1836. Colistin Resistance in Patients with Carbapenem-resistant Klebsiella pneumoniae is Associated with Increased Mortality
Session: Poster Abstract Session: Treatment of HAIs/Antimicrobial Resistant Infections
Saturday, October 10, 2015
Room: Poster Hall

Background:   Colistin is a last-line treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP). Emergence of colistin resistance (ColR) is a growing threat. Here, we describe risk factors for and impact of ColR in CRKP.

Methods:   The Consortium on Resistance against Carbapenems in K. pneumoniae (CRaCKle) is a prospective multicenter consortium. Each patient was included once at the time of the first positive culture for a colistin-tested isolate between 12/24/2011 and 10/1/2014.  ColR was defined per EUCAST guidelines. Infection presence and severity were defined by standard criteria.

Results:   29/293 unique patients (10%) had ColR-CRKP.  Overall, 132 (45%) episodes represented CRKP infection.  Most CRKP were recovered from urine (170, 58%).  Time from admission to first positive culture was significantly shorter in ColR-CRKP than colistin-susceptible (ColS)-CRKP isolates (ColR median: 0 d; IQR 0-2.5 d vs ColS median 1d; IQR: 0-10.75d; p=0.01).   Receipt of colistin in the preceding 14 days before initial positive culture was uncommon in both groups (ColR 1/29 [3%] vs ColS 3/264 [1%]). Use of ampicillin/sulbactam was associated with ColR-CRKP (ColR: 4/29 [14%] vs ColS 6/264 [2%]; p=0.01). Neither infection vs. colonization status, gender, age, Charlson comorbidity index, nor Pitt Bacteremia Score (PBS) were associated with ColR-CRKP.  Overall 30-day mortality was 69/293 (24%); 12/29 (41%) in ColR, and 57/264 (22%) in ColS (p=0.02).  In a Cox proportional hazards model that also included PBS, culture source, and infection vs. colonization status, patients with ColR-CRKP were at increased risk of death (HR: 2.35; 95% CI: 1.19-4.29 [p=0.016]) (Figure).

Conclusion:   ColR was present in 10% of this nested cohort of patients with CRKP and was associated with increased risk of mortality. Many patients with ColR-CRKP were likely to have been colonized prior to hospitalization.

Madiha Salim, MD, Wayne State University, detroit, MI, Federico Perez, MD, Cleveland VAMC Case Western Reserve University, Cleveland, OH, Eric Cober, MD, Infectious Disease, Cleveland Clinic, Cleveland, OH, Sandra S. Richter, MD, FIDSA, Laboratory Medicine, Cleveland Clinic, Cleveland, OH, Robert Kalayjian, MD, Infectious Diseases, The Metrohealth Medical Center, Cleveland, OH, Robert Salata, MD, FIDSA, University Hospitals Case Medical Center, Cleveland, OH, Nikole Scalera, MD, MS, Summa Health, Akron, OH, Richard R. Watkins, MD, MS, FACP, Infectious Diseases, Akron General Medical Center, Akron, OH, Yohei Doi, MD, PhD, University of Pittsburgh Medical Center, Pittsburgh, PA, Scott Evans, PhD, MS, Harvard University, Boston, MA, Vance G. Fowler Jr., MD, Duke University Medical Center, Durham, NC, Robert Bonomo, MD, Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH, Keith Kaye, MD, MPH, FIDSA, FSHEA, Medicine, Wayne State University, Detroit, MI, David Van Duin, MD, PhD, Infectious Diseases, University of North Carolina, Chapel Hill, NC and The Antibacterial Resistance Leadership Group

Disclosures:

M. Salim, None

F. Perez, None

E. Cober, None

S. S. Richter, BD diagnostics: Investigator , Research support
OpGen: Investigator , Research support
bioMerieux: Investigator , Research support
Nanosphere: Investigator , Research support
Cerexa: Investigator , Research support
Pocared: Investigator , Research support
Biofire: Investigator , Research support
Achaogen: Investigator , Research support

R. Kalayjian, None

R. Salata, None

N. Scalera, None

R. R. Watkins, None

Y. Doi, Shionogi: Scientific Advisor , Consulting fee
Merck: Investigator , Research grant
Melinta: Consultant , Consulting fee

S. Evans, Soceity for Clinical Trials: Board Member , Unpaid
Fogarty: Grant Investigator , Salary
NIAID / NIH: Grant Investigator , Salary
Takeda/Millennium: Scientific Advisor , Consulting fee
Pfizer: Scientific Advisor , Consulting fee
Roche: Scientific Advisor , Consulting fee
Novartis: Scientific Advisor , Consulting fee
Achaogen: Scientific Advisor , Consulting fee
Alcon: Scientific Advisor , Consulting fee
Merck: Scientific Advisor , Consulting fee
Chelsea: Scientific Advisor , Consulting fee
Mannkind: Scientific Advisor , Consulting fee
QRx Pharma: Scientific Advisor , Consulting fee
IMMPACT: Scientific Advisor , Speaker honorarium
Genentech: Scientific Advisor , Consulting fee
Affymax: Scientific Advisor , Consulting fee
FzioMed: Scientific Advisor , Consulting fee
Auspex: Scientific Advisor , Consulting fee
Amgen: Scientific Advisor , Consulting fee
GSK: Scientific Advisor , Consulting fee
Boehringer-Ingelheim: Scientific Advisor , Consulting fee
American Statistical Association: Speaker , Speaker honorarium
FDA: Scientific Advisor , Speaker and Avisory honoaria
Osaka University: Speaker / teacher , Speaker honorarium
City of Hope: Speaker , Speaker honorarium
National Cerebral and Cardiovascular Center of Japan: Speaker , Speaker honorarium
PMDA (Japan): Speaker , Speaker honorarium
Drug Information Association: Speaker , Speaker honorarium
CITI: Speaker , Travel expenses
PPRECISE: Scientific Advisor , Speaker honorarium
Degruyter: Editor-in-Chief , Editor honoraria

V. G. Fowler Jr., Merck: Investigator and Scientific Advisor , Consulting fee and Research support
Pfizer: Consultant and Investigator , Consulting fee and Research support
Novartis: Consultant and Investigator , Consulting fee and Research support
Galderma: Consultant , Consulting fee
Novadigm: Consultant , Consulting fee
Durata: Consultant , Consulting fee
Debiopharm: Consultant , Consulting fee
Genentech: Consultant , Consulting fee
Achaogen: Consultant , Consulting fee
Affinium: Consultant , Consulting fee
Medicines Co.: Consultant , Consulting fee
Cerexa: Consultant and Investigator , Consulting fee and Research support
Tetraphase: Consultant , Consulting fee
Trius: Consultant , Consulting fee
MedImmune: Consultant and Investigator , Consulting fee and Research support
Bayer: Consultant , Consulting fee
Theravance: Consultant and Investigator , Consulting fee and Research support
Cubist: Consultant and Investigator , Consulting fee and Research support
Basilea: Consultant , Consulting fee
Advanced Liquid Logics: Investigator , Research support
Green Cross: educational development , Consulting fee

R. Bonomo, Astrazeneca: Investigator , Research support
Merck: Investigator , Research support
Melinta: Investigator , Research support

K. Kaye, Actavis: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium

D. Van Duin, Sanofi-Pasteur: Consultant , Consulting fee
Scynexis: Investigator , Research support

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