CPO Complete, a novel test for fast, accurate phenotypic detection and classification of carbapenemases.

Gina K Thomson,Kenneth S Thomson,Sameh Abdelghani,Rosa Del Campo

doi:10.1371/journal.pone.0220586

Gina K Thomson, Kenneth S Thomson + Show 2 more

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https://doi.org/10.1371/journal.pone.0220586

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Abstract

Carbapenemase-producing organisms (CPOs) are Gram-negative bacteria that are typically resistant to most or all antibiotics and are responsible for a global pandemic of high mortality. Rapid, accurate detection of CPOs and the classification of their carbapenemases are valuable tools for reducing the mortality of the CPO-associated infections, preventing the spread of CPOs, and optimizing use of new β-lactamase inhibitor combinations such as ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam. The current study evaluated the performance of CPO Complete, a novel, manual, phenotypic carbapenemase detection and classification test. The test was evaluated for sensitivity and specificity against 262 CPO isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii and 67 non-CPO isolates. It was also evaluated for carbapenemase classification accuracy against 205 CPOs that produced a single carbapenemase class. The test exhibited 100% sensitivity 98.5% specificity for carbapenemase detection within 90 minutes and detected 74.1% of carbapenemases within 10 minutes. In the classification evaluation, 99.0% of carbapenemases were correctly classified for isolates that produced a single carbapenemase. The test is technically simple and has potential for adaptation to automated instruments. With lyophilized kit storage at temperatures up to 38°C, the CPO Complete test has the potential to provide rapid, accurate carbapenemase detection and classification in both limited resource and technologically advanced laboratories.

Highlights

Carbapenemase-producing organisms (CPOs) are Gram-negative bacteria that are typically resistant to most or all antibiotics
Three hundred twenty nine isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii from two culture collections, that of the University of Louisville and the Antimicrobial Resistance Isolate Bank of the Centers for Disease Control and Prevention and Food and Drug Administration, were characterized for types of β-lactamase production by PCR, microarray, DNA sequencing, whole genome sequencing, phenotypic and biochemical tests. Those tested in the carbapenemase detection phase of the study included isolates of high diagnostic difficulty
Classification potential was assessed for 205 CPOs that produced a single carbapenemase class

Summary

Introduction

Carbapenemase-producing organisms (CPOs) are Gram-negative bacteria that are typically resistant to most or all antibiotics. The infections they cause can be difficult or impossible to treat and constitute a major global health threat of high mortality that has been compared to that of Ebola [1,2,3,4]. CPOs threaten to take away the utility of antibiotics to both treat infections. National Institute Of Child Health & Human Development (NICHD), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Nursing Research (NINR), National Human Genome Research Institute (NHGRI), National Institute On Drug Abuse (NIDA), National Institute On Minority Health And Health Disparities (NIMHD), National Library Of Medicine (NLM), National Institute Of Biomedical Imaging And Bioengineering (NIBIB). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication

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