Core pharmacology

Class Group

ANTIBIOTIC:
CARBAPENEM

Legacy Cicm Level

Level 1

Introduction

Carbapenem (contain a fused beta-lactam & a -5-member ring system that differs from penicillins
because it is unsaturated and contains a carbon instead of a sulphur atom)

Indications Uses

broader spectrum of action than other beta lactams
used in serious infections only
Unlike other carbapenems Meropenems do not require coadministration with cilastatin because
it is not degraded by renal dipeptidase

Presentation

IV: White crystals for reconstitution- 500mg or 1gm.
Very expensive

Mechanism of action

Binds to several penicillin binding protein and
prevents crosslinking of bacterial peptidoglycan
inhibits cell wall synthesis
BROADEST SPECTRUM

Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested

Configuration: Stability against Betalactamases and ESBLs

Antimicrobial Spectrum

v.broad spectrum, gram positive, gram
negative (incl pseudomonal) and anaerobic
coverage (resistant to beta lactamases and
cephalosporinases)

Resistance Mechanism

Carbapenemases Metallobetalactamases
(Sternotrophomonas)
Efflux pumps.
Pseudomonas: Change PBP, diminish permeability thru porin modification

Adverse Effects Toxicity

May cause injection site irritation. May cause seizures similar to Benpen but only in
susceptible patients. Caution in renal patients due to large amount excreted
unchanged. Should not be used concurrenly with probenecid. Can cause
confusion

Absorption

IV route only
Dose is 500mg-1g TDS
On/dur peak at 1hr

Distribution

Crosses BBB with CSF conc = plasma

Protein binding

2% PB
Minimally protein bound

Volume of distribution

small Vd 0.3 L/kg

Metabolism

partially hepatic

Excretion

excreted in urine 70% unchanged

Half-life

half life 1-1.5 hrs
renal failure significantly increases half life

Special Points

PK changes in Critical Illness:
----------------

D:
Vd ↑’s in critical illness
loading dose (LD = Vd x desired concentration) may increase
Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs

M:
minimal change due to lack of metabolism

E:
excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose reduction required)
Low protein binding → Meropenem is cleared via CRRT →↑dose freq