Carbapenemase-producing Pseudomonas aeruginosa –an emerging challenge

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) is a major healthcare-associated pathogen worldwide. In the United States, 10–30% of P. aeruginosa isolates are carbapenem-resistant, while globally the percentage varies considerably. A subset of carbapenem-resistant P. aeruginosa isolates harbour carbapenemases, although due in part to limited screening for these enzymes in clinical laboratories, the actual percentage is unknown. Carbapenemase-mediated carbapenem resistance in P. aeruginosa is a significant concern as it greatly limits the choice of anti-infective strategies, although detecting carbapenemase-producing P. aeruginosa in the clinical laboratory can be challenging. Such organisms also have been associated with nosocomial spread requiring infection prevention interventions. The carbapenemases present in P. aeruginosa vary widely by region but include the Class A beta-lactamases, KPC and GES; metallo-beta-lactamases IMP, NDM, SPM, and VIM; and the Class D, OXA-48 enzymes. Rapid confirmation and differentiation among the various classes of carbapenemases is key to the initiation of early effective therapy. This may be accomplished using either molecular genotypic methods or phenotypic methods, although both have their limitations. Prompt evidence that rules out carbapenemases guides clinicians to more optimal therapeutic selections based on local phenotypic profiling of non-carbapenemase-producing, carbapenem-resistant P. aeruginosa . This article will review the testing strategies available for optimizing therapy of P. aeruginosa infections.

Carbapenem-resistant Pseudomonas aeruginosa: an assessment of frequency of isolation from ICU versus non-ICU, phenotypic and genotypic profiles in a multinational population of hospitalized patients

“…In this model, expanded agents (e.g., ceftolozane/tazobactam and ceftazidime/avibactam) are tested when specific criteria are met (e.g., carbapenem-non-susceptibility). Of note, novel agents may not be immediately available on automated susceptibility testing platforms and clinical laboratories must utilize other methods for testing such as gradient diffusion strips or disk diffusion which may take another 24 h for results [ 11 ]. A quasi-experimental study in a regional health system found that the median time from known meropenem-non-susceptibility to ceftolozane/tazobactam testing results was 25.4 h [ 12 ].…”

Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis

“…Moreover, the 3R rules [ 36 ] (Hubrecht and Carter, 2019) prevent us from increasing the numbers of animals to test the same hypothesis in male mice. As strengths of the study, the chosen isolates from the GEMARA/REIPI collection [ 23 ], both for the in vitro and in vivo studies, are representative of high-risk clones and widespread acquired carbapenemases [ 15 , 37 , 38 , 39 ].…”

Detection of blaOXA-145, blaOXA-224, blaOXA-539, and blaOXA-675 Genes and Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) in Clinical Isolates of Pseudomonas aeruginosa Collected from West of Iran, Hamadan

“…Some OXA-type β -lactamases may also hydrolyze carbapenems. However, at least at a significant level, they cannot combine such carbapenem-hydrolyzing activities with traditional ESBL hydrolytic profiles [ 14 , 15 ].…”

“…The CHDLs described so far in this opportunistic pathogen are very likely chromosomally located. These acquired enzymes, OXA-23 and OXA-58, have contributed significantly to carbapenem resistance [ 15 ]. Naturally-occurring CHDLs include OXA enzymes such as OXA-24, OXA-51, and OXA-69, all from NFGNB [ 16 ].…”