scholarly journals Fitness barriers to spread of colistin-resistant Klebsiella pneumoniae overcome by establishing niche in patient population with elevated colistin use

2021 ◽  
Author(s):  
Zena Lapp ◽  
Jennifer H Han ◽  
Divya Choudhary ◽  
Stuart Castaneda ◽  
Ali Pirani ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Clinical Data ◽  
General Pattern ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Cost Of Resistance ◽  
Resistant Strains ◽  
Secondary Variants ◽  
Large Clusters

To combat antibiotic resistance, it is critical to improve our understanding of how new resistant strains emerge and spread. An antibiotic resistance threat of critical priority is the epidemic ST258 strain of carbapenem-resistant Klebsiella pneumoniae (CRKP). Here, we studied the spread of resistance among ST258 to an antibiotic of last resort, colistin, by tracking its evolution across 21 U.S. long-term acute care hospitals over the course of a year. Phylogenetic analysis suggested that a significant cost was associated with colistin resistance in most cases, as resistance emergence was common but resistance variants were rarely transmitted. The high cost of resistance was further supported by the observation that several of the resistance variants that were transmitted had acquired secondary variants that reverted the strain to colistin susceptibility. The exceptions to the general pattern of instability associated with colistin resistance were two large clusters of resistant strains in one ST258 clade II sublineage (clade IIB) present across 11 of the 12 sampled Southern California hospitals. Quantification of transmission fitness in the healthcare environment using time-scaled haplotypic density indicated that while resistant isolates from other clades were less fit than their susceptible counterparts, clade IIB resistant isolates were more fit. Overlaying patient clinical data suggested that the increased fitness of colistin-resistant clade IIB isolates is in part driven by a lineage defining variant that increased clade IIB's association with patient subpopulations who were more likely to be treated with colistin. These results show that a favorable genetic background and sustained selective pressure led to the emergence and spread of a colistin-resistant ST258 sublineage across a regional healthcare network. More broadly, these findings highlight the utility of integrating pathogen genomic and corresponding clinical data from regional healthcare networks to detect and understand the origin and dissemination of antibiotic resistance threats.

The changing epidemiology of carbapenemase-producing Klebsiella pneumoniae in Italy: toward polyclonal evolution with emergence of high-risk lineages

2020 ◽  
Author(s):  
Vincenzo Di Pilato ◽  
Giulia Errico ◽  
Monica Monaco ◽  
Tommaso Giani ◽  
Maria Del Grosso ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Close Association ◽  
Sensu Stricto ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Invasive Infections ◽  
Encoding Gene ◽  
Genotypic Characteristics

Abstract Background Previous studies showed that the epidemic of carbapenem-resistant Klebsiella pneumoniae (CR-KP) observed in Italy since 2010 was sustained mostly by strains of clonal group (CG) 258 producing KPC-type carbapenemases. In the framework of the National Antibiotic-Resistance Surveillance (AR-ISS), a countrywide survey was conducted in 2016 to explore the evolution of the phenotypic and genotypic characteristics of CR-KP isolates. Methods From March to July 2016, hospital laboratories participating in AR-ISS were requested to provide consecutive, non-duplicated CR-KP (meropenem and/or imipenem MIC >1 mg/L) from invasive infections. Antibiotic susceptibility was determined according to EUCAST recommendations. A WGS approach was adopted to characterize the isolates by investigating phylogeny, resistome and virulome. Results Twenty-four laboratories provided 157 CR-KP isolates, of which 156 were confirmed as K. pneumoniae sensu stricto by WGS and found to carry at least one carbapenemase-encoding gene, corresponding in most cases (96.1%) to blaKPC. MLST- and SNP-based phylogeny revealed that 87.8% of the isolates clustered in four major lineages: CG258 (47.4%), with ST512 as the most common clone, CG307 (19.9%), ST101 (15.4%) and ST395 (5.1%). A close association was identified between lineages and antibiotic resistance phenotypes and genotypes, virulence traits and capsular types. Colistin resistance, mainly associated with mgrB mutations, was common in all major lineages except ST395. Conclusions This WGS-based survey showed that, although CG258 remained the most common CR-KP lineage in Italy, a polyclonal population has emerged with the spread of the new high-risk lineages CG307, ST101 and ST395, while KPC remained the most common carbapenemase.

scholarly journals The Acquisition of Colistin Resistance Is Associated to the Amplification of a Large Chromosomal Region in Klebsiella pneumoniae kp52145

2021 ◽  
Vol 22 (2) ◽  
pp. 649
Author(s):  
María Blanca Sánchez ◽  
Alicia Sánchez-Gorostiaga ◽  
Trinidad Cuesta ◽  
José Luis Martínez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Experimental Evolution ◽  
Chromosomal Region ◽  
Genetic Change ◽  
Cross Resistance ◽  
Common Mutation ◽  
Colistin Resistance ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Resistant Strains

The appearance of carbapenem-resistant Klebsiella pneumoniae has increased the use of colistin as a last-resort antibiotic for treating infections by this pathogen. A consequence of its use has been the spread of colistin-resistant strains, in several cases carrying colistin resistance genes. In addition, when susceptible strains are confronted with colistin during treatment, mutation is a major cause of the acquisition of resistance. To analyze the mechanisms of resistance that might be selected during colistin treatment, an experimental evolution assay for 30 days using as a model the clinical K. pneumoniae kp52145 isolate in the presence of increasing amounts of colistin was performed. All evolved populations presented a decreased susceptibility to colistin, without showing cross-resistance to antibiotics belonging to other structural families. We did not find any common mutation in the evolved mutants, neither in already known genes, previously known to be associated with the resistance phenotype, nor in new ones. The only common genetic change observed in the strains that evolved in the presence of colistin was the amplification of a 34 Kb sequence, homologous to a prophage (Enterobacteria phage Fels-2). Our data support that gene amplification can be a driving force in the acquisition of colistin resistance by K. pneumoniae.

scholarly journals Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan

2015 ◽  
Vol 59 (5) ◽  
pp. 2909-2913 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Jiun Pan ◽  
Yu-Ping Wang ◽  
Yi-Tsung Lin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Resistance Mechanisms ◽  
Single Amino Acid ◽  
Colistin Resistance ◽  
Amino Acid Mutation ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Sequence Types

ABSTRACTColistin is one of the antibiotics of last resort for the treatment of carbapenem-resistantKlebsiella pneumoniaeinfection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) inmgrBare the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.

scholarly journals A Bibliometric Meta-Analysis of Colistin Resistance in Klebsiella pneumoniae

Diseases ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 44
Author(s):  
Ozioma Forstinus Nwabor ◽  
Pawarisa Terbtothakun ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Klebsiella Pneumoniae ◽  
Research Collaboration ◽  
Research Output ◽  
Meta Analysis ◽  
Research Articles ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
The Usa ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Linkage Strength

Colistin is a last resort antibiotic medication for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. In recent years, various mechanisms have been reported to mediate colistin resistance in K. pneumoniae. This study reports a bibliometric analysis of published articles retrieved from the Scopus database relating to colistin resistance in K. pneumoniae. The research trends in colistin resistance and mechanisms of resistance were considered. A total of 1819 research articles published between 1995 and 2019 were retrieved, and the results indicated that 50.19% of the documents were published within 2017–2019. The USA had the highest participation with 340 (14.31%) articles and 14087 (17.61%) citations. Classification based on the WHO global epidemiological regions showed that the European Region contributed 42% of the articles while the American Region contributed 21%. The result further indicated that 45 countries had published at least 10 documents with strong international collaborations amounting to 272 links and a total linkage strength of 735. A total of 2282 keywords were retrieved; however, 57 keywords had ≥15 occurrences with 764 links and a total linkage strength of 2388. Furthermore, mcr-1, colistin resistance, NDM, mgrB, ceftazidime-avibactam, MDR, combination therapy, and carbapenem-resistant Enterobacteriaceae were the trending keywords. Concerning funders, the USA National Institute of Health funded 9.1% of the total research articles, topping the list. The analysis indicated poor research output, collaboration, and funding from Africa and South-East Asia and demands for improvement in international research collaboration.

scholarly journals Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Plasmid Dna ◽  
Clonal Expansion ◽  
Genetic Alterations ◽  
Sequence Type ◽  
Chromosomal Integration ◽  
Colistin Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

scholarly journals Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Björn Berglund ◽  
Ngoc Thi Bich Hoang ◽  
Maria Tärnberg ◽  
Ngai Kien Le ◽  
Maud Nilsson ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Resistance Rate ◽  
Clinical Isolates ◽  
Phenotypic Characterization ◽  
Polymorphism Analysis ◽  
Pediatric Hospital ◽  
Carbapenem Resistant ◽  
Global Epidemiology

Abstract Background Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae. Methods In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015. Results Aside from the carbapenem resistance gene blaKPC-2, which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone. Conclusions The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones.

Sign in / Sign up

Export Citation Format

Share Document