Multicenter clinical evaluation of VITEK® 2 meropenem-vaborbactam for susceptibility testing of Enterobacterales and Pseudomonas aeruginosa

The carbapenem/beta-lactamase inhibitor (meropenem-vaborbactam; MEV) used to treat complicated urinary tract infections and pyelonephritis in adults was approved in 2017 by the U.S. Food and Drug Administration (FDA). We evaluated VITEK 2 MEV (bioMérieux, Durham, NC) compared to the reference broth microdilution (BMD) method. Of 449 Enterobacterales isolates analyzed per FDA/CLSI breakpoints, overall performance was 98.2% Essential Agreement (EA), 98.7% Category Agreement (CA), and 0% Very Major Errors (VME) or Major Errors (ME). For FDA intended for use 438 Enterobacterales isolates, performance was 98.2% EA, 98.6% CA, and 0% VME or ME. Evaluable EA was 81.0% but with only 42 on-scale evaluable results. Individual species demonstrated EA and CA rates ≥ 90% without any VME or ME. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, overall VITEK 2 MEV performance for Enterobacterales and Pseudomonas aeruginosa demonstrated 97.3% EA, 99.2% CA, 2.3% VME, and 0.6% ME (after error resolution: 97.3% EA, 99.4% CA, 2.2% VME, and 0.4% ME) compared to the reference BMD method. Performance for P. aeruginosa included 92.2% EA, 97.4% CA, 0% VME, and 3.0% ME (after error resolution: 92.2% EA, 98.7% CA, 0% VME, and 1.5% ME). Performance for Enterobacterales included 98.2% EA, 99.6% CA, 3.0% VME, and 0.2% ME. Evaluable EA was 80.6% but due to only 67 evaluable results. These findings support VITEK 2 MEV as an accurate automated system for MEV susceptibility testing of Enterobacterales and P. aeruginosa and could be an alternate solution to the manual labor intensive reference BMD method.

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Multicenter Evaluation of Ceftazidime-Avibactam Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa on the VITEK® 2 System

Journal of Clinical Microbiology ◽

10.1128/jcm.01870-20 ◽

2020 ◽

Author(s):

Romney Humphries ◽

Shelley Campeau ◽

Thomas E. Davis ◽

Kristin J. Nagaro ◽

Vincent J. LaBombardi ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Error Rate ◽

Susceptibility Testing ◽

Reference Method ◽

Error Rates ◽

Performance Criteria ◽

Test Results ◽

Major Error ◽

Overall Performance ◽

Vitek 2

In this multisite study, VITEK® 2 AST-Gram-Negative Ceftazidime-Avibactam (CZA) test results for 1073 isolates (866 Enterobacterales and 207 Pseudomonas aeruginosa) were compared to the Clinical & Laboratory Standards Institute (CLSI) broth microdilution (BMD) reference method. The results were analyzed for essential agreement (EA), category agreement (CA), major error rates, and very major error rates following FDA/ISO performance criteria using the FDA-recognized CLSI/EUCAST breakpoints (S ≤8/4 μg/ml and R ≥16/4 μg/ml). The overall EA was 94.5% (1014/1073) and CA was 98.7% (1059/1073). No very major errors were reported. The major error rate was 1.4% (14/998). Out of 14 major errors, 9 were within EA. Based on the EA and lack of an intermediate category for CZA, the adjusted major error rate for FDA criteria was 0.5% (5/998). The performance for ISO criteria after error resolutions included EA 94.5% (1014/1073), CA 98.9% (1061/1073), major error 1.2% (12/998), and no very major error. Vitek 2 met the ISO and FDA criteria of ≥95% reproducibility and ≥95% quality control (QC) results within acceptable ranges for QC organisms. Vitek 2 overall performance for Enterobacterales and P. aeruginosa met or exceeded the FDA and ISO performance criteria and thus is a reliable alternative to BMD reference method for routine CZA susceptibility testing.

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Multicenter Clinical Evaluation of Etest Meropenem-Vaborbactam (bioMérieux) for Susceptibility Testing of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa

Journal of Clinical Microbiology ◽

10.1128/jcm.01205-19 ◽

2019 ◽

Vol 58 (1) ◽

Cited By ~ 1

Author(s):

Sophonie Jean ◽

Sheri Garrett ◽

Claire Anglade ◽

Laurence Bridon ◽

Leanne Davies ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Susceptibility Testing ◽

Reference Method ◽

Individual Species ◽

Beta Lactamase ◽

Content Type ◽

European Committee ◽

Tract Infections ◽

Inhibitor Combination ◽

Lactamase Inhibitor

ABSTRACT Meropenem-vaborbactam (MEV) is a novel carbapenem–beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including pyelonephritis, in adults. In this study, we evaluated the performance of Etest MEV (bioMérieux, Marcy l’Etoile, France) compared to that of broth microdilution for 629 Enterobacterales and 163 Pseudomonas aeruginosa isolates. According to CLSI/FDA breakpoints, 13 Enterobacterales isolates (12 clinical and 1 challenge) were resistant to MEV. Overall, Etest MEV demonstrated 92.4% essential agreement (EA), 99.2% category agreement (CA), 0% very major errors (VME), 0% major errors (ME), and 0.8% minor errors (mE) with clinical and challenge isolates of Enterobacterales. Individual species demonstrated EA rates of ≥80%, with the exception of Proteus mirabilis, for which clinical and challenge isolates demonstrated 34.3% EA, 97.1% CA, 0% ME, and 2.9% mE, precluding the use of Etest MEV with this species. Excluding P. mirabilis, MEV Etest MEV demonstrated 95.8% EA, 99.3% CA, 0% VME, 0% ME, and 0.7% mE with Enterobacterales isolates. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, Etest MEV performance with clinical (16 MEV resistant) and challenge (12 MEV resistant) isolates of Enterobacterales (excluding P. mirabilis) and P. aeruginosa demonstrated an unacceptably high VME rate of 7.1% despite 95.2% EA, 99.2% CA, and 0.5% ME compared to the reference method. In conclusion, we report that Etest MEV is accurate and reproducible for MEV susceptibility testing for P. aeruginosa and Enterobacterales, with the exception of P. mirabilis, using CLSI/FDA breakpoints. Etest MEV should not be used with P. mirabilis due to unacceptable analytical performance.

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Prospective Evaluation of Light Scatter Technology Paired with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Rapid Diagnosis of Urinary Tract Infections

Journal of Clinical Microbiology ◽

10.1128/jcm.00027-17 ◽

2017 ◽

Vol 55 (6) ◽

pp. 1802-1811 ◽

Cited By ~ 9

Author(s):

Sandra Montgomery ◽

Kiana Roman ◽

Lan Ngyuen ◽

Ana Maria Cardenas ◽

James Knox ◽

...

Keyword(s):

Susceptibility Testing ◽

Automated System ◽

Light Scatter ◽

Laser Desorption Ionization ◽

Ionization Time ◽

Maldi Tof Ms ◽

Maldi Tof ◽

Tract Infections ◽

Organism Identification ◽

Tof Ms

ABSTRACTUrinary tract infections are one of the most common reasons for health care visits. Diagnosis and optimal treatment often require a urine culture, which takes an average of 1.5 to 2 days from urine collection to results, delaying optimal therapy. Faster, but accurate, alternatives are needed. Light scatter technology has been proposed for several years as a rapid screening tool, whereby negative specimens are excluded from culture. A commercially available light scatter device, BacterioScan 216Dx (BacterioScan, Inc.), has recently been advertised for this application. Paired use of mass spectrometry (MS) for bacterial identification and automated-system-based susceptibility testing straight from the light scatter suspension might provide dramatic improvement in times to a result. The present study prospectively evaluated the BacterioScan device, with culture as the reference standard. Positive light scatter specimens were used for downstream rapid matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS organism identification and automated-system-based antimicrobial susceptibility testing. Prospective evaluation of 439 urine samples showed a sensitivity of 96.5%, a specificity of 71.4%, and positive and negative predictive values of 45.1% and 98.8%, respectively. MALDI-TOF MS analysis of the suspension after density-based selection yielded a sensitivity of 72.1% and a specificity of 96.9%. Antimicrobial susceptibility testing of the samples identified by MALDI-TOF MS produced an overall categorical agreement of 99.2%. Given the high sensitivity and negative predictive value of results obtained, BacterioScan 216Dx is a reasonable approach for urine screening and might produce negative results in as few as 3 h, with no downstream workup. Paired rapid identification and susceptibility testing might be useful when MALDI-TOF MS results in an organism identification, and it might decrease the time to a result by more than 24 h.

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Multicenter Evaluation of the Etest Gradient Diffusion Method for Ceftolozane-Tazobactam Susceptibility Testing of Enterobacteriaceae and Pseudomonas aeruginosa

Journal of Clinical Microbiology ◽

10.1128/jcm.00717-18 ◽

2018 ◽

Vol 56 (9) ◽

Cited By ~ 2

Author(s):

Adam L. Bailey ◽

Tom Armstrong ◽

Hari-Prakash Dwivedi ◽

Gerald A. Denys ◽

Janet Hindler ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Susceptibility Testing ◽

Clinical Isolates ◽

Diffusion Method ◽

Beta Lactam ◽

Content Type ◽

Gradient Diffusion ◽

Tract Infections ◽

Abdominal Infections ◽

Inhibitor Combination

ABSTRACT Ceftolozane-tazobactam (C/T) is a novel beta-lactam–beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration in 2014 for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections. In this study, we evaluated the performance of the C/T Etest, a gradient diffusion method. C/T Etest was compared to broth microdilution (BMD) for 51 Enterobacteriaceae challenge isolates and 39 Pseudomonas aeruginosa challenge isolates at three clinical sites. Essential agreement (EA) between the methods ranged from 47 to 49/51 (92.2 to 96.1%) for the Enterobacteriaceae, and categorical agreement (CA) ranged from 49 to 51/51 (96.1 to 100.0%). EA and CA for P. aeruginosa were 100% at all sites. The C/T Etest was also compared to BMD for susceptibility testing on 966 clinical isolates (793 Enterobacteriaceae, including 167 Klebsiella pneumoniae and 159 Escherichia coli isolates, in addition to 173 P. aeruginosa isolates) collected at four clinical sites. EA between Etest and BMD was 96.9% for Enterobacteriaceae isolates and 98.8% for P. aeruginosa isolates. Within the Enterobacteriaceae, isolates from each species examined had >96% CA. For the clinical isolates, no very major errors were identified but two major errors were found (one for K. pneumoniae and one for Providencia rettgeri). By BMD, 47.0% of Enterobacteriaceae and 46.2% of P. aeruginosa challenge strains were nonsusceptible to C/T by CLSI breakpoint criteria; 8.2% of clinical Enterobacteriaceae isolates and 12.1% of clinical P. aeruginosa isolates were nonsusceptible to C/T by CLSI breakpoint criteria. In conclusion, Etest is accurate and reproducible for C/T susceptibility testing of Enterobacteriaceae and P. aeruginosa.

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