Multicenter, Prospective Validation of a Phenotypic Algorithm to Guide Carbapenemase Testing in Carbapenem-Resistant Pseudomonas aeruginosa using the ERACE-PA Global Surveillance Program
Abstract Background Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are a global challenge. However, detection efforts can be laborious because numerous mechanisms produce carbapenem resistance. An MIC based algorithm (imipenem or meropenem-resistant plus ceftazidime-non-susceptible plus cefepime-non-susceptible) was proposed to identify isolates most likely to harbor a carbapenemase; however, prospective validation in geographies displaying genotypic diversity and varied carbapenemase prevalence is warranted. Methods CRPA were collected during the ERACE-PA global surveillance program from 17 sites in 12 countries. Isolates underwent susceptibility testing following local standards to ceftazidime, cefepime, and ceftolozane/tazobactam. Isolates underwent initial phenotypic carbapenemase screening followed by molecular testing if positive. The primary algorithm criteria were applied and results compared to phenotypic carbapenemase results to assess the performance of the algorithm. A secondary criteria of (the algorithm criteria or imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible) was assessed. Results 807 CRPA were assessed and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by GES. Addition of the criteria of imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible decreased the number of CP-CRPA missed by the algorithm (21 versus 40 isolates, respectively) still reducing number of isolates tested by 39%. Conclusions Application of the initial algorithm (imipenem or meropenem-resistant plus ceftazidime-non-susceptible plus cefepime-non-susceptible) performed well in a global cohort with 33% phenotypically carbapenemase-positive isolates. Addition of imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES.