💊 WEEKS 6 & 7 MUST-KNOW NOTES

Cell Wall Inhibitors Protein Synthesis Inhibitors Quinolones Folate Antagonists Antimycobacterials Key Points ## Cell Wall Inhibitors Protein Synthesis Inhibitors Quinolones Folate Antagonists Antimycobacterials ## WEEK 6 — CELL WALL INHIBITORS ## Beta-Lactams — Core Recap - MOA : Mimic D-Ala-D-Ala → bind PBPs (transpeptidases) irreversibly → no peptidoglycan crosslinking → osmotic lysis → bactericidal, time-dependent - Beta-lactam ring is essential for activity — beta-lactamases cleave this ring = resistance ### Penicillins Drug Spectrum Key Clinical Use --- --- --- Benzylpenicillin (Pen G) Narrow Gram+ Strep, meningitis, syphilis, endocarditis Phenoxymethylpenicillin (Pen V) Narrow Gram+ Oral; strep throat; asplenia prophylaxis Flucloxacillin MSSA only Staph skin, bone, endocarditis Amoxicillin Gram+, some Gram- RTI, UTI, H. pylori , Listeria Co-amoxiclav Broad + anaerobes Bites, abscesses, mixed infections Piperacillin-tazobactam Broad + Pseudomonas Severe hospital infections, febrile neutropenia - Flucloxacillin = penicillinase-resistant → used specifically for S. aureus (MSSA) - Flucloxacillin side effect : cholestatic hepatitis (especially prolonged use, elderly) ### Cephalosporins — Generation Rules Generation Example Key Coverage --- --- --- 1st Cefalexin, Cefazolin Gram+ (surgical prophylaxis) 2nd Cefuroxime Gram+ + better Gram- 3rd Ceftriaxone, Ceftazidime Gram- (meningitis); Ceftazidime = Pseudomonas 4th Cefepime Pseudomonas + Gram+ 5th Ceftaroline MRSA activity Detailed Notes --- WEEK 6 — CELL WALL INHIBITORS Beta-Lactams — Core Recap - MOA : Mimic D-Ala-D-Ala → bind PBPs (transpeptidases) irreversibly → no peptidoglycan crosslinking → osmotic lysis → bactericidal, time-dependent - Beta-lactam ring is essential for activity — beta-lactamases cleave this ring = resistance Penicillins Drug Spectrum Key Clinical Use --- --- --- Benzylpenicillin (Pen G) Narrow Gram+ Strep, meningitis, syphilis, endocarditis Phenoxymethylpenicillin (Pen V) Narrow Gram+ Oral; strep throat; asplenia prophylaxis Flucloxacillin MSSA only Staph skin, bone, endocarditis Amoxicillin Gram+, some Gram- RTI, UTI, H. pylori , Listeria Co-amoxiclav Broad + anaerobes Bites, abscesses, mixed infections Piperacillin-tazobactam Broad + Pseudomonas Severe hospital infections, febrile neutropenia Flucloxacillin = penicillinase-resistant → used specifically for S. aureus (MSSA) - Flucloxacillin side effect : cholestatic hepatitis (especially prolonged use, elderly) Cephalosporins — Generation Rules Generation Example Key Coverage --- --- --- 1st Cefalexin, Cefazolin Gram+ (surgical prophylaxis) 2nd Cefuroxime Gram+ + better Gram- 3rd Ceftriaxone, Ceftazidime Gram- (meningitis); Ceftazidime = Pseudomonas 4th Cefepime Pseudomonas + Gram+ 5th Ceftaroline MRSA activity Higher generation = better Gram-negative, less Gram-positive (except 5th gen) - Ceftriaxone : once daily, biliary excretion, meningitis, gonorrhoea, CAP - Ceftazidime-avibactam : covers carbapenemase-producers (KPC, OXA-48) Carbapenems Drug Key Feature --- --- Meropenem Broadest; CNS safe; Pseudomonas Imipenem-cilastatin Cilastatin prevents renal inactivation; seizure risk Ertapenem Once daily; NO Pseudomonas/Acinetobacter Doripenem Similar to meropenem Resistant to most beta-lactamases except carbapenemases (KPC, NDM, OXA-48) - Ertapenem trap : looks like a carbapenem but misses Pseudomonas — don't use empirically for suspected MDR Monobactams - Aztreonam : Gram-negative only, no anaerobes, no Gram+ - Safe in penicillin allergy (minimal cross-reactivity) - Used in CF, febrile neutropenia (penicillin-allergic) Beta-Lactamase Inhibitors Combination Inhibitor Extra Coverage Gained --- --- --- Co-amoxiclav Clavulanate Beta-lactamase producing organisms Tazocin Tazobactam As above + Pseudomonas Ceftazidime-avibactam Avibactam KPC, OXA-48 carbapenemases Meropenem-vaborbactam Vaborbactam KPC carbapenemases --- Glycopeptides Vancomycin - MOA : Binds D-Ala-D-Ala terminus → physically blocks transglycosylation + transpeptidation - Gram-positive only (too large for Gram-negative outer membrane) - Bactericidal against staph; bacteriostatic against enterococci - Routes: IV systemic; oral = C. diff only (not absorbed) - TDM : AUC/MIC 400–600 or trough 10–20 mg/L - Red Man Syndrome : histamine release → flushing, rash, hypotension → NOT allergy → slow infusion, antihistamine - Toxicity : nephrotoxicity (↑ risk with aminoglycosides), ototoxicity Teicoplanin - Same MOA as vancomycin - Longer half-life → once daily (after loading) - Less nephrotoxic; IM or IV VRE Resistance Mechanisms Gene Resistance --- --- VanA Vancomycin + teicoplanin resistant (D-Ala-D- Lac ) VanB Vancomycin only resistant; teicoplanin susceptible VanC Low-level, intrinsic in E. gallinarum --- Other Cell Wall Agents Fosfomycin - Inhibits MurA (first step in peptidoglycan synthesis) - Oral or IV - Uncomplicated UTI (single oral dose), MDR Gram-negatives (IV — combination) - Well tolerated; mainly GI side effects Daptomyci