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

Meropenem for Severe Bacterial Infections

Standard Dosing and Administration

For most severe bacterial infections in adults, administer meropenem 1 gram IV every 8 hours as a 15-30 minute infusion, with higher doses (2 grams every 8 hours) reserved for pneumonia, meningitis, or infections caused by less susceptible organisms. 1

Adult Dosing by Infection Type

• 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 when Pseudomonas aeruginosa is suspected 2, 1
• Nosocomial pneumonia: 2 grams IV every 8 hours by extended infusion 3
• Bloodstream infections/sepsis: 1 gram IV every 8 hours by extended infusion 3

Pediatric Dosing (≥3 Months of Age)

• Complicated skin/skin structure infections: 10 mg/kg (maximum 500 mg) every 8 hours 1
• Complicated intra-abdominal infections: 20 mg/kg (maximum 1 gram) every 8 hours 1
• Bacterial meningitis: 40 mg/kg (maximum 2 grams) every 8 hours 1
• For pediatric patients weighing >50 kg, use adult dosing 1

Neonates and Infants <3 Months

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

Extended Infusion Strategy

For critically ill patients, carbapenem-resistant organisms, or when MIC ≥8 mg/L, administer meropenem as a 3-hour extended infusion to optimize pharmacodynamic targets. 3, 4

• Extended infusion maximizes time above MIC, which is critical for beta-lactam efficacy 3
• This approach is particularly important for healthcare-associated infections in ICU patients 3
• Standard bolus administration over 3-5 minutes is acceptable for doses ≤1 gram in non-critically ill patients 1

Renal Dose Adjustment

• CrCl 26-50 mL/min: Give recommended dose every 12 hours 1
• CrCl 10-25 mL/min: Give one-half recommended dose every 12 hours 1
• CrCl <10 mL/min: Give one-half recommended dose every 24 hours 1
• No loading dose is required even in renal impairment 3

Treatment Duration

Treat complicated intra-abdominal infections for 5-7 days after adequate source control, individualizing based on clinical response and inflammatory marker trends. 3, 4

• Duration should be guided by adequacy of source control (surgical intervention) and clinical improvement 2, 3
• For cholecystitis with cholecystectomy, discontinue within 24 hours if no infection extends beyond the gallbladder wall 3
• Bloodstream infections typically require 7-14 days depending on source control 3
• Complicated urinary tract infections: 5-7 days 3

Combination Therapy Considerations

When Meropenem Monotherapy is Insufficient

For necrotizing/gangrenous infections, combine meropenem 1 gram IV every 8 hours with an anti-MRSA agent (linezolid 600 mg every 12 hours or vancomycin 15-20 mg/kg every 8-12 hours) plus clindamycin 600 mg every 6 hours. 5

• Meropenem does not cover MRSA or VRE 3, 5
• Clindamycin provides toxin suppression and synergy against streptococcal species 5
• For high-risk enterococcal infections (immunocompromised, recent antibiotics, healthcare-associated), add ampicillin 2 grams IV every 6 hours 5

Carbapenem-Resistant Organisms

• CRE infections: 1 gram IV every 8 hours by 3-hour extended infusion as part of combination therapy with two in vitro active agents 3, 4
• High MIC KPC-producing organisms (MIC ≥16 mg/L): 2 grams IV every 8 hours by 3-hour extended infusion 3
• CRAB with meropenem MIC ≤8 mg/L: Consider high-dose extended-infusion meropenem as part of combination therapy 3, 4
• Polymyxin-meropenem combination is NOT recommended for CRAB 4

Spectrum of Activity

Covered Organisms

• Methicillin-susceptible Staphylococcus aureus (MSSA) 3, 1
• Streptococcal species including S. pyogenes, S. agalactiae, viridans group 1
• Vancomycin-susceptible Enterococcus faecalis 1
• Gram-negative aerobes: E. coli, K. pneumoniae, P. aeruginosa, Proteus mirabilis 1
• Anaerobes: Bacteroides fragilis, Peptostreptococcus species 1
• ESBL-producing Enterobacteriaceae 6

NOT Covered

• MRSA (methicillin-resistant S. aureus) 3, 5
• VRE (vancomycin-resistant enterococci) 3
• Stenotrophomonas maltophilia 7

Critical Pitfalls to Avoid

• Never use meropenem monotherapy for necrotizing/gangrenous infections due to polymicrobial nature and MRSA risk 5
• Surgical source control is mandatory for intra-abdominal and necrotizing infections—antibiotics alone are insufficient 5
• Do not delay antibiotics for cultures—start empiric therapy immediately upon suspicion of severe infection 5
• Obtain intraoperative cultures at index operation to guide de-escalation 5
• Monitor renal function when combining with nephrotoxic agents like vancomycin 5
• Meropenem is unstable during continuous infusion; extended 3-hour infusions are preferred over 24-hour continuous infusions 3

Administration Methods

• IV infusion: 15-30 minutes for standard dosing 1
• IV bolus: 3-5 minutes for doses ≤1 gram (acceptable but not optimal for critically ill) 1
• Extended infusion: 3 hours for resistant organisms or critically ill patients 3, 4
• Administer over 30 minutes in neonates and infants <3 months 1

Safety Profile

• Most common adverse events: diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), injection site inflammation (1.1%) 8
• Low seizure risk compared to imipenem, making it the only carbapenem approved for bacterial meningitis 6, 9
• Drug-related seizure incidence in non-meningitis patients: 0.08% 8
• Well tolerated in children, neutropenic patients, and with higher doses up to 6 grams daily 7, 8