What is the use and dosage of meropenem in microbiology?

Meropenem Microbiology and Clinical Use

Antimicrobial Spectrum

Meropenem is a broad-spectrum carbapenem with potent bactericidal activity against aerobic gram-positive, aerobic gram-negative, and anaerobic bacteria, making it highly effective for serious polymicrobial infections. 1, 2

Gram-Negative Coverage

• Excellent activity against Enterobacteriaceae including E. coli, Klebsiella pneumoniae, Enterobacter species, Citrobacter species, and Serratia marcescens 1, 2
• Superior activity against Pseudomonas aeruginosa compared to imipenem 2
• Highly effective against Haemophilus influenzae and Neisseria meningitidis 1, 2
• Stable against extended-spectrum beta-lactamases (ESBLs) and AmpC-producing organisms 3, 2

Gram-Positive Coverage

• Active against penicillin-susceptible Streptococcus pneumoniae 1
• Moderate activity against viridans group streptococci and group B, C, G streptococci 1
• Less active than imipenem against staphylococci, but covers methicillin-susceptible S. aureus 2
• Uniformly resistant: methicillin-resistant staphylococci and Enterococcus faecium 2

Anaerobic Coverage

• Excellent activity against Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species 1, 2

FDA-Approved Indications and Dosing

Adult Dosing (Normal Renal Function)

• Complicated skin and skin structure infections: 500 mg IV every 8 hours 1
• Complicated intra-abdominal infections: 1 gram IV every 8 hours 1
• When treating P. aeruginosa in skin infections: 1 gram IV every 8 hours 1
• Administration: 15-30 minute infusion or 3-5 minute bolus injection 1

Pediatric Dosing (≥3 Months, Normal Renal Function)

• Complicated skin/skin structure infections: 10 mg/kg every 8 hours (max 500 mg) 1
• Complicated intra-abdominal infections: 20 mg/kg every 8 hours (max 1 gram) 1
• Bacterial meningitis: 40 mg/kg every 8 hours (max 2 grams) 1
• For children >50 kg: Use adult dosing 1

Neonates and Infants <3 Months

• <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

Renal Impairment Dosing (Adults)

• CrCl 26-50 mL/min: Full 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

Optimized Dosing for Resistant Organisms

Extended Infusion Strategy

For carbapenem-resistant Enterobacteriaceae (CRE) or organisms with meropenem MIC ≥8 mg/L, administer 1-2 grams IV over 3 hours (extended infusion) every 8 hours as part of combination therapy. 4, 5

• High-dose regimen: 2 grams IV every 8 hours via 3-hour infusion for MIC ≥16 mg/L 4
• Rationale: Extended infusion maximizes time above MIC, critical for beta-lactam pharmacodynamics 4
• No loading dose required for meropenem, unlike colistin or tigecycline 4

Combination Therapy Considerations

• For CRE infections: Combine meropenem with a second active agent when MIC ≤8 mg/L 5, 4
• For CRAB infections: Polymyxin-meropenem combination may be considered for severe infections, though evidence shows no mortality benefit in recent trials 5
• Critical caveat: The AIDA trial demonstrated no benefit of colistin-meropenem over colistin alone for CRAB 5

Specific Clinical Scenarios

Necrotizing Soft Tissue Infections

Meropenem 1 gram IV every 8 hours is an effective single-agent option for mixed necrotizing infections of skin, fascia, and muscle. 5

• Alternative regimens include imipenem/cilastatin or ertapenem 5
• Provides coverage for aerobic gram-negatives, gram-positives, and anaerobes 5

Bacterial Meningitis

Meropenem is recommended as an alternative to cefotaxime or ceftriaxone for bacterial meningitis in pediatric patients ≥3 months, with equivalent clinical and microbiological outcomes. 5

• Dose: 40 mg/kg every 8 hours (max 2 grams) 1
• Advantage: Lower seizure risk compared to imipenem (0.07% in non-meningitis infections) 6
• Limitation: Not reliable for highly penicillin- and cephalosporin-resistant S. pneumoniae (13/20 isolates resistant in one study) 5
• Preferred use: Gram-negative meningitis, especially ESBL-producers or AmpC-hyperproducers 5

Complicated Intra-Abdominal Infections

The Surgical Infection Society recommends meropenem as effective monotherapy for complicated intra-abdominal infections, with typical treatment duration of 5-7 days based on source control and clinical response. 4

• Standard dose: 1 gram IV every 8 hours 1
• Covers: Enteric gram-negatives, anaerobes, and streptococci 1

Safety Profile

Adverse Events

• Most common: Diarrhea (2.5%), rash (1.4%), nausea/vomiting (1.2%) 6
• Seizure incidence: 0.07% in non-meningitis infections, not considered drug-related in meningitis patients 6
• CNS tolerability: Superior to imipenem, allowing use in meningitis and at high doses 7, 6
• GI tolerability: Excellent, with low nausea/vomiting rates that do not increase with dose or infusion speed 7

Key Clinical Advantages

• Can be given as bolus or infusion without increased adverse events 7, 6
• Well tolerated in pediatrics, with safety data in >1000 children 6, 8
• No unexpected adverse events identified across 6,154 patient exposures 6

Critical Pitfalls to Avoid

1. Do not use meropenem for MRSA or E. faecium - these organisms are uniformly resistant 2
2. Do not rely on meropenem alone for highly resistant pneumococcus - consider alternative agents if MIC data suggest resistance 5
3. Do not assume combination therapy benefits for CRAB - recent high-quality RCTs show no mortality advantage for polymyxin-meropenem over monotherapy 5
4. Do not use standard infusions for high-MIC organisms - switch to 3-hour extended infusion when MIC ≥8 mg/L 4
5. Do not forget renal dose adjustment - reduce dose when CrCl ≤50 mL/min 1