Meropenem Pharmacology

Class and mechanism of action

• Class: carbapenem β-lactam antibiotic.
• Pharmacodynamics: bactericidal with time-dependent killing.
• Binds penicillin-binding proteins and inhibits transpeptidation / cross-linking of peptidoglycan.
• Cell-wall synthesis is arrested while autolytic enzymes continue to act → bacterial cell lysis.

Spectrum of activity

• Very broad spectrum against many Gram-positive, Gram-negative and anaerobic organisms.
• Includes Pseudomonas aeruginosa and many ESBL-producing Enterobacterales.
• Relatively stable to many β-lactamases.
• Important gaps include MRSA, Enterococcus faecium, Stenotrophomonas maltophilia and atypical organisms.

Indications

• Usually reserved for severe infection when narrower-spectrum therapy is inappropriate.
• Hospital-acquired infection / severe sepsis with resistant Gram-negative risk.
• Suspected or proven ESBL infection.
• Polymicrobial intra-abdominal or necrotising infection.
• Severe pseudomonal infection.
• Melioidosis.
• Meningitis where meropenem is appropriate.
• Failure of suitable first-line therapy.

Pharmacokinetics

• IV administration.
• Hydrophilic with low protein binding (~2%).
• Small volume of distribution (~0.3 L/kg), predominantly extracellular.
• Minimal metabolism; mainly non-hepatic hydrolysis to an inactive metabolite.
• Predominantly renally eliminated; approximately 70% excreted unchanged.
• Elimination half-life is approximately 1 hour with normal renal function.
• Hepatic impairment alone has little effect on clearance.

Dosing considerations in critical illness

• As a time-dependent β-lactam, efficacy depends on maintaining free drug concentration above the organism MIC for an adequate proportion of the dosing interval.
• Prolonged or continuous infusion may improve target attainment when clearance is high, MIC is high, or infection is severe.
• Loading dose is mainly determined by Vd; maintenance dose / dosing rate is mainly determined by clearance.