Pharmacology: Antibiotics- Dr.

Walters
Intro notes:

BacterSTATIC abx do not directly kill the bacteria. Instead they inhibit the
metabolic pathways thus weakening the organism, thus enabling the immune
system to clear the infection
BacteriCIDAL abx do kill the bacteria, often by lysis
Factors to consider when choosing an abx: Resistance, Age, Hepatic function,
Genetics, Disease State, Pregnancy, Site of Infection, and Route of
Administration.

Sulfonamides
Sulfonamides (broad spectrum bacterstatic abx vs gram +/- bacteria)
Structural analogs of PABA, thus inhibiting dihydropteropate synthase, the first step
in the synthesis of folic acid. Folic acid goes to FH4, which is used to synthesize
thymidine. Often used with DHFR inhibitors, which prevent reduction of FH2 to
FH4, aiding in inhibition of folic acid synthesis.
Drug Name

Mechanism of
Action

Sulfisoxazole w/
erythromycin
Sulfamethoxazole
w/ trimethoprim
(Bactrim, Septra)

Dapsone (Aczone)

Indications

Contraindication
s

Otitis Media

Crystalluriacrystals in urine
Kernicterus- form
of jaundice due to
bilirubin
displacement
Blood dyscrasiasacute hemolytic
anemia,
angranulocytosis,
aplastic anemia.
Specific to topicals
Hypersensitivityerythema
multiforme, StevenJohnson, Rx fever
Hyperkalemia- high
K+

Urinary, respiratory,
and GI infections
Inhibits
dihydropteropate
synthase, preventing
downstream
thymidine synthesis.
Often paired with
DHFRIs

Side Effects

(Streptococcus,
Staphylococcus
aureus, E. coli,
haemophilius
influenzae, and oral
anaerobes)
Leprosy,
pneumocystis carinii
PNA

Table #1- Oral Sulfonamides

Drug Name

Mechanism of
Action

Indications

Contraindication
s

Side Effects

Sulfacetamide

Inhibits
dihydropteropate
synthase, preventing
downstream
thymidine synthesis.
Often paired with
DHFRIs

Ulcerative
blepharitis
(S.aureus and S.
epidermidis)
Bacterial
conjunctivitis (S.
aureus, strep
pneumoniae, H.
influenzae, and

Sulfa drug sensitivity

due to local irritation
and contact
dermatitis

Crystalluriacrystals in urine
Kernicterus- form
of jaundice due to
bilirubin
displacement
Blood dyscrasiasacute hemolytic
anemia,

Moraxella
catarrhalis)
Burns for sepsis
prevention

Silver Sulfadiazine

Mafenide

Burns, but limited

use

Large burn areas

due to absorption
potential
Sulfonamide allergy
due to carbonic
anhydrase inhibition

angranulocytosis,
aplastic anemia.
Specific to topicals
Hypersensitivityerythema
multiforme, StevenJohnson, Rx fever
Hyperkalemia- high
K+

Table #2- Topical Sulfonamides

Fluoroquinones
Broad spectrum CIDAL agents used for gram - (mostly) and some gram +
Mechanisms:

Gram (-): inhibits DNA gyrase (topoisomerase II in humans). Normally, this

enzyme unwinds DNA during replication by cutting DNA and is then rejoined
by ligase. FQs inhibit re-ligation step.
Gram (+): inhibits topoisomerase IV, an enzyme that normally separates
daughter strands into 2 daughter cells
Note: both processes are occurring; its the primary mechanism
that differs depending on the organism

Drug Name

Mechanism of
Action

Ciprofloxin
Best for gram (-).
Comes in multiple
forms for various
administrations.

Ofloxacin
Oral is generic
Also in eye drops
and ear drops

Inhibits DNA gyrase

(type II
topoisomerase) and
topoisomerase IV

Indications

Contraindication
s

Side Effects

Decreased clearance
of theophylline
(bronchodilator)
leads to toxicity.

Phototoxicityburning, redness,
swelling, blisters,
rash
Arthropathydamages growing
cartilage
Tendon ruptureBLACK BOX
WARNING, 65+ or
PO
Diabetics- FQs can
increase or decrease
BS if taking insulin
CNS stimulationconvulsions, anxiety
N/V/D- major cause
of C.diff induced
diarrhea. Produces
two exotoxins that
increase fluid
secretion, mucosal
injury, inflammation,
bloody diarrhea, and
disrupt tight
junctions.

Inhibits CYP3A4 and

CYP1A2 increases
methadone and
tizanidinerespirato
ry depression,
sedation,
hypotension,
hallucinations
Reduced use due to
bacterial resistance
(STDs)
Liver disease

Table #1- 2nd Generation Drugs (Less active against S.pneumoniae than 3 rd generation)

Drug Name

Mechanism of
Action

Gatifloxacin
(Zymar)
Only non-respiratory
fxn
Eye drops only
Gemifloxacin
(Factive)
Levofloxacin
(Levaquin)
Active L isomer of
ofloxacin

Moxifloxacin
(Avelox)
Metabolized by the
liver
Table #2- 3rd

Drug Name
Besifloxacin
(Besivance)
Finafloxacin
(Xtoro)

Indications

Contraindication
s

Side Effects

Diabetes

Phototoxicityburning, redness,
swelling, blisters,
rash
Arthropathydamages growing
cartilage
Tendon ruptureBLACK BOX
WARNING, 65+ or
PO
Diabetics- FQs can
increase or decrease
BS if taking insulin
CNS stimulationconvulsions, anxiety
N/V/D- major cause
of C.diff induced
diarrhea. Produces
two exotoxins that
increase fluid
secretion, mucosal
injury, inflammation,
bloody diarrhea, and
disrupt tight
junctions.

Chronic bronchitis
and mild-tomoderate PNA
Cardiac conduction
anomalies, due to
increase QT interval
in elderly
Rare risk of hepatitis
and fatal events

Inhibits DNA gyrase

(type II
topoisomerase) and
topoisomerase IV

Inhibits DNA gyrase

(type II
topoisomerase) and
topoisomerase IV

Pre-existing hepatic
disease
Risk for prolonged
QT interval in
healthy pts
generation FQs (more active against S. pneumonia than 2 nd generation)

Mechanism of
Action

Same as 2nd and 3rd

generation

Indications

Contraindication
s

Side Effects
Same as 2nd and 3rd
generation

Bacterial
conjunctivitis
Acute otitis externa
(swimmers ear)
Drug specific side
effects: itching in
ear, nausea

Table #3- 4th generation FQs

Drug Name

Mechanism of
Action

Fidaxomicin
Inhibition of RNA
(Dificid)
polymerase, but
Possesses both
metabolite may also
STATIC and CIDAL
have significant
properties
post-abx activity
Table #4- Special FQs

Indications
C. difficile-induced
diarrhea

Contraindication
s

Side Effects
Nausea, vomiting, GI
hemorrhage,
anemia, and
neutropenia

NOTE: General contraindication for all FQs is to avoid antacids and iron
supplements, as they tend to chelate with cations resulting in decreased
absorption
Penicillins (PCNs)

Mechanism of Action: CIDAL- disrupts peptidoglycan cell wall synthesis by

inhibiting transpeptidase (PBP), the enzyme that facilitates NAM crosslinking.
This leads to lysis via the osmotic effect.
Only works against peptidoglycan synthesizers, not protozoa or fungi
(eukaryotes)
Mechanism of Resistance: Beta-lactamase enzymes or PCNases (enzymes
possessed by the bacteria) destroy the beta-lactam ring of PCN, inactivating
the abx
Drug Name

Mechanism of
Action

Indications

Pfizerpen
Solution for IM/IV
Procaine
Local anesthetic w/
PCN
IM suspension
Longer duration of
action

Contraindication
s

Side Effects

Hypersensitivity to
PCN
Allergic rxn if allergic
to esters

HypersensitivityIgE mediated in
response to
metabolites that act
as haptens
Diarrhea- PCN kills
normal flora, leading
to fluid inbalance
SuperinfectionBenzathine
Hypersensitivity
killing off certain
IM suspension
Renal impairment
organisms allows
Treatment of
Longest lasting
due to 90%
others to grow
Disrupts NAM
infections caused by
Can combine with
elimination by
without competition
crosslinking by
a variety of
Procaine for Bicillin
tubular secretion
Seizures- if
inhibiting
susceptible
C-R
penetrates BBB via
transpeptidase (PBP) organisms (both
GABA-A antagonism,
gram + and gram - )
leading to
predominant
excitatory
stimulation
JarischHerxheimer Rxnsecondary syphilis,
resolves
spontaneously, not
allergic rxn, treat
with ASA
Table #1: PCN G (aka benzylPCN), which comes in three main forms. IV-IM only because not stable in
the gut

Drug Name

Mechanism of
Action

Indications

PCN V
Acid stable
PO use, but take w/o
food

Disrupts NAM
crosslinking by
inhibiting
transpeptidase (PBP)

Treatment of
infections caused by
a variety of
susceptible
organisms (both
gram + and gram - )

Contraindication
s

Side Effects
HypersensitivityIgE mediated in
response to
metabolites that act
as haptens
Diarrhea- PCN kills

normal flora, leading

to fluid inbalance
Superinfectionkilling off certain
organisms allows
others to grow
without competition
Seizures- if
penetrates BBB via
GABA-A antagonism,
leading to
predominant
excitatory
stimulation
JarischHerxheimer Rxnsecondary syphilis,
resolves
spontaneously, not
allergic rxn, treat
with ASA
Table #2: PCN V (aka phenoxymethyl PCN)

Drug Name

Mechanism of
Action

Dicloxacillin
Disrupts NAM
PO
Oxacillin
crosslinking by
Parenteral
inhibiting
Nafcillin
transpeptidase (PBP)
Parenteral
Table #3: Beta-lactamase resistant PCNs.
hepatic or renal disease

Drug Name

Mechanism of
Action

Ampicillin
IV or PO
Can be given with
Sulbactam (PCNase
inhibitor)

Indications

Used if microbe
does not respond
to PCN G or V

Side Effects

Methicillin resistant
s. aureus infection

Same as general
PCNs

Note: eliminated by biliary and renal excretion, which is beneficial in

Indications

Need for greater

gram (-) coverage
Disrupts NAM
crosslinking by
inhibiting
transpeptidase (PBP)

Contraindication
s

Need for greater

gram (-) coverage
Peritonitis
Otis Media
High risk patients as
a prophylaxis

Contraindication
s

Side Effects

Use Unasyn instead

if infected with B.
fragilis
Strains that utilize
PCNases, because
still susceptible
Strains that utilize
PCNases, because
still susceptible

Same as general
PCNs

Amoxicillin
Better PO absorption
and longer half life
Combined with
Clavulanate (betalactamase inhibitor)
to form Augmentin
Table #4: Aminopenicillins (aka extended

spectrum PCNs)

Drug Name

Mechanism of
Action

Indications

Contraindication
s

Side Effects

Ticarcillin +
Clavulanate
(Timentin)
Parenteral
Piperacillin +
Tazobactam

Disrupts NAM
crosslinking by
inhibiting
transpeptidase (PBP)

Effective against
some Pseudomonas
and some resistant
Proteus

Strains that utilize

PCNases, because
still susceptible

Same as general
PCNs

(Zosyn)
Same uses as
Timentin
Table #5: Antipseudomonas PCN

Cephalosporins
Beta-lactam antibiotic originally derived from a fungus
Mechanism of Action: Generally the same as PCNs, but are less susceptible
to beta-lactamases compared to PCNS. Cephalosporins are also resistant to
many PCNases.
1st generation are active predominately against gram (+) bacteria. 2 nd and 3rd
generations have had increased activity against gram (-)
Drug Name
Cefazolin
IV
Cephalexin (Keflex)
PO
Cefadroxil
PO

Mechanism of
Action

Indications

Contraindication
s

Gram (+) bacteria

Prevent
peptidoglycan
synthesis by
inhibition
transpeptidase
(PBP), which
prevents NAM
crosslinking

Side Effects
General
Hypersensitivityesp cross-reactivity
w/ PCN for 1st gen
cephalosporins
Nephrotoxicitybut low risk
compared to
aminoglycosides
Risk of immune
mediated
hemolytic anemia

Gram (-) bacteria:

Proteus mirabilis,
E.coli, Klebsiella
pneumonia (PEcK)

Table #1: 1st generation cephalosporins

Drug Name

Mechanism of
Action

Cefaclor
PO

Cefuroxime
PO= Ceftin
IM/IV= Zinacef
Cefoxitin

Prevent
peptidoglycan
synthesis by
inhibition
transpeptidase
(PBP), which
prevents NAM
crosslinking

Cefotetan
Must supplement
with K+ due to MTT
antagonist
Cefprozil
PO
Table #2: 2nd generation cephalosporins

Indications

Contraindication
s

All:
More gram (-)
bacteria: PEcK + H.
influenza and
some Neisseria=
HNPEcK
Drug specific:
active vs B. fragilis
(Ampicillin
contraindication)

Fewer gram (+)

microbes

Side Effects
Drug specific: sx of
serum sickness
(arthralgias,
urticaria,
glomerulonephritis)
General
Hypersensitivityesp cross-reactivity
w/ PCN for 1st gen
cephalosporins
Nephrotoxicitybut low risk
compared to
aminoglycosides
Risk of immune
mediated
hemolytic anemia

Drug Name

Mechanism of
Action

Ceftriaxone
(Rocephin)
Both renal and
biliary excretion

Cefotaxime
(Claforan)
IV/IM
Parent and
metabolite active

Contraindication
s

Side Effects

All: Much fewer

gram (+) bacteria
All: Much more gram
(-) bacteria,
including HNPEcK

Prevent
peptidoglycan
synthesis by
inhibition
transpeptidase
(PBP), which
prevents NAM
crosslinking

Ceftazidime
Cefpodoxime
Cefdinir
Excreted mostly
unchanged due to Fe
binding
Reddens feces in
infants with formula
high in Fe
Table #3: 3rd generation cephalosporins

Drug Name

Indications

Mechanism of
Action

Effective against
meningitis (from
strep pneumonia
and N. meningitidis)

Do not use with

Ca2+ to avoid ppt
in lungs/kidney
All: Much fewer
gram (+) bacteria

All: Much more gram

(-) bacteria,
including HNPEcK

History of epilepsy
due to neurologic SE

General
Hypersensitivityesp cross-reactivity
w/ PCN for 1st gen
cephalosporins
Nephrotoxicitybut low risk
compared to
aminoglycosides
Risk of immune
mediated
hemolytic anemia

All: Much fewer

gram (+) bacteria

Indications

Cefepime
Prevent
(Maxipime)
peptidoglycan
Mostly renal
synthesis by
excretion
inhibition
Cefditoren
transpeptidase
(Spectracef)
(PBP), which
Pro-drug that is
prevents NAM
activated via
crosslinking
esterase hydrolysis
th
Table #4: 4 generation cephalosporins

Gram (-) rods

resistant to 3rd
generation
cephalosporins

Drug Name

Indications

Mechanism of
Action

<3 month old pt

with risk of
kernicterus unless
as a single dose
for gonorrhoeae
conjunctivitis

Prevent
Community-acquired
peptidoglycan
pneumonia. MRSA
synthesis by
Ceftolozane
inhibition
(Zerbaxa)
transpeptidase
Complicated
(PBP), which
UTIs/pyelonephritis
prevents NAM
crosslinking
Table #5: Advanced generation cephalosporins

Contraindication
s
History of epilepsy

Contraindication
s

Ceftaroline
(Teflaro)

Side Effects
Disorientation,
myoclonus, and EEG
changes due to good
CNS penetration

Side Effects
Drug specific:
Nausea, diarrhea,
rash

Renal impairment

Drug specific:
Nausea, diarrhea,
headache, fever