Does meropenem cover Pseudomonas aeruginosa and Escherichia coli (E. coli)?

Meropenem Coverage for Pseudomonas aeruginosa and E. coli

Yes, meropenem provides excellent coverage against both Pseudomonas aeruginosa and Escherichia coli, making it an effective choice for infections caused by these pathogens.

Antimicrobial Spectrum of Meropenem

Meropenem is a carbapenem antibiotic with broad-spectrum activity against many gram-positive and gram-negative bacteria. According to the FDA drug label, meropenem has demonstrated antimicrobial activity against:

• Pseudomonas aeruginosa: Meropenem has excellent activity against P. aeruginosa, which is particularly important as this organism is often resistant to multiple antibiotics 1
• Escherichia coli: Meropenem shows 100% susceptibility against E. coli isolates 2

Mechanism of Action

Meropenem exerts its bactericidal activity by:

• Inhibiting bacterial cell wall synthesis
• Penetrating the cell wall of most gram-positive and gram-negative bacteria
• Binding to penicillin-binding proteins (PBPs) 2,3, and 4 of E. coli and P. aeruginosa 1
• Achieving bactericidal concentrations typically 1-2 times the bacteriostatic concentrations 1

Comparative Efficacy

When compared to other antibiotics:

• Meropenem displays lower MICs against Enterobacteriaceae (including E. coli) and P. aeruginosa compared to imipenem 2
• Against Enterobacteriaceae, susceptibility rates are approximately:
  • Meropenem: 99-100%
  • Imipenem: 98-100%
  • Piperacillin/tazobactam: 90% 2

Clinical Applications

Meropenem is particularly useful in:

1. Hospital-acquired pneumonia: Especially when P. aeruginosa is suspected 3
2. Ventilator-associated pneumonia: When resistant gram-negative pathogens are a concern 3
3. Infections caused by ESBL-producing organisms: Meropenem is effective against extended-spectrum beta-lactamase producing E. coli 3

Important Considerations

Dosing

• Standard dosing: 1g IV every 8 hours
• For severe infections or suspected P. aeruginosa: High-dose, prolonged infusion (2g every 8 hours as 3-hour infusion) may be more effective 4
• Dose adjustment required in renal impairment 1

Resistance Concerns

• While meropenem has excellent activity against both organisms, resistance can develop through:

  1. Decreased permeability of the outer membrane
  2. Reduced affinity of target PBPs
  3. Increased expression of efflux pumps
  4. Production of carbapenemases or metallo-β-lactamases 1

• For carbapenem-resistant P. aeruginosa (CRPA), novel β-lactam agents such as ceftolozane/tazobactam and ceftazidime/avibactam are recommended as first-line options 3

Pharmacodynamics

• Optimal killing of P. aeruginosa and E. coli is associated with maintaining drug concentrations above the MIC for at least 40% of the dosing interval (40% T>MIC) 5
• Dividing the exposure into multiple shorter periods may enhance bacterial killing and reduce resistance emergence in P. aeruginosa 5

When to Consider Alternative Agents

• For DTR-PA (difficult-to-treat resistant P. aeruginosa): Consider ceftolozane/tazobactam or ceftazidime/avibactam 3
• For carbapenemase-producing organisms: Consider combination therapy or newer agents like ceftazidime/avibactam 6
• For ESBL-producing strains without P. aeruginosa risk: Ertapenem may be an alternative 3

In summary, meropenem remains a highly effective antibiotic against both P. aeruginosa and E. coli with excellent in vitro activity and clinical efficacy, making it an important option for serious infections caused by these pathogens.