Dataset Information

A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infections: tigecycline significantly increases the mortality.

ABSTRACT: Background:Carbapenem-nonsusceptible Klebsiella pneumoniae (CnSKP) is rapidly emerging as a life-threatening nosocomial infection. The efficacy of tigecycline in the treatment of bloodstream infections (BSIs) remains controversial. Methods:Data from a total of 428 patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) and CnSKP BSIs were collected at a single center between January 2013 and December 2015. A three-part analysis was conducted to identify the risk factors associated with CnSKP, explore prognosis, and evaluate treatments. Results:Data from 428 patients with Klebsiella pneumoniae (KP) BSIs were included, 31.5% (n=135) of them with CnSKP. Multivariate analysis showed that prior hospitalization, urinary catheterization, the use of immunosuppressive agents, prior use of antibiotics, pulmonary disease, and high Acute Physiology and Chronic Health Evaluation (APACHE) II scores were independent risk factors for CnSKP-BSIs. The 30-day mortality was higher in patients with CnSKP than in those with CSKP (58.5% vs 15.4%; P<0.001). In patients with KP-BSIs, neutropenia, multiple organ dysfunction, respiratory failure, CnSKP infection, high APACHE II score, and tigecycline therapy were independently associated with higher mortality risk. Among patients whose APACHE II score was <15, higher mortality rates were observed in patients treated with tigecycline than in those treated with other antibiotics (45.3% vs 7.7%; P<0.001). Central venous catheterization, multiple organ dysfunction, and high APACHE II scores were independent risk factors for death from CnSKP. Conclusion:A significant increase in the incidence of CnSKP-BSIs was observed during the study period, with a higher mortality rate found in these patients. Exposure to carbapenems and severe illness were independent risk factors for the development of CnSKP-BSIs, and tigecycline therapy resulted in a significant increase in mortality.

SUBMITTER: Xiao T

PROVIDER: S-EPMC5926074 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible <i>Klebsiella pneumoniae</i> bloodstream infections: tigecycline significantly increases the mortality.

Xiao Tingting T Yu Wei W Niu Tianshui T Huang Chen C Xiao Yonghong Y

Infection and drug resistance 20180424

<h4>Background</h4>Carbapenem-nonsusceptible <i>Klebsiella pneumoniae</i> (CnSKP) is rapidly emerging as a life-threatening nosocomial infection. The efficacy of tigecycline in the treatment of bloodstream infections (BSIs) remains controversial.<h4>Methods</h4>Data from a total of 428 patients with carbapenem-susceptible <i>Klebsiella pneumoniae</i> (CSKP) and CnSKP BSIs were collected at a single center between January 2013 and December 2015. A three-part analysis was conducted to identify the ...[more]

PMID: 29731648

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Project description:Abstract Background Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3–9] vs 6 [4–9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074–1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort. Piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible Enterobacterales have been increasingly identified in the New York metropolitan area. In noncritically ill patients with uncomplicated infections of this phenotype, carbapenem-sparing agents, including third-generation cephalosporins, may be considered.

Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a significant public health challenge worldwide, but research on IMP-producing CR-hvKP and its tigecycline resistance is extremely scarce. We report herein the recovery of two IMP-4-producing, capsular serotype K2, sequence type 65 (K2-ST65), hypervirulent K. pneumoniae isolates (C1672 and C2051), which caused severe and fatal infections in ICU patients, after retrospectively screening 3,285 carbapenem-resistant K. pneumoniae isolates from 26 provinces in China. Notably, C2051 also demonstrated tigecycline nonsusceptibility, mediated by a frameshift mutation in the TetR/AcrR family transcriptional regulator. Both strains harbored blaIMP-4 and critical plasmid-borne virulence genes (rmpA/rmpA2, iucA, and iroN) and demonstrated high virulence in Galleria mellonella, indicating CR-hvKP. The blaIMP-4 gene was located on the IncU- and IncN-type plasmids, which showed high stability in C1672 and C2051 after serial passage for 5 days, with retention rates of 87% and 93.7%, respectively. No significant differences in growth rates were observed among the parental strains and the corresponding resistance plasmid-cured mutants (P = 0.5273), suggesting that strains carrying the blaIMP and virulence plasmids have the potential to exist for a long time without compromising fitness. The genetic environments of the blaIMP-4 gene in both strains were similar, and it has been inferred that the genetic regions of blaIMP-4 were inserted into different backbones. Several conjugal transfer genes, such as traO, traE, traN, and traBCD, were identified in the blaIMP-4-bearing plasmid of C2051, suggesting a higher ability for plasmid transmission. The convergence of IMP carbapenemase and tigecycline nonsusceptibility in a classic hypervirulent K. pneumoniae lineage highlights the need to enhance clinical awareness and epidemiologic surveillance. IMPORTANCE To date, research on IMP-producing CR-hvKP is extremely scarce. Only one case of urinary tract infection caused by an IMP-6-producing K1-ST23 hypervirulent K. pneumoniae isolate in Japan was recorded, with a limited description of clinical information and genomic features. None of the published studies examined the virulence of the reported strains or the stability and fitness of resistance plasmids or presented a phylogenetic analysis. This dearth of data is notable because CR-hvKP infections are increasingly identified, but critical characteristics of the emerging resistance mediated by IMP carbapenemases in CR-hvKP remain unknown. Here, we report the emergence of two IMP-4 carbapenemase-producing K2-ST65 hypervirulent K. pneumoniae isolates that caused severe and fatal infections in clinical settings in China. Notably, one of them also demonstrated tigecycline nonsusceptibility. These strains carrying blaIMP and virulence plasmids had the potential to exist for a long time without compromising their fitness, highlighting the urgent need to enhance clinical awareness and epidemiologic surveillance to prevent their dissemination.

Project description:Background:The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP), especially the emergence of tigecycline-resistant K. pneumoniae (KP), is a serious public health concern. However, the underlying mechanism of tigecycline resistance is unclear. In this study, we evaluated the role of the CusS-CusR two-component system (TCS), which is associated with copper/silver resistance, in tigecycline resistance in CRKP. Methods:Following the in vitro evolution of tigecycline-resistant KP, the minimum inhibitory concentrations of tigecycline were determined using the micro-broth dilution method. RNA sequencing and data analysis were performed to identify differentially expressed genes. Quantitative PCR (qPCR) was performed to verify the genes of interest. Genes associated with tigecycline resistance, such as ramR, tex (T), and tet (A), were detected by PCR, and then mutants were confirmed by sequencing. Additionally, the efflux pump-associated genes soxS, oqxA, oqxB, acrE, and acrF were also analyzed by qPCR. CusR was deleted and complemented by the suicide vector pKO3-Km plasmid and pGEM-T-easy plasmid, respectively. Results:Nine strains of KP were evaluated in our study. Strains A2 and A3 were evolved from A1, B2, and B3 were evolved from B1, and C2 and C3 were evolved from C1. The tigecycline minimum inhibitory concentration for A1, B1, and C1 was 0.5 ?g/mL; that for A2, B2, and C3 was 16.0 ?g/mL; and that for A3, B3, and C3 was 32.0 ?g/mL. RNA-sequencing and qPCR confirmed that the differentially expressed genes cusE, cusS, cusR, cusC, cusF, cusB, and cusA showed higher expression in C2 and C3 than in C1. Genes related to the efflux pump AcrAB-TolC showed higher expression in B2 and B3 than in B1. No mutants of ramR, tex (T), or tet (A) were detected. SoxS, oqxA, oqxB, acrE, and acrF did not show increased expression in any group. After deletion and complementation of cusR among C3, the MIC of tigecycline decreased to 4 ?g/mL, and then recovered to 32 ?g/mL. The expression of cusFBCA, correspondingly decreased and increased significantly. Conclusion:In addition to its primary function in resistance to copper/silver, the CusS-CusR two-component system is associated with CRKP resistance to tigecycline.

Dataset Information

A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infections: tigecycline significantly increases the mortality.

Publications

A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible <i>Klebsiella pneumoniae</i> bloodstream infections: tigecycline significantly increases the mortality.

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