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

Author(s):  
Vincenzo Di Pilato ◽  
Giulia Errico ◽  
Monica Monaco ◽  
Tommaso Giani ◽  
Maria Del Grosso ◽  
...  

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.

2021 ◽  
Author(s):  
Zena Lapp ◽  
Jennifer H Han ◽  
Divya Choudhary ◽  
Stuart Castaneda ◽  
Ali Pirani ◽  
...  

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.


2018 ◽  
Vol 69 (5) ◽  
pp. 1240-1243
Author(s):  
Manuela Arbune ◽  
Mioara Decusara ◽  
Luana Andreea Macovei ◽  
Aurelia Romila ◽  
Alina Viorica Iancu ◽  
...  

The aim of the present study was to characterize the antibiotic resistance profile of enterobacteriaceae strains isolated in Infectious Diseases Hospital Galati, Romania, during 2016, in order to guide the local antibiotic stewardship strategy. There are 597 biological samples with positive cultures for enterobacteriaceae, related to invasive and non-invasive infections. The main bacterial genus were E. coli 62%, Klebsiella spp 15%, Proteus spp 11% and Salmonella spp 6%. Over a half of isolated strains have one or more antibiotic resistance. The resistance level depends on bacterial genus, with highest level found among the rare isolates: Enterobacter spp, Citrobacter spp, Morganella spp and Serratia spp. The rate of MDR was 17.,6% for E. coli, 40.9% for Klebsiella spp and 50.7% for Proteus spp. while the rate of strains producing Extended Spectrum of Beta Lactamase are 7.2% for E. coli, 28.4% for Klebsiella spp and 12.3% for Proteus spp. The carbapenem resistant strains were found in 1.1% cases.


Diseases ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 44
Author(s):  
Ozioma Forstinus Nwabor ◽  
Pawarisa Terbtothakun ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri

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.


2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez

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.


Author(s):  
Po-Han Huang ◽  
Yi-Hsiang Cheng ◽  
Wen-Yin Chen ◽  
Chih-Han Juan ◽  
Sheng-Hua Chou ◽  
...  

Author(s):  
Jihui Chen ◽  
Yu Yang ◽  
Huimin Yao ◽  
Shuhong Bu ◽  
Lixia Li ◽  
...  

ObjectiveCarbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens.MethodsAdult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed.ResultsA total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80–0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06–0.99) but not in the low-risk group. Ceftazidime–avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98–2.94; P = 0.061).ConclusionThe antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.


2019 ◽  
Author(s):  
Qiqiang Liang ◽  
Fang Qian ◽  
Yibing Chen ◽  
Zhijun Xu ◽  
Zhijiang Xu ◽  
...  

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.


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