Comparison of Two Phenotypic Algorithms To Detect Carbapenemase-Producing Enterobacteriaceae

Abstract

A novel algorithm designed for the screening of carbapenemase-producing Enterobacteriaceae (CPE), based on faropenem and temocillin disks, was compared to that of the Committee of the Antibiogram of the French Society of Microbiology (CA-SFM), which is based on ticarcillin-clavulanate, imipenem, and temocillin disks. The two algorithms presented comparable negative predictive values (98.6% versus 97.5%) for CPE screening among carbapenem-nonsusceptible Enterobacteriaceae. However, since 46.2% (n ϭ 49) of the CPE were correctly identified as OXA-48-like producers by the faropenem/temocillin-based algorithm, it significantly decreased the number of complementary tests needed (42.2% versus 62.6% with the CA-SFM algorithm).KEYWORDS OXA-48, KPC, NDM, VIM, IMP disk diffusion susceptibility testing, bacterial susceptibility testing, carbapenemase, disk diffusion C arbapenem resistance caused by carbapenemase production has been increasingly reported worldwide in Enterobacteriaceae (1, 2). In most of the cases, these carbapenemases belong to Ambler class A (mostly KPC and GES types) (3), Ambler class B or metallo-␤-lactamases (MBLs) of VIM, IMP (1, 2), and NDM types (4), or carbapenemhydrolyzing Ambler class D ␤-lactamases (CHDLs) (mostly OXA-48-like) (5). The spread of carbapenemase-producing Enterobacteriaceae (CPE) represents a serious threat for public health and requires their rapid identification to implement proper infection control measures to prevent further spread in hospitals and initiate proper treatments. Although very few novel antibiotics are, or will be, available for the treatment of CPE, the most promising therapies involve combinations of a broad-spectrum ␤-lactam and novel ␤-lactamase inhibitors (e.g., ceftazidime-avibactam, imipenem-relebactam) active on class A carbapenemases and on class D (for avibactam only) but not on MBLs (6, 7). During the last 3 years, several methods have been developed for the detection of CPE, including (i) tests able to detect carbapenem-hydrolyzing activity (Carba NP test and derivatives [8][9][10] , (iii) combination disk diffusion assays (20), and (iv) molecular-based techniques that aim to detect the most widespread carbapenemase-encoding genes (21-23).The ability to infer from routine antibiogram the presence of a carbapenemase is often complicated and requires complementary tests, leading to additional delay and cost for clinical laboratories. Accordingly, it is of importance to develop solutions (e.g., algorithms) with high sensitivities and negative predictive values (NPVs) to discriminate

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“…Despite reports of faropenem performing well, we found it to be a poor predictor of OXA-48 producers (58% truepositives). 8,11 Similarly Koroska et al (2017) demonstrated a sensitivity of only 57.1% when using CAT-ID to explicitly identify OXA-48. 6 In addition, our OXA-48 producers were typically meropenem and ertapenem susceptible (table I) in contrast to previous studies with only carbapenem-resistant isolates, demonstrating that resistance to faropenem alone may miss many OXA-48 producers.…”

“…6 In addition, our OXA-48 producers were typically meropenem and ertapenem susceptible (table I) in contrast to previous studies with only carbapenem-resistant isolates, demonstrating that resistance to faropenem alone may miss many OXA-48 producers. 8,11 Furthermore, AST results between March and August 2016 revealed that meropenem and ertapenem resistance (10% and 52%, respectively) were also unreliable indicators of OXA-48 production, in contrast to temocillin resistance (100%). Therefore, faropenem resistance was replaced with interpretive reading of the antibiogram to ensure optimal recovery of all OXA-48 producers.…”

“…Other studies have proposed diagnostic algorithms for CPE screening; employing faropenem and temocillin susceptibility to differentiate non-CPE, CPE and OXA-48 producers. 6,11 While they show that a combination of methods increases the sensitivity of CPE detection, there are also disadvantages. One relied on reduced carbapenem susceptibility to trigger a confirmatory CPE test (CAT-ID), which isunlikely to be practical if the majority of OXA-48 producers are carbapenem susceptible.…”

“…One relied on reduced carbapenem susceptibility to trigger a confirmatory CPE test (CAT-ID), which isunlikely to be practical if the majority of OXA-48 producers are carbapenem susceptible. 11 Another study detected OXA-48 using a lateral flow device (LFD) to compensate for the poor performance of faropenem. 6 While simple and rapid, LFD devices capable of detecting carbapenemases also increase CPE screening costs and may limit widespread use in high-throughput diagnostic laboratories.…”