Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections

doi:10.1016/j.cmi.2016.01.023

Observational Study

. 2016 Jun;22(6):513-9.

doi: 10.1016/j.cmi.2016.01.023. Epub 2016 Feb 3.

Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections

C Hauck¹, E Cober², S S Richter³, F Perez⁴, R A Salata⁵, R C Kalayjian⁶, R R Watkins⁷, N M Scalera⁸, Y Doi⁹, K S Kaye¹⁰, S Evans¹¹, V G Fowler Jr¹², R A Bonomo¹³, D van Duin¹⁴; Antibacterial Resistance Leadership Group

Affiliations

¹ Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.
² Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, USA.
³ Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
⁴ Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁵ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁶ Department of Medicine, MetroHealth Medical Center, Cleveland, OH, USA.
⁷ Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH, USA; Division of Infectious Diseases, Akron General Medical Center, Akron, OH, USA.
⁸ Division of Infectious Diseases, Summa Health System, Akron, OH, USA.
⁹ Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA.
¹¹ Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, USA.
¹² Division of Infectious Diseases, Duke University, Durham, NC, USA; Duke Clinical Research Institute, Duke University, Durham, NC, USA.
¹³ Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁴ Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA. Electronic address: david_vanduin@med.unc.edu.

PMID: 26850824
PMCID: PMC4930369
DOI: 10.1016/j.cmi.2016.01.023

Observational Study

Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections

C Hauck et al. Clin Microbiol Infect. 2016 Jun.

. 2016 Jun;22(6):513-9.

doi: 10.1016/j.cmi.2016.01.023. Epub 2016 Feb 3.

Authors

Affiliations

¹ Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.
² Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, USA.
³ Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.
⁴ Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁵ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁶ Department of Medicine, MetroHealth Medical Center, Cleveland, OH, USA.
⁷ Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH, USA; Division of Infectious Diseases, Akron General Medical Center, Akron, OH, USA.
⁸ Division of Infectious Diseases, Summa Health System, Akron, OH, USA.
⁹ Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA.
¹¹ Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, USA.
¹² Division of Infectious Diseases, Duke University, Durham, NC, USA; Duke Clinical Research Institute, Duke University, Durham, NC, USA.
¹³ Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹⁴ Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA. Electronic address: david_vanduin@med.unc.edu.

PMID: 26850824
PMCID: PMC4930369
DOI: 10.1016/j.cmi.2016.01.023

Abstract

Patients infected or colonized with carbapenem-resistant Klebsiella pneumoniae (CRKp) are often chronically and acutely ill, which results in substantial mortality unrelated to infection. Therefore, estimating excess mortality due to CRKp infections is challenging. The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) is a prospective multicenter study. Here, patients in CRACKLE were evaluated at the time of their first CRKp bloodstream infection (BSI), pneumonia or urinary tract infection (UTI). A control cohort of patients with CRKp urinary colonization without CRKp infection was constructed. Excess hospital mortality was defined as mortality in cases after subtracting mortality in controls. In addition, the adjusted hazard ratios (aHR) for time-to-hospital-mortality at 30 days associated with infection compared with colonization were calculated in Cox proportional hazard models. In the study period, 260 patients with CRKp infections were included in the BSI (90 patients), pneumonia (49 patients) and UTI (121 patients) groups, who were compared with 223 controls. All-cause hospital mortality in controls was 12%. Excess hospital mortality was 27% in both patients with BSI and those with pneumonia. Excess hospital mortality was not observed in patients with UTI. In multivariable analyses, BSI and pneumonia compared with controls were associated with aHR of 2.59 (95% CI 1.52-4.50, p <0.001) and 3.44 (95% CI 1.80-6.48, p <0.001), respectively. In conclusion, in patients with CRKp infection, pneumonia is associated with the highest excess hospital mortality. Patients with BSI have slightly lower excess hospital mortality rates, whereas excess hospital mortality was not observed in hospitalized patients with UTI.

Keywords: Klebsiella pneumoniae; carbapenem-resistant Enterobacteriaceae; epidemiology; mortality; pneumonia.

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Conflict of interest statement

Conflict of Interest:

No potential conflicts: J.A.M, E.C., F.P., R.A.S., R.C.K., R.R.W., N.M.S., and S.E.

Potential conflicts of interest: S.S.R: Research support from bioMerieux, BD Diagnostics, BioFire, OpGen, Forest Laboratories, Achaogen, Nanosphere and Pocared. Honorarium from bioMerieux. Y.D.: Grant support: Merck, NIH. Consulting fee: Melinta. Advisory board: Shionogi. K.K: Forest Laboratories, Inc., Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. R.A.B.: AstraZeneca: Grant Investigator, Grant recipient, Merck: Grant Investigator, Grant recipient, Melinta: Grant Investigator, Grant recipient, Steris: Grant Investigator, Grant recipient, NIH: Grant Investigator, Grant recipient, VA Merit Review: Grant Investigator, Grant recipient. V.G.F.: Grant/Research Support: Advanced Liquid Logic, Cubist, Cerexa, MedImmune, Merck, NIH, Novartis, Pfizer, Theravance. Paid Consultant: Affinium, Baxter, Cerexa, Cubist, Debiopharm, Durata, Merck, Novartis, NovaDigm, The Medicines Company, MedImmune, Pfizer, Theravance, Trius. Honoraria: Arpida, Astellas, Cubist, Inhibitex, Merck, Pfizer, Targanta, Theravance, Wyeth, Ortho-McNeil, Novartis, Vertex Pharmaceuticals. Membership: Merck Co-Chair V710 Vaccine.

D.v.D.: Actavis, Tetraphase, Sanofi-Pasteur, Advisory Board. Steris Inc., Research funding. Scynexis Research funding

All other authors: no conflicts reported

Figures

**Figure 1. Time-to-hospital-mortality compared between patients infected vs. colonized with carbapenem-resistant *K. pneumoniae* (CRKp)**
Kaplan-Meier curves are shown and groups were compared using log-rank testing. Data were censored at the time of hospital discharge. A. Time-to-hospital-mortality in patients with CRKp bloodstream infection. B. Time-to-hospital-mortality in patients with CRKp pneumonia. C. Time-to-hospital-mortality in patients with CRKp urinary tract infection.

See this image and copyright information in PMC

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References

1. Perez F, van Duin D. Carbapenem-resistant enterobacteriaceae: A menace to our most vulnerable patients. Cleve Clin J Med. 2013;80:225–33. - PMC - PubMed
1. van Duin D, Perez F, Rudin SD, et al. Surveillance of carbapenem-resistant klebsiella pneumoniae: Tracking molecular epidemiology and outcomes through a regional network. Antimicrob Agents Chemother. 2014;58:4035–41. - PMC - PubMed
1. Nouvenne A, Ticinesi A, Lauretani F, et al. Comorbidities and disease severity as risk factors for carbapenem-resistant klebsiella pneumoniae colonization: Report of an experience in an internal medicine unit. PLoS One. 2014;9:e110001. - PMC - PubMed
1. Martin ET, Tansek R, Collins V, et al. The carbapenem-resistant enterobacteriaceae score: A bedside score to rule out infection with carbapenem-resistant enterobacteriaceae among hospitalized patients. Am J Infect Control. 2013;41:180–2. - PubMed
1. Nguyen M, Eschenauer GA, Bryan M, et al. Carbapenem-resistant klebsiella pneumoniae bacteremia: Factors correlated with clinical and microbiologic outcomes. Diagn Microbiol Infect Dis. 67:180–4. - PubMed

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[1] Perez F, van Duin D. Carbapenem-resistant enterobacteriaceae: A menace to our most vulnerable patients. Cleve Clin J Med. 2013;80:225–33. - PMC - PubMed

[2] Perez F, van Duin D. Carbapenem-resistant enterobacteriaceae: A menace to our most vulnerable patients. Cleve Clin J Med. 2013;80:225–33. - PMC - PubMed

[3] van Duin D, Perez F, Rudin SD, et al. Surveillance of carbapenem-resistant klebsiella pneumoniae: Tracking molecular epidemiology and outcomes through a regional network. Antimicrob Agents Chemother. 2014;58:4035–41. - PMC - PubMed

[4] van Duin D, Perez F, Rudin SD, et al. Surveillance of carbapenem-resistant klebsiella pneumoniae: Tracking molecular epidemiology and outcomes through a regional network. Antimicrob Agents Chemother. 2014;58:4035–41. - PMC - PubMed

[5] Nouvenne A, Ticinesi A, Lauretani F, et al. Comorbidities and disease severity as risk factors for carbapenem-resistant klebsiella pneumoniae colonization: Report of an experience in an internal medicine unit. PLoS One. 2014;9:e110001. - PMC - PubMed

[6] Nouvenne A, Ticinesi A, Lauretani F, et al. Comorbidities and disease severity as risk factors for carbapenem-resistant klebsiella pneumoniae colonization: Report of an experience in an internal medicine unit. PLoS One. 2014;9:e110001. - PMC - PubMed

[7] Martin ET, Tansek R, Collins V, et al. The carbapenem-resistant enterobacteriaceae score: A bedside score to rule out infection with carbapenem-resistant enterobacteriaceae among hospitalized patients. Am J Infect Control. 2013;41:180–2. - PubMed

[8] Martin ET, Tansek R, Collins V, et al. The carbapenem-resistant enterobacteriaceae score: A bedside score to rule out infection with carbapenem-resistant enterobacteriaceae among hospitalized patients. Am J Infect Control. 2013;41:180–2. - PubMed

[9] Nguyen M, Eschenauer GA, Bryan M, et al. Carbapenem-resistant klebsiella pneumoniae bacteremia: Factors correlated with clinical and microbiologic outcomes. Diagn Microbiol Infect Dis. 67:180–4. - PubMed

[10] Nguyen M, Eschenauer GA, Bryan M, et al. Carbapenem-resistant klebsiella pneumoniae bacteremia: Factors correlated with clinical and microbiologic outcomes. Diagn Microbiol Infect Dis. 67:180–4. - PubMed

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Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections

Affiliations

Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections

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