Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007–09

Davies, Todd A.; Queenan, Anne Marie; Morrow, Brian J.; Shang, Wenchi; Amsler, Karen; He, Wenping; Lynch, A. Simon; Pillar, Chris M.; Flamm, Robert K.

doi:10.1093/jac/dkr290

Cited by 88 publications

(68 citation statements)

References 54 publications

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“…Forty-nine A. baumannii isolates had imipenem MICs of Ն2 mg/liter, of which 18 (10%) were carbapenem intermediate or carbapenem resistant. More recently, imipenem nonsusceptibility rates of 34 to 75% were reported and confirm the increasing carbapenem resistance seen in this species (1,8,12).…”

Section: Resultssupporting

confidence: 61%

“…Therefore, the acquisition of ISAba1 by A. baumannii has occurred earlier than previously described and may have represented the first step in the evolution of resistance against the carbapenems. Several recent studies investigating carbapenem-resistant A. baumannii from the United States have shown ISAba1 to be associated with bla OXA-51 in 46 to 65% of isolates (1,8).…”

Section: Resultsmentioning

confidence: 99%

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Molecular Epidemiology of Acinetobacter baumannii Bloodstream Isolates Obtained in the United States from 1995 to 2004 Using rep-PCR and Multilocus Sequence Typing

et al. 2012

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Molecular Epidemiology of Acinetobacter baumannii Bloodstream Isolates Obtained in the United States from 1995 to 2004 Using rep-PCR and Multilocus Sequence Typing

et al. 2012

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“…Preliminary experiments with MacConkey broth in our laboratory demonstrated a 30 to 50% reduction in viable counts of several P. aeruginosa isolates on MacConkey agar versus sheep blood agar after overnight incubation in MacConkey broth, providing support for this hypothesis (data not shown). The bla VIM determinants have also been detected in a number of nonfermenting organisms in the United States, including P. aeruginosa and A. baumannii (38). To date, there have been no reports documenting the spread of bla KPC or bla VIM to anaerobic flora, but this remains a possible explanation of the results.…”

Section: Discussionmentioning

confidence: 99%

Detection of Colonization by Carbapenemase-Producing Gram-Negative Bacilli in Patients by Use of the Xpert MDRO Assay

Tenover¹,

Cantón

Kop³

et al. 2013

J Clin Microbiol

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cDetecting colonization of patients with carbapenemase-producing bacteria can be difficult. This study compared the sensitivity and specificity of a PCR-based method (Xpert MDRO) for detecting bla KPC , bla NDM , and bla VIM carbapenem resistance genes using GeneXpert cartridges to the results of culture with and without a broth enrichment step on 328 rectal, perirectal, and stool samples. The culture method included direct inoculation of a MacConkey agar plate on which a 10-g meropenem disk was placed and plating on MacConkey agar after overnight enrichment of the sample in MacConkey broth containing 1 g/ml of meropenem. Forty-three (13.1%) samples were positive by PCR for bla KPC and 11 (3.4%) were positive for bla VIM ; none were positive for bla NDM . The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PCR assay for bla KPC were 100%, 99.0%, 93.0%, and 100%, respectively, compared to broth enrichment culture and sequencing of target genes. The sensitivity, specificity, PPV, and NPV of the assay for bla VIM were 100%, 99.4%, 81.8%, and 100%, respectively. Since none of the clinical samples contained organisms with bla NDM , 66 contrived stool samples were prepared at various dilutions using three Klebsiella pneumoniae isolates containing bla NDM . The PCR assay showed 100% positivity at dilutions from 300 to 1,800 CFU/ml and 93.3% at 150 CFU/ml. The Xpert MDRO PCR assay required 2 min of hands-on time and 47 min to complete. Rapid identification of patients colonized with carbapenemase-producing organisms using multiplex PCR may help hospitals to improve infection control activities.

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“…However, different strains possessing the same KPC gene show widely differing levels of inhibition by carbapenems, with MICs spanning the range of susceptibility to frank resistance. 13 Furthermore, transfer of carbapenemase-containing plasmids into E. coli K-12 is associated with a substantially lower MIC in the recipient. 14 These observations suggest that attributes of the host strain contribute substantially to the phenotypic expression of carbapenem resistance.…”

Section: Introductionmentioning

confidence: 99%

Validation of a High-Throughput Screening Assay for Identification of Adjunctive and Directly Acting Antimicrobials Targeting Carbapenem-Resistant Enterobacteriaceae

Smith

Kirby

2016

ASSAY and Drug Development Technologies

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We describe development and validation of a high-throughput screen (HTS) for identifying small molecules that restore the efficacy of carbapenems (adjunctives) and/or directly inhibit growth of carbapenem-resistant Enterobacteriaceae (CRE). Our HTS assay is based on a screen-counterscreen approach using a representative multidrug-resistant CRE strain, Klebsiella pneumoniae BIDMC12A. Specifically, we tested the ability of small molecules to inhibit bacterial growth in the presence (screen) or absence (counterscreen) of meropenem, a representative carbapenem antibiotic. Primary screening of 11,698 known bioactive compounds identified 14 with adjunctive activity and 79 with direct antimicrobial effect. Secondary screening identified triclosan as a strongly synergistic meropenem adjunctive (fractional inhibitory concentration = 0.48) and confirmed azidothymidine (AZT) (minimal inhibitory concentration [MIC] = 4 lg mL ) as potent direct antimicrobials. Spectrum of activity of AZT and spectinomycin was tested against a collection of 103 representative Enterobacteriaceae strains (&50% CRE). AZT, a nucleoside analog used to treat human immunodeficiency virus, demonstrated an MIC 50 of 2 lg mL -1 . Spectinomycin, an antibiotic used to treat gonorrhea, had an MIC 50 of 32 lg mL -1 . Therefore, a significant percentage of CRE strains appeared relatively susceptible to these antimicrobials. These data identified AZT and spectinomycin as available agents warranting further study for potential treatment of multidrug-resistant CRE infection. Our results provide proof of principle and impetus for performing a largescale HTS for discovery of novel, small-molecule adjunctives and antibacterial agents directly targeting CRE.

show abstract

Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007–09

Cited by 88 publications

References 54 publications

Molecular Epidemiology of Acinetobacter baumannii Bloodstream Isolates Obtained in the United States from 1995 to 2004 Using rep-PCR and Multilocus Sequence Typing

Molecular Epidemiology of Acinetobacter baumannii Bloodstream Isolates Obtained in the United States from 1995 to 2004 Using rep-PCR and Multilocus Sequence Typing

Detection of Colonization by Carbapenemase-Producing Gram-Negative Bacilli in Patients by Use of the Xpert MDRO Assay

Validation of a High-Throughput Screening Assay for Identification of Adjunctive and Directly Acting Antimicrobials Targeting Carbapenem-Resistant Enterobacteriaceae

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