meropenem
Brand: Merrem
Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: carbapenem / beta-lactam
Organ Systems: infectious-disease
Mechanism of Action
Carbapenem beta-lactam with the broadest antibacterial spectrum; stable to most beta-lactamases including AmpC and ESBLs (not carbapenemases); covers gram-positives (not MRSA), gram-negatives including Pseudomonas, and anaerobes.
penicillin-binding proteins (PBPs)
Indications
- carbapenem-spectrum infections: ESBL-producing Enterobacteriaceae
- Pseudomonas aeruginosa infections (susceptible)
- complicated intra-abdominal infections
- complicated UTI
- hospital-acquired pneumonia
- febrile neutropenia
- bacterial meningitis (pediatric/adult)
Contraindications
- severe penicillin or carbapenem allergy
Adverse Effects
Common
- nausea
- diarrhea
- rash
- elevated LFTs
- headache
Serious
- seizures (less common than imipenem; still a risk — especially in CNS disease, renal failure)
- C. difficile colitis
- anaphylaxis
- thrombocytopenia and neutropenia
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | Protein binding 2%; excellent CSF penetration for meningitis dosing; Vd ~0.3 L/kg |
| Metabolism | Minimal; hydrolysis by renal dehydropeptidase-I (DHP-I) — cilastatin not required (unlike imipenem) because meropenem has some inherent DHP-I stability |
| Excretion | Renal (~70% unchanged); significant dose reduction for CrCl <26 mL/min |
| Half-life | 1 hour |
| Onset | End of infusion |
| Peak | End of infusion |
| Duration | q8h standard; extended 3-4h infusion used for PD optimization |
| Protein Binding | 2% |
| Vd | ~0.3 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| valproate | carbapenems markedly reduce valproate levels (>50%) via inhibiting valproate's glucuronidation re-conversion; seizures may recur | major |
| probenecid | reduces meropenem renal tubular secretion; avoid combination | moderate |
Nursing Considerations
- Meropenem dramatically reduces valproate levels — if a patient on valproate requires carbapenem therapy, expect seizure breakthrough; anticipate need for alternative anticonvulsant
- Renal dose adjustment is critical; meropenem accumulates in renal failure; calculate CrCl before initiation and reassess every 48 hours in critically ill patients
- Extended infusion (3–4 hours) improves pharmacodynamic target attainment (time above MIC) for less-susceptible organisms — used increasingly in ICU settings
- Carbapenems are reserved for serious infections caused by resistant organisms; inappropriate use drives carbapenem-resistant Enterobacteriaceae (CRE) — antimicrobial stewardship consultation recommended
Clinical Pearls
- Carbapenems are the drug of choice for ESBL-producing Enterobacteriaceae — however, carbapenem-resistant Enterobacteriaceae (CRE) are increasing globally, requiring tigecycline, colistin, or novel beta-lactam/beta-lactamase inhibitor combinations
- Unlike imipenem-cilastatin, meropenem does not require cilastatin co-formulation and has a lower seizure risk — it is preferred for meningitis and patients with seizure disorders
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.