Publications by authors named "Kathy Fauntleroy"

8 Publications

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Multidrug-resistant Pseudomonas aeruginosa in healthcare facilities in Port-au-Prince, Haiti.

J Glob Antimicrob Resist 2021 Mar 1;25:60-65. Epub 2021 Mar 1.

Center for Global Health, Weill Cornell Medicine, New York, NY, USA.

Objectives: Pseudomonas aeruginosa is a leading cause of opportunistic infections worldwide, particularly in healthcare settings, and frequently demonstrates resistance to commonly prescribed antimicrobials. Carbapenem resistance is prevalent worldwide, however there are currently limited data available from Haiti. The aim of this study was to characterise and document this phenotype in Port-au-Prince, Haiti, to further inform the need for appropriate infection control, empirical treatment guidelines and laboratory screening measures, both in Haiti and globally.

Methods: A total of 50 P. aeruginosa isolates were characterised by multilocus sequence typing (MLST) and antimicrobial susceptibility testing, of which 8 isolates were also subjected to whole-genome sequencing (WGS) to identify potential genetic correlations of phenotypic resistance.

Results: By MLST, 23 sequence types (STs) were identified, including 13 new STs. Nineteen isolates belonged to a single, previously characterised ST (ST654), all of which demonstrated a multidrug-resistant phenotype, including resistance to meropenem, imipenem and ceftazidime; two isolates were also resistant to colistin. WGS revealed the presence of genes encoding several previously characterised resistance determinants in ST654; notably ACC(6')-Ib3-cr and GES-7. Metallo-β-lactamase genes (bla) were also detected in three isolates.

Conclusion: These findings confirm that drug-resistant clones of P. aeruginosa are present in Haiti, supporting the need for appropriate screening and control measures and confirming that drug-resistant micro-organisms pose a global threat. Further investigations are required to guide appropriate antimicrobial prescribing in this region.
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http://dx.doi.org/10.1016/j.jgar.2021.02.016DOI Listing
March 2021

Comparison of Two High-Throughput Reverse Transcription-PCR Systems for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

J Clin Microbiol 2020 Jul 23;58(8). Epub 2020 Jul 23.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-PCR (RT-PCR) assays have received Emergency Use Authorization from the U.S. Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays, with a collection of 389 nasopharyngeal specimens. The overall agreement between the platforms was 96.4% (375/389). Cohen's kappa analysis rated the strength of agreement between the two platforms as "almost perfect" (κ = 0.922; standard error, 0.051). Furthermore, there was no significant difference between corresponding cycle threshold values generated on the two systems ( value = 0.88; Student's test). Taken together, these data imply that the two platforms can be considered comparable in terms of their clinical performance. We believe that this information will be useful for those who have already adopted these platforms or are seeking to implement high-throughput RT-PCR testing to stem the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1128/JCM.00890-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383551PMC
July 2020

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

J Clin Microbiol 2020 06 24;58(7). Epub 2020 Jun 24.

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

NG-Test Carba 5 is a rapid 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 (= 3) in the United States, where 309 and 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 and 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 and 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.
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http://dx.doi.org/10.1128/JCM.00344-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315033PMC
June 2020

Spheroplast-Mediated Carbapenem Tolerance in Gram-Negative Pathogens.

Antimicrob Agents Chemother 2019 09 23;63(9). Epub 2019 Aug 23.

Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA

Antibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen can tolerate exposure to the typically bactericidal β-lactam antibiotics by assuming a spherical morphotype devoid of detectable cell wall material. However, it is unclear how widespread β-lactam tolerance is. Here, we tested a panel of clinically significant Gram-negative pathogens for their response to the potent, broad-spectrum carbapenem antibiotic meropenem. We show that clinical isolates of , , and , but not , exhibited moderate to high levels of tolerance of meropenem, both in laboratory growth medium and in human serum. Importantly, tolerance was mediated by cell wall-deficient spheroplasts, which readily recovered wild-type morphology and growth upon removal of antibiotic. Our results suggest that carbapenem tolerance is prevalent in clinically significant bacterial species, and we suggest that this could contribute to treatment failure associated with these organisms.
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http://dx.doi.org/10.1128/AAC.00756-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709500PMC
September 2019

Activity of Imipenem-Relebactam and Comparator Agents against Genetically Characterized Isolates of Carbapenem-Resistant Enterobacteriaceae.

Antimicrob Agents Chemother 2019 09 23;63(9). Epub 2019 Aug 23.

New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA

Carbapenem-resistant (CRE) strains are an urgent public health threat. We evaluated the activities of 19 antimicrobial agents, including imipenem-relebactam, against (i) 106 CRE bloodstream isolates that primarily expressed carbapenemase (KPC) and (ii) 20 OXA-48-like-expressing CRE isolates. Ninety-five percent of CRE bloodstream isolates were susceptible to imipenem-relebactam. In contrast to their comparable activities against KPC-producing CRE strains, ceftazidime-avibactam was more active against OXA-48-like CRE strains than was imipenem-relebactam (90% susceptible versus 15% susceptible).
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http://dx.doi.org/10.1128/AAC.00672-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709495PMC
September 2019

Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies.

Leuk Lymphoma 2013 Apr 14;54(4):799-806. Epub 2012 Sep 14.

Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent pathogens. However, little is known about their emergence in patients with hematologic malignancies. We identified 18 patients with hematologic malignancies over 3.5 years who developed bloodstream infections (BSIs) caused by CRE. Fourteen BSIs were caused by Klebsiella pneumoniae, three by Enterobacter cloacae, and one was polymicrobial. Initial empirical antimicrobial therapy was active in two patients (11%), and a median of 55 h elapsed between culture collection and receipt of an active agent. Ten patients (56%) died, including nine (69%) of 13 neutropenic patients, with a median of 4 days from culture collection until death. CRE isolates were analyzed for carbapenemase production, β-lactamase genes and outer membrane porin deletions and characterized by multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Carbapenem resistance mechanisms included Klebsiella pneumoniae carbapenemase production and CTX-M-15 production with an absent outer membrane porin protein. No isolate had ≥95% homology on PFGE, indicating a heterogeneous, non-outbreak population of isolates. CRE BSIs are emerging in patients with hematologic malignancies and are associated with ineffective initial empirical therapy, long delays in administration of active antimicrobials and high mortality rates. New diagnostic, therapeutic and preventive strategies for CRE infections in this vulnerable population are needed.
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http://dx.doi.org/10.3109/10428194.2012.723210DOI Listing
April 2013

Comparison of polymyxin B, tigecycline, cefepime, and meropenem MICs for KPC-producing Klebsiella pneumoniae by broth microdilution, Vitek 2, and Etest.

J Clin Microbiol 2011 May 2;49(5):1795-8. Epub 2011 Mar 2.

Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA.

We report MIC agreement and error rates between broth microdilution (BMD), Vitek 2, and Etest against 48 clinical KPC-producing Klebsiella pneumoniae isolates for polymyxin B, tigecycline, cefepime, and meropenem. Both commercial testing methods were useful for tigecycline testing; Etest provided a conservative estimate of polymyxin B susceptibility. We suggest that laboratories consider the supplemental use of reference BMD or Etest for cefepime and meropenem for susceptibility testing of KPC-producing K. pneumoniae, as Vitek 2 did not provide reliable results.
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http://dx.doi.org/10.1128/JCM.02534-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122677PMC
May 2011

Comparison of meropenem MICs and susceptibilities for carbapenemase-producing Klebsiella pneumoniae isolates by various testing methods.

J Clin Microbiol 2010 Jul 19;48(7):2402-6. Epub 2010 May 19.

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.

We describe the levels of agreement between broth microdilution, Etest, Vitek 2, Sensititre, and MicroScan methods to accurately define the meropenem MIC and categorical interpretation of susceptibility against carbapenemase-producing Klebsiella pneumoniae (KPC). A total of 46 clinical K. pneumoniae isolates with KPC genotypes, all modified Hodge test and bla(KPC) positive, collected from two hospitals in NY were included. Results obtained by each method were compared with those from broth microdilution (the reference method), and agreement was assessed based on MICs and Clinical Laboratory Standards Institute (CLSI) interpretative criteria using 2010 susceptibility breakpoints. Based on broth microdilution, 0%, 2.2%, and 97.8% of the KPC isolates were classified as susceptible, intermediate, and resistant to meropenem, respectively. Results from MicroScan demonstrated the most agreement with those from broth microdilution, with 95.6% agreement based on the MIC and 2.2% classified as minor errors, and no major or very major errors. Etest demonstrated 82.6% agreement with broth microdilution MICs, a very major error rate of 2.2%, and a minor error rate of 2.2%. Vitek 2 MIC agreement was 30.4%, with a 23.9% very major error rate and a 39.1% minor error rate. Sensititre demonstrated MIC agreement for 26.1% of isolates, with a 3% very major error rate and a 26.1% minor error rate. Application of FDA breakpoints had little effect on minor error rates but increased very major error rates to 58.7% for Vitek 2 and Sensititre. Meropenem MIC results and categorical interpretations for carbapenemase-producing K. pneumoniae differ by methodology. Confirmation of testing results is encouraged when an accurate MIC is required for antibiotic dosing optimization.
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http://dx.doi.org/10.1128/JCM.00267-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897473PMC
July 2010