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Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa.

ABSTRACT: Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. In this study, we collected 76 intestinal carbapenem-resistant P. aeruginosa (CRPA) strains from clinical inpatients admitted to our hospital from 2014 to 2019, together with their medical data. We aim to analyze the clinical risk factors associated with CRPA infection and its molecular features. We found that the prevalence of CRPA in P. aeruginosa strains was 41.3% (95% confidence interval [CI], 34.1 to 48.8%). We also identified four variables associated with intestinal CRPA positivity, prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. bla_KPC-2 is the only detected carbapenemase gene, accounting for 21.1% of CRPA strains. The genetic environment showed that the bla_KPC-2 gene was flanked immediately by ISKpn8 and ISKpn6 and several other mobile elements further upstream or downstream. Four sequence types (STs) were identified, with ST463 as the dominant sequence type. In conclusion, screening for P. aeruginosa colonization upon hospital admission could reduce the risk of P. aeruginosa infection and spread of CRPA in the hospital. IMPORTANCE Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes. Risk factor analysis and molecular epidemiology are critical for preventing their potential dissemination. Here, we identified four risk factors associated with intestinal CRPA-prior antibiotic exposure to aminoglycosides or carbapenems, underlying diabetes mellitus, and extraintestinal P. aeruginosa isolation. Further, we found similar genetic environments with several mobile elements surrounding the bla_KPC gene, a carbapenemase gene only detected in intestinal CRPA strains in this study. These findings are of significant public health importance, as the information will facilitate the control of the emergence and spread of CRPA.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8612150 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:All (236) Pseudomonas aeruginosa isolates resistant to imipenem and/or meropenem collected during a multicenter (127-hospital) study in Spain were analyzed. Carbapenem-resistant isolates were found to be more frequently resistant to all beta-lactams and non-beta-lactam antibiotics than carbapenem-susceptible isolates (P < 0.001), and up to 46% of the carbapenem-resistant isolates met the criteria used to define multidrug resistance (MDR). Pulsed-field gel electrophoresis revealed remarkable clonal diversity (165 different clones were identified), and with few exceptions, the levels of intra- and interhospital dissemination of clones were found to be low. Carbapenem resistance was driven mainly by the mutational inactivation of OprD, accompanied or not by the hyperexpression of AmpC or MexAB-OprM. Class B carbapenemases (metallo-beta-lactamases [MBLs]) were detected in a single isolate, although interestingly, this isolate belonged to one of the few epidemic clones documented. The MBL-encoding gene (bla(VIM-2)), along with the aminoglycoside resistance determinants, was transferred to strain PAO1 by electroporation, demonstrating its plasmid location. The class 1 integron harboring bla(VIM-2) was characterized as well, and two interesting features were revealed: intI1 was found to be disrupted by a 1.1-kb insertion sequence, and a previously undescribed aminoglycoside acetyltransferase-encoding gene [designated aac(6')-32] preceded bla(VIM-2). AAC(6')-32 showed 80% identity to AAC(6')-Ib' and the recently described AAC(6')-31, and when aac(6')-32 was cloned into Escherichia coli, it conferred resistance to tobramycin and reduced susceptibility to gentamicin and amikacin. Despite the currently low prevalence of epidemic clones with MDR, active surveillance is needed to detect and prevent the dissemination of these clones, particularly those producing integron- and plasmid-encoded MBLs, given their additional capacity for the intra- and interspecies spread of MDR.

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Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa.

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