scholarly journals Emergence of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam in a Widespread ST11 Carbapenem-Resistant Klebsiella pneumoniae Clone in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Xi Li ◽  
Jingjing Quan ◽  
Huanhuan Ke ◽  
Wenhao Wu ◽  
Yu Feng ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Tertiary Structure ◽  
Hydrolytic Activity ◽  
Clinical Settings ◽  
The Novel ◽  
S1 Nuclease ◽  
Carbapenem Resistant ◽  
Loop Region ◽  
Cloning Assay ◽  
Omega Loop

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection poses a great threat to public health worldwide, and KPC-2-producing strains are the main factors responsible for resistance to carbapenems in China. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with good activity against KPC-2 carbapenemase and is becoming the most important option for treating KPC-producing CRKP infection. Here, we report the emergence of a novel KPC-2 variant, designated KPC-74, produced by K. pneumoniae strain KP55, that conferred CZA resistance in a patient after CZA exposure. The novel blaKPC–74 variant showed a deletion of 6 nucleotides at positions 712–717 compared with blaKPC–2, and this deletion resulted in the consequent deletion of glycine and valine at positions 239 and 240. Antimicrobial susceptibility testing showed that KP55 presents multidrug resistance, including resistance to CZA and ertapenem, but is susceptible to imipenem, meropenem, and colistin. The blaKPC–74 gene was located on a plasmid, as determined by S1-nuclease pulsed-field gel electrophoresis followed by southern blotting, and confirmed to be 133,766 bp in length by whole-genome sequencing on both the Illumina and MinION platforms. The CZA resistance phenotype of the novel KPC variant was confirmed by both transformation of the blaKPC–74-harboring plasmid and a blaKPC–74 gene cloning assay, showing a 64-fold higher CZA minimum inhibitory concentration (MIC) than the recipient strains. The G239_V240del observed in KPC-74 was outside the omega-loop region but was still close to the active site Ser70 and omega-loop in the protein tertiary structure. The enzyme kinetic parameters and IC50 values further indicated that the hydrolytic activity of the KPC-74 enzyme against ceftazidime was potentiated twofold and that the affinity between KPC-74 and avibactam was alleviated 17-fold compared with that of the KPC-2 allele. This CZA resistance mediated by KPC-74 could be selected after CZA therapy and evolved to be more diverse and heterogeneous. Surveillance of CZA resistance is urgently needed in clinical settings.

scholarly journals Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae producing NDM-1 in Lebanon

2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
New Delhi ◽  
Beta Lactamase ◽  
The Novel ◽  
First Report ◽  
Carbapenem Resistant ◽  
Lactamase Gene ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.

scholarly journals VIM-19, a Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli and Klebsiella pneumoniae

2009 ◽  
Vol 54 (1) ◽  
pp. 471-476 ◽  
Author(s):  
Jose-Manuel Rodriguez-Martinez ◽  
Patrice Nordmann ◽  
Nicolas Fortineau ◽  
Laurent Poirel
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Hydrolytic Activity ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Amino Acid Substitutions ◽  
Class 1 Integron ◽  
Carbapenem Resistant ◽  
Class 1

ABSTRACT Two carbapenem-resistant isolates, one Escherichia coli isolate and one Klebsiella pneumoniae isolate, recovered from an Algerian patient expressed a novel VIM-type metallo-β-lactamase (MBL). The identified bla VIM-19 gene was located on a ca. 160-kb plasmid and located inside a class 1 integron in both isolates. VIM-19 differed from VIM-1 by the Asn215Lys and Ser228Arg substitutions, increasing its hydrolytic activity toward carbapenems. Site-directed mutagenesis experiments showed that both substitutions were necessary for the increased carbapenemase activity of VIM-19. This study indicates that MBLs with enhanced activity toward carbapenems may be obtained as a result of very few amino acid substitutions.

scholarly journals Detection of the novel IMP-38 among carbapenemase-producing Enterobacteriaceae in a university hospital, China

2014 ◽  
Vol 8 (08) ◽  
pp. 1044-1048 ◽  
Author(s):  
Zijuan Jian ◽  
Yanming Li ◽  
Wenen Liu ◽  
Hongling Li ◽  
Yunli Zhang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Molecular Epidemiology ◽  
Gel Electrophoresis ◽  
Pulsed Field Gel Electrophoresis ◽  
University Hospital ◽  
The Novel ◽  
Pulsed Field ◽  
Carbapenem Resistant ◽  
Neonatal Ward ◽  
Carbapenem Resistant Enterobacteriaceae

Introduction: This study set out to investigate the molecular epidemiology of carbapenemase-producing Enterobacteriaceae isolates collected from Xiang Ya Hospital, Hunan, China. Methodology: The carbapenemase genes from Enterobacteriaceae isolates were determined by PCR and sequencing. Relatedness of Klebsiella pneumoniae isolates was evaluated by pulsed-field gel electrophoresis. Results: Twenty-four out of 738 non-repetitive Enterobacteriaceae isolates harbored carbapenemase genes including IMP-38, a novel IMP-type metallo-enzyme. Nine IMP-38-producing isolates were shown to originate from the same clone and caused a small outbreak in the neonatal ward. Conclusions: IMP-38, a novel IMP-type metallo-enzyme, was one of the predominant types of carbapenemase in the clinical carbapenem-resistant Enterobacteriaceae isolates in our hospital.

scholarly journals Emergence of a KPC-90 Variant that Confers Resistance to Ceftazidime-Avibactam in an ST463 Carbapenem-Resistant Pseudomonas aeruginosa Strain

2022 ◽  
Author(s):  
Yuexing Tu ◽  
Dairong Wang ◽  
Yiwei Zhu ◽  
Jiayan Li ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Carbapenem Resistant ◽  
Loop Region ◽  
Amino Acid Insertion ◽  
Omega Loop ◽  
First Time

For the first time, we reported a KPC variant, KPC-90, in a clinical ST463 CRPA strain with CZA resistance. CZA resistance was mediated by a 2 amino acid insertion outside the KPC omega-loop region in CRPA.

scholarly journals KPC-2-Producing Carbapenem-Resistant Klebsiella pneumoniae of the Uncommon ST29 Type Carrying OXA-926, a Novel Narrow-Spectrum OXA β-Lactamase

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Liu ◽  
Yu Feng ◽  
Li Wei ◽  
Yuling Xiao ◽  
Zhiyong Zong
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Strain ◽  
Phylogenomic Analysis ◽  
The Novel ◽  
Single Nucleotide ◽  
Narrow Spectrum ◽  
Carbapenem Resistant ◽  
Long Read ◽  
Single Allele ◽  
Encoding Genes

We isolated and characterized a carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical strain from blood carrying a novel blaOXA gene, blaOXA–926, and belonging to ST29, an uncommon CRKP type. The strain, 130002, was genome sequenced using both short- and long-read sequencing and has a 94.9-kb self-transmissible IncFII plasmid carrying blaKPC–2. K. pneumoniae genomes of the ST29 complex (ST29 and its single-allele variants) were retrieved and were subjected to single nucleotide polymorphism-based phylogenomic analysis. A total of 157 genomes of the ST29 complex were identified. This complex is commonly associated with extended-spectrum β-lactamase-encoding genes, in particular, blaCTX–M–15 but rarely has carbapenemase genes. The novel plasmid-encoded β-lactamase-encoding gene blaOXA–926 was identified on a 117.8-kb IncFIA-IncFII plasmid, which was transferrable in the presence of the blaKPC–2-carrying plasmid. blaOXA–926 was cloned and MICs of β-lactams in the transformants were determined using microdilution. OXA-926 has a narrow spectrum conferring reduced susceptibility only to piperacillin, piperacillin-tazobactam, and cephalothin. Avibactam cannot fully inhibit OXA-926. blaOXA–926 and its variants have been seen in Klebsiella strains in Asia and Brazil. OXA-926 is the closest in sequence identity (89.9%) to a chromosome-encoding OXA-type enzyme of Variovorax guangxiensis. In conclusion, OXA-926 is novel plasmid-borne narrow-spectrum β-lactamase that cannot be fully inhibited by avibactam. It is likely that blaOXA–926 originates from a species closely related to V. guangxiensis and was introduced into Klebsiella > 10 years ago.

scholarly journals Novel Carbapenem-Hydrolyzing β-Lactamase, KPC-1, from a Carbapenem-Resistant Strain of Klebsiella pneumoniae

2001 ◽  
Vol 45 (4) ◽  
pp. 1151-1161 ◽  
Author(s):  
Hesna Yigit ◽  
Anne Marie Queenan ◽  
Gregory J. Anderson ◽  
Antonio Domenech-Sanchez ◽  
James W. Biddle ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clavulanic Acid ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Kinetic Studies ◽  
The Novel ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
High Level

ABSTRACT A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 μg/ml. The β-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three β-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla SHV andbla TEM genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies withEscherichia coli showed that the β-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene,bla KPC-1, was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing β-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing β-lactamase, Sme-1, fromSerratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing β-lactamase, KPC-1, although alterations in porin expression may also play a role.

A rare emergence of resistance to ceftolozane/tazobactam in Klebsiella pneumoniae causing urinary tract infection

2021 ◽  
Vol 14 (2) ◽  
pp. e240351
Author(s):  
Antony Arumairaj ◽  
Sanket Agarwal ◽  
Tarun Popli ◽  
Eliana Lopez
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
The Novel ◽  
Beta Lactam ◽  
Carbapenem Resistant ◽  
Emergence Of Resistance ◽  
Timely Administration

The management of infections caused by carbapenem-resistant organisms has been a challenge. We report a rare emergence of resistance to the novel beta-lactam/ beta-lactamase combination ceftolozane/tazobactam by Klebsiella pneumoniae, causing urinary tract infection. The K. pneumoniae, in this case, was reported to be sensitive to the other novel beta-lactam/ beta-lactamase combination of ceftazidime/avibactam. The timely administration of ceftazidime/avibactam resulted in prompt clinical resolution of the urinary tract infection caused by an extensively drug-resistant K. pneumoniae.

scholarly journals Co-conjugation of Virulence Plasmid and KPC Plasmid in a Clinical Klebsiella pneumoniae Strain

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuemei Yang ◽  
Ning Dong ◽  
Xiaoxuan Liu ◽  
Chen Yang ◽  
Lianwei Ye ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Sharp Increase ◽  
Multi Drug Resistance ◽  
Virulence Plasmid ◽  
Clinical Settings ◽  
Multiple Resistance ◽  
Evolutionary Mechanisms ◽  
Highly Pathogenic ◽  
Carbapenem Resistant ◽  
Multiple Resistance Genes

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains have been increasingly reported, and it is important to understand the evolutionary mechanisms of these highly pathogenic and resistant bacterial pathogens. In this study, we characterized a ST11 carbapenem-resistant K. pneumoniae strain which harbored an IncFIB/IncHI1B type virulence plasmid and an IncFII/IncR type blaKPC–2-bearing plasmid. The virulence plasmid was found to be conjugative and harbored a 35-kbp fragment including aerobactin encoding cluster from virulence plasmid pLVPK and multiple resistance genes, resulting in a mosaic multi-drug resistance and virulence plasmid. This virulence plasmid could be transferred via conjugation to Escherichia coli and K. pneumoniae strains alone as well as together with the blaKPC–2-bearing plasmid. Co-transmission of virulence and blaKPC–2-bearing plasmids would directly convert a classic K. pneumoniae strain into CR-HvKP strain, leading to a sharp increase in the prevalence of CR-HvKP in clinical settings, which poses a great threat to human health.

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