TY - JOUR
T1 - Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections
AU - Antibacterial Resistance Leadership Group
AU - Hauck, C.
AU - Cober, E.
AU - Richter, S. S.
AU - Perez, F.
AU - Salata, R. A.
AU - Kalayjian, R. C.
AU - Watkins, R. R.
AU - Scalera, N. M.
AU - Doi, Y.
AU - Kaye, K. S.
AU - Evans, S.
AU - Fowler, V. G.
AU - Bonomo, R. A.
AU - van Duin, D.
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681, and by funding to DVD and FP from the Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the NIH and the NIH roadmap for Medical Research. VGF was supported by Mid-Career Mentoring Award K24-AI093969 from NIH. In addition, this work was supported in part by the Veterans Affairs Merit Review Program (RAB), the National Institutes of Health (Grant AI072219-05 and AI063517-07 to RAB), and the Geriatric Research Education and Clinical Center VISN 10 (RAB), the Research Program Committees of the Cleveland Clinic (DVD), an unrestricted research grant from the STERIS Corporation (DVD). YD was supported by research awards R01AI104895 and R21AI107302 from the NIH. KSK is supported by the National Institute of Allergy and Infectious Diseases (Division of Microbiology and Infectious Diseases protocol 10-0065 and RO1 1R01AI119446-01).
Funding Information:
JAM, EC, FP, RAS, RCK, RRW, NMS and SE have no conflicts of interest. SSR has received research support from bioMérieux, BD Diagnostics, BioFire, OpGen, Forest Laboratories, Achaogen, Nanosphere and Pocared; and honorarium from bioMérieux. YD has received grant support from Merck and NIH; consulting fee from Melinta; and is on the advisory board for Shionogi. KK has acted as a consultant and grant investigator for Forest Laboratories, Inc., and has received consulting fee, grant and speaker's honorarium from Speaker's Bureau. RAB is both grant recipient and grant investigator for AstraZeneca , Merck, Melinta , Steris , NIH and VA Merit Review . VGF has received grant or research support from Advanced Liquid Logic , Cubist , Cerexa , MedImmune , Merck, NIH, Novartis , Pfizer and Theravance ; has acted as a paid consultant for Affinium, Baxter, Cerexa, Cubist, Debiopharm, Durata, Merck, Novartis, NovaDigm, The Medicines Company, MedImmune, Pfizer, Theravance and Trius; and received honoraria from Arpida, Astellas, Cubist, Inhibitex, Merck, Pfizer, Targanta, Theravance, Wyeth, Ortho-McNeil, Novartis and Vertex Pharmaceuticals. He is a member of Merck Co-Chair V710 Vaccine. DvD is on the advisory boards of Actavis, Tetraphase and Sanofi-Pasteur, and has received research funding from Steris Inc. and Scynexis. All other authors have no conflicts to report.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmi.2016.01.023
DO - 10.1016/j.cmi.2016.01.023
M3 - Article
C2 - 26850824
AN - SCOPUS:84961267158
VL - 22
SP - 513
EP - 519
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
SN - 1198-743X
IS - 6
ER -