scholarly journals Continuing Challenges for the Clinical Laboratory for Detection of Carbapenem-Resistant Enterobacteriaceae

2015 ◽  
Vol 53 (12) ◽  
pp. 3712-3714 ◽  
Author(s):  
Romney M. Humphries ◽  
James A. McKinnell
Keyword(s):  
Active Surveillance ◽  
Antimicrobial Susceptibility ◽  
Clinical Microbiology ◽  
Clinical Laboratory ◽  
Research Use ◽  
Antimicrobial Susceptibility Test ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surveillance Specimens ◽  
Carbapenem Resistant Enterobacteriaceae

Detecting carbapenem-resistantEnterobacteriaceae(CRE) can be difficult. In particular, the absence of FDA-cleared automated antimicrobial susceptibility test (AST) devices that use revised Clinical and Laboratory Standards Institute (CLSI) carbapenem breakpoints forEnterobacteriaceaeand the lack of active surveillance tests hamper the clinical laboratory. In this issue of theJournal of Clinical Microbiology, Lau and colleagues (A. F. Lau, G. A. Fahle, M. A. Kemp, A. N. Jassem, J. P. Dekker, and K. M. Frank, J Clin Microbiol 53:3729–3737, 2015,http://dx.doi.org/10.1128/JCM.01921-15) evaluate the performance of a research-use-only PCR for the detection of CRE in rectal surveillance specimens.

scholarly journals Performance of Vitek 2 for Antimicrobial Susceptibility Testing of Enterobacteriaceae with Vitek 2 (2009 FDA) and 2014 CLSI Breakpoints

2014 ◽  
Vol 53 (3) ◽  
pp. 816-823 ◽  
Author(s):  
April M. Bobenchik ◽  
Eszter Deak ◽  
Janet A. Hindler ◽  
Carmen L. Charlton ◽  
Romney M. Humphries
Keyword(s):  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Test System ◽  
Broth Microdilution ◽  
Antimicrobial Susceptibility Test ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Clinical Laboratories ◽  
Vitek 2

Vitek 2 (bioMérieux Inc., Durham, NC) is a widely used commercial antimicrobial susceptibility test system. We compared the MIC results obtained using the Vitek 2 AST-GN69 and AST-XN06 cards to those obtained by CLSI broth microdilution (BMD) for 255 isolates ofEnterobacteriaceae, including 25 isolates of carbapenem-resistantEnterobacteriaceae. In total, 25 antimicrobial agents were examined. For 10 agents, the MIC data were evaluated using two sets of breakpoints: (i) the Vitek 2 breakpoints, which utilized the 2009 FDA breakpoints at the time of the study and are equivalent to the 2009 CLSI M100-S19 breakpoints, and (ii) the 2014 CLSI M100-S24 breakpoints. There was an overall 98.7% essential agreement (EA). The categorical agreement was 95.5% (CA) using the Vitek 2 breakpoints and 95.7% using the CLSI breakpoints. There was 1 very major error (VME) (0.05%) observed using the Vitek 2 breakpoints (cefazolin) and 8 VMEs (0.5%) using the CLSI breakpoints (2 each for aztreonam, cefepime, and ceftriaxone, and 1 for cefazolin and ceftazidime). Fifteen major errors (MEs) (0.4%) were noted using the Vitek 2 breakpoints and 8 (0.5%) using the CLSI breakpoints. Overall, the Vitek 2 performance was comparable to that of BMD for testing a limited number ofEnterobacteriaceaecommonly isolated by clinical laboratories. Ongoing studies are warranted to assess performance in isolates with emerging resistance.

scholarly journals Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

2016 ◽  
Vol 60 (10) ◽  
pp. 6425-6429 ◽  
Author(s):  
Pranita D. Tamma ◽  
Yanjie Huang ◽  
Belita N. A. Opene ◽  
Patricia J. Simner
Keyword(s):  
Infection Control ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Rapid Spread ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACTCarbapenemase-producing (CP)Enterobacteriaceaeare largely responsible for the rapid spread of carbapenem-resistantEnterobacteriaceae(CRE). Distinguishing CP-CRE from non-CP-CRE has important infection control implications. In a cohort of 198 CRE isolates, for isolates that remained susceptible or intermediate to some carbapenem antibiotics, an ertapenem MIC of 0.5 μg/ml and meropenem, imipenem, and doripenem MICs of 2 μg/ml were best able to distinguish CP-CRE from non-CP-CRE isolates.

scholarly journals Estimating the Size of the U.S. Market for New Antibiotics with Activity against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Cornelius J. Clancy ◽  
M. Hong Nguyen
Keyword(s):  
United States ◽  
The United States ◽  
Content Type ◽  
Antibiotic Development ◽  
Development Models ◽  
Carbapenem Resistant ◽  
Financial Difficulties ◽  
New Antibiotics ◽  
The U.S ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT New antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin in the United States totaled $101 million from February 2018 to January 2019. We estimate that the current annual U.S. market for new anti-CRE antibiotics is $289 million (range, $169 to $439 million). Without new antibiotic development models and/or reimbursement reform, the majority of anti-CRE drugs will be commercially inviable.

scholarly journals Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Thomas Nolan ◽  
Jonathan Parkinson ◽  
Debora Rubio-Aparicio ◽  
...  
Keyword(s):  
Body Weight ◽  
Lung Infection ◽  
Infection Model ◽  
Bacterial Killing ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Infection Models ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae. The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

scholarly journals Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Yunliang Zhang ◽  
Ankita Kashikar ◽  
C. Adam Brown ◽  
Gerald Denys ◽  
Karen Bush
Keyword(s):  
Escherichia Coli ◽  
Health Care ◽  
Gene Duplication ◽  
Insertion Sequence ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Health Care Centers ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.

scholarly journals Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
William R. Wilson ◽  
Ellen G. Kline ◽  
Chelsea E. Jones ◽  
Kristin T. Morder ◽  
Roberta T. Mettus ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Strip Testing ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.

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