Risk factors and mechanisms of in vivo emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae

2021 ◽  
pp. 106342
Author(s):  
Po-Han Huang ◽  
Yi-Hsiang Cheng ◽  
Wen-Yin Chen ◽  
Chih-Han Juan ◽  
Sheng-Hua Chou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Klebsiella Pneumoniae ◽  
Colistin Resistance ◽  
Carbapenem Resistant

scholarly journals In vivo Emergence of Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Premature Termination of the mgrB Gene Regulator

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Kong ◽  
Chao Li ◽  
Hangfei Chen ◽  
Wei Zheng ◽  
Qingyang Sun ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genome Sequence ◽  
Whole Genome Sequence ◽  
Resistant Isolate ◽  
Whole Genome ◽  
Wild Type ◽  
Colistin Resistance ◽  
Putative Gene ◽  
Carbapenem Resistant

Multidrug-resistant (MDR) Klebsiella pneumoniae is a severe threat to public health worldwide. Worryingly, colistin resistance, one of the last-line antibiotics for the treatment of MDR K. pneumoniae infection, has been increasingly reported. This study aims to investigate the emergence of evolved colistin resistance in a carbapenem-resistant K. pneumoniae isolate during colistin treatment. In this study, a pair of sequential carbapenem-resistant K. pneumoniae isolates were recovered from the same patient before and after colistin treatment, named KP1-1 and KP1-2, respectively. Antibiotic susceptibility testing was performed by the microdilution broth method. Whole genome sequencing was performed, and putative gene variations were analyzed in comparison of the genome sequence of both isolates. The bacterial whole genome sequence typing and source tracking analysis were performed by BacWGSTdb 2.0 server. Validation of the role of these variations in colistin resistance was examined by complementation experiments. The association between colistin resistance and the expression level of PhoP/PhoQ signaling system and its regulated genes was evaluated by quantitative real-time PCR (qRT-PCR) assay. Our study indicated that KP1-1 displayed extensively antibiotic resistant trait, but only susceptible to colistin. KP1-2 showed additional resistance to colistin. Both isolates belonged to Sequence Type 11 (ST11). The whole genome sequence analysis uncovered multiple resistance genes and virulence genes in both isolates. No plasmid-mediated mcr genes were found, but genetic variations in five chromosomal genes, especially the Gln30∗ alteration in MgrB, were detected in colistin-resistant isolate KP1-2. Moreover, only complementation with wild-type mgrB gene restored colistin susceptibility, with colistin MIC decreased from 32 to 1 mg/L. Expression assays revealed an overexpression of the phoP, phoQ, and pmrD genes in the mgrB-mutated isolate KP1-2 compared to the wild-type isolate KP1-1, confirming the MgrB alterations was responsible for increased expression levels of those genes. This study provides direct in vivo evidence that Gln30∗ alteration of MgrB is a critical region responsible for colistin resistance in K. pneumoniae clinical strains.

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.

Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis

2021 ◽  
Author(s):  
Yuzhen Qiu ◽  
Wen Xu ◽  
Yunqi Dai ◽  
Ruoming Tan ◽  
Jialin Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Critically Ill Patients ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Mortality Rates ◽  
Carbapenem Resistant ◽  
All Cause Mortality ◽  
Independent Risk Factors

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.

Machine Learning Algorithms to Predict the Mortality of Carbapenem Resistant Klebsiella Pneumoniae bacteremia

2019 ◽  
Author(s):  
Qiqiang Liang ◽  
Fang Qian ◽  
Yibing Chen ◽  
Zhijun Xu ◽  
Zhijiang Xu ◽  
...  
Keyword(s):  
Machine Learning ◽  
Risk Factors ◽  
Septic Shock ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Severe Thrombocytopenia ◽  
Acute Renal Injury ◽  
High Risk Factors ◽  
Carbapenem Resistant ◽  
Logical Regression

Abstract Purpose To establish mortality prediction models in 14 days of Carbapenem-Resistant Klebsiella Pneumoniae bacteremia using Machine learning.Materials and Methods It is a single-center retrospective study. We collect the relevant clinical information of all patients with Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) bacteremia in the past 5 years using the local database. Data analysis and verification are carried out by multiple logical regression, decision tree, random forest, support vector machine (SVM), and XGBoost.Result This study includes 187 patients with 40 related variables. In multiple logical regression, acute renal injury (P=0.003), Apache II score (P=0.036), immunodeficiency (P=0.025), severe thrombocytopenia (P=0.025) and septic shock (P=0.044) are the high-risk factors for 14 days mortality of CRKP bloodstream infections. According to the importance of those parameters, risk scoring is established to predict the survival rate of CRKP bacteremia. The analysis of the five models, with 70% training set and 30% test set, show the comprehensive performance of random forest (AUROC=0.953, precision=91.85%) is slightly better than that of XGBoost (AUROC=0.912, precision=86.41%) and SVM (AUROC=0.936, precision=79.89%) in predicting 14-day mortality of CRKP bacteremia. The multiple logical regression model (AUROC=0.825, precision=81.52%) is the second, and the decision tree model (AUROC=0.712, precision=79.89%) is not very ideal.Conclusion Machine learning has good performances in predicting 14-day mortality of CRKP bacteremia than multiple logical regression. Acute renal injury, severe thrombocytopenia, and septic shock are the high-risk factors of CRKP bacteremia mortality.

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.

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