Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres

2019 ◽  
Vol 74 (10) ◽  
pp. 2938-2942 ◽  
Author(s):  
Zeb Khan ◽  
Alejandro Iregui ◽  
David Landman ◽  
John Quale
Keyword(s):  
New York ◽  
Pseudomonas Aeruginosa ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Resistance Mechanisms ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Excellent Activity ◽  
Susceptibility Tests

Abstract Background The combination of cefepime and zidebactam (WCK5222), a novel β-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. Objectives To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. Methods Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). Results More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria). Conclusions Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.

scholarly journals Activity of Meropenem with a Novel Broader-Spectrum β-Lactamase Inhibitor, WCK 4234, against Gram-Negative Pathogens Endemic to New York City

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John Quale
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT WCK 4234 is a novel diazabicyclooctane with potent inhibitory activity against class A and D carbapenemases and class C enzymes. We examined the in vitro activity of meropenem plus WCK 4234 (4 or 8 μg/ml) against Gram-negative pathogens from New York City. Three groups of isolates were analyzed: a contemporary collection of isolates, a collection of known carbapenem-resistant isolates, and a collection of isolates with defined resistance mechanisms. From the contemporary collection, we found (i) that all Enterobacteriaceae were susceptible to meropenem plus WCK 4234, (ii) that susceptibility rates for Acinetobacter baumannii were 56.5% for meropenem alone, 82.6% with 4 μg/ml WCK 4234, and 95.7% with 8 μg/ml WCK 4234, and (iii) that WCK 4234 had a modest effect on susceptibility of Pseudomonas aeruginosa. Against a collection of carbapenem-resistant isolates, the addition of WCK 4234 to meropenem (i) restored meropenem susceptibility against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates, (ii) improved susceptibility against A. baumannii, and (iii) had a negligible effect against P. aeruginosa. When tested against isolates with defined mechanisms of resistance, MICs of meropenem plus WCK 4234 were higher for K. pneumoniae with blaKPC albeit well below the susceptibility breakpoint; efflux systems or porins did not correlate with susceptibility. For A. baumannii, MICs of meropenem plus WCK 4234 did not correlate with efflux systems, outer membrane protein, blaampC, or blaoxa-51; however, MICs were higher in isolates with extended-spectrum β-lactamases (ESBLs). For P. aeruginosa, isolates with relatively higher MICs of meropenem plus WCK 4234 had increased expression of ampC. WCK 4234 is a potent β-lactamase inhibitor that, when combined with meropenem, displays promising activity against multidrug-resistant pathogens.

Reduction in the prevalence of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in New York City

2015 ◽  
Vol 43 (6) ◽  
pp. 650-652 ◽  
Author(s):  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
Clayton Charles ◽  
...  
Keyword(s):  
New York ◽  
Pseudomonas Aeruginosa ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Carbapenem Resistant

scholarly journals Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City

2015 ◽  
Vol 59 (8) ◽  
pp. 5029-5031 ◽  
Author(s):  
Amabel Lapuebla ◽  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
New York ◽  
Pseudomonas Aeruginosa ◽  
New York City ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Added Benefit

ABSTRACTImipenem with relebactam was active againstEscherichia coli,Klebsiella pneumoniae, andEnterobacterspp., includingK. pneumoniaecarbapenemase (KPC)-producing isolates. Loss of OmpK36 in KPC-producingK. pneumoniaeisolates affected the susceptibility of this combination. Enhanced activity was evident againstPseudomonas aeruginosa, including isolates with depressedoprDand increasedampCexpression. However, the addition of relebactam to imipenem did not provide added benefit againstAcinetobacter baumannii. The combination of imipenem with relebactam demonstrated activity against KPC-producingEnterobacteriaceaeand multidrug-resistantP. aeruginosa.

scholarly journals Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City

2014 ◽  
Vol 59 (3) ◽  
pp. 1802-1805 ◽  
Author(s):  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
David Landman ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Acinetobacter Baumannii ◽  
York City ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type

ABSTRACTEravacycline demonstratedin vitroactivity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90values, respectively, forEscherichia coliof 0.12/0.5 μg/ml,Klebsiella pneumoniaeof 0.25/1 μg/ml,Enterobacter aerogenesof 0.25/1 μg/ml,Enterobacter cloacae0.5/1 μg/ml, andAcinetobacter baumanniiof 0.5/1 μg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. ForA. baumannii, eravacycline MICs correlated with increased expression of theadeBgene.

scholarly journals 695. Activity of Imipenem–Relebactam and Ceftolozane–Tazobactam Against a Contemporary Collection of Gram-Negative Bacteria from New York City

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S315
Author(s):  
Alejandro Iregui ◽  
Zeb Khan ◽  
David Landman ◽  
John M Quale
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Agar Dilution

Abstract Background Carbapenem-resistant Gram-negative bacteria are important nosocomial pathogens, and therapeutic options are often limited. Methods Clinical isolates were gathered during a surveillance study in 2017 involving 7 hospitals in Brooklyn, NY. Isolates underwent susceptibility testing using the agar dilution method; for the combination of imipenem-relebactam and ceftolozane-tazobactam, the concentrations of relebactam and tazobactam were fixed at 4 µg/mL. Breakpoints were defined according to CLSI criteria; for imipenem-relebactam, the breakpoint of imipenem was utilized. Isolates were screened by PCR for common carbapenemases. Results Overall susceptibility patterns are given in the Table. Of 1805 isolates of E. coli (including 4 with blaKPC), 100% were susceptible to imipenem and imipenem-relebactam. Of 503 isolates of K. pneumoniae (including 19 isolates with blaKPC), all were susceptible to imipenem-relebactam. Of 171 isolates of Enterobacter spp. (including 3 with blaKPC), 100% were susceptible to imipenem-relebactam. Of 260 isolates of P. aeruginosa, 96% were susceptible to imipenem-relebactam and nearly all to ceftolozane-tazobactam. Against A. baumannii, the activity of imipenem-relebactam was the same as imipenem and the ceftolozane-tazobactam MIC was ≤ 4 µg/mL in 65% of isolates. Conclusion Imipenem-relebactam possesses promising activity against multidrug-resistant Enterobacteriaceae endemic to New York City. Ceftolozane-tazobactam demonstrated excellent activity against P. aeruginosa, including isolates resistant to carbapenems. Disclosures All authors: No reported disclosures.

scholarly journals Complete Sequence of ablaKPC-2-Harboring IncFIIK1Plasmid from a Klebsiella pneumoniae Sequence Type 258 Strain

2013 ◽  
Vol 57 (3) ◽  
pp. 1542-1545 ◽  
Author(s):  
Liang Chen ◽  
Kalyan D. Chavda ◽  
Roberto G. Melano ◽  
Michael R. Jacobs ◽  
Michael H. Levi ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Nucleotide Sequence ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Complete Sequence ◽  
Sequence Type ◽  
Content Type ◽  
City Area ◽  
Carbapenem Resistant

ABSTRACTWe report the nucleotide sequence of a novelblaKPC-2-harboring IncFIIK1plasmid, pBK32179, isolated from a carbapenem-resistantKlebsiella pneumoniaeST258 strain from a New York City patient. pBK32179 is 165 kb long, consists of a large backbone of pKPN3-like plasmid, and carries an 18.5-kbblaKPC-2-containing element that is highly similar to plasmid pKpQIL. pBK32179-like plasmids were identified in 8.3% of strains in a collection of 96K. pneumoniaeisolates from hospitals in the New York City area.

scholarly journals Detection of mcr-1-Carrying Escherichia coli Causing Bloodstream Infection in a New York City Hospital: Avian Origins, Human Concerns?

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Nenad Macesic ◽  
Daniel Green ◽  
Zheng Wang ◽  
Sean B. Sullivan ◽  
Kevin Shim ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
New York ◽  
New York City ◽  
York City ◽  
The United States ◽  
Genomic Sequencing ◽  
City Hospital ◽  
Gram Negative ◽  
E Coli

Abstract The spread of mcr-1 in the United States remains poorly defined. mcr-1-producing Escherichia coli that also carried blaSHV-12 was detected in a hospitalized patient. No additional cases were identified during screening of 801 Gram-negative isolates. Genomic sequencing identified an IncX4 mcr-1- harboring plasmid and ST117 clonal background associated with avian pathogenic E coli.

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