There is an urgent need for rapid, accurate detection and classification of carbapenemases. The current study evaluated the automated BD Phoenix CPO Detect and the manual bioMérieux Rapidec Carba NP tests for meeting these needs. Both tests were challenged with 294 isolates of Enterobacteriaceae spp., Pseudomonas aeruginosa, and Acinetobacter baumannii chosen to provide extreme diagnostic difficulty. Carbapenemases such as KPC, NMC-A, IMI, SME, NDM, SPM, IMP, VIM, and OXA-23, 40, 48, 58, 72, 181, and 232 were produced by 243 isolates and 51 carbapenemase-negative isolates included porin mutants and producers of extended-spectrum β-lactamases (ESBLs), AmpCs, K1, and broad-spectrum β-lactamases. Both tests exhibited high sensitivity of carbapenemase detection (>97%). Due to the highly challenging carbapenemase-negative isolates, specificities were lower than typical for evaluations involving mostly routine clinical isolates. BD Phoenix CPO Detect was 68.6% specific and Rapidec Carba NP was 60.8% to 78.4% specific, depending on how borderline results were interpreted. Only BD Phoenix CPO Detect classified carbapenemases. It correctly classified 85.0% of class A, 72.4% of class B, and 88.6% of class D carbapenemases. Importantly with respect to empirical therapy with new β-lactamase inhibitor combinations such as ceftazidime/avibactam, no class B carbapenemases were misclassified as class A carbapenemases. Both tests offer advantages. Used alone, without initial susceptibility tests, Rapidec Carba NP can provide positive results for some isolates after only 10 to 30 min incubation. BD Phoenix CPO Detect provides novel advantages such as automated carbapenemase detection, inclusion in susceptibility panels to eliminate delays and subjectivity in initiating carbapenemase tests, and classification of most carbapenemases.

This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected currently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates chosen to provide an extreme challenge for antibacterial activity. FEP–ZID had a very broad and potent in vitro spectrum of activity, and was highly active against many MDR isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates producing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple resistance mechanisms including combinations of upregulated efflux, diminished or non-functional OprD porins, and AmpC overproduction. Its clinical role will be determined initially by the breakpoints assigned to it, comparison studies with other investigational β-lactamase inhibitor combinations, and ultimately by the developing body of therapeutic outcome data.

The accurate detection of carbapenemase-producing organisms is a major challenge for clinical laboratories. The Carba NP test is highly accurate but inconvenient, as it requires frequent preparation of fresh imipenem solution. The current study was designed to compare the Carba NP test to two alternative tests for accuracy and convenience. These were a modified Carba NP test that utilized intravenous (i.v.) imipenem-cilastatin, which is less expensive than reference standard imipenem powder, and an updated version of the Rosco Neo-Rapid Carb kit, which does not require the preparation of imipenem solution and has a shelf life of 2 years. The comparison included 87 isolates that produced class A carbapenemases (including KPC-2, -3, -4, -5, -6, and -8, NMC-A, and SME type), 40 isolates that produced metallo-␤-lactamases (including NDM-1, GIM-1, SPM-1, IMP-1, -2, -7, -8, -18, and -27, and VIM-1, -2, and -7), 11 isolates that produced OXA-48, and one isolate that produced OXA-181. Negative controls consisted of 50 isolates that produced extended-spectrum ␤-lactamases (ESBLs), AmpCs (including hyperproducers), K1, other limited-spectrum ␤-lactamases, and porin and efflux mutants. Each test exhibited 100% specificity and high sensitivity (Carba NP, 100%; Rosco, 99% using modified interpretation guidelines; and modified Carba NP, 96%). A modified approach to interpretation of the Rosco test was necessary to achieve the sensitivity of 99%. If the accuracy of the modified interpretation is confirmed, the Rosco test is an accurate and more convenient alternative to the Carba NP test.T he accurate detection of carbapenemase-producing organisms (CPOs) is a major challenge for clinical laboratories. In some laboratories, detection of carbapenem-resistant Enterobacteriaceae (CRE) is the primary focus, and the need to detect carbapenemase production is considered optional and for epidemiologic purposes only (1). CRE detection is based on detection of resistance or nonsusceptibility of Enterobacteriaceae to carbapenems and certain cephalosporins and does not distinguish between carbapenemase producers and non-carbapenemase producers. Although carbapenem-resistant non-carbapenemase producers are important, they should not trigger the same level of concern as CPOs such as NDM-and other carbapenemase-producing isolates (2-6). Furthermore, the focus on CRE detection ignores carbapenemase producers that either are not Enterobacteriaceae or are carbapenemase-producing Enterobacteriaceae that are carbapenem susceptible, such as the VIM-producing Klebsiella pneumoniae isolates with imipenem MICs as low as 0.12 g/ml that were involved in a large outbreak with high mortality in Greece (7).Clinical laboratories aiming to detect carbapenemase producers need a test that is accurate and convenient. The Carba NP test is highly accurate (8, 9) but labor-intensive and inconvenient due to the instability of imipenem in solution, which necessitates extemporaneous preparation (1, 10). Another disadvantage of this test is the high cost of reference...

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