Abstract
The rise in diversity of antimicrobial resistance phenotypes seen in Klebsiella pneumoniae is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR) K. pneumoniae isolated from different nosocomial bloodstream infections (BSIs) patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients (P = 0.015). In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality (P = 0.016). Antimicrobial susceptibility tests, molecular detection of antibiotic resistance determinants, conjugation experiments, multilocus sequence typing (MLST), S1-PFGE, Southern blot, SDS-PAGE, immunoblot analysis, and pulsed-field gel electrophoresis (PFGE) were used to characterize these isolates. These XDR K. pneumoniae strains were resistant to conventional antimicrobials except tigecycline and polymyxin B and co-harbored diverse resistance determinants. rmtB, blaKPC−2 as well as blaCTX−M−9 were located on a transferable plasmid of ~54.2 kb and the most predominant replicon type was IncF. 23 of the 35 isolates belonging the predominant clone were found to incorporate the globally-disseminated sequence type ST11, but others including a unique, previously undiscovered lineage ST2281 (allelic profile: 4-1-1-22-7-4-35) were also found and characterized. The porins OmpK35 and OmpK36 were deficient in two carbapenemase-negative carbapenem-resistant strains, suggesting decreased drug uptake as a mechanism for carbapenem resistance. This study highlights the importance of tracking hospital acquired infections, monitoring modes of antibiotic resistance to improve health outcomes of BSIs patients and to highlight the problems of XDR K. pneumoniae dissemination in healthcare settings.
Highlights
The Gram-negative bacterium Klebsiella pneumoniae is widely distributed in the environment and increasingly reported as a cause of invasive infections in healthcare settings, particulary in immunocompromised patients (Bagley, 1985; Lee et al, 2016; Paczosa and Mecsas, 2016; Wyres and Holt, 2016)
The current study focused on pinpointing the antibiotic resistance determinants of XDR K. pneumoniae isolated from nosocomial bloodstream infections (BSIs) patients and factors closely related to clinical outcome, with emphasis on determining appropriate antimicrobial drug therapy
The mortality rate attributed to BSIs caused by XDR K. pneumoniae was 40.0%, i.e., 14 of the 35 patients died from the BSI
Summary
The Gram-negative bacterium Klebsiella pneumoniae is widely distributed in the environment and increasingly reported as a cause of invasive infections in healthcare settings, particulary in immunocompromised patients (Bagley, 1985; Lee et al, 2016; Paczosa and Mecsas, 2016; Wyres and Holt, 2016). Antimicrobial resistance in K. pneumoniae is increasing, beta-lactamases and carbapenemases having been well-characterized as increasing the infection threat (Mathers et al, 2015; Campos et al, 2016; Lee et al, 2016). This seriously antibiotic management problem is frequently seeing both nosocomial and community associated infections. The availability of alternative, effective antimicrobial agents is limited (Tang et al, 2016)
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