The frequency of AmpC overproduction, OprD downregulation and OprM efflux pump expression in Pseudomonas aeruginosa: A comprehensive meta-analysis

J Glob Antimicrob Resist. 2024 Dec:39:159-169. doi: 10.1016/j.jgar.2024.08.014. Epub 2024 Sep 18.

Abstract

Objectives: Pseudomonas aeruginosa is a major opportunistic pathogen responsible for a wide range of infections. The emergence of antibiotic resistance in this pathogen poses a significant public health challenge. This study aims to conduct a comprehensive meta-analysis of studies conducted in Iran to determine the frequency of key antibiotic resistance mechanisms in Pseudomonas aeruginosa and their association with multidrug-resistant and extensively drug-resistant strains or pandrug-resistant strains.

Methods: Systematic database searches encompassing literature up to June 2023 were undertaken. The selected studies centered on OprD downregulation, efflux pump (mexAB-OprM, mexXY-OprM) expression, and AmpC overproduction. Extracted data were synthesised in a meta-analysis for pooled frequency determination of each resistance mechanism.

Results: In total, 24 studies were included. OprD downregulation exhibited a pooled frequency of 61%. Efflux pump component frequency ranged from 48% to 77.5%. AmpC overproduction was identified in 29.1% of isolates. Polymyxin B and colistin demonstrated lower antibiotic resistance rates, with pooled frequency of 1% and 1.6%, respectively. Conversely, resistance to other antibiotics ranged widely, with pooled frequency spanning 38.4% to 98.2%.

Conclusions: This study underscores the concerning frequency of diverse antibiotic resistance mechanisms in Pseudomonas aeruginosa strains from Iran. Concurrent OprD downregulation, mexAB, mexXY, OprM expression, and AmpC overproduction highlight the urgent need for stringent infection control and prudent antibiotic usage to curb the dissemination of these resistant strains.

Prospero: CRD42022379311.

Keywords: AmpC; OprD; Pseudomonas aeruginosa; Pseudomonas aeruginosa antimicrobial resistance; RND multidrug efflux pump; mexAB-OprM; mexXY-OprM.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Outer Membrane Proteins* / genetics
  • Bacterial Outer Membrane Proteins* / metabolism
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Down-Regulation
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Gene Expression Regulation, Bacterial
  • Humans
  • Iran
  • Membrane Transport Proteins* / genetics
  • Membrane Transport Proteins* / metabolism
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa* / drug effects
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / metabolism
  • beta-Lactamases* / genetics
  • beta-Lactamases* / metabolism

Substances

  • AmpC beta-lactamases
  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • beta-Lactamases
  • Membrane Transport Proteins
  • OprD protein, Pseudomonas aeruginosa
  • OprM protein, Pseudomonas aeruginosa