MOA Antimicrobial activity
Streptogramins - semisynth
etic from Steptomyces prist
inaespiralis
 Quinpristin (stre
ptogramin B) +
dalfopristin (stre
ptogramin A)
Polymyxins = from Bacillus
polymyxa
= mix of polymyxins b1 & b
2 olipids & disrupts structure
= Colistin (polymyxin E) fro
m B. colistinus, marketed a
s colistimethate (IV) or colis
tin base (topical use)
Lipopeptides
= Daptomycin, the only m
ember of this class
= cyclic lipopeptide from St
reptomyces roseosporus
= bactericidal: g(+) bacteri
a & vancomycin-resistant
Resistance
 Bind to 50s Effective against:
 Quinupristin = b G(+) cocci
ind at same site M. Pneumoniae
oas macrolides Legionella
, similar effect C. Pneumoniae
 Dalfopristin = bi Streptococci & strains of st
nd at site nearb aphylococcus (bactericidal)
y enhancing qui Enterococcus faecium (bac
nupristin bindin teriostatic)
g min A) or ATP-binding efflu
 Directly interfer Ineffective against: g(-) mic
es with polypept roorganisms
ide formation
 Cooperstive & s
ynergistic bindin
g = BACTERICI
DAL activity
Simple basic peptides that Restricted to g(-) bacteria,
act as cationic detergents aerobes
Interact strongly w/ phosph
Susceptible :
of cell membranes Pseudomonas
Acinetobacter
Enterobacteriaceae
Resistant:
Proteus
Serratia
Stenotrophomonas
Burkholderia
Binds to bacterial membran Bactericidal: aerobic, facult
es => depolarization, loss o ative, and anaerobic g(+) b
f membrane potential, cell d acteria; vancomycin-resista
eath nt strains (MICs tend to be
higher for vancomycin-susc
eptible counterparts)
ADME Therapeutic Uses
Quinupristin: ribosomal met
hylase (prevents binding of
drug to its target; renders a
ctivity into bacteriostatic) or
lactonase (Inactivates stre
ptogramin B)
Dalfopristin: acetyltransfera
ses (inactivates streptogra
x pumps (pump streptogra
min A out of cell)
Resistance determinants lo
cated in plasmids
Resistance to QD combo a
ssociated with resistance to
streptogramin A
Rare, recentkt documented
in Acinetobacter & Klebsiel
la
From tx of high-inoculum in
fections (endocarditis) and
enterococcal infections
X IM
- chages in cell surface cha
rge that impede daptomyci
n binding
-reversed by coadministrati
on of B-lactams + daptomy
Adverse effects
IV infusion over at least 1 h
r ucture infections cb MSSA
Half life = 0.85 h (quinuprist
in)
0.7 h (dalfopristin)
Vd= 0.87 L/kg (quinupristin
); 0.71 l/kg (dalfopristin)
Hepatic metabolism by con
jugation ( both)
80% biliary elimination
The rest is renal excretion
No dosage adjustment is n
ecessary for renal insufficie
nt px
PK not altered by peritonea
l or hemodialysis
Hepatic insufficiency increa
se AUC by 180% (quinupris
tin) and 50% (dalfopristin)
Poly B & E (colistin) = poorl
y absorbed orally, from mu
cous membranes & surface
s of large burns
CMS (colistimethate) = pro
drug, IV, hydrolyzed slowly
into colistin sulfate moiety i
n the blood
- can also be administered
thru inhalation (prevention
& adjunctive measure of lu
ng infections)
- For CNS infections = IV or
IT administration
- cleared renally ( not colisti
n) ergo dose must be modif
ied for renal impaired px
Poly B- nonrenal clearance
Poorly absorbed orally (IV
only)
Direct toxicity to muscle on
Serum half life = 8-9 h
Once daily dosing
80% excreted in urine
Penetrates adequately in lu
ngs but inactivates by pulm
Complicated skin & skin-str
or S. Pyogenes
Infections cb vancomycin-r
esistant E. Faecium (dose=
7.5 mg/kg q8-12h)
Nosocomial pneumonia
MRSA infections
Reserved for tx of serios inf
ections cb multi-drug resist
and g(+)
Systemic: serious infection
s cb tx resistant pathogens;
bacteremia, bone/joint infe
ctions, burns, cellulitis, CF,
endocarditis, gynecologic i
nfections, meningitis, vertic
ulitis
Topical: ophthalmic, otic inf
ections (colistin otic drops);
skin mucous membrane, e
ye and ear infectiion cb pol
yB-sensitive pathogens (po
ly b sol’n or ointment)
External otitis cb Pseudom
onas
Corneal ulcers cb P. aerugi
nosa = local application or
subconjunctival injection of
poly B
Complicated skin and soft-t
issue infections = 4 mg/kg/
d
Complicated bacteremia an
d right-sided endocarditis =
6 mg/kg/d (comparable to
vancomycin or antistaph B-
lactams)
Common : pain, phlebitis at
infusion site (relieved thru
central venous catheter) ,
arthalgia, myalgia (commo
n in hepatic insufficient px)
Drug interactions:
Inhibits CYP3A4
Concominant administratio
n w/ other cyp3a4 substrate
s increases toxicity
Caution and monitoring for
drugs with toxic therapeutic
window that prolong QTc i
nterval
Toxicity is dose related nep
hrotoxicity
Muscle weekness, apnea,
paresthesiasm vertigo, slur
red speech
Elevated creatine kinase
Rhabdomyolysis (rare)
Drug interactions:
Dooes not afect CYPs p
Caution when daptomycin i
s coadministered w/ amino
glycosides or statins = pote

Metronidazole
= nitroimidazole, broad acti
vity vs. parasites & anaerob
ic bacteria
Nitro group is reduced prod
ucing active drug that intera
cts w/ DNA disrupting its str
ucture & inhibiting replicatio
n Bacteroides
cin even when it is b-lactam onary surfactant (not useful 8-10 mg/kg/d high dose is ntial risk of nephrotoxicity a
resistant for pneumonia tx) well tolerated, may provide nd myopathy, respectively
Creatinine clearance <30ml tx for difficult- to-treat infect
/min = dose q48h ions
Should be given immediate
ly after hemodialysis
Restricted to anaerobic ba Resistance of Bacteroides IV or PO
cteria, some protozoans, = nitroimidazole reductase Inexpensive and versatile
(nim gene) coonverts 5-nitr Broad spectrum of anaerob
Effective against: oimidazole to 5-aminoimida ic bacteria
zole Typical dose = 250-500 mg
Clostridium TLD
Fusobacterium Frequently in cobo w/ other
Peptococcus antimicrobials
Peptostreptococcus Component of prophylaxis f
Eubacterium or colorectal surgery
Single agent tx for bacterial
Less effective: vaginosis
Gardnerella Combo w/ other antibiotics
Helicobacter + proton pump inhibitor = H
. pylori infections
Resistant: Tx for mild-moderate C. diff
Actinomyces icile (vancomycin is more e
Propionibacterium ffective for severe dx)
Lactobacillus