Defining the Relationship Between Phenotypic and Genotypic Resistance Profiles of Multidrug-Resistant Enterobacterial Clinical Isolates

Adv Exp Med Biol. 2019:1214:9-21. doi: 10.1007/5584_2018_208.

Abstract

Fluoroquinolones and aminoglycosides offer effective therapy for extended-spectrum beta-lactamase (ESBL)-producing enterobacterial infections, but their usefulness is threatened by increasing resistant strains.

Objective: This study was conducted to demonstrate the phenotypic outcomes of the coexistence of genetic determinants mediating resistance to extended-spectrum cephalosporins and quinolones in enterobacterial isolates collected from patients with health-care-associated infections in Egypt.

Methods: ESBL phenotype was determined using double-disk synergy test (DDST). The PCR technique was used to detect the presence of the genes mediating quinolone resistance (qnr and aac(6')-Ib-cr) and coexistence with ESBL genes. We also examined the association between the genetic makeup of the isolates and their resistance profiles including effect on MIC results.

Results: Phenotypically ESBLs were detected in 60-82% of the enterobacterial isolates. ESBL, qnr and aac(6')-Ib-cr genes were detected with the following percentages in Citrobacter isolates (69%, 69%, and 43%, respectively), E.coli isolates (65%, 70%, and 45%, respectively), Enterobacter isolates (56%, 67%, and 33%, respectively), and finally Klebsiella isolates (42%, 66%, and 25%, respectively). The coexistence of these multiresistant genetic elements significantly increased the MIC values of the tested antibiotics from different classes.

Conclusion: We suggest using blaTEM, blaCTX-M-15, qnr, and aac(6')-Ib-cr genes for better and faster prediction of suitable antibiotic therapy with effective doses against ESBL-producing isolates harboring plasmid-mediated quinolone resistance (PMQR) determinants. Amikacin, meropenem, gentamicin, and imipenem seem to be better choices of treatment for such life-threatening infections, because of their remaining highest activity.

Keywords: Co-resistance; Extended-spectrum beta-lactamases; MDR; PMQR; Quinolone resistance.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins / genetics
  • Cross Infection / microbiology
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae* / drug effects
  • Enterobacteriaceae* / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Phenotype
  • Plasmids / genetics
  • Polymerase Chain Reaction
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases