What is the recommended use and dosage of meropenem (Merrem) tazobactam for treating severe bacterial infections?

Meropenem Dosing and Administration for Severe Bacterial Infections

For severe bacterial infections, administer meropenem 1 gram IV every 8 hours via extended infusion over 3 hours, particularly when treating resistant organisms or critically ill patients, with treatment duration typically 5-7 days based on clinical response. 1, 2

Standard Dosing Regimens

Adult Patients with Normal Renal Function

• Complicated intra-abdominal infections: 1 gram IV every 8 hours 1, 3
• Complicated skin and skin structure infections: 500 mg IV every 8 hours (or 1 gram every 8 hours if P. aeruginosa suspected) 3
• Carbapenem-resistant Enterobacteriaceae (CRE): 1 gram IV every 8 hours by extended 3-hour infusion as part of combination therapy 1, 2
• High MIC organisms (≥8 mg/L): Extended 3-hour infusion is essential to optimize pharmacodynamic targets 1, 4

Pediatric Patients (≥3 Months)

• Complicated skin/soft tissue infections: 10 mg/kg every 8 hours (maximum 500 mg) 3
• Complicated intra-abdominal infections: 20 mg/kg every 8 hours (maximum 1 gram) 3
• Meningitis: 40 mg/kg every 8 hours (maximum 2 grams) 3
• For children >50 kg, use adult dosing 3

Infants <3 Months

• <32 weeks gestational age, <2 weeks postnatal: 20 mg/kg every 12 hours 3
• <32 weeks gestational age, ≥2 weeks postnatal: 20 mg/kg every 8 hours 3
• ≥32 weeks gestational age, <2 weeks postnatal: 20 mg/kg every 8 hours 3
• ≥32 weeks gestational age, ≥2 weeks postnatal: 30 mg/kg every 8 hours 3

Administration Techniques

Extended Infusion Strategy

Extended infusion over 3 hours is strongly recommended for critically ill patients and resistant organisms to maintain plasma concentrations above MIC for >70% of the dosing interval. 5, 1

• Standard administration: 15-30 minute IV infusion 3
• Extended infusion (3 hours): Required when MIC ≥8 mg/L or treating CRE 1, 2
• Bolus injection (3-5 minutes): Acceptable for doses ≤1 gram in stable patients 3
• No loading dose is required for meropenem, unlike colistin or vancomycin 1

Pharmacodynamic Optimization

• Target: Maintain plasma concentration >4-6 times the MIC for optimal bactericidal activity 5
• Extended/continuous infusion prevents pharmacodynamic failure in deep-seated infections and patients with altered pharmacokinetics 5
• Continuous infusion may be considered for carbapenems in severe infections with high MIC organisms 5

Renal Dose Adjustments

Reduce dosing in patients with creatinine clearance ≤50 mL/min: 3

• CrCl 26-50 mL/min: Standard dose every 12 hours
• CrCl 10-25 mL/min: Half dose every 12 hours
• CrCl <10 mL/min: Half dose every 24 hours
• Inadequate data exists for hemodialysis or peritoneal dialysis patients 3

Treatment Duration

• Complicated intra-abdominal infections: 5-7 days, individualized based on source control adequacy and clinical response 1, 4
• Cholecystitis with cholecystectomy: Discontinue within 24 hours if no infection beyond gallbladder wall 1
• General severe infections: Continue until clinical improvement and source control achieved 1

Clinical Considerations

Spectrum of Activity

• Effective against: Methicillin-susceptible S. aureus, Streptococcus spp., E. faecalis (vancomycin-susceptible), P. aeruginosa, Enterobacteriaceae including ESBL-producers, B. fragilis, anaerobes 3, 6
• NOT effective against: MRSA, VRE, Stenotrophomonas maltophilia 1, 7

Combination Therapy Indications

• CRE infections: Always use combination therapy with meropenem 1, 2
• Carbapenem-resistant Acinetobacter baumannii (CRAB): Consider high-dose extended-infusion meropenem with colistin if MIC ≤8 mg/L 1, 4
• Septic shock or neutropenia: Empirical combination therapy recommended until susceptibilities known 5

Monotherapy vs. Combination

• Monotherapy is appropriate for complicated intra-abdominal infections without risk factors for multidrug-resistant organisms 5, 1
• Combination therapy required for patients with shock, neutropenia, or suspected multidrug-resistant pathogens 5

Common Pitfalls to Avoid

• Do not use standard 30-minute infusions when treating organisms with MIC ≥8 mg/L—this risks pharmacodynamic failure 1, 2
• Avoid monotherapy for CRE—combination therapy is essential for these infections 1, 2
• Do not continue beyond 7 days for intra-abdominal infections with adequate source control unless clinically indicated 1
• Remember meropenem lacks MRSA and VRE coverage—add appropriate agents if these pathogens are suspected 1
• Meropenem has superior CNS tolerability compared to imipenem, making it the preferred carbapenem for meningitis 6, 8