HHS Public Access Author manuscript Author Manuscript
Am J Transplant. Author manuscript; available in PMC 2017 February 06. Published in final edited form as: Am J Transplant. 2015 November ; 15(11): 2970–2977. doi:10.1111/ajt.13491.
Hospital-Onset Clostridium difficile Infection among Solid Organ Transplant Recipients John P. Donnelly, MSPH1,2,3, Henry E. Wang, MD, MS1, Jayme E. Locke, MD, MPH4, Roslyn B. Mannon, MD5,6, Monika M. Safford, MD2, and John W. Baddley, MD, MSPH7 1Department
of Emergency Medicine, University of Alabama School of Medicine, Birmingham AL
Author Manuscript
2Department
of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham AL 3School
of Public Health, Department of Epidemiology, University of Alabama at Birmingham, Birmingham AL 4Comprehensive
Transplant Institute, University of Alabama at Birmingham, Birmingham AL
5Department
of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham AL 6Department
of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham AL 7Department
Author Manuscript
of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham AL
Abstract
Author Manuscript
Clostridium difficile infection (CDI) is a considerable health issue in the United States, and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can impact graft as well as patient survival. However, little is known about the impact of CDI on health services utilization post-transplant. We examined hospital-onset CDI from 2012-2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the US. Infection was five times more common among transplant recipients compared to general inpatients (209 vs. 40 per 10,000 discharges) and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional riskstandardized CDI varied more than three-fold across high-volume hospitals (infection ratio 0.54-1.82; median 1.04; interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications and cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were Corresponding Author: John W. Baddley, MD, MSPH, University of Alabama at Birmingham, Department of Medicine, Division of Infectious Diseases, 1900 University Boulevard, 229 Tinsley Harrison Tower, Birmingham, AL 35294-0006, Phone: 1-(205) 934-5191, Fax: 1-(205) 934-5155, [email protected]. This work was presented at the World Transplant Congress, San Francisco, CA, USA, July 31, 2014. Disclosure: The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr. Baddley reports consulting for Merck, Astellas and Pfizer. Dr. Safford reports investigator initiated research from Amgen. The other authors have no conflicts of interest to disclose.
Donnelly et al.
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substantially higher than risk-standardized expected values (40,094 vs. 22,843 days; $198,728,368 vs. $154,020,528 costs). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.
Introduction
Author Manuscript
Clostridium difficile infection (CDI) is an important problem in the United States (US), and the epidemiology of this infection has changed dramatically in recent years.(1) There were 453,000 cases in 2011, which represents a substantial increase over the prior decade, and associations with common treatment modalities have been identified.(1-3) Nearly two-thirds of infections are thought to be healthcare-associated, making this the most common healthcare-associated infection in the US.(1, 4) Importantly, CDI is associated with significant morbidity and mortality, leading to nearly 30,000 deaths within 30 days of onset in 2011, with healthcare-associated infections accounting for the majority.(1, 5, 6)
Author Manuscript
CDI is particularly problematic in organ transplant recipients, which constitute a substantial and growing population, with nearly 30,000 US patients receiving a solid organ transplant (SOT) in 2012.(7) Among SOT recipients included in a national study, CDI occurred in 2.7%, with over 1,300 US cases in 2009.(8) SOT recipients experience a generalized period of increased infection risk following transplant due to the use of immunosuppressive agents, surgical complications, and extended hospital stays.(8-11) In addition to this generalized risk, SOT recipients experience an elevated risk of CDI compared to the general patient population due to use of antibiotic prophylaxis and gastric acid suppressing agents as well as post-transplant hypogammaglobulinemia.(2, 3, 12) This infection can greatly impact the health of SOT recipients, as prior studies have shown that CDI is associated with increased mortality and graft loss.(13, 14) Although several prior efforts have examined the epidemiology of CDI among SOT recipients, there are few data on hospital-onset CDI during the transplant hospitalization, as well as utilization of health services and institutional variation in CDI.(8, 14, 15) In this study, we determined factors associated with CDI, examined risk-adjusted institutional variation in infection, and assessed the impact of CDI on outcomes following SOT in a consortium of academic medical center-affiliated hospitals.
Materials and Methods Study Design
Author Manuscript
This retrospective cohort study used hospital discharge data from the University HealthSystem Consortium (UHC) clinical database (CDB). The study received approval from the Institutional Review Board of the University of Alabama at Birmingham. Data Source The UHC is a collaborative effort encompassing academic medical centers and affiliated hospitals in the US. Representing 42 states, UHC aims to improve institutional clinical, operational and financial performance. For quality improvement purposes, UHC maintains
Am J Transplant. Author manuscript; available in PMC 2017 February 06.
Donnelly et al.
Page 3
Author Manuscript
the CDB, which contains administrative data submitted by hospitals in the consortium. This data source captures the elements of the standard UB-04 reporting form and encompasses data pertaining to patient demographics, discharge diagnoses, procedures and outcomes. The CDB has been described in detail previously.(16, 17) We used UHC CDB data for reporting member institutions for the period January 1, 2012 through December 31, 2014. Cohort Selection
Author Manuscript
This analysis consisted of discharges receiving SOT in a UHC hospital. SOTs were identified using International Classification of Diseases 9th Revision (ICD-9) procedure codes, including transplants of the lung (ICD-9: 33.5), heart (37.5), intestines (46.97), liver (50.5), pancreas (52.8), and kidney (55.6). Kidney-pancreas and kidney-liver co-transplants were defined if codes for both organs were identified. We excluded patients 1 is worse than average. Infection Ratio < 1 better than average. Y-axis shown on logarithmic scale. Triangle markers represent hospitals significantly above or below the average consortium performance.
Author Manuscript Author Manuscript Am J Transplant. Author manuscript; available in PMC 2017 February 06.
Author Manuscript
Author Manuscript 4,629 (8.7) 146 (0.3) 1,497 (2.8) 984 (1.9)
Heart
Intestines
Kidney-Pancreas Co-Transplant
Kidney-Liver Co-Transplant
Am J Transplant. Author manuscript; available in PMC 2017 February 06. Published in final edited form as: Am J Transplant. 2015 November ; 15(11): 2970–2977. doi:10.1111/ajt.13491.
Hospital-Onset Clostridium difficile Infection among Solid Organ Transplant Recipients John P. Donnelly, MSPH1,2,3, Henry E. Wang, MD, MS1, Jayme E. Locke, MD, MPH4, Roslyn B. Mannon, MD5,6, Monika M. Safford, MD2, and John W. Baddley, MD, MSPH7 1Department
of Emergency Medicine, University of Alabama School of Medicine, Birmingham AL
Author Manuscript
2Department
of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham AL 3School
of Public Health, Department of Epidemiology, University of Alabama at Birmingham, Birmingham AL 4Comprehensive
Transplant Institute, University of Alabama at Birmingham, Birmingham AL
5Department
of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham AL 6Department
of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham AL 7Department
Author Manuscript
of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham AL
Abstract
Author Manuscript
Clostridium difficile infection (CDI) is a considerable health issue in the United States, and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can impact graft as well as patient survival. However, little is known about the impact of CDI on health services utilization post-transplant. We examined hospital-onset CDI from 2012-2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the US. Infection was five times more common among transplant recipients compared to general inpatients (209 vs. 40 per 10,000 discharges) and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional riskstandardized CDI varied more than three-fold across high-volume hospitals (infection ratio 0.54-1.82; median 1.04; interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications and cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were Corresponding Author: John W. Baddley, MD, MSPH, University of Alabama at Birmingham, Department of Medicine, Division of Infectious Diseases, 1900 University Boulevard, 229 Tinsley Harrison Tower, Birmingham, AL 35294-0006, Phone: 1-(205) 934-5191, Fax: 1-(205) 934-5155, [email protected]. This work was presented at the World Transplant Congress, San Francisco, CA, USA, July 31, 2014. Disclosure: The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr. Baddley reports consulting for Merck, Astellas and Pfizer. Dr. Safford reports investigator initiated research from Amgen. The other authors have no conflicts of interest to disclose.
Donnelly et al.
Page 2
Author Manuscript
substantially higher than risk-standardized expected values (40,094 vs. 22,843 days; $198,728,368 vs. $154,020,528 costs). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.
Introduction
Author Manuscript
Clostridium difficile infection (CDI) is an important problem in the United States (US), and the epidemiology of this infection has changed dramatically in recent years.(1) There were 453,000 cases in 2011, which represents a substantial increase over the prior decade, and associations with common treatment modalities have been identified.(1-3) Nearly two-thirds of infections are thought to be healthcare-associated, making this the most common healthcare-associated infection in the US.(1, 4) Importantly, CDI is associated with significant morbidity and mortality, leading to nearly 30,000 deaths within 30 days of onset in 2011, with healthcare-associated infections accounting for the majority.(1, 5, 6)
Author Manuscript
CDI is particularly problematic in organ transplant recipients, which constitute a substantial and growing population, with nearly 30,000 US patients receiving a solid organ transplant (SOT) in 2012.(7) Among SOT recipients included in a national study, CDI occurred in 2.7%, with over 1,300 US cases in 2009.(8) SOT recipients experience a generalized period of increased infection risk following transplant due to the use of immunosuppressive agents, surgical complications, and extended hospital stays.(8-11) In addition to this generalized risk, SOT recipients experience an elevated risk of CDI compared to the general patient population due to use of antibiotic prophylaxis and gastric acid suppressing agents as well as post-transplant hypogammaglobulinemia.(2, 3, 12) This infection can greatly impact the health of SOT recipients, as prior studies have shown that CDI is associated with increased mortality and graft loss.(13, 14) Although several prior efforts have examined the epidemiology of CDI among SOT recipients, there are few data on hospital-onset CDI during the transplant hospitalization, as well as utilization of health services and institutional variation in CDI.(8, 14, 15) In this study, we determined factors associated with CDI, examined risk-adjusted institutional variation in infection, and assessed the impact of CDI on outcomes following SOT in a consortium of academic medical center-affiliated hospitals.
Materials and Methods Study Design
Author Manuscript
This retrospective cohort study used hospital discharge data from the University HealthSystem Consortium (UHC) clinical database (CDB). The study received approval from the Institutional Review Board of the University of Alabama at Birmingham. Data Source The UHC is a collaborative effort encompassing academic medical centers and affiliated hospitals in the US. Representing 42 states, UHC aims to improve institutional clinical, operational and financial performance. For quality improvement purposes, UHC maintains
Am J Transplant. Author manuscript; available in PMC 2017 February 06.
Donnelly et al.
Page 3
Author Manuscript
the CDB, which contains administrative data submitted by hospitals in the consortium. This data source captures the elements of the standard UB-04 reporting form and encompasses data pertaining to patient demographics, discharge diagnoses, procedures and outcomes. The CDB has been described in detail previously.(16, 17) We used UHC CDB data for reporting member institutions for the period January 1, 2012 through December 31, 2014. Cohort Selection
Author Manuscript
This analysis consisted of discharges receiving SOT in a UHC hospital. SOTs were identified using International Classification of Diseases 9th Revision (ICD-9) procedure codes, including transplants of the lung (ICD-9: 33.5), heart (37.5), intestines (46.97), liver (50.5), pancreas (52.8), and kidney (55.6). Kidney-pancreas and kidney-liver co-transplants were defined if codes for both organs were identified. We excluded patients 1 is worse than average. Infection Ratio < 1 better than average. Y-axis shown on logarithmic scale. Triangle markers represent hospitals significantly above or below the average consortium performance.
Author Manuscript Author Manuscript Am J Transplant. Author manuscript; available in PMC 2017 February 06.
Author Manuscript
Author Manuscript 4,629 (8.7) 146 (0.3) 1,497 (2.8) 984 (1.9)
Heart
Intestines
Kidney-Pancreas Co-Transplant
Kidney-Liver Co-Transplant
