The Magnitude and Duration of Clostridium difficile Infection Risk Associated with Antibiotic Therapy: A Hospital Cohort Study

Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and M...

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Published in:	PloS one Vol. 9; no. 8; p. e105454
Main Authors:	Brown, Kevin A., Fisman, David N., Moineddin, Rahim, Daneman, Nick
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 26.08.2014 Public Library of Science (PLoS)
Subjects:	Adult Adults Aged Aged, 80 and over Anti-Bacterial Agents - adverse effects Anti-Bacterial Agents - therapeutic use Antibiotics Bacteria Biology and Life Sciences Clostridium difficile Clostridium difficile - isolation & purification Clostridium Infections - epidemiology Cohort analysis Cohort Studies Confidence intervals Cross Infection - epidemiology Diarrhea Epidemiology Female Health aspects Health risks Health sciences Health surveillance Hospitals Humans Incidence Infection Infections Infectious diseases Male Medical research Medicine and Health Sciences Middle Aged Nosocomial infection Nosocomial infections Patients Penicillin Physical Sciences Poisson density functions Prospective Studies Public health Regression analysis Regression models Research and Analysis Methods Risk Factors Staphylococcus infections Statistical analysis Statistical methods Studies Survival analysis Systematic review Therapy Toronto Ontario Canada Canada
ISSN:	1932-6203, 1932-6203
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Abstract	Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.
AbstractList	Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought. Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.
Audience	Academic
Author	Brown, Kevin A. Moineddin, Rahim Fisman, David N. Daneman, Nick
AuthorAffiliation	3 Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada 1 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada The University of Tokyo, Japan 2 Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/25157757$$D View this record in MEDLINE/PubMed
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: KAB DNF RM ND. Performed the experiments: KAB ND. Analyzed the data: KAB DNF RM ND. Contributed reagents/materials/analysis tools: KAB RM. Wrote the paper: KAB DF ND. Drafted the manuscript: KAB ND. Critically revised the manuscript: DNF RM ND. Competing Interests: The authors have read the journal's policy and have the following conflicts: Dr. Fisman has received research funding from Novartis, Sanofi-Pasteur, and GlaxoSmithKline vaccine divisions. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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SubjectTerms	Adult Adults Aged Aged, 80 and over Anti-Bacterial Agents - adverse effects Anti-Bacterial Agents - therapeutic use Antibiotics Bacteria Biology and Life Sciences Clostridium difficile Clostridium difficile - isolation & purification Clostridium Infections - epidemiology Cohort analysis Cohort Studies Confidence intervals Cross Infection - epidemiology Diarrhea Epidemiology Female Health aspects Health risks Health sciences Health surveillance Hospitals Humans Incidence Infection Infections Infectious diseases Male Medical research Medicine and Health Sciences Middle Aged Nosocomial infection Nosocomial infections Patients Penicillin Physical Sciences Poisson density functions Prospective Studies Public health Regression analysis Regression models Research and Analysis Methods Risk Factors Staphylococcus infections Statistical analysis Statistical methods Studies Survival analysis Systematic review Therapy
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Title	The Magnitude and Duration of Clostridium difficile Infection Risk Associated with Antibiotic Therapy: A Hospital Cohort Study
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