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 dosed at 1 gram IV every 8 hours for most serious infections, with extended 3-hour infusions recommended for critically ill patients or when treating resistant organisms with MIC ≥8 mg/L. 1, 2

Standard Dosing by Infection Type

Complicated Intra-Abdominal Infections

• 1 gram IV every 8 hours is the standard dose for adults with complicated appendicitis, peritonitis, and other intra-abdominal infections 3, 4
• Treatment duration is 5-7 days, individualized based on adequate source control and clinical response 1, 2
• For pediatric patients ≥3 months: 20 mg/kg every 8 hours (maximum 1 gram per dose) 4
• For infants <3 months with normal renal function: dosing varies by gestational and postnatal age, ranging from 20-30 mg/kg every 8-12 hours 4

Complicated Skin and Soft Tissue Infections

• 500 mg IV every 8 hours for standard cases 3, 4
• 1 gram IV every 8 hours when Pseudomonas aeruginosa is suspected or confirmed 3, 4
• For pediatric patients ≥3 months: 10 mg/kg every 8 hours (maximum 500 mg per dose) 4

Necrotizing Infections

• 1 gram IV every 8 hours as part of combination therapy 1
• Must combine with 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 for gangrenous bowel or necrotizing soft tissue infections 5
• Meropenem monotherapy is inadequate due to lack of MRSA coverage 5

Hospital-Acquired and Ventilator-Associated Pneumonia

• 1 gram IV every 8 hours for low-risk multidrug-resistant organisms 1
• 2 grams IV every 8 hours by extended infusion for severe pneumonia or high-risk MDR organisms 1

Bacterial Meningitis (Pediatric Patients ≥3 Months)

• 40 mg/kg every 8 hours (maximum 2 grams per dose) 4
• Treatment duration: 10 days for pneumococcal or H. influenzae meningitis, 21 days for Enterobacteriaceae or Listeria meningitis 1

Critical Dosing Optimization Strategies

Extended Infusion Protocol

Extended infusion over 3 hours is strongly recommended in the following scenarios 1, 2:

• Critically ill patients with healthcare-associated infections
• Carbapenem-resistant Enterobacteriaceae (CRE) infections
• When meropenem MIC ≥8 mg/L
• Severe pneumonia requiring 2-gram doses

The rationale: beta-lactams require plasma concentrations above MIC for at least 70% of the dosing interval, with higher targets (Cmin/MIC >4-6) increasing success rates in critically ill patients 1

Standard Administration

• 15-30 minute IV infusion for standard dosing 4
• 3-5 minute IV bolus is acceptable for 1-gram doses in stable patients 4
• Bolus administration of 2-gram doses has limited safety data in pediatric patients 4

Renal Dose Adjustment

For creatinine clearance ≤50 mL/min, adjust as follows 3, 4:

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

Combination Therapy Requirements

When Meropenem Monotherapy is Insufficient

Meropenem does not cover 1:

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant enterococci (VRE)

Add ampicillin 2 grams IV every 6 hours for high-risk enterococcal infections in 5:

• Immunocompromised patients
• Recent antibiotic exposure
• Healthcare-associated infections

Carbapenem-Resistant Organisms

For CRE infections 1, 2:

• 1 gram IV every 8 hours by 3-hour extended infusion in combination with a second active agent
• For high MIC (≥16 mg/L) KPC-producing organisms: 2 grams IV every 8 hours by 3-hour extended infusion 1

For carbapenem-resistant Acinetobacter baumannii (CRAB) with meropenem MIC ≤8 mg/L 1, 2:

• Consider high-dose extended-infusion meropenem as part of combination therapy with two in vitro active agents
• Avoid polymyxin-meropenem combination (not recommended) 2

Spectrum of Activity

Covered Organisms 4, 6

• Methicillin-susceptible S. aureus (MSSA)
• Streptococci (including S. pyogenes, S. agalactiae, viridans group)
• Vancomycin-susceptible Enterococcus faecalis
• Pseudomonas aeruginosa
• Enterobacteriaceae (E. coli, K. pneumoniae, Proteus mirabilis)
• Anaerobes (Bacteroides fragilis, Peptostreptococcus species)
• Haemophilus influenzae, Neisseria meningitidis

Not Covered 1

• MRSA
• VRE
• Stenotrophomonas maltophilia

Critical Clinical Pearls

Surgical source control is mandatory for intra-abdominal infections and necrotizing infections—antibiotics alone are insufficient 5

Obtain intraoperative cultures at the index operation to guide de-escalation, but never delay empiric antibiotics for culture results 5

Monitor for resistance emergence during treatment of P. aeruginosa infections, as resistance can develop during therapy 6, 7

De-escalation is appropriate once cultures and susceptibilities return, provided clinical improvement is documented 5

Meropenem has superior CNS tolerability compared to imipenem/cilastatin, with lower seizure risk, making it the preferred carbapenem for meningitis 6, 8

Maximum daily dose is 6 grams (2 grams every 8 hours), which can be safely administered when needed for severe infections 7