Extensively Drug-Resistant Klebsiella pneumoniae Causing Nosocomial Bloodstream Infections in China: Molecular Investigation of Antibiotic Resistance Determinants, Informing Therapy, and Clinical Outcomes

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.

Epidemiology and risk factors of neurosurgical bacterial meningitis/encephalitis induced by carbapenem resistant Enterobacteriaceae

“…Unfortunately, these types of antibiotics possess severe adverse effects, which blocked substantial clinical applications. From this study, for carbapenems, the susceptibility was 83.6%, and despite the low ratio of CRE (16.4%), it can result in extremely grievous consequences [15]. Depending on the present study, antibiotic prophylaxis and empirical are routine manipulation during the neurosurgery operation.…”

Amino Acid Biosynthetic Pathways Are Required for Klebsiella pneumoniae Growth in Immunocompromised Lungs and Are Druggable Targets during Infection

“…Selection of spontaneous glyphosate-resistant and generation of aroA catalytically active-site glyphosate-resistant mutants in K. pneumoniae. As K. pneumoniae rapidly acquires resistance to antibiotics (28,29), we evaluated the rate of spontaneous glyphosate resistance of K. pneumoniae (see Materials and Methods). WT K. pneumoniae was grown overnight in L and plated on M9ϩglucose containing 1,000 g/ml glyphosate, 50 g/ml rifampin (RIF), or 200 g/ml streptomycin (STR).…”

Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa

“…Wenzi Bi. et al, in 2017, reported the dissemination and epidemicity of clinical XDR K. pneumoniae strains result from horizontal transmission of multiple resistance determinants via IncF plasmids [67]. More so, the multi replicon nature of the p18-43_01 plasmid was not peculiar, as a diversity of plasmid incompatibility groups (Inc), including IncX, IncR, IncN, IncL/M, IncA/C, and IncF have been linked with NDM variants [26,27,68,69].…”