types I and I I
DNA using reverse transcriptase HTL V types I and 1 1
enzyme

237
 CHAPTER 23. VIRAL REPLICATION AND TAXONOMY

N U C LEIC ACID SYMMETRY PRESENCE OR PH$tCAL &TTE

ABSENCE (NAKED) . OF': N.UC&J;tC.ACID
OF ENVELOPE

SS L I N EAR

DS C I R C U LA R
NAKED

DS L I N EAR
I COSAH E D RAL

DNA DS L I N EAR

ENVELOPED

DS C I R C U LAR

DS L I N EAR
COMPLEX COMPLEX ENVELOPE

N o t e : D e l t a v i r u s (causes h epatitis) i s a n i ncomplete R N A v i r u s . It n e e d s t h e coi nfect i o n with hepatitis B virus to c a u s e disease

Figure 23- 19 (continued)

238
 CHAPTER 23. VIRAL REPLICATION AND TAXONOMY

PO S I TI V E
( +) OR FAMILY SPECIFIC PATHOGENIC VIRUSES
NEGATIVE ( -) (OR DISEASES CAUSED)
STRAN DED

PAR VO vi ridae E rythema i nfectiosum

Transient aplastic anemia crisis

PAPOVA vi ridae Human papilloma virus

BK polyomavirus
JC polyomavirus

ADENO viridae Childhood respi ratory illness ("cold")

Epidemic keratoconjunctivitis

HERPES viridae Herpes simplex virus types 1 & 2

Varicella-zoster virus
Cytomegalovirus
Epstein-Barr vi rus
Human Herpesvirus 6 (roseola}

HEPADNA vi ridae *Hepatitis B virus (see note)

POX vi ridae Smallpox

Vaccinia
Moll uscum contagiosum

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 CHAPTER 24. ORTHOMYXOVIRIDAE AND PARAMYXOVIRIDAE

NAME M O R P H OLOGY V I RULENCE FACTO R S

ORTHOMYXO VIRUS

I nfluenza 1 . Negative ( - ) single-stranded RNA 1. Hemagglutinin (HA) glycoprotein:

type A: human 2. Segmented (7-8) binds to red blood cells. Also binds
and animal strain 3. Lipid containing envelope to cells of the upper respi ratory tract.
type B : human 4. Helical sym metry The HA is then cleaved i nto two pieces
only strain 5. Repl icates in the nucleus! (Retrovi ruses (HA 1 & HA2) by host cel l proteases,
type C : h u man are the only other type of RNA viruses which allows HA to activate fusion.
only strain that replicate in the n ucleus) The vi ral RNA is then dumped i nto
these cells.
2. Neuraminidase (NA) glycoprotein:
breaks down neuraminic acid , an
important component of mucin

Parainfluenza 1. Negative ( ) single-stranded RNA

- 1 . Glycoproteins with combined HA
2. U nsegmented and NA activity
3. Lipid containing envelope 2 . F-protein ( Fusion protein): results
4. Hel ical symmetry in multinucleated giant cells (called
5 . Replicates in the cytoplasm syncytial cells)

Respiratory syncytial Same as above 1 . F-protein

virus 2 . NO HA nor NA glycoproteins

Metapneumovi rus Same as above l ntegrin alpha-V-beta receptor

allows i nfection of respi ratory
tract epithelial cells.

M umps Same as above 1 . G lycoproteins with combi ned HA

and NA activity
2. F-protein

Figure 24- 12 ORTHOMYXOVIRIDAE AND PARAMYXOVIRIDAE

250
 CHAPTER 24.
CLINICAL
The Flu: Fever, runny nose ,
cough, myalgias arthralgias, etc.
Complications
1 . Secondary bacterial pneumonias
in the elderly
2 . Reyes Syndrome in children who
use aspiri n ; get liver and brain
disease
3. I ncreased mortality in the elderly
and in those with underlying
pulmonary and cardiac disease.
1 . Upper respi ratory tract infection
in adults: bronchitis, pharyngitis,
rh initis
2 . Viral pneumonia in childre n ,
elderly a n d immuno-
compromised
3. Croup: Children develop a
barking cough due to infection
and swelling (narrowi ng)
of the larynx
4. Bronchiolitis in children
1 . Most common cause of
pneumonia in infants less
than 6 months of age
2. Acute otitis media occu rs in
up to 33% of children with
RSV ill ness
U pper and lower respi ratory tract
infections in young children
and older adu lts.
Mumps
1 . Parotid gland swelling (painful)
2 . Testicular inflam mation
(very painful)
3 . Meningitis
4 . Encephalitis
ORTHOMYXOVIRIDAE AND PARAMYXOVIRIDAE
TREATMENT & PREVENTION
1 . Vaccine: contraindicated
in egg allergies. (vaccine
grown in eggs)
2. Amantadine & Rimantidine:
prevent viral u ncoating of
infl uenza A
3. Zanamivir (inhaled) &
Oseltamivir (oral) are
neuraminidase inhibitors .
Can shorten cou rse of
influenza A and B.
Supportive
1 . Palivizumab: a monoclonal
antibody against RSV that is
produced by a recombinant
DNA. It is given intramuscularly.
Indicated for prophylaxis in
premature infants (less than
32 weeks) or i nfants younger
than 2 years with severe
chronic lung disease
2. Ribavirin
Supportive
Prevention: M M R vaccine:
1 . Measles
2. Mumps (live attenuated)
3. Rubella
251
MISCELLANEOUS
1 . Antigenic drift. small
mutations, resulting in mi nor
changes in the antigenicity of HA
or NA. This results in epidemics
of the common flu
2. Antigenic shift (only occu rs
with influenza type A) : reassert-
ment. Major changes of the
HA or NA (including acqu isition
of ani mal HA or NA) . This
results in devastating influenza
pandemics
3. Avian i nfluenza vi ruses such
as H5N1 and H7N9 pose great
risk for human pandemics.
Diagnose with RT-PCR of
respiratory samples.
Only one antigenic type.
Therefore, the vaccine
is protective
 CHAPTER 24. ORTHOMYXOVIRIDAE AND PARAMYXOVIRIDAE

NAME M O R P H OLOGY VIRULENCE FACTORS

ORTHOMYXO VIRUS

Measles (rubeola) Same as above 1 . HA, but no NA

2. F-protein

Figure 24- 12 (continued)

252
 CHAPTER 24. ORTHOMYXOVIRIDAE AND PARAMYXOVIRIDAE

CLINICAL T R EATM ENT & P R EVENTION M I SC E L L A N E O U S

Measles Prevention : M M R vaccine: Biopsy of rash or Koplik's spots

1 . Prodrome: high fever, hacking 1 . Measles (l ive attenuated) reveals multin ucleated giant cells
cough and conjunctivitis 2. Mumps
2 . Koplik's spots : small red based 3. Rubella
bl ue-white centered lesions i n
t h e mouth
3. Rash : from head, then to neck &
torso, then to feet. As the rash
spreads, it coalesces
4 . Compl ications:
A. Pneumonia, eye damage,
myocarditis and encephalitis
B. 20% risk of fetal death if
acqu i red by a pregnant woman
early in her pregnancy
C. Subacute Sclerosing
Panencephalitis: slow form
of encephalitis that occurs
many years after a
measles i nfection .

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