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

Meropenem for Severe Bacterial Infections

Meropenem is a broad-spectrum carbapenem antibiotic indicated for complicated intra-abdominal infections, complicated skin and soft tissue infections, bacterial meningitis (pediatric patients ≥3 months), and severe nosocomial infections, with standard adult dosing of 1 gram IV every 8 hours for most indications and 2 grams IV every 8 hours for meningitis or severe pneumonia. 1

FDA-Approved Indications

Adult and Pediatric Patients (≥3 months)

• Complicated skin and skin structure infections (cSSSI): Active against methicillin-susceptible S. aureus, Streptococcus species, E. faecalis (vancomycin-susceptible), P. aeruginosa, E. coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species 1
• Complicated intra-abdominal infections: Effective against viridans group streptococci, E. coli, K. pneumoniae, P. aeruginosa, B. fragilis, B. thetaiotaomicron, and Peptostreptococcus species 1

Pediatric Patients Only (≥3 months)

• Bacterial meningitis: Indicated for H. influenzae, N. meningitidis, and penicillin-susceptible S. pneumoniae 1

Standard Dosing Regimens

Adult Patients with Normal Renal Function

• cSSSI: 500 mg IV every 8 hours 1
• cSSSI caused by P. aeruginosa: 1 gram IV every 8 hours 1
• Complicated intra-abdominal infections: 1 gram IV every 8 hours 1, 2
• Severe infections/pneumonia: 2 grams IV every 8 hours 2, 3
• Administration: 15-30 minute IV infusion; 1 gram doses may be given as 3-5 minute IV bolus 1

Pediatric Patients ≥3 Months with Normal Renal Function

• cSSSI: 10 mg/kg every 8 hours (maximum 500 mg per dose) 1
• cSSSI caused by P. aeruginosa: 20 mg/kg every 8 hours (maximum 1 gram per dose) 1
• Complicated intra-abdominal infections: 20 mg/kg every 8 hours (maximum 1 gram per dose) 1
• Meningitis: 40 mg/kg every 8 hours (maximum 2 grams per dose) 1
• Pediatric patients >50 kg: Use adult dosing 1

Pediatric Patients <3 Months with Complicated Intra-abdominal Infections

• <32 weeks gestational age (GA) and <2 weeks postnatal age (PNA): 20 mg/kg every 12 hours 1
• <32 weeks GA and ≥2 weeks PNA: 20 mg/kg every 8 hours 1
• ≥32 weeks GA and <2 weeks PNA: 20 mg/kg every 8 hours 1
• ≥32 weeks GA and ≥2 weeks PNA: 30 mg/kg every 8 hours 1

Renal Dose Adjustments (Adults)

Creatinine Clearance	Dose	Interval
>50 mL/min	Standard dose	Every 8 hours
26-50 mL/min	Standard dose	Every 12 hours
10-25 mL/min	Half standard dose	Every 12 hours
<10 mL/min	Half standard dose	Every 24 hours

1

Important: No loading dose is required for meropenem in any clinical scenario 2, 3

Optimized Dosing for Resistant Organisms

Extended Infusion Strategy

• Carbapenem-resistant Enterobacteriaceae (CRE): 1 gram IV every 8 hours as 3-hour extended infusion in combination therapy 2, 3
• High MIC organisms (≥8 mg/L): Administer as 3-hour extended infusion to maximize time above MIC 2, 3
• KPC-producing K. pneumoniae with MIC ≥16 mg/L: 2 grams IV every 8 hours as 3-hour extended infusion 2
• Critically ill patients: Consider prolonged or continuous infusions to achieve pharmacodynamic targets (plasma concentration >MIC for ≥70% of dosing interval) 2, 3

Combination Therapy Recommendations

• CRE infections: Meropenem plus a second active agent (e.g., colistin, aminoglycoside, or tigecycline) 2
• Carbapenem-resistant Acinetobacter baumannii (CRAB) with MIC ≤8 mg/L: High-dose extended-infusion meropenem with colistin 2, 3
• Severe necrotizing infections: Meropenem 1 gram every 8 hours plus vancomycin for empiric MRSA coverage 4

Treatment Duration

• Complicated intra-abdominal infections: 5-7 days, individualized based on source control adequacy and clinical response 2, 3
• Complicated skin and soft tissue infections: 5 days minimum; extend if infection has not improved 4
• Bloodstream infections/sepsis: 7-14 days depending on source control 2
• Complicated urinary tract infections: 5-7 days 2
• Pneumonia: Minimum 7 days 2
• Meningitis: Duration based on pathogen and clinical response 1

Guideline-Based Empiric Use

Necrotizing Skin and Soft Tissue Infections

For severely compromised patients with necrotizing fasciitis or myonecrosis, vancomycin plus either piperacillin-tazobactam or imipenem-meropenem is recommended as empiric therapy 4

• Meropenem 1 gram IV every 8 hours provides broad coverage against mixed aerobic-anaerobic infections 4
• Add vancomycin for MRSA coverage 4

Severe Community-Acquired Pneumonia with P. aeruginosa Risk

• Antipseudomonal carbapenem (meropenem preferred, up to 6 grams daily possible as 3 doses of 2 grams in 3-hour infusions) plus either ciprofloxacin OR macrolide plus aminoglycoside 4

Aspiration Pneumonia (ICU or Nursing Home-Acquired)

• Meropenem provides appropriate coverage for mixed aerobic-anaerobic infections 4

Clinical Advantages and Considerations

Advantages Over Imipenem

• No cilastatin required: Meropenem is stable to renal dehydropeptidase-I 5, 6, 7
• Lower seizure risk: Suitable for meningitis treatment; only carbapenem FDA-approved for this indication 1, 5
• Greater activity against Gram-negative organisms: Particularly Enterobacteriaceae and P. aeruginosa 6, 7
• Higher maximum daily dose: Up to 6 grams daily vs. 4 grams for imipenem 4, 6

Spectrum Limitations

• Not active against: MRSA, vancomycin-resistant enterococci (VRE), Stenotrophomonas maltophilia 2, 6
• Resistance concerns: May emerge during treatment of P. aeruginosa infections 6

Safety and Tolerability

• Well tolerated: Adverse events comparable to other beta-lactams 5, 8, 9
• Most common adverse effects: Elevated liver enzymes, infusion-related nausea/vomiting 8
• CNS effects: Low propensity for seizures compared to imipenem 5, 7
• Superinfection rate: Low (approximately 2-3% in clinical trials) 9

Critical Pitfalls to Avoid

• Do not use for MRSA or VRE: Meropenem lacks activity against these organisms; add vancomycin, linezolid, or daptomycin when suspected 4, 2
• Adjust for renal impairment: Failure to reduce dose in creatinine clearance <50 mL/min increases seizure risk 1
• Consider extended infusion for resistant organisms: Standard bolus dosing may be inadequate for MIC ≥8 mg/L 2, 3
• Avoid monotherapy for CRE or CRAB: Combination therapy significantly improves outcomes 2, 3
• Stability concerns with continuous infusion: Meropenem degrades over time; use extended infusion (3 hours) rather than 24-hour continuous infusion when possible 2