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RavLect13: Penem/Bac

Carbepenems & Monobactams

Carbepenem drugs Imipenem/Cilastatin (Primaxin) Meropenem (Merrem) Doripenem (Doribax) Ertapenem (Invanz)
Monobactam drugs Aztreonam (Azactam)
Carbepenem MoA bactericidal B-lactams (stable b/c C-base) Cell wall active (inhibit synthesis) bind to PBPs; inhibit wall-building enzymes Go thru porin protein channels; enter periplasmic space synergistic w/ aminoglycosides (G+/-); additive w/ quinolones (G-)
Mech of Resistance to Carbepenems Beta-lactamase Altered cell wall penetration PBP affinity alteration Altered porin channels for gram negatives
Cilastin dehydropeptidase inhibitor (not a beta lactamase inhibitor). Added to imepenem to prevent its breakdown in kidney
Imipenem zwitterion: better G- penetration very broad spectrum! synergistic combination
Primaxin (Imipenem/Cilastin) SoA ESBLs! Staph, Strep, Pneumococci, B. Fragilis, Listeria, Pseudomonas Enterococcus faecalis is ok, faecium coverage poor SPACE (covers pseudomonas, G-) Doesn't cover MRSA, VRE (faecium), C. dif, S. maltophilia, B. cepacia, atypicals, carbenemase-p
Primaxin (Imipenem/Cilastin) ADRs leads to overgrowth of S. maltiphilia & B. cepacia (need to be Tx'd with Septra) seen in cystic fibrosis kids Renal dysfxn (CrCl<20) -> accumulation -> seizure IM infusion irritation: give w/ Lidocaine b/c it burns N&V Cross rxn w/ pen allergy
Imipenem PK Cleared by kidney! Renal damage may lead to SEIZURES b/c of drug accumulation. Do NOT use in ptx with meningitis!! Concentration INdepedent (time-dependent) b/c beta-lactam
Meropenem (Merrem) zwitterion resistant to dehydropeptidase so it doesn't need Cilastin for stability; thus, reduced seizure risk b/c quicker clearance
Meropenem (Merrem) SoA Meningitis caused by: Strep. pneumonia Listeria (1st line is Septra. Meropenem is 2nd in case of septra allergy) Can treat B. cepacia (from imipenem use) More G- (pseudomonas), less Enterococcus activity than Imipenem (don't use) ESBL
Doripenem (Doribax) SoA close to Meropenem's SoA Most active for B. cepacia Mainly used for Pseudomonas Can treat ESBL Not used as often for meningitis as meropenem
Doripenem (Doribax) PK Dose adjust for Renal impairment
Ertapenem (Invanz) SoA step down penem; more similar to 2nd/3rd Ceph b/c it doesn't cover entercoccus at all Mainly for IAB or pelvic infections also for diabetic foot infections Can Tx UTI/pyelonephritic ESBL, but not systemic ESBL
Ertapenem (Invanz) empiric use in community intra-abdominal infections like acute appendix NOT for severe systemic or institutional Enterococcus & Pseudomonas infectoin
Ertapenem (Invanz) PK Dose adjusted in renal patients Given IM with lidocaine
Ertapenem (Invanz) ADRs Headache Diarrhea/Nausea fairly frequent Phlebitis Increased LFT’s low incidence but happens CNS: tremors, dyskinesias, myoclonus
Aztreonam (Azactam) SoA  Pseudomonas  Enterobacter  E. coli  non ESBL producing organisms  NDM-1  Carbepenemase-producers Must be combined w/ AGs for effective activity Not for ESBL, or atypicals
Aztreonam (Azactam) PK Concentration INdependent (beta-lactam)
Aztreonam MoA Binds PBP like beta-lactamase Must be combined w/ AGs for effective activity (should NOT be combined with PCNs or Cephs b/c NO synergistic effect)
Aztreonam (Azactam) ADRs Monitor PT/INR Phlebitis Pyrexia (fever), esp in kids Good: No PCN allergy cross-over!
Created by: cheeoh