scholarly journals Carbapenemase Detection among Carbapenem-Resistant Glucose-Nonfermenting Gram-Negative Bacilli

2017 ◽  
Vol 55 (9) ◽  
pp. 2858-2864 ◽  
Author(s):  
Patricia J. Simner ◽  
Belita N. A. Opene ◽  
Krizia K. Chambers ◽  
Matthew E. Naumann ◽  
Karen C. Carroll ◽  
...  
Keyword(s):  
Method Comparison ◽  
Comparison Study ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Class B ◽  
Synergy Test ◽  
Method Comparison Study ◽  
Phenotypic Tests

ABSTRACT Accurate detection of carbapenemase-producing glucose-nonfermenting Gram-negative bacilli (CPNFs), including Pseudomonas aeruginosa and Acinetobacter baumannii , is necessary to prevent their dissemination within health care settings. We performed a method comparison study of 11 phenotypic carbapenemase detection assays to evaluate their accuracy for the detection of CPNFs. A total of 96 carbapenem-resistant glucose-nonfermenting isolates were included, of which 29% produced carbapenemases. All CPNFs were molecularly characterized to identify β-lactamase genes. A total of 86% of the carbapenemase-producing P. aeruginosa isolates produced class B carbapenemases. Several assays performed with a sensitivity of >90% for the detection of carbapenemase-producing P. aeruginosa , including all rapid chromogenic assays and the modified carbapenem inactivation method. Most included assays, with the exception of the Manual Blue Carba assay, the Modified Carba NP assay, the boronic acid synergy test, and the metallo-β-lactamase Etest, had specificities of >90% for detecting carbapenemase-producing P. aeruginosa . Class D carbapenemases were the most prevalent carbapenemases among the carbapenemase-producing A. baumannii strains, with 60% of the carbapenemase-producing A. baumannii isolates producing acquired OXA-type carbapenemases. Although several assays achieved >90% specificity in identifying carbapenemase-producing A. baumannii , no assays achieved a sensitivity of greater than 90%. Our findings suggest that the available phenotypic tests generally appear to have excellent sensitivity and specificity for detecting carbapenemase-producing P. aeruginosa isolates. However, further modifications to existing assays or novel assays may be necessary to accurately detect carbapenemase-producing A. baumannii .

scholarly journals In VivoEfficacy of Humanized Exposures of Ceftazidime-Avibactam in Comparison with Ceftazidime against Contemporary Enterobacteriaceae Isolates

2014 ◽  
Vol 58 (11) ◽  
pp. 6913-6919 ◽  
Author(s):  
Shawn H. MacVane ◽  
Jared L. Crandon ◽  
Wright W. Nichols ◽  
David P. Nicolau
Keyword(s):  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Variable Activity ◽  
Resistant Strains ◽  
The Impact ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTCeftazidime-avibactam is a β-lactam β-lactamase inhibitor combination under investigation for the treatment of serious Gram-negative infections. When combined with avibactam, a novel non-β-lactam β-lactamase inhibitor, ceftazidime has activity against isolates that produce Ambler class A, class C, and some class D β-lactamases. However, little is known of thein vivoefficacy of the combination against these targeted ceftazidime- and carbapenem-resistantEnterobacteriaceae. Using humanized exposures in the murine thigh model, we evaluated the efficacy of ceftazidime-avibactam againstEnterobacteriaceaeexhibiting MICs of ≥8 μg/ml to aid in the assignment of interpretive susceptibility criteria. Eighteen clinicalEnterobacteriaceaeisolates, including nine carbapenem-resistant strains, were evaluated against ceftazidime-avibactam (2,000 mg/500 mg) as a 2-h infusion every 8 h. To highlight the impact of avibactam, 13 select isolates were tested in the neutropenic model against a humanized regimen of 2,000 mg ceftazidime every 8 h (2-h infusion). Additionally, nine isolates were evaluated in immunocompetent animals. The efficacy was evaluated as the change in log10CFU compared with that of 0-h controls after 24 h. The vast majority (17/18, 94%) of the isolates were resistant to ceftazidime alone. The ceftazidime monotherapy failed to have activity against 10 of 13 isolates, while ceftazidime-avibactam produced reductions in bacterial density against 16 of 18 isolates. Ceftazidime-avibactam (2,000 mg/500 mg) every 8 h (2-h infusion) displayed dependable activity against theEnterobacteriaceaeisolates, exhibiting MICs of ≤16 μg/ml (free drug concentration above the MIC [fT>MIC] of ≥62%) and variable activity was noted at an MIC of 32 μg/ml (fT>MICof 34%). The presence of a functioning immune system enhanced the efficacy for both regimens against all tested isolates. These data support further examination of the use of ceftazidime-avibactam as an effective therapy against infections due to Gram-negative infections, including carbapenem-resistantEnterobacteriaceae.

A new method to assess the influence of textiles properties on human thermophysiology. Part I

2015 ◽  
Vol 27 (2) ◽  
pp. 272-282 ◽  
Author(s):  
Simon Annaheim ◽  
Li-chu Wang ◽  
Agnieszka Psikuta ◽  
Matthew Patrick Morrissey ◽  
Martin Alois Camenzind ◽  
...  
Keyword(s):  
Thermal Resistance ◽  
Method Comparison ◽  
Similar Data ◽  
Comparison Study ◽  
Content Type ◽  
Industry Standard ◽  
Three Phase ◽  
High Thermal Resistance ◽  
Dry Thermal Resistance ◽  
Method Comparison Study

Purpose – The purpose of this paper is to determine the validity and inter-/intra-laboratory repeatability of the first part of a novel, three-phase experimental procedure using a sweating Torso device. Design/methodology/approach – Results from a method comparison study (comparison with the industry-standard sweating guarded hotplate method) and an inter-laboratory comparison study are presented. Findings – A high correlation was observed for thermal resistance in the method comparison study (r=0.97, p<0.01) as well as in the inter-laboratory comparison study (r=0.99, p<0.01). Research limitations/implications – The authors conclude that the first phase of the standardised procedure for the sweating Torso provides reliable data for the determination of the dry thermal resistance of single and multi-layer textiles, and is therefore suitable as standard method to be used by different laboratories with this type of device. Further work is required to validate the applicability of the method for textiles with high thermal resistance. Originality/value – This study provides the first “round-robin” data for measuring thermal resistance using a Torso device. In future publications the authors will provide similar data examining the repeatability of measurements that quantify combined heat and mass transfer.

scholarly journals Comparison of 11 Phenotypic Assays for Accurate Detection of Carbapenemase-Producing Enterobacteriaceae

2017 ◽  
Vol 55 (4) ◽  
pp. 1046-1055 ◽  
Author(s):  
Pranita D. Tamma ◽  
Belita N. A. Opene ◽  
Andrew Gluck ◽  
Krizia K. Chambers ◽  
Karen C. Carroll ◽  
...  
Keyword(s):  
Gold Standard ◽  
Boronic Acid ◽  
Retrospective Cohort ◽  
Turnaround Time ◽  
Content Type ◽  
Health Care Settings ◽  
Carbapenem Resistant ◽  
Synergy Test ◽  
Phenotypic Tests ◽  
Laboratory Workflow

ABSTRACT Early identification of carbapenemase-producing Enterobacteriaceae (CPE) is essential to prevent their dissemination within health care settings. Our objective was to evaluate the accuracy of 11 phenotypic assays for the detection of CPE. Two collections of carbapenem-resistant Enterobacteriaceae (CRE) isolates were evaluated, including 191 retrospective isolates (122 CP-CRE and 69 non-CP isolates) as well as 45 prospective clinical isolates (15 CP-CRE and 30 non-CP-CRE) obtained over a 3-month period. The sensitivity and specificity of each test was determined, with molecular genotype serving as the gold standard. Among the retrospective cohort, sensitivities ranged from 72% for the boronic acid synergy test for the detection of KPC producers to ≥98% for the modified Carba NP, the Rapidec Carba NP, the manual Blue Carba, and the modified carbapenem inactivation method for the detection of any CPE. Sensitivity differed among tests across enzyme classes. All assays had excellent specificity exceeding 95%, with the exception of the boronic acid synergy test (88%) and modified Hodge test (91%). Prospectively, 45 CRE isolates were encountered over a 3-month period, including 15 CPE (33%) and 30 non-CP-CRE (67%). Results from the prospective cohort were similar. However, a decrease in specificity was observed across most tests, likely due to restricted inclusion of non-CP-CRE to assess the specificity of the assays. Overall, accuracy of CPE detection varied across phenotypic tests. Local epidemiology of CP genotypes, turnaround time, and ease of incorporation into the laboratory workflow should be considered when selecting a phenotypic assay for clinical use.

scholarly journals Evaluation of NG-Test Carba 5 for Rapid Phenotypic Detection and Differentiation of Five Common Carbapenemase Families: Results of a Multicenter Clinical Evaluation

2020 ◽  
Vol 58 (7) ◽  
Author(s):  
Stephen Jenkins ◽  
Nathan A. Ledeboer ◽  
Lars F. Westblade ◽  
Carey-Ann D. Burnham ◽  
Matthew L. Faron ◽  
...  
Keyword(s):  
Medical Center ◽  
Method Comparison ◽  
Reference Method ◽  
The United States ◽  
Comparison Study ◽  
Content Type ◽  
Percent Agreement ◽  
Mueller Hinton ◽  
Method Comparison Study

ABSTRACT NG-Test Carba 5 is a rapid in vitro multiplex immunoassay for the phenotypic detection and differentiation of five common carbapenemase families (KPC, OXA-48-like, VIM, IMP, and NDM) directly from bacterial colonies. The assay is simple to perform and has recently received U.S. Food and Drug Administration clearance. A method comparison study was performed at geographically diverse medical centers (n = 3) in the United States, where 309 Enterobacterales and Pseudomonas aeruginosa isolates were evaluated by NG-Test Carba 5 (NG Biotech, Guipry, France), the Xpert Carba-R assay (Cepheid, Inc., Sunnyvale, CA), the modified carbapenem inactivation method (mCIM), the EDTA-modified carbapenem inactivation method, and disk diffusion with carbapenems. Colonies from tryptic soy agar with 5% sheep blood (blood agar) and MacConkey agar were tested, and the results were compared to those obtained by a composite reference method. Additionally, a fourth medical center performed a medium comparison study by evaluating the performance characteristics of NG-Test Carba 5 from blood, MacConkey, and Mueller-Hinton agars with 110 isolates of Enterobacterales and P. aeruginosa. These results were compared to the expected genotypic and mCIM results. For the multicenter method comparison study, the overall positive percent agreement (PPA) and the overall negative percent agreement (NPA) of NG-Test Carba 5 with the composite reference method were 100% for both blood and MacConkey agars. The medium comparison study at the fourth site showed that the PPA ranged from 98.9% to 100% and that the NPA ranged from 95.2% to 100% for blood, MacConkey, and Mueller-Hinton agars. NG-Test Carba 5 accurately detected and differentiated five common carbapenemase families from Enterobacterales and P. aeruginosa colonies on commonly used agar media. The results of this test will support a streamlined laboratory work flow and will expedite therapeutic and infection control decisions.

scholarly journals Assessment of theIn VitroActivity of Ceftazidime-Avibactam against Multidrug-Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study, 2012 to 2014

2016 ◽  
Vol 60 (8) ◽  
pp. 4677-4683 ◽  
Author(s):  
Meredith Hackel ◽  
Krystyna M. Kazmierczak ◽  
Daryl J. Hoban ◽  
Douglas J. Biedenbach ◽  
Samuel K. Bouchillon ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Surveillance Study ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Highly Active ◽  
Class D ◽  
Class B ◽  
Klebsiella Spp

ABSTRACTIncreasing resistance in Gram-negative bacilli, includingKlebsiellaspp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-β-lactam β-lactamase inhibitor, protects β-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) and serine carbapenemases, including Ambler class A and/or class C and some class D enzymes. In this analysis, we report thein vitroactivity of ceftazidime-avibactam and comparators against multidrug-resistant (MDR)Klebsiellaspp. from the 2012-2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%)Klebsiellaspecies isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an ESBL screen-positive phenotype, and 27.4% were not susceptible to meropenem as an example of a carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90values of 0.5/2 μg/ml and 96.6% of all MDR isolates and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value of ≤8 μg/ml). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-β-lactamases) either alone or in combination with other enzymes. Thesein vitroresults support the continued investigation of ceftazidime-avibactam for the treatment of MDRKlebsiellaspecies infections.

scholarly journals Optimization of PV array inclination in India using ANN estimator: Method comparison study

Sadhana ◽  
2015 ◽  
Vol 40 (5) ◽  
pp. 1457-1472 ◽  
Author(s):  
T V DIXIT ◽  
ANAMIKA YADAV ◽  
S GUPTA
Keyword(s):  
Method Comparison ◽  
Comparison Study ◽  
Pv Array ◽  
Method Comparison Study

scholarly journals High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Alina Iovleva ◽  
Roberta T. Mettus ◽  
Christi L. McElheny ◽  
Marissa P. Griffith ◽  
Mustapha M. Mustapha ◽  
...  
Keyword(s):  
Rapid Development ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Clinical Microbiology Laboratory ◽  
Loss Of Function ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Fold Reduction ◽  
High Level

ABSTRACT OXA-232 is an OXA-48-group class D β-lactamase that hydrolyzes expanded-spectrum cephalosporins and carbapenems at low levels. Clinical strains producing OXA-232 are sometimes susceptible to carbapenems, making it difficult to identify them in the clinical microbiology laboratory. We describe the development of carbapenem resistance in sequential clinical isolates of Raoultella ornithinolytica carrying blaOXA-232 in a hospitalized patient, where the ertapenem MIC increased from 0.5 μg/ml to 512 μg/ml and the meropenem MIC increased from 0.125 μg/ml to 32 μg/ml during the course of ertapenem therapy. Whole-genome sequencing (WGS) analysis identified loss-of-function mutations in ompC and ompF in carbapenem-resistant isolates that were not present in the initial carbapenem-susceptible isolate. Complementation of a carbapenem-resistant isolate with an intact ompF gene resulted in 16- to 32-fold reductions in carbapenem MICs, whereas complementation with intact ompC resulted in a 2-fold reduction in carbapenem MICs. Additionally, blaOXA-232 expression increased 2.9-fold in a carbapenem-resistant isolate. Rapid development of high-level carbapenem resistance in initially carbapenem-susceptible OXA-232-producing R. ornithinolytica under selective pressure from carbapenem therapy highlights the diagnostic challenges in detecting Enterobacteriaceae strains producing this inefficient carbapenemase.

scholarly journals Cyclic Boronates Inhibit All Classes of β-Lactamases

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Samuel T. Cahill ◽  
Ricky Cain ◽  
David Y. Wang ◽  
Christopher T. Lohans ◽  
David W. Wareham ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Bacterial Infections ◽  
Binding Mode ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Class D ◽  
Dual Action ◽  
The Common ◽  
Continued Use

ABSTRACT β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyze their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Coproduction of MBLs and SBLs in resistant infections is thus of major clinical concern. The development of “dual-action” inhibitors, targeting both SBLs and MBLs, is of interest, but this is considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactamases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase CTX-M-15, the class C enzyme AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolyzing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small-molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis.

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