Project description:The spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) worldwide is a serious problem. This retrospective, matched case-control, parallel study in a tertiary teaching hospital analyzed the microbiological and clinical characteristics of CPKP infection, focusing on the risk factors for carbapenem resistance and patient mortality. The hospital department with the highest incidence of CPKP infections was the intensive care unit. All CPKP strains examined were positive for blakpc-2, and 84.8% of CPKP were ST11. Hypervirulent phenotype was identified in 22.7% of the patients with CPKP, with these strains displaying a high incidence of positivity for entB, ybtS, and iutA. Multivariate conditional logistic regression analysis demonstrated that Pitt bacteremia score >4, prior stomach tube, continuous renal replacement therapy (CRRT), and previous carbapenem exposure were associated with CPKP infection. Higher albumin concentration and use of cephalosporins after diagnosis were strong prognostic factors for crude 28-day mortality. Further, high APACHE II score, CRRT, use of carbapenems after diagnosis, and bacteremia were risk factors for crude in-hospital mortality. CPKP isolates showed clonal spread and were resistant to most antibiotics, resulting in higher financial burden. Critical illness was associated with increased mortality.
Project description:We report the emergence of OXA-232, a newly described OXA-48-like carbapenemase variant, in Southeast Asia. Molecular characterization of eight Klebsiella pneumoniae obtained from local and foreign patients reveals clonality of the isolates. bla OXA-232 was located on a non-conjugative plasmid of 6141 base pairs (GenBank accession number JX423831.1).
Project description:Background:Identification of gut microbiota features associated with antibiotic-resistant bacterial colonization may reveal new infection prevention targets. Methods:We conducted a matched, case-control study of long-term acute care hospital (LTACH) patients to identify gut microbiota and clinical features associated with colonization by Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), an urgent antibiotic resistance threat. Fecal or rectal swab specimens were collected and tested for KPC-Kp; 16S rRNA gene-based sequencing was performed. Comparisons were made between cases and controls in calibration and validation subsamples using microbiota similarity indices, logistic regression, and unit-weighted predictive models. Results:Case (n = 32) and control (n = 99) patients had distinct fecal microbiota communities, but neither microbiota diversity nor inherent clustering into community types distinguished case and control specimens. Comparison of differentially abundant operational taxonomic units (OTUs) revealed 1 OTU associated with case status in both calibration (n = 51) and validation (n = 80) subsamples that matched the canonical KPC-Kp strain ST258. Permutation analysis using the presence or absence of OTUs and hierarchical logistic regression identified 2 OTUs (belonging to genus Desulfovibrio and family Ruminococcaceae) associated with KPC-Kp colonization. Among clinical variables, the presence of a decubitus ulcer alone was independently and consistently associated with case status. Combining the presence of the OTUs Desulfovibrio and Ruminococcaceae with decubitus ulcer increased the likelihood of KPC-Kp colonization to >38% in a unit-weighted predictive model. Conclusions:We identified microbiota and clinical features that distinguished KPC-Kp gut colonization in LTACH patients, a population particularly susceptible to KPC-Kp infection. These features may warrant further investigation as markers of risk for KPC-Kp colonization.
Project description:The emergence of Klebsiella pneumoniae producing carbapenemase (KPC) has now become a global concern. As a part of a nationwide multicentre surveillance study in Cuba, three K. pneumoniae clinical isolates resistant to carbapenems were detected for a 1-month period (September to October 2011). PCR and sequence analysis revealed that the three strains harboured bla KPC-2. They showed resistance or intermediate susceptibility to expanded-spectrum cephalosporins, other ?-lactams, a ?-lactam/?-lactamase inhibitor combination, and gentamicin. Two strains were susceptible only to colistin, whereas the other strain showing colistin resistance was susceptible to fluoroquinolones. These bla KPC -2-positive K. pneumoniae strains were classified into ST1271 (CC29), a novel clone harbouring bla KPC -2, and were revealed to be genetically identical by PCR-based DNA fingerprinting. The three patients infected with the KPC-producing K. pneumoniae had common risk factors, and had no overseas travel experience outside Cuba, suggesting local acquisition of the resistant pathogen. This is the first report of a KPC-producing K. pneumoniae in Cuba. Although detection of KPC in Enterobacteriaceae is still rare in Cuba, our finding indicated that KPC-producing bacteria are a global concern and highlighted the need to identify these microorganisms in clinical laboratories.
Project description:Klebsiella pneumoniae carbapenemases (KPCs) were first identified in 1996 in the USA. Since then, regional outbreaks of KPC-producing K. pneumoniae (KPC-Kp) have occurred in the USA, and have spread internationally. Dissemination of blaKPC involves both horizontal transfer of blaKPC genes and plasmids, and clonal spread. Of epidemiological significance, the international spread of KPC-producing K. pneumoniae is primarily associated with a single multilocus sequence type (ST), ST258, and its related variants. However, the molecular factors contributing to the success of ST258 largely remain unclear. In this review, we discuss the recent progresses in understanding KPC-producing K. pneumoniae that are contributing to our knowledge of plasmid and genome composition and structure among the KPC epidemic clone, and we identify possible factors that influence its epidemiological success.
Project description:We identified a novel ceftazidime/avibactam resistance mechanism in sequence type 11 Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae. Plasmid recombination and chromosomal integration formed a novel virulence plasmid and provided an additional promoter for blaSHV-12, leading to blaSHV-12 overexpression and ceftazidime/avibactam resistance. Genetic rearrangement contributed to convergence of hypervirulence and ceftazidime/avibactam resistance.
Project description:We report the emergence of colistin resistance in Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae after 8 days of colistin-based therapy, resulting in relapse of bloodstream infection and death. Disruption of the mgrB gene by insertion of a mobile genetic element was found to be the mechanism, which was replicated in vitro after exposure to subinhibitory concentrations of colistin and meropenem.
Project description:The increasing resistence and/or bacterial tolerance to bactericides, such as chlorhexidine, causes worrisome public health problems. Using transcriptomical and microbiological studies, we analysed the molecular mechanisms associated with the adaptation to chlorhexidine in two carbapenemase-producing strains of Klebsiella pneumoniae belonging ST258-KPC3 and ST846-OXA48.
Project description:Increasing occurrence of multidrug-resistant (MDR) and hypervirulent (hv) Klebsiella pneumoniae (MDR-hvKp) convergent clones is being observed. Those strains have the potential of causing difficult-to-treat infections in healthy adults with an increased capacity for mortality. It is therefore crucial to track their dissemination to prevent their further spread. The aim of our study was to investigate the occurrence of carbapenemase-producing hvKp isolates in Switzerland and to determine their genetic profile. A total of 279 MDR carbapenemase-producing K. pneumoniae from patients hospitalized all over Switzerland was investigated, and a rate of 9.0% K. pneumoniae presenting a virulence genotype was identified. Those isolates produced either KPC, NDM, or OXA-48 and had been either recovered from rectal swabs, urine, and blood. A series of previously reported K. pneumoniae clones such as ST23-K1, ST395-K2, and ST147-K20 or ST147-K64 were identified. All the isolates defined as MDR-hvKp (4.7%) possessed the aerobactin and the yersiniabactin clusters. The ST23-K1s were the only isolates presenting the colibactin cluster and achieved higher virulence scores. This study highlights the occurrence and circulation of worrisome MDR-hvKp and MDR nonhypervirulent K. pneumoniae (MDR-nhv-Kp) isolates in Switzerland. Our findings raise an alert regarding the need for active surveillance networks to track and monitor the spread of such successful hybrid clones representing a public health threat worldwide.