Heterogeneous hydrolytic features for OXA-48-like β-lactamases

Oueslati, Saoussen; Nordmann, Patrice; Poirel, Laurent

doi:10.1093/jac/dku524

Cited by 120 publications

(158 citation statements)

References 17 publications

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“…Another important consideration is the prevalence of OXA-48-like enzymes among isolates in a given geographic area. Isolates carrying OXA-48-like ␤-lactamases have a propensity to demonstrate a limited increase in carbapenem MICs unless they also harbor a permeability defect (20), making it difficult to identify some isolates by phenotypic methods. Meropenem nonsusceptibility is a highly specific phenotypic marker for carbapenemase production but shows poor sensitivity for OXA-48 producers (21).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

Karlowsky

Lob²,

Kazmierczak³

et al. 2017

J Clin Microbiol

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The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, Ն1 g/ml; n ϭ 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-␤-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points,

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

Karlowsky

Lob²,

Kazmierczak³

et al. 2017

J Clin Microbiol

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“…Kinetic studies of OXA enzymes show that the k cat values for 1β‐methyl‐substituted carbapenems tend to be 10–100‐fold less than for those with a 1β‐proton 17, 18. Non‐covalent interaction plots indicate that the 1β‐methyl group may interact sterically with the hydroxyethyl group in the acyl‐enzyme complex, which is largely alleviated in the corresponding 1β‐proton system (Figure 2 B).…”

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confidence: 99%

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

et al. 2018

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Abstractβ‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required.

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“…Chromogenic selective media have improved screening methods but have shown wide ranges of sensitivities and specificities of 43% to 97% and 39% to 97%, respectively (10)(11)(12)(13)(14)(15). Such variable performance has been attributed to bla and other carbapenemases showing low-level expression and/or poor hydrolyzing characteristics that result in low carbapenem MICs (16). Additionally, CPO/carbapenem-resistant organism (CRO) chromogenic media have limited availability in the United States, with only HardyCHROM CRE (Hardy Diagnostics, Santa Maria, CA), Chromagar KPC (Chromagar, Paris, France), and Remel Spectra CRE (Remel Inc., Lenexa, KS) available (for research purposes only).…”

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confidence: 99%

Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla _KPC , bla _NDM and/or bla _VIM , and bla _OXA-48 from Perirectal Swabs

et al. 2015

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We evaluated the clinical performance of Check-Direct CPE for carbapenemase detection directly from 301 perirectal swabs (258 patients) in a nonoutbreak setting. Culture of a PCR-confirmed, carbapenemase-containing organism, or history of colonization with such organism within the previous 2 weeks, was used as the reference standard. Check-Direct CPE demonstrated a sensitivity value, specificity value, positive predictive value (PPV), and negative predictive value (NPV) of 100% (all bla KPC ), 88%, 21%, and 100%, respectively. False positives accounted for 79% (n ‫؍‬ 34) of samples for which a cycle threshold (C T ) value was reached. Simulated studies to evaluate specimen pooling as an approach to minimize costs showed no difference in C T values for pooled groups of three or five that each contained a single specimen spiked with ϳ1,500 CFU bla KPC Klebsiella pneumoniae; however, the detection rate dropped to 60% at a seeded concentration of ϳ150 CFU. When data were pooled, C T values for bla KPC were higher for heavy-feces-containing than for light-feces-containing liquid-suspended specimens. Furthermore, C T values for liquid-suspended specimens were 4 to 5 C T values lower (i.e., represented greater sensitivity) than those seen in direct swab analysis. Culture was equivalent to or better than Check-Direct CPE for 13/15 (87%) isolates tested in a limit-of-detection analysis. Detection of a carbapenemase gene at a C T cutoff value of <35 was culture confirmed in 23/24 (96%) of cases; however, C T values of >35 overlapped broadly between culture-positive (n ‫؍‬ 21) and culture-negative (n ‫؍‬ 36) specimens. Check-Direct CPE will likely prove most useful in high-prevalence areas or in outbreak settings where rapid carbapenemase detection is critical for infection control management. C arbapenemase-producing organism (CPO) infections are now globally epidemic, causing rising concern as they demonstrate easy transmissibility between patients and the environment, with increasing numbers of reported outbreaks (1-4). The morbidity and mortality associated with CPO infections are high, and effective therapeutic options are limited. Recent data show that bla KPC , bla NDM , and bla OXA-48 are the most common carbapenemases worldwide (5). Carbapenemase detection, however, can be complicated, and detection methods are not standardized among laboratories. Because gastrointestinal colonization with a CPO is a reservoir for transmission (6), routine CPO surveillance via collection of rectal/perirectal swabs or stool samples is increasingly being utilized in many infection control programs (7) and is recommended by public health agencies such as the Centers for Disease Control and Prevention (CDC) (8).Current methods for CPO surveillance generally rely on culture using selective media. The Clinical and Laboratory Standards Institute (CLSI) recommends performing carbapenemase testing on Enterobacteriaceae isolates (i) with imipenem or meropenem MICs of 2 to 4 g/ml or an ertapenem MIC of 2 g/ml (if using the 2010 M100-S20 brea...

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Heterogeneous hydrolytic features for OXA-48-like β-lactamases

Abstract: A detailed comparative analysis of the kinetic properties of the OXA-48-like β-lactamases is provided here. It clarifies the respective features of each OXA-48-like variant and their respective impacts in terms of carbapenem resistance.

Cited by 120 publications

References 17 publications

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla _KPC , bla _NDM and/or bla _VIM , and bla _OXA-48 from Perirectal Swabs

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Heterogeneous hydrolytic features for OXA-48-like β-lactamases

Abstract: A detailed comparative analysis of the kinetic properties of the OXA-48-like β-lactamases is provided here. It clarifies the respective features of each OXA-48-like variant and their respective impacts in terms of carbapenem resistance.

Cited by 120 publications

References 17 publications

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla KPC , bla NDM and/or bla VIM , and bla OXA-48 from Perirectal Swabs

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Product

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Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla _KPC , bla _NDM and/or bla _VIM , and bla _OXA-48 from Perirectal Swabs