What is the recommended dose and use of Meropenem for treating bacterial infections?

Meropenem Dosing and Clinical Use

For most bacterial infections, administer meropenem 1 gram IV every 8 hours as a 15-30 minute infusion, with extended 3-hour infusions reserved for resistant organisms (MIC ≥8 mg/L) or carbapenem-resistant pathogens. 1

Standard Dosing Regimens

Adult Patients with Normal Renal Function

• Complicated intra-abdominal infections: 1 gram IV every 8 hours 2, 1
• Complicated skin and skin structure infections: 500 mg IV every 8 hours (standard) or 1 gram IV every 8 hours if P. aeruginosa suspected 1
• Severe infections/ICU patients: 2 grams IV every 8 hours 2
• Administration: 15-30 minute infusion or 3-5 minute bolus for 1 gram doses 1

Pediatric Dosing (≥3 Months)

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

Neonates and Infants <3 Months

Dosing is based on gestational age (GA) and postnatal age (PNA) for complicated intra-abdominal infections 1:

• <32 weeks GA, PNA <2 weeks: 20 mg/kg every 12 hours 1
• <32 weeks GA, PNA ≥2 weeks: 20 mg/kg every 8 hours 1
• ≥32 weeks GA, PNA <2 weeks: 20 mg/kg every 8 hours 1
• ≥32 weeks GA, PNA ≥2 weeks: 30 mg/kg every 8 hours 1

Extended Infusion Strategy

Use 3-hour extended infusions in these specific scenarios to optimize pharmacodynamic targets 2, 3:

• Carbapenem-resistant Enterobacteriaceae (CRE) infections 2, 4
• Any pathogen with meropenem MIC ≥8 mg/L 2, 3
• Critically ill patients with healthcare-associated infections 4
• High-dose regimens (2 grams every 8 hours) for resistant organisms 2

The rationale: Extended infusions maximize the time above MIC, which is the critical pharmacodynamic parameter for beta-lactam antibiotics 2. This becomes essential when treating organisms with elevated MICs where standard infusions may not achieve adequate drug exposure 5.

Renal Dose Adjustment

Reduce dosing when creatinine clearance ≤50 mL/min 1:

• CrCl 26-50 mL/min: Standard dose every 12 hours 1
• CrCl 10-25 mL/min: Half dose every 12 hours 1
• CrCl <10 mL/min: Half dose every 24 hours 1

Important caveat: No established dosing for hemodialysis or peritoneal dialysis patients 1.

Treatment Duration

• Complicated intra-abdominal infections: 5-7 days, individualized based on source control adequacy and clinical response 2, 3
• Cholecystitis with cholecystectomy: Discontinue within 24 hours if no infection beyond gallbladder wall 2
• Duration should be guided by infection site, adequacy of source control, and clinical improvement rather than arbitrary timeframes 4

Resistant Organism Considerations

Carbapenem-Resistant Enterobacteriaceae (CRE)

• Dose: 1 gram IV every 8 hours by 3-hour extended infusion 2, 4
• Always use combination therapy with at least one other active agent 4
• Consider meropenem-vaborbactam 4 grams IV every 8 hours for KPC-producing CRE when susceptible 2, 4

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• Do NOT use polymyxin-meropenem combination - two high-quality RCTs (AIDA and OVERCOME) showed no benefit over colistin monotherapy 5
• Exception: If meropenem MIC <8 mg/L, consider high-dose extended-infusion meropenem as part of combination therapy with two in vitro active agents 5, 3
• The AIDA trial included 312 CRAB patients and found no difference in clinical failure or mortality between colistin monotherapy versus colistin-meropenem (RR 0.97 for failure, RR 1.11 for mortality) 5

Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)

• If susceptible to other agents, use anti-pseudomonal penicillins, cephalosporins, or fluoroquinolones with or without aminoglycosides 5
• Resistance can emerge during treatment, requiring vigilance 6

Spectrum of Activity

Meropenem covers 6, 7, 8:

• Streptococci and methicillin-susceptible Staphylococcus aureus
• Neisseria and Haemophilus species
• Anaerobes (excellent activity)
• Aerobic gram-negative nosocomial pathogens including Pseudomonas
• Enterococci (inhibitory activity)
• Extended-spectrum beta-lactamase (ESBL) and AmpC-producing organisms 7

Meropenem does NOT cover 2:

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant enterococci (VRE)
• Stenotrophomonas maltophilia (typically resistant) 6

Critical Clinical Pearls

No loading dose required: Unlike colistin, tigecycline, or vancomycin, meropenem does not require a loading dose 2. The key to optimization is extended infusion duration, not front-loading 2.

Compared to imipenem: Meropenem has greater activity against gram-negative bacilli and Pseudomonas, slightly less activity against gram-positive cocci, and does not require a dehydropeptidase inhibitor 6, 7, 9. Meropenem has a lower seizure risk than imipenem 9.

Maximum daily dose: Can be safely increased to 6 grams daily (2 grams every 8 hours) for severe infections 6, whereas imipenem is typically limited to 4 grams daily.

Avoid indiscriminate use: Reserve meropenem for mixed bacterial infections and aerobic gram-negative bacteria not susceptible to other beta-lactams to prevent resistance development 6.