Cell Wall Synthesis

PBP transpeptidation : cross-linking cell wall

1. Penicillins
- Structure: B-lactam ring + 6-penicillanic acid
- MOA: 1. Inhibit PBP (Penicillin-binding-protein); 2. Inh transpeptidation; 3. Autolytic
enzymes
- Resistance : B-lactamase enzymatic hydrolysis
- Bactericidal
- PK : renal excretion (tubular secretion)
- SE : hypersensitivity
a. Amoxicillin
i. Broad spectrum
ii. + clavulanic acid (B-lactamase inhibitor) = Co-amoxiclav
b. Piperacillin
i. Extended (anti-pseudomonal)
ii. Inc. activity on G- rods
iii. + tazobactam
2. Cephalosporin
- Structure: B-lactam ring + 7-aminocephalosporanic acid
- MOA: 1. Inhibit PBP (Penicillin-binding-protein); 2. Inh transpeptidation; 3. Autolytic
enzymes
- Resistance : B-lactamase enzymatic hydrolysis (less sensitive as generation increases)
- Bactericidal
o 1st Gen : +++, - (Gram activity), B-lactamase sensitive
o 2nd Gen : ++, --, B-lactamase sensitive ---- cefuroxime
o 3rd Gen : ++, ---, less B-lactamase sensitive, CSF penetration ---- ceftriaxone,
cefpodoxine
o 4th Gen : +++, ---, least B-lactamase sensitive, CSF penetration
- PK : renal excretion (tubular secretion), ceftriaxone - bile
- SE : hypersensitivity
- CI : macrolide
3. Vancomycin
- Glycoprotein, bactericidal
- MOA : binds with D-ala-D-ala inhibiting transglycosylation and eventually cross-linking
- Narrow spectrum, G+, MRSA
- PK : via IV and PO (no GI absorption), renal filtration
- SE : Red Man syndrome, oto and nephrotoxicity
4. Carbapenems
- MOA: 1. Inhibit PBP (Penicillin-binding-protein); 2. Inh transpeptidation; 3. Autolytic
enzymes
 - Resistance : B-lactamase (less sensitive)
- Broad spectrum
- PK : renal
- SE: GI distress, seizures
a. Ertapenem
i. No/less pseudomonal activity
ii. Long half-life
b. Meropenem
i. For Imipenem Resistant Pseudomonas aeruginosa

Protein Synthesis

1. Aminoglycosides
- MOA: binds with polysome (30s) misreading and premature termination abnormal
complexes
- Resistance: uptake is dependent on O2 uptake anaerobes are resistant; inactivation
- PK : renal, poor GI absorption IM or INH
- SE: nephro (accumulate in renal cortex), oto (accumulate in perilymph and endolymph)
- CI: pregnant hearing loss to child
- Dosing with B-lactams: 1. Inc. empiric range; 2. Synergistic killing; 3. Dec. resistance
a. Amikacin
a. Resistant to inactivation
b. Broadest; for nosocomial infection
b. Tobramycin
a. Superior action against P. aeruginosa
2. Tetracyclines Doxycycline
- Bacteriostatic, broad spectrum
- MOA: binds with 30s inhibit binding of aminoacyl tRNA with acceptor site of mRNA
- Resistance: 1. Dec. concentration; 2. protection protein; 3. Inactivation
- PK: low oral absorption; liver mainly for excretion, good distribution
- CI : chelators (Mg, Ca, Fe) dec. bioavailability
- SE : teeth discoloration, GI, phototoxicity
3. Macrolide
- Static, broad high dose cidal
- MOA: binds with 50s inhibit translocation
- PK: good absorption with alkaline pH; inactivated by acid (thus enteric coated formulation)
- Resistance: 1. Efflux; 2. Protection protein; 3. Hydrolysis; 4. Mutation
- SE: GI, hepatotoxicity; inc. QT interval
a. Clarithromycin
a. Renal excretion, good GI absorption and tissue distribution
b. Azithromycin
 a. Rapid GI absorption
b. Biliary excretion
c. Greater tissue distribution; fibroblast reservoir
4. Linezolid
a. Class: oxazolidonine
b. MOA : binds with 50s (23s subunit) inhibit fMet-tRNA complex : initiates CHON
synthesis
c. Spectrum : G+, MRSA (Methicillin Resistant S. aureus) , PRSP, VRE
d. Resistance: point mutation in 23s
e. PK : good oral absorption 100% bioavailability; E: urine
f. SE: hematologic toxicity (myelosupression)
g. CI: SSRI

Nucleic Acid Synthesis

1. Fluoroquinolones
a. 3rd generation Respiratory (Moxi, Gemi, Levo) broadest spectrum
b. MOA :
i. G+ -- inhibit topoisomerase IV no separation
ii. G- -- inhibit topoiomerase II no relaxation after supercoiling
c. Cidal
d. Resistance : 1. Efflux, 2. Point mutation sensitivity
e. PK: good oral absorption and good tissue distribution; E: kidney, moxifloxacin liver
f. SE: increase QTc interval; GI distress; phototoxicity; could lead to infection of
opportunistic pathogens
g. CI: anti-arrhythmics, methylxanthines,