Role of β-lactamases and efflux pumps in multidrug resistance inPseudomonas aeruginosaisolated from patients in the Intensive Care Unit in the northeast of Brazil

Abstract Pseudomonas aeruginosa is an opportunistic pathogen with high clinical relevance in intensive care units (ICU) due to its elevated resistance to various antimicrobials, which lead to high morbidity and mortality in patients in critical situations. In this study, we aimed to detect variants of genes encoding β-lactamases and efflux pumps in P. aeruginosa isolates resistant to β-lactams, fluoroquinolones and aminoglycosides. All genes belonging to the subfamilies were included in this study: bla SHV , bla TEM , bla NDM , bla KPC , bla GES , bla CTX-M . In addition, we investigated the most relevant variants of the bla OXA subfamily and genes belonging to the efflux pumps of the Mex family. We tested 54 isolates of P. aeruginosa with a high prevalence of resistance to the antimicrobials piperacillin/tazobactam, ceftazidime, cefepime, imipenem and meropenem. Resistance genes related to carbapenems and spectrum β-lactamases extended were found, which included bla KPC genes (81.49%), bla CTXM-2 (72.22%) and bla CTXM-1 (66.66%). In relation to the presence of Mex family efflux pumps genes, 100% of positivity were detected. These findings suggest that P. aeruginosa isolates exhibit an arsenal of genes encoding β-lactamases able to induce phenotypic patterns of resistance to several antimicrobials commonly used as first-line treatment. Author Summary Since the introduction of the use of antimicrobials, resistance to antimicrobials has been growing and becoming a global public health problem, as it leads to ineffective treatment and an increased risk of mortality. P. aeruginosa is included in the World Health Organization (WHO) critical list of bacteria that have a higher rate of resistance to antimicrobials, requiring constant epidemiological investigation of the strains, especially in hospital environments, to correctly approach them. In this work, we used a methodology that detects 740 variants of different classes of β-lactamases to evaluate the genotype of the study strains against the phenotype found. We evidenced a high prevalence of strains carrying genes related to carbapenems and extended-spectrum β-lactamases, demonstrating a correlation with the phenotypes. Furthermore, we found a 100% positivity rate among the efflux pumps tested belonging to the MEX family.