scholarly journals Case Report of an Extensively Drug-Resistant Klebsiella pneumoniae Infection With Genomic Characterization of the Strain and Review of Similar Cases in the United States

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
Fiorella Krapp ◽  
Egon A Ozer ◽  
Chao Qi ◽  
Alan R Hauser
Keyword(s):  
United States ◽  
Case Report ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
The United States ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Genomic Characterization

Abstract Reports of extensively drug-resistant and pan-drug-resistant Klebsiella pneumoniae (XDR-KP and PDR-KP) cases are increasing worldwide. Here, we report a case of XDR-KP with an in-depth molecular characterization of resistance genes using whole-genome sequencing, and we review all cases of XDR-KP and PDR-KP reported in the United States to date.

scholarly journals Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117771 ◽  
Author(s):  
Asho Ali ◽  
Zahra Hasan ◽  
Ruth McNerney ◽  
Kim Mallard ◽  
Grant Hill-Cawthorne ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Genomic characterization of an extensively drug-resistant KPC-2-producing Klebsiella pneumoniae ST855 (CC258) only susceptible to ceftazidime-avibactam isolated in Brazil

2017 ◽  
Vol 89 (4) ◽  
pp. 324-327 ◽  
Author(s):  
Caio Augusto Martins Aires ◽  
Michael J. Rybak ◽  
Juwon Yim ◽  
Polyana Silva Pereira ◽  
Cláudio M. Rocha-de-Souza ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Genomic Characterization

scholarly journals Genomic Analysis of a Pan-Resistant Isolate ofKlebsiella pneumoniae, United States 2016

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Tom J. B. de Man ◽  
Joseph D. Lutgring ◽  
David R. Lonsway ◽  
Karen F. Anderson ◽  
Julia A. Kiehlbauch ◽  
...  
Keyword(s):  
Public Health ◽  
United States ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
The United States ◽  
Whole Genome ◽  
Beta Lactams ◽  
Content Type

ABSTRACTAntimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusualKlebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. patient. The isolate harbored four known beta-lactamase genes, including plasmid-mediatedblaNDM-1andblaCMY-6, as well as chromosomalblaCTX-M-15andblaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the firstK. pneumoniaeisolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCEAntimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. AKlebsiella pneumoniaestrain that was nonsusceptible to all tested antibiotics was isolated from a U.S. patient. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.

scholarly journals Molecular Epidemiological Analysis of ST11-K64 Extensively Drug-Resistant Klebsiella pneumoniae Infections Outbreak in Intensive Care and Neurosurgery Units Based on Whole-Genome Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Liuxin Xiong ◽  
Lebin Su ◽  
Hanqing Tan ◽  
Wansha Zhao ◽  
Shuying Li ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genetic Relatedness ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Phenotypic Traits ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Klebsiella pneumoniae (Kp) is the primary causative bacteria for nosocomial infections and hospital outbreaks. In particular, extensively drug-resistant K. pneumoniae (XDRKp) causes severe clinical infections in hospitalized patients. Here, we used pulsed-field gel electrophoresis (PFGE), drug susceptibility tests, and the whole-genome sequencing (WGS) technology to examine genetic relatedness and phenotypic traits of the strains isolated during an outbreak period. Based on PFGE, a distinct clones cluster comprised of eight XDRKp was observed. These strains were confirmed as ST11-K64 via multiple-locus sequence typing database of Kp. The strains also had genes related to the regulation of biofilm biosynthesis (type 1 & 3 fimbriae, type IV pili biosynthesis, RcsAB, and type VI secretion system) and multiple drug resistance (β-lactamase and aminoglycoside antibiotic resistance). WGS data based on core-single nucleotide polymorphisms and epidemiological investigation showed that the neurosurgery unit was likely the source of the outbreak, the strain was likely to have been transmitted to the ICU through patients. In addition, the two highly probable transmission routes were in the ICU (exposure through shared hospital beds) and the neurosurgery units (all cases were treated by the same rehabilitation physician and were most likely infected during the physical therapy). Notably, the bed mattress had played a crucial transmission role of this outbreak, served as a pathogen reservoir.

scholarly journals Multifactorial Chromosomal Variants Regulate Polymyxin Resistance in Extensively Drug-Resistant Klebsiella pneumoniae

2017 ◽  
Author(s):  
Miranda E Pitt ◽  
Alysha G Elliott ◽  
Minh Duc Cao ◽  
Devika Ganesamoorthy ◽  
Ilias Karaiskos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Drug Resistant ◽  
Missense Mutations ◽  
Novel Mutations ◽  
Suppressor Mutations ◽  
Extensively Drug Resistant

ABSTRACTExtensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including nineteen polymyxin-resistant and five polymyxin-susceptible strains, underwent whole genome sequencing. Approximately 90% of polymyxin resistance was enabled by alterations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB and another strain had an ISKpn25 insertion at 133 bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D31E) affecting mgrB. Complementation assays revealed all mgrB perturbations contributed to resistance. Missense mutations in phoQ (T281M, G385C) were also found to facilitate resistance. Several variants in phoPQ co-segregating with the ISKpn26-like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance conferring mutations, including the ISKpn26-like insertion colonising with a novel mutation in pmrB (P158R), both confirmed via complementation assays. We also characterized a new multi-drug resistant Klebsiella quasipneumoniae strain ST2401 which was susceptible to polymyxins. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in K. pneumoniae.DATA SUMMARYWhole genome sequencing of the 24 clinical isolates has been deposited under BioProject PRJNA307517 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA307517).IMPACT STATEMENTKlebsiella pneumoniae contributes to a high abundance of nosocomial infections and the rapid emergence of antimicrobial resistance hinders treatment. Polymyxins are predominantly utilized to treat multidrug-resistant infections, however, resistance to the polymyxins is arising. This increasing prevalence in polymyxin resistance is evident especially in Greece and Brazil. Identifying the genomic variations conferring resistance in clinical isolates from these regions assists with potentially detecting novel alterations and tracing the spread of particular strains. This study commonly found mutations in the gene mgrB, the negative regulator of PhoPQ, known to cause resistance in KP. In the remaining isolates, missense mutations in phoQ were accountable for resistance. Multiple novel mutations were detected to be segregating with mgrB perturbations. This was either due to a mixed heterogeneous sample of two polymyxin-resistant strains, or because of multiple mutations within the same strain. Of interest was the validation of novel mutations inphoPQ segregating with a previously known ISKpn26-like element in disrupted mgrB isolates. Complementation of these phoPQ mutations revealed a reduction in minimum inhibitory concentrations and suggests the first evidence of partial suppressor mutations in KP. This research builds upon our current understanding of heteroresistance, lineage specific mutations and regulatory variations relating to polymyxin resistance.

scholarly journals 603. Identification of a Carbapenemase-Producing, Extensively Drug-Resistant Klebsiella pneumoniae Isolate Carrying a blaNDM-1-Bearing, Hypervirulent Plasmid, United States 2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S282-S283
Author(s):  
Richard A Stanton ◽  
Gillian A McAllister ◽  
Amelia Bhatnagar ◽  
Maria Karlsson ◽  
Allison C Brown ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Critical Role ◽  
Illumina Miseq ◽  
The United States ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Classes ◽  
Carbapenemase Gene

Abstract Background The recent discovery of carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-HvKP) has signaled the convergence of multidrug resistance and pathogenicity, with the potential for increased mortality. While previous studies of CP-HvKP isolates revealed that most carried carbapenemase genes and hypervirulence elements on separate plasmids, a 2018 report from China confirmed that both could be harbored on a single, hybrid carbapenemase-hypervirulent plasmid. As part of a project sequencing isolates carrying multiple carbapenemase genes identified through CDC’s Antibiotic Resistance Laboratory Network (AR Lab Network), we discovered a blaNDM-1-bearing hypervirulent plasmid found in a KPC- and NDM-positive K. pneumoniae from the United States. Methods Antimicrobial susceptibility testing (AST) was performed by reference broth microdilution against 23 agents. Whole-genome sequencing (WGS) was performed on Illumina MiSeq and PacBio RS II platforms. Results AST results indicated the isolate was extensively drug-resistant, as it was non-susceptible to at least one agent in all but two drug classes; it was susceptible to only tigecycline and tetracycline. Analysis of WGS data showed the isolate was ST11, the same sequence type that caused a fatal outbreak of CP-HvKP in China in 2016. The genome included two plasmids. The smaller one (129kbp) carried seven antibiotic resistance (AR) genes, including the carbapenemase gene blaKPC-2. The larger plasmid (354kbp) harbored 11 AR genes, including the metallo-β-lactamase gene blaNDM-1, as well as virulence factors iucABCD/iutA, peg-344, rmpA, and rmpA2, which comprise four of the five genes previously identified as predictors of hypervirulence in K. pneumoniae. Conclusion This is the first report of a hybrid carbapenemase-hypervirulent plasmid in the United States. The presence of both blaNDM-1 and hypervirulence elements on the same plasmid suggests that the CP-Hv pathotype could spread rapidly through horizontal transfer. This discovery demonstrates the critical role of genomic characterization of emerging resistance and virulence phenotypes by the AR Lab Network as part of US containment efforts. Disclosures All authors: No reported disclosures.

scholarly journals First Report on a Hyperepidemic Clone of KPC-3-Producing Klebsiella pneumoniae in Israel Genetically Related to a Strain Causing Outbreaks in the United States

2008 ◽  
Vol 53 (2) ◽  
pp. 818-820 ◽  
Author(s):  
Shiri Navon-Venezia ◽  
Azita Leavitt ◽  
Mitchell J. Schwaber ◽  
J. Kamile Rasheed ◽  
Arjun Srinivasan ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
The United States ◽  
Drug Resistant ◽  
Resistant Clone ◽  
Bacterial Strains ◽  
First Report ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Global Spread

ABSTRACT A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.

scholarly journals 1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen
Keyword(s):  
United States ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Antibiotic Use ◽  
The United States ◽  
Drug Resistant ◽  
E Coli ◽  
Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

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