Dataset Information

No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia.

ABSTRACT: The objective of this study was to correlate resistance mutations of extended spectrum beta-lactamases (ESBL) and AmpC beta-lactamases and virulence factors (VF) with 30-day mortality in patients treated with either piperacillin-tazobactam or carbapenems. A post-hoc analysis on 123 patients with ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia treated empirically with piperacillin-tazobactam and carbapenems was performed. Beta-lactamase resistance mutations and VF were identified by whole genome sequencing (WGS). The primary endpoint was 30-day mortality. Multivariate analyses were performed using logistic regression. WGS showed diverse multilocus sequence types (MLST) in 43?K. pneumoniae strains, while ST131 predominated in E. coli strains (57/80). CTX-M was most commonly detected (76/80 [95%] of E. coli; 39/43 [91%] of K pneumoniae.), followed by OXA (53/80 [66%] of E. coli; 34/43 [79%] of K. pneumoniae). A significant correlation was found between the number of genes encoding third-generation cephalosporin-resistant beta-lactamases and 30-day mortality (p?=?0.045). The positive association was not significant after controlling for empiric carbapenem, Pitt score 3 and K. pneumoniae (OR 2.43, P?=?0.073). None of the VF was associated with 30-day mortality. No association was found between 30-day mortality and any ESBL and AmpC beta-lactamases or VF when piperacillin-tazobactam or carbapenems were given. No significant association between 30-day mortality and active empiric therapy was found.

SUBMITTER: Heng ST

PROVIDER: S-EPMC6109088 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia.

Heng Shi Thong ST Chen Swaine L SL Wong Joshua G X JGX Lye David C DC Ng Tat Ming TM

Scientific reports 20180824 1

The objective of this study was to correlate resistance mutations of extended spectrum beta-lactamases (ESBL) and AmpC beta-lactamases and virulence factors (VF) with 30-day mortality in patients treated with either piperacillin-tazobactam or carbapenems. A post-hoc analysis on 123 patients with ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia treated empirically with piperacillin-tazobactam and carbapenems was performed. Beta-lactamase resistance mutations and VF were ...[more]

PMID: 30143706

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Project description:Antibiotic-resistant infections caused by gram-negative bacteria are a major healthcare concern. Repurposing drugs circumvents the time and money limitations associated with developing new antimicrobial agents needed to combat these antibiotic-resistant infections. Here we identified the off-patent antifungal agent, ciclopirox, as a candidate to repurpose for antibiotic use. To test the efficacy of ciclopirox against antibiotic-resistant pathogens, we used a curated collection of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates that are representative of known antibiotic resistance phenotypes. We found that ciclopirox, at 5-15 µg/ml concentrations, inhibited bacterial growth regardless of the antibiotic resistance status. At these same concentrations, ciclopirox reduced growth of Pseudomonas aeruginosa clinical isolates, but some of these pathogens required higher ciclopirox concentrations to completely block growth. To determine how ciclopirox inhibits bacterial growth, we performed an overexpression screen in E. coli. This screen revealed that galE, which encodes UDP-glucose 4-epimerase, rescued bacterial growth at otherwise restrictive ciclopirox concentrations. We found that ciclopirox does not inhibit epimerization of UDP-galactose by purified E. coli GalE; however, ?galU, ?galE, ?rfaI, or ?rfaB mutant strains all have lower ciclopirox minimum inhibitory concentrations than the parent strain. The galU, galE, rfaI, and rfaB genes all encode enzymes that use UDP-galactose or UDP-glucose for galactose metabolism and lipopolysaccharide (LPS) biosynthesis. Indeed, we found that ciclopirox altered LPS composition of an E. coli clinical isolate. Taken together, our data demonstrate that ciclopirox affects galactose metabolism and LPS biosynthesis, two pathways important for bacterial growth and virulence. The lack of any reported fungal resistance to ciclopirox in over twenty years of use in the clinic, its excellent safety profiles, novel target(s), and efficacy, make ciclopirox a promising potential antimicrobial agent to use against multidrug-resistant problematic gram-negative pathogens.

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Project description:Klebsiella pneumoniae is one of the most common Gram-negative bacilli isolated from bloodstream infections worldwide, and recently an increased rate of carbapenem resistance has been reported in this pathogen. This study aims to describe the genomic characteristics of carbapenem-resistant K. pneumoniae (CRKP) isolated from patients with bacteremia in China. We analyzed 147 isolates from patients with bacteremia attended in 12 referral hospitals in China between April 2015 and November 2018. We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis to characterize antimicrobial resistance profile, virulence genes, and dominant clones among CRKP. ST11 accounted for most infections (n = 98, 66.6%), followed by ST45 (n = 12, 8.2%), ST15 and ST290 (n = 8, 5.4% each). KPC (n = 98, 66.7%) and NDM (n = 27, 18.4%) are the main carbapenemases detected in the CRKP isolates. We detected yersiniabactin (n = 123, 83.7%) and aerobactin (49.9%) siderophores, and both rmpA and aerobactin genes in 21 ST11 isolates (21.43%), which are considered characteristic biomarkers of hypervirulent strains. Isolates showed high resistance rates to the β-lactams (>90%) and other antibiotics classes such as fluoroquinolones, aminoglycosides and tetracyclines (50%), but were susceptible to ceftazidime-avibactam (74.8%). In addition, we detected intra-hospital transmission of ST11 and ST45 strains in single and multiple wards in several hospitals, whereas inter-hospital transmission was relatively uncommon. In summary, we observed significantly genomic diversity of CRKP bacteremia isolates in China, although KPC-2 producing ST11 strains were found to be the most common clonal types. Reducing intra-hospital transmission remains to be the key to control CRKP caused bloodstream infections in China. IMPORTANCE K. pneumoniae is one of the most frequent Gram-negative bacilli isolated from bloodstream infections worldwide and recent studies have shown an increased rate of carbapenem resistance in China. Among carbapenem-resistant K. pneumoniae (CRKP) diverse clones have been reported, especially the high-risk clone ST11, which also exhibited a multidrug resistant phenotype. In addition to the antimicrobial resistance, previous studies have detected strains co-harboring virulent traits, highlighting the potential of transmission of both antimicrobial resistant and virulent strains. Here we studied the antimicrobial resistance profile, virulence genes and hospital transmission of CRKP from bacteremic patients in China. This study showed a high clonal diversity among CRKP, with the predominance of ST11 lineages. We detected virulence markers among multidrug resistant strains, and a high number of genetically similar isolates, suggesting intra-hospital transmission within single and multiple wards. Reducing intra-hospital transmission remains to be the key to control CRKP caused bacteremia in China.

Dataset Information

No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia.

Publications

No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia.

Similar Datasets

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