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Improved Strategies to Predict Carbapenemase Gene Presence for Carbapenem Resistant Pseudomonas aeruginosa

Reviewed by Dr. Michael Payne, MD, London Health Sciences Centre

Multidrug-resistant Pseudomonas aeruginosa is an antibiotic resistance threat, causing difficult to treat infections particularly amongst patients with chronic lung disease, who are critically ill, or immunocompromised.  The majority of carbapenem-resistant Pseudomonas aeruginosa (CRPA) do not carry genes for carbapenemase enzyme production. However, 2-3% of CRPA do carry carbapenemase-producing (CP) genes, which are commonly found on mobile genetic elements that facilitate transfer of resistance and possible spread within a health care facility. Screening of all CRPA for CP would be associated with increased demands for limited laboratory resources. This study utilized CRPA isolates collected by CDC’s Antibiotic Resistance Laboratory Network (AR Lab Network) and the Emerging Infections Program (EIP) during 2017 to 2019.  Among the AR Lab Network isolates, a total of 195/6192 (3%) were CP-CRPA, blaVIM (n = 120), blaKPC (n = 51), blaIMP (n = 13), and blaNDM (n = 12). Screening for non-susceptibility (NS) to either cefepime or ceftazidime for CRPA had 91% sensitivity and 50% specificity for predicting presence of CP-CRPA.  Screening for NS to ceftolozane-tazobactam for CRPA had 100% sensitivity and 86% specificity. Of the 965 EIP isolates with CP gene testing results available, 7 were CP-CRPA. Among these, 6 of the 7 were NS to cefepime and ceftazidime and all 7 were NS to ceftolozane-tazobactam. The number needed to test (NNT) to identify one CP-CRPA isolate decreased from 138 to 64 if screening by NS to cefepime or ceftazidime and to 7 if screening by NS to ceftolozane-tazobactam. This study suggests that non-susceptibility to ceftolozane-tazobactam is a sensitive and specific flag for predicting the presence of carbapenemase genes in carbapenem resistant Pseudomonas aeruginosa, allowing for improved targeted screening programs to identify CP-CRPA.

Reference:

Vallabhaneni S, Huang JY, Grass JE, Bhatnagar A, Sabour S, Lutgring JD, Campbell D, Karlsson M, Kallen AJ, Nazarian E, Snavely EA,Morris S, Wang C, Lee R, Koag M, Lewis R, Garcia B, EIP Work Group, Brown AC, Walters MS. 2021. Antimicrobial susceptibility profiles to predict the presence of carbapenemase genes among carbapenem-resistant Pseudomonas aeruginosa isolates. J Clin Microbiol 59:e02874-20. https://doi.org/10.1128/JCM.02874-20

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