Emergence of Carbapenem-Resistant Klebsiella Species Possessing the Class A Carbapenem-Hydrolyzing KPC-2 and Inhibitor-Resistant TEM-30  -Lactamases in New York City

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.

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Carbapenem-Resistant Klebsiella pneumoniae Infection in Three New York City Hospitals Trended Downwards From 2006 to 2014

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw222 ◽

2016 ◽

Vol 3 (4) ◽

Cited By ~ 12

Author(s):

Sun O. Park ◽

Jianfang Liu ◽

E. Yoko Furuya ◽

Elaine L. Larson

Keyword(s):

New York ◽

New York City ◽

Klebsiella Pneumoniae ◽

York City ◽

Trend Test ◽

Anatomical Site ◽

Carbapenem Resistant ◽

Annual Trends ◽

Armitage Trend Test ◽

Hospital Acquired

Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a rising public health threat since its first outbreaks in New York City (NYC) in the early 2000s. We investigated annual trends of CRKP infection in hospital-acquired infections (HAIs) and community-onset infections (COIs) treated in 3 NYC hospitals from 2006 to 2014. Methods We extracted K pneumoniae infection data including carbapenem susceptibility and anatomical sites, compared clinical characteristics between CRKP and carbapenem-susceptible K pneumoniae infections, and determined CRKP infection proportions in total K pneumoniae infections in HAI and COI to identify statistically significant trends from 2006 to 2014 using the Cochran-Armitage trend test. Results Carbapenem-resistant K pneumoniae contributed 17.3% (601 of 3477) of hospital-acquired K pneumoniae infection compared with 7.7% (149 of 1926) in COI from 2006 to 2014. Carbapenem-resistant K pneumoniae proportions in HAI and COI were positively correlated over time (r = 0.83, P < .01), and there were downward annual trends of CRKP proportions from 2006 to 2014 in both HAI and COI (25.8% to 10.5% in HAI, P < .001; 13.6% to 3.1% in COI, P < .001). By anatomical site, significant downward annual trends were present only in urinary tract infection (P < .001 for both HAI and COI) from 2006 to 2014. Conclusions Annual trends of CRKP proportions from 2006 to 2014 were downward in both HAI and COI, and HAI and COI were positively correlated. Efforts to reduce and prevent CRKP infections in both hospital and community settings were successful and warrant continuation.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01666-19 ◽

2019 ◽

Vol 64 (1) ◽

Cited By ~ 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.

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

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz294 ◽

2019 ◽

Vol 74 (10) ◽

pp. 2938-2942 ◽

Cited By ~ 8

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.

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Comment on: CG258Klebsiella pneumoniaeisolates without β-lactam resistance at the onset of the carbapenem-resistant Enterobacteriaceae epidemic in New York City

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dky472 ◽

2018 ◽

Vol 74 (3) ◽

pp. 831-833 ◽

Cited By ~ 1

Author(s):

Kelly L Wyres ◽

Margaret M C Lam ◽

Kathryn E Holt

Keyword(s):

New York ◽

New York City ◽

York City ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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High-Level Carbapenem Resistance in a Klebsiella pneumoniae Clinical Isolate Is Due to the Combination of blaACT-1 β-Lactamase Production, Porin OmpK35/36 Insertional Inactivation, and Down-Regulation of the Phosphate Transport Porin PhoE

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00285-06 ◽

2006 ◽

Vol 50 (10) ◽

pp. 3396-3406 ◽

Cited By ~ 141

Author(s):

Frank M. Kaczmarek ◽

Fadia Dib-Hajj ◽

Wenchi Shang ◽

Thomas D. Gootz

Keyword(s):

New York ◽

New York City ◽

Klebsiella Pneumoniae ◽

York City ◽

Carbapenem Resistance ◽

Clinical Isolates ◽

Wild Type ◽

Down Regulation ◽

Carbapenem Resistant ◽

Insertional Inactivation

ABSTRACT Clinical isolates of Klebsiella pneumoniae resistant to carbapenems and essentially all other antibiotics (multidrug resistant) are being isolated from some hospitals in New York City with increasing frequency. A highly related pair of K. pneumoniae strains isolated on the same day from one patient in a hospital in New York City were studied for antibiotic resistance. One (KP-2) was resistant to imipenem, meropenem, and sulopenem (MICs of 16 to 32 μg/ml) while the other (KP-1) was susceptible (MIC of 0.5 μg/ml); both contained the bla ACT-1, bla SHV-1, and bla TEM-1 β-lactamases. bla ACT-1 in both strains was encoded on a large ∼150-kb plasmid. Both isolates contained an identical class 1 integron encoding resistance to aminoglycosides and chloramphenicol. They each had identical insertions in ompK35 and ompK36, resulting in disruption of these key porin genes. The carbapenem-resistant and -susceptible isolates were extensively studied for differences in the structural and regulatory genes for the operons acrRAB, marORAB, romA-ramA, soxRS, micF, micC, phoE, phoBR, rpoS, and hfq. No changes were detected between the isolates except for a significant down-regulation of ompK37, phoB, and phoE in KP-2 as deduced from reverse transcription-PCR analysis of mRNA and polyacrylamide gel electrophoresis separation of outer membrane proteins. Backcross analysis was conducted using the wild-type phoE gene cloned into the vector pGEM under regulation of its native promoter as well as the lacZ promoter following transformation into the resistant KP-2 isolate. The wild-type gene reversed carbapenem resistance only when under control of the heterologous lacZ promoter. In the background of ompK35-ompK36 gene disruption, the up-regulation of phoE in KP-1 apparently compensated for porin loss and conferred carbapenem susceptibility. Down-regulation of phoE in KP-2 may represent the normal state of this gene, or it may have been selected from KP-1 in vivo under antibiotic pressure, generating the carbapenem-resistant clone. This is the first study in the Enterobacteriaceae where expression of the phosphate-regulated PhoE porin has been associated with resistance to antimicrobials. Our results with this pair of Klebsiella clinical isolates highlight the complex and evolving nature of multiple drug resistance in this species.

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Rapid Spread of Carbapenem-Resistant Klebsiella pneumoniae in New York City

Archives of Internal Medicine ◽

10.1001/archinte.165.12.1430 ◽

2005 ◽

Vol 165 (12) ◽

pp. 1430 ◽

Cited By ~ 388

Author(s):

Simona Bratu ◽

David Landman ◽

Robin Haag ◽

Rose Recco ◽

Antonella Eramo ◽

...

Keyword(s):

New York ◽

New York City ◽

Klebsiella Pneumoniae ◽

York City ◽

Carbapenem Resistant ◽

Rapid Spread

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.763 ◽

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.

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