What is the recommended dosage and usage of Meropenem (generic name) for treating severe bacterial infections, including considerations for patients with impaired renal function?

Meropenem Pharmacology: Dosing and Clinical Use

Standard Dosing Regimens

For most serious bacterial infections in adults with normal renal function, meropenem is dosed at 1 gram IV every 8 hours, administered as a 15-30 minute infusion or 3-5 minute bolus injection. 1

Adult Dosing by Indication

• Complicated intra-abdominal infections: 1 gram IV every 8 hours 1, 2
• Complicated skin and soft tissue infections: 500 mg IV every 8 hours (standard); 1 gram IV every 8 hours if Pseudomonas aeruginosa suspected 1
• Nosocomial pneumonia and septicemia: 1 gram IV every 8 hours 3
• Maximum daily dose: Up to 6 grams per day (2 grams every 8 hours) for severe infections 4

Pediatric Dosing (≥3 months of age)

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

Renal Dose Adjustments

Dosage reduction is mandatory for creatinine clearance ≤50 mL/min to prevent drug accumulation and seizure risk. 1

Renal Dosing Table

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

Critical caveat: Inadequate data exist for dosing in hemodialysis or peritoneal dialysis patients—consult nephrology and consider therapeutic drug monitoring if available 1.

Extended Infusion Strategies for Resistant Organisms

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

When to Use Extended Infusion

• CRE bloodstream or intra-abdominal infections: 1 gram over 3 hours every 8 hours 2, 5
• High MIC organisms (≥8 mg/L): Extended infusion optimizes time above MIC 2, 6
• Critically ill patients with healthcare-associated infections: Prolonged infusions improve pharmacodynamic target attainment 2, 5

Pharmacodynamic rationale: Meropenem exhibits time-dependent killing; efficacy correlates with the percentage of time free drug concentrations exceed the MIC (target: 40% T>MIC) 7. Extended infusion maximizes this parameter for resistant pathogens 7.

Resistant Organism Considerations

Carbapenem-Resistant Enterobacteriaceae (CRE)

Meropenem-vaborbactam 4 grams IV every 8 hours is the preferred carbapenem for KPC-producing CRE infections when susceptible. 8, 5

• Standard meropenem should be used in combination therapy for CRE, not as monotherapy 2, 5
• For KPC-producing K. pneumoniae with MIC ≥16 mg/L: 2 grams over 3 hours every 8 hours 2

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

For CRAB with meropenem MIC ≤8 mg/L, consider high-dose extended-infusion meropenem as part of combination therapy with two in vitro active agents. 8, 6

• Do not use polymyxin-meropenem combination for CRAB (strong recommendation against) 8
• Combination therapy suggested only for severe, high-risk CRAB infections 8, 6

Pseudomonas aeruginosa

• Increase dose to 1 gram every 8 hours for complicated skin/soft tissue infections 1
• Resistance may emerge during therapy; monitor clinical response closely 4

Treatment Duration

For complicated intra-abdominal infections, treat for 5-7 days, individualized based on source control adequacy and clinical response. 2, 6, 5

• Cholecystitis with cholecystectomy: Discontinue within 24 hours if no infection beyond gallbladder wall 8
• Necrotizing enterocolitis: Continue until clinical resolution with source control 8
• No fixed duration for other indications; base on infection site and response 8, 2

Administration Techniques

No loading dose is required for meropenem, unlike colistin or tigecycline which require loading. 2

Standard Administration

• 15-30 minute infusion: Preferred for most indications 1
• 3-5 minute bolus: Acceptable for 1 gram doses 1
• Extended 3-hour infusion: For resistant organisms or high MIC values 2, 5

Preparation

• Reconstitute 500 mg vial with 10 mL sterile water (final concentration 50 mg/mL) 1
• Reconstitute 1 gram vial with 20 mL sterile water (final concentration 50 mg/mL) 1
• May further dilute in compatible IV fluids for infusion 1
• Do not mix with other drugs—compatibility not established 1

Safety Profile and Adverse Events

Meropenem has a favorable safety profile with seizure incidence of only 0.08% in non-meningitis patients, making it the only carbapenem approved for bacterial meningitis. 3, 9

Common Adverse Events

• Diarrhea (2.3%) 9
• Rash (1.4%) 9
• Nausea/vomiting (1.4%) 9
• Injection site inflammation (1.1%) 9
• Thrombocytosis (1.6%) and elevated hepatic enzymes (1.5-4.3%) 9

Critical Safety Considerations

• Seizure risk is dose-dependent and increased in renal impairment—always adjust for creatinine clearance 1, 9
• Well tolerated in children, neutropenic patients, and elderly 9
• No increased adverse events with doses up to 6 grams daily 9

Spectrum of Activity

Meropenem provides broad-spectrum coverage against Gram-positive cocci (excluding MRSA and VRE), Gram-negative bacilli including Pseudomonas, anaerobes, and ESBL-producing Enterobacteriaceae. 3, 4

Key Susceptible Organisms

• Methicillin-susceptible S. aureus (MSSA) 1, 3
• Streptococci (including S. pneumoniae, S. pyogenes, S. agalactiae) 1, 3
• Enterococcus faecalis (vancomycin-susceptible only) 1
• Pseudomonas aeruginosa 1, 3
• Enterobacteriaceae including ESBL-producers 3
• Bacteroides fragilis and other anaerobes 1, 3

Organisms NOT Covered

• MRSA (methicillin-resistant S. aureus) 8
• VRE (vancomycin-resistant enterococci) 8
• Stenotrophomonas maltophilia (typically resistant) 4

Clinical Efficacy Data

Meropenem demonstrates equivalent efficacy to imipenem/cilastatin across serious bacterial infections with similar tolerability. 10

• Clinical success rate: 76-77% in serious infections 10
• Bacteriological eradication: 77-83% 10
• Effective as monotherapy for complicated intra-abdominal infections per Surgical Infection Society guidelines 8, 2