Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?

Area of Science:

• Clinical Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative bacterium frequently implicated in serious infections.
• While other bacteria like Klebsiella pneumoniae and Enterobacter species also exhibit antimicrobial resistance, P. aeruginosa presents a unique challenge.
• Its resistance patterns differ from Stenotrophomonas maltophilia, another intrinsically resistant bacterium.

Purpose of the Study:

• To elucidate the specific factors contributing to the problematic nature of Pseudomonas aeruginosa infections.
• To highlight the unique combination of inherent resistance, acquired resistance, and epidemiological factors that make P. aeruginosa a significant clinical concern.
• To discuss the implications of emerging resistance mechanisms, such as those involving integrons and specific resistance genes.

Main Methods:

• Comparative analysis of resistance mechanisms and prevalence across different bacterial species (P. aeruginosa, K. pneumoniae, Enterobacter species, S. maltophilia).
• Review of P. aeruginosa's inherent resistance profiles to various antibiotic classes.
• Examination of P. aeruginosa's capacity for acquiring mutational resistance to antibiotics.
• Assessment of local resistance rates and the role of P. aeruginosa in severe infections.
• Analysis of emerging resistance determinants, including integrons and specific gene cassettes (e.g., carbapenemases, amikacin acetyltransferases).

Main Results:

• P. aeruginosa exhibits inherent resistance to multiple drug classes.
• The bacterium readily acquires mutational resistance, potentially to all available treatments.
• Local rates of P. aeruginosa resistance are high and increasing.
• Emergence of integrons carrying carbapenemase and amikacin acetyltransferase genes is observed, leading to pan-resistance in some isolates.
• P. aeruginosa is frequently involved in serious, difficult-to-treat infections.

Conclusions:

• The combination of inherent resistance, rapid acquisition of resistance, high local prevalence, and role in severe infections makes P. aeruginosa a uniquely problematic pathogen.
• The emergence of novel resistance mechanisms, such as those mediated by integrons, exacerbates the challenge of treating P. aeruginosa infections.
• Urgent strategies are needed to combat the growing threat of multidrug-resistant P. aeruginosa.