Risk factors for Klebsiella pneumoniae carbapenemase (KPC) gene acquisition and clinical outcomes across multiple bacterial species

Abstract Background Carbapenemase-producing Klebsiella pneumoniae has become a global priority, not least in low- and middle-income countries. Here, we report the emergence and clinical impact of a novel Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-KP) sequence type (ST) 16 clone in a clonal complex (CC) 258–endemic setting. Methods In a teaching Brazilian hospital, a retrospective cohort of adult KPC-KP bloodstream infection (BSI) cases (January 2014 to December 2016) was established to study the molecular epidemiology and its impact on outcome (30-day all-cause mortality). KPC-KP isolates underwent multilocus sequence typing. Survival analysis between ST/CC groups and risk factors for fatal outcome (logistic regression) were evaluated. Representative isolates underwent whole-genome sequencing and had their virulence tested in a Galleria larvae model. Results One hundred sixty-five unique KPC-KP BSI cases were identified. CC258 was predominant (66%), followed by ST16 (12%). The overall 30-day mortality rate was 60%; in contrast, 95% of ST16 cases were fatal. Patients’ severity scores were high and baseline clinical variables were not statistically different across STs. In multivariate analysis, ST16 (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3–202.8; P = .008) and septic shock (OR, 11.9; 95% CI, 4.2–34.1; P < .001) were independent risk factors for fatal outcome. The ST16 clone carried up to 14 resistance genes, including blaKPC-2 in an IncFIBpQIL plasmid, KL51 capsule, and yersiniabactin virulence determinants. The ST16 clone was highly pathogenic in the larvae model. Conclusions Mortality rates were high in this KPC-KP BSI cohort, where CC258 is endemic. An emerging ST16 clone was associated with high mortality. Our results suggest that even in endemic settings, highly virulent clones can rapidly emerge demanding constant monitoring.

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Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-017-3160-z ◽

2017 ◽

Vol 37 (4) ◽

pp. 679-689 ◽

Cited By ~ 15

Author(s):

Jiayang Li ◽

Jianan Ren ◽

Weiping Wang ◽

Gefei Wang ◽

Guosheng Gu ◽

...

Keyword(s):

Risk Factors ◽

Klebsiella Pneumoniae ◽

Clinical Outcomes ◽

Bloodstream Infections

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Risk Factors and Outcomes for Carbapenem-Resistant Klebsiella pneumoniae Isolation, Stratified by Its Multilocus Sequence Typing: ST258 Versus Non-ST258

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv213 ◽

2016 ◽

Vol 3 (1) ◽

Cited By ~ 9

Author(s):

Sorabh Dhar ◽

Emily T. Martin ◽

Paul R. Lephart ◽

John P. McRoberts ◽

Teena Chopra ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Klebsiella Pneumoniae ◽

Molecular Epidemiology ◽

Clinical Outcomes ◽

Multilocus Sequence Typing ◽

Clinical Impact ◽

Sequence Type ◽

Epidemiological Investigation ◽

Carbapenem Resistant

Abstract A “high risk” clone of carbapenem-resistant Klebsiella pneumoniae (CRKP) identified by multilocus sequence typing (MLST) as sequence type (ST) 258 has disseminated worldwide. As the molecular epidemiology of the CRE pandemic continues to evolve, the clinical impact of non-ST258 strains is less well defined. We conducted an epidemiological investigation of CRKP based on strains MLST. Among 68 CRKP patients, 61 were ST258 and 7 belonged to non-ST258. Klebsiella pneumoniae ST258 strains were significantly associated with blaKPC production and with resistance to an increased number of antimicrobials. Clinical outcomes were not different. Based on this analysis, one cannot rely solely on the presence of blaKPC in order to diagnose CRKP.

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Risk Factors and Clinical Impact of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae

Infection Control and Hospital Epidemiology ◽

10.1086/648451 ◽

2009 ◽

Vol 30 (12) ◽

pp. 1180-1185 ◽

Cited By ~ 193

Author(s):

Leanne B. Gasink ◽

Paul H. Edelstein ◽

Ebbing Lautenbach ◽

Marie Synnestvedt ◽

Neil O. Fishman

Keyword(s):

Risk Factors ◽

Klebsiella Pneumoniae ◽

Infection Control ◽

Hospital Mortality ◽

Multivariable Analysis ◽

Severe Illness ◽

Emerging Pathogen ◽

Klebsiella Pneumoniae Carbapenemase ◽

Control Subjects ◽

Anatomic Locations

Background.Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is an emerging pathogen with serious clinical and infection control implications. To our knowledge, no study has specifically examined risk factors for KPC-producing K. pneumoniae or its impact on mortality.Methods.To identify risk factors for infection or colonization with KPC-producing K. pneumoniae, a case-control study was performed. Case patients with KPC-producing K. pneumoniae were compared with control subjects with carbapenem-susceptible K. pneumoniae. A cohort study evaluated the association between KPC-producing K. pneumoniae and in-hospital mortality.Results.Fifty-six case patients and 863 control subjects were identified. In multivariable analysis, independent risk factors for KPC-producing K. pneumoniae were (1) severe illness (adjusted odds ratio [AOR], 4.31; 95% confidence interval [CI], 2.25–8.25), (2) prior fluoroquinolone use (AOR, 3.39; 95% CI, 1.50, 7.66), and (3) prior extended-spectrum cephalosporin use (AOR, 2.55; 95% CI, 1.18, 5.52). Compared with samples from other anatomic locations, K. pneumoniae isolates from blood samples were less likely to harbor KPC (AOR, 0.33; 95% CI, 0.12, 0.86). KPC-producing K. pneumoniae was independently associated with in-hospital mortality (AOR, 3.60; 95% CI, 1.87–6.91).Conclusions.KPC-producing K. pneumoniae is an emerging pathogen associated with significant mortality. Our findings highlight the urgent need to develop strategies for prevention and infection control. Limiting use of certain antimicrobials, specifically fluoroquinolones and cephalosporins, use may be effective strategies.

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