Meropenem

Meropenem is the most widely used carbapenem for severe sepsis, febrile neutropenia, hospital-acquired pneumonia, meningitis and ESBL or AmpC infection. It has lower seizure risk than imipenem.

Classification. Beta-lactam, carbapenem.

Mechanism. Blocks penicillin-binding proteins; resists hydrolysis by most beta-lactamases including ESBL and AmpC, but not carbapenemases.

Spectrum. MSSA, streptococci, pneumococci, Enterococcus faecalis, Enterobacterales including ESBL and AmpC producers, Pseudomonas aeruginosa, Haemophilus, Neisseria, Bacteroides and other anaerobes, and Listeria. Not active against MRSA, Enterococcus faecium, Stenotrophomonas, or carbapenemase producers (KPC, NDM, VIM, OXA-48 and most Acinetobacter).

Pharmacokinetics. IV only. Half-life about 1 hour. Protein binding under 3%. About 70% excreted unchanged in urine. Good CSF penetration in meningitis.

No loading dose except extended infusion. Maximum 6 g daily.

Adults.

• Complicated urinary, skin and soft tissue infection: 500 mg to 1 g IV every 8 hours.
• Intra-abdominal infection, pneumonia, sepsis, febrile neutropenia: 1 g IV every 8 hours; ESBL bacteraemia 1 g every 8 hours for 7 to 14 days.
• Meningitis: 2 g IV every 8 hours for 7 to 21 days depending on organism.
• Pseudomonas and critical illness: 2 g every 8 hours, or extended infusion of 1 to 2 g over 3 hours every 8 hours after a 1 g loading dose over 30 minutes.

Children. 3 months to 11 years under 50 kg: 10 to 20 mg/kg every 8 hours; meningitis 40 mg/kg every 8 hours; 50 kg and over use adult doses. Neonates: 20 mg/kg every 12 hours in the first week and every 8 hours from 7 to 28 days; meningitis 40 mg/kg every 8 hours.

Alternatives. Imipenem cilastatin, ertapenem, doripenem, piperacillin tazobactam for non-ESBL organisms, cefepime.

Contraindications. Hypersensitivity to carbapenems; severe hypersensitivity to other beta-lactams. Cross-reactivity with penicillin allergy is under 1%.

Adverse effects. Diarrhoea, nausea, headache, rash, phlebitis, thrombocytosis, raised liver enzymes. Serious: seizures (less than imipenem), anaphylaxis, Clostridioides difficile infection, severe skin reactions, cytopenias, positive direct Coombs test.

Interactions. - Valproate: carbapenems lower valproate levels by 60 to 100% within 24 hours; avoid the combination. - Probenecid raises meropenem levels. - Warfarin: INR changes.

Common prescribing errors. Giving with valproate, full doses in renal failure, 1 g for meningitis, prolonged use when a narrower agent is possible, and unstable infusion bags in extended infusion.

Special groups.

• Pregnancy and breastfeeding: limited data; use only if needed.
• Older adults: adjust by kidney function.
• Kidney impairment: creatinine clearance 26 to 50 mL/min usual dose every 12 hours; 10 to 25 mL/min half the usual dose every 12 hours; under 10 mL/min half the usual dose every 24 hours. Give the first 24 hours at full dose in sepsis. Haemodialysis: dose after the session; continuous renal replacement usually allows full dosing.
• Liver impairment: no adjustment; monitor liver tests.
• Obesity: use full dose; extended infusion favoured.

Preparation. IV bolus: dissolve 1 g in 20 mL water for injection and inject over 5 minutes. Infusion: dilute in 50 to 100 mL of 0.9% sodium chloride and infuse over 15 to 30 minutes (3 hours in extended infusion). Stability at room temperature is short, so prepare extended-infusion bags freshly and follow local stability data.

Baseline and monitoring. - Baseline: allergy history, medication review (valproate), cultures, creatinine, full blood count. - During treatment: creatinine daily in acute illness; full blood count and liver tests twice weekly; neurological status. - No therapeutic drug monitoring.

Stop rules. Stop for seizures, anaphylaxis, severe skin reaction or cytopenia. De-escalate once susceptibility results allow.

Referral and escalation. Infectious diseases involvement for carbapenem-resistant isolates and for CNS infection.