Activity of Ceftazidime–Avibactam Against Clinical Isolates of Klebsiella pneumoniae, Including KPC-Carrying Isolates, Endemic to New York City

2018 ◽  
Vol 24 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Nyla Manning ◽  
Gregory Balabanian ◽  
Michael Rose ◽  
David Landman ◽  
John Quale
Keyword(s):  
New York ◽  
New York City ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Clinical Isolates

scholarly journals 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

2006 ◽  
Vol 50 (10) ◽  
pp. 3396-3406 ◽  
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.

scholarly journals Epidemiology of Resistance to Metronidazole in Clinical Isolates of Bacteroides fragilis in a New York City Hospital

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Sharon Vuppula ◽  
Sharon Vuppula ◽  
Carla Lee ◽  
Carla Lee ◽  
Henry Pollack
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Bacteroides Fragilis ◽  
Clinical Isolates ◽  
City Hospital

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 A Ceftazidime-Avibactam-Resistant and Carbapenem-Susceptible Klebsiella pneumoniae Strain Harboring blaKPC-14 Isolated in New York City

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Siqiang Niu ◽  
Kalyan D. Chavda ◽  
Jie Wei ◽  
Chunhong Zou ◽  
Steven H. Marshall ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
The United States ◽  
Genomic Sequencing ◽  
Content Type ◽  
Clinical Variants ◽  
Genetic Structures ◽  
Antibiotic Combination

ABSTRACT Ceftazidime-avibactam is a potent antibiotic combination against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Here, we describe a unique ceftazidime-avibactam-resistant and carbapenem-susceptible K. pneumoniae strain harboring a novel blaKPC-14 variant. This strain was isolated from a New York City patient in 2003, which predates the introduction of avibactam. Despite resistance to ceftazidime-avibactam, the strain was susceptible to imipenem-relebactam and meropenem-vaborbactam. Comprehensive genomic sequencing revealed that blaKPC-14 is harbored on an ST6 IncN plasmid associated with the early spread of blaKPC. IMPORTANCE KPC is currently the most common carbapenemase identified in the United States. More than 40 KPC variants have been described, of which KPC-2 and KPC-3 are the most frequent clinical variants. However, our understanding of the genetic structures and β-lactam resistance profiles of other novel KPC variants remains incomplete. Here, we report a novel blaKPC variant (blaKPC-14) and the complete genome sequence of blaKPC-14-harboring K. pneumoniae strain BK13048, which is susceptible to carbapenems but resistant to ceftazidime-avibactam. To the best of our knowledge, this is one of the earliest KPC-producing K. pneumoniae strains exhibiting resistance to ceftazidime-avibactam.

scholarly journals Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

2015 ◽  
Vol 53 (7) ◽  
pp. 2060-2067 ◽  
Author(s):  
Angela Gomez-Simmonds ◽  
Michelle Greenman ◽  
Sean B. Sullivan ◽  
Joshua P. Tanner ◽  
Madeleine G. Sowash ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Bloodstream Infections ◽  
Mortality Rates ◽  
Care Hospital ◽  
Content Type

Despite the growing importance of carbapenem-resistantKlebsiella pneumoniae(CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R)K. pneumoniae, and susceptibleK. pneumoniaeisolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of thewziandblaKPCgenes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. TheblaKPC-3gene (30%) was restricted to ST258/wzi154, whereasblaKPC-2(70%) was observed for severalwziallele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas theK. pneumoniaesusceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and thewzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.

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