Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance

D M Livermore1, Y J Yang

  • 1Department of Medical Microbiology, The London Hospital Medical College, UK.

Insights

Meropenem shows reduced effectiveness against Pseudomonas aeruginosa with intrinsic resistance or D2-protein deficiency. However, it maintains activity against strains with most common beta-lactamases, offering a potential treatment option.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Bacterial Pathogenesis

Background:

  • Pseudomonas aeruginosa is a significant opportunistic pathogen.
  • Beta-lactam antibiotics are crucial for treating P. aeruginosa infections.
  • Mechanisms of beta-lactam resistance in P. aeruginosa include cell wall impermeability, outer membrane protein loss, plasmid-mediated beta-lactamases, and chromosomal beta-lactamase hyper-production.

Purpose of the Study:

  • To evaluate the in vitro activity of meropenem against Pseudomonas aeruginosa isolates expressing known resistance mechanisms.
  • To determine if meropenem can overcome common resistance pathways in P. aeruginosa.

Main Methods:

  • In vitro testing of meropenem against P. aeruginosa isolates, mutants, and transconjugants.
  • Characterization of isolates based on four major beta-lactam resistance mechanisms.
  • Determination of meropenem minimum inhibitory concentrations (MICs).

Main Results:

  • Meropenem exhibited impaired activity against P. aeruginosa with broad-spectrum intrinsic resistance (MIC 1-2 mg/l) and D2-protein deficiency (MIC 1-2 mg/l).
  • Most common plasmid-mediated beta-lactamases (TEM, OXA, PSE) did not significantly affect meropenem MICs (0.12 mg/l).
  • Reduced susceptibility to meropenem (MIC 4 mg/l) was noted with specific uncommon beta-lactamases (NPS-1, PSE-2, OXA-3).
  • Chromosomal beta-lactamase expression did not impact meropenem MICs.

Conclusions:

  • Meropenem retains activity against P. aeruginosa strains possessing most common beta-lactam resistance mechanisms.
  • Meropenem's efficacy may be compromised by intrinsic resistance and specific uncommon beta-lactamases.
  • Meropenem demonstrates potential as a treatment option for P. aeruginosa infections, but resistance monitoring is essential.

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