Meropenem
Meropenem
Generic Name
Meropenem
Mechanism
- Inhibits bacterial cell‑wall synthesis by binding to penicillin‑binding proteins (PBPs), mainly PBP‑2 and PBP‑3.
- Forms irreversible acylated complexes, preventing transpeptidation of peptidoglycan strands.
- Resistant to most β‑lactamases (including extended‑spectrum β‑lactamases and carbapenemases) because of its carbapenem core and steric hindrance.
Pharmacokinetics
| Parameter | Value (standard adult) | Notes |
| Absorption | IV only | Oral bioavailability < 5% |
| Distribution | 0.42‑0.61 L/kg; CSF ~30‑40% of plasma | Well‑distributed to the central nervous system, skin, bone, and pleural fluid |
| Protein binding | 50–65% | Moderate; not highly displaced by other drugs |
| Metabolism | Mainly renal excretion (≈ 80% unchanged) | Minor hydrolysis by plasma esterases |
| Half‑life | 1.2–1.5 h (clearance 0.96 L h⁻¹ m²) | Short; supports flat dosing |
| Clearance | 0.32 L h⁻¹ m² (creatinine‑clearance dependent) | Dose adjustment needed in renal impairment |
Indications
- Complicated intra‑abdominal infections (cIAIs)
- Complicated urinary tract infections (cUTIs)
- Bacterial meningitis (when other agents inadequate)
- Complicated skin and soft‑tissue infections (cSSTIs)
- Hospital‑acquired pneumonia (HAP) and ventilator‑associated pneumonia (VAP)
- Community‑acquired pneumonia (CAP) in patients with risk factors for multidrug‑resistant organisms
*Approved for parenteral use; not indicated for outpatient oral therapy.*
Contraindications
- Allergy to carbapenems or concomitant cephalosporins (cross‑reactivity).
- Hypersensitivity to β‑lactam antibiotics (penicillins, cefalosporins, monobactams).
- Severe hepatic impairment (absorption not affected, but safety data limited).
- History of drug‑related anaphylaxis; may precipitate severe hypersensitivity reactions.
- Severe renal failure: dose adjustment mandatory to avoid accumulation.
Warnings
• Neurological effects: seizures (especially in renal dysfunction or in patients with CNS disease).
• Aminoglycoside interaction: potential for nephro‑ and ototoxicity when used concurrently.
• Cross‑reactivity: higher risk of allergic reactions with other β‑lactams, notably penicillins and cephalosporins.
Dosing
| Indication | Normal Renal Function | CrCl 10‑30 mL min⁻¹ | CrCl ≤10 mL min⁻¹ | Hemodialysis |
| cIAI/cUTI | 1 g IV q8 h (or 2 g q12 h) | 0.5 g IV q12 h | 0.5 g IV q24 h | 1 g / HD session (or 0.5 g / HD) |
| HAP/VAP | 1 g IV q8 h | 0.5 g IV q12 h | 0.4 g IV q24 h | 1 g / HD session |
| Bacterial meningitis | 1 g IV q8 h (if CRB‑65 >2) | 0.5 g IV q12 h | 0.5 g IV q24 h | 1 g / HD session |
| cSSTI | 1 g IV q8 h | 0.5 g IV q12 h | 0.5 g IV q24 h | 1 g / HD session |
• Infuse over 30–60 min to reduce infusion‑related reactions.
• Flat dosing is common (1 g q8 h), but individualization per kidney function reduces toxicity.
• Use a 10 % saline or 0.9 % NaCl solution; avoid high‑osmolar solvents.
Adverse Effects
Common (≥5 %)
• Hypersensitivity reactions (urticaria, rash)
• Infusion‑related reactions (fever, chills)
• Gastrointestinal upset (diarrhea, nausea)
• Neutropenia and thrombocytopenia (rare)
Serious (≤1 %)
• Severe allergic reactions (anaphylaxis)
• Prolonged QT interval (rare)
• Seizures or convulsions (higher risk in renal impairment or in CNS disease)
• Clostridioides difficile–associated diarrhea (antibiotic‑associated colitis)
• Hypotension, bradycardia (infusion‑related)
Monitoring
- Renal function: Serum creatinine and CrCl daily (or more frequently in CKD).
- Neurologic status: Monitor for seizures, especially in renal failure or CNS infection.
- Complete blood count: Baseline and weekly to detect cytopenias.
- Infusion site: Check for irritation or phlebitis.
- Drug‑interaction screening: Renal‑excreted drugs (e.g., aminoglycosides, vancomycin).
- Serum ammonia: In patients with hepatic dysfunction (rare).
Clinical Pearls
- “Meropenem on a timer”: Administer at baseline, 30 min, and 60 min intervals for extended‑infusion (q8 h) to maximize time above MIC in critical infections.
- Avoid cross‑reactivity: A patient with a penicillin allergy may tolerate a carbapenem, but the risk is higher. Verify allergy history and perform allergy testing if possible.
- Hemodialysis dosing: Administer 1 g during each HD session; no adjustment needed for other anticoagulants.
- Antifungal synergy: Add meropenem to echinocandins when treating polymicrobial intra‑abdominal infections; evidence shows enhanced reduction of Enterococcus spp.
- Neurotoxicity prevention: In patients with GFR < 30 mL min⁻¹, use extended‑infusion with dose reduction or alternative β‑lactam (e.g., doripenem).
- Use in neonates: Dosed by weight (15‑20 mg/kg q8 h) and cleared via kidney; monitor for seizures.
--
• *This drug card is intended for educational purposes and should not replace detailed prescribing information. Always consult the latest guidelines, drug monographs, and institutional protocols before use.*