Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis: A Genetic-Based Chronicle of

T Nicholas Domitrovic1,2, Andrea M Hujer1,2, Federico Perez1,2

  • 1Louis Stokes Cleveland Department of Veterans Affairs Medical Center.

Insights

This study tracked multidrug-resistant Pseudomonas aeruginosa in a prosthetic valve endocarditis patient, revealing how mutations in regulatory genes drive antibiotic resistance and treatment failure.

Area of Science:

  • Medical Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Multidrug-resistant (MDR) *Pseudomonas aeruginosa* poses a significant challenge in treating infections, particularly those involving prosthetic devices like prosthetic valve endocarditis (PVE).
  • Antibiotic resistance and biofilm formation are key factors complicating treatment outcomes.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying the emergence of antibiotic resistance in MDR *P. aeruginosa* during treatment for PVE.
  • To identify specific genetic mutations contributing to the observed resistance patterns.

Main Methods:

  • Analysis of five sequential MDR *P. aeruginosa* blood isolates from a PVE patient over seven months.
  • Determination of antibiotic resistance profiles using Minimum Inhibitory Concentrations (MICs).
  • Molecular characterization including multilocus sequence typing (MLST), repetitive sequence-based PCR, and gene sequencing (regulatory and resistance genes).

Main Results:

  • All isolates belonged to Sequence Type 298 (ST 298) and exhibited resistance to fluoroquinolones and carbapenems, possessing the *bla*PDC-16 gene.
  • A significant increase in cephalosporin resistance was observed during therapy, correlated with a D135N mutation in the *amp*R regulator.
  • Mutations were identified in the outer membrane protein OprD, quinolone resistance-determining regions of *gyr*A and *par*C, and the efflux pump regulator *nal*C.

Conclusions:

  • The study elucidates the molecular evolution of β-lactam resistance in *P. aeruginosa* within a PVE context.
  • Mutations in regulatory genes governing efflux pumps and cephalosporinase production are critical contributors to the MDR phenotype, impacting treatment efficacy.

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