Meropenem: Carbapenem Antibiotic for Severe Infections
Meropenem (Meronem) is a broad-spectrum carbapenem beta-lactam antibiotic with activity against most Gram-positive, Gram-negative (including Pseudomonas), and anaerobic bacteria. It is stable against most beta-lactamases, including extended-spectrum beta-lactamases (ESBL).
Reserved for severe, hospital-acquired, or multidrug-resistant infections. A last-resort class of antibiotic — inappropriate use accelerates carbapenem resistance (CRE — carbapenem-resistant Enterobacteriaceae).
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to multiple penicillin-binding proteins (PBPs), preventing peptidoglycan cross-linking. More stable against renal dehydropeptidase (DHP-1) than imipenem — does not require co-administration of cilastatin. Bactericidal — time-dependent killing.
Indications & Use
Hospital-acquired pneumonia (HAP/VAP), complicated intra-abdominal infections (with metronidazole for anaerobic coverage), complicated UTI (including pyelonephritis), febrile neutropaenia in haematological patients, meningitis caused by susceptible organisms, severe skin and soft tissue infections, sepsis.
Dosage
Standard: 500 mg–2 g IV every 8 hours. Meningitis: 2 g every 8 hours. Febrile neutropaenia: 1 g every 8 hours. Renal dose adjustment (GFR-based): reduce dose or extend interval in renal impairment. Extended infusion (3-hour infusion of 2 g) increasingly used to optimise PK/PD target attainment against resistant pathogens.
Side Effects
Generally well tolerated. Nausea, vomiting, diarrhoea. Seizures (less than imipenem — more relevant in CNS disease). Hepatotoxicity (LFT elevation). C. difficile diarrhoea (broad-spectrum antibiotic effect). Hypersensitivity reactions (less cross-reactivity with penicillin allergy than older carbapenems).
Drug Interactions
Valproic acid: meropenem markedly reduces valproic acid levels (inhibits valproate absorption and increases its metabolism) — can precipitate seizures; avoid combination or switch antibiotic/antiepileptic. Probenecid: increases meropenem AUC.
Contraindications
Hypersensitivity to carbapenems. Cross-reactivity with penicillins is low (~1%). Use with caution in patients with seizure disorders (though risk is lower than imipenem).
Frequently Asked Questions
Why does meropenem not need cilastatin like imipenem?
Imipenem is hydrolysed by renal dehydropeptidase-1 (DHP-1), producing nephrotoxic metabolites — requires cilastatin to inhibit DHP-1. Meropenem has a methyl group making it stable against DHP-1, so cilastatin is not required.
Why does meropenem interact with valproic acid?
Meropenem markedly reduces valproic acid (VPA) plasma levels by 50–70% within hours — via inhibition of intestinal absorption and induction of VPA metabolism. This can cause seizures in epileptic patients. Alternative antibiotics or anticonvulsants should be used.
What is carbapenem-resistant Enterobacteriaceae (CRE)?
CRE are bacteria (e.g., Klebsiella, E. coli) that produce carbapenemases (e.g., KPC, NDM, OXA-48), enzymes that hydrolyse carbapenems. CRE infections have very limited treatment options (colistin, ceftazidime-avibactam, cefiderocol). Prevention through antibiotic stewardship is critical.
References
- EMA Meronem SPC 2023
- EUCAST Breakpoints carbapenems 2023
- Tamma PD et al. CID 2021 (IDSA guidance on resistant organisms)
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.