American Journal of Transplantation 2014; 14: 1901–1907 Wiley Periodicals Inc.
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Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12798
Brief Communication
Clostridium difficile Infection in Liver Transplant Recipients: A Retrospective Study of Rates, Risk Factors and Outcomes C. Mittal1,*, S. Hassan1, S. Arshad1, S. Jeepalyam1, S. Bruni2, M. Miceli1, G. Jacobsen1, M. Abouljoud3, I. Bajjoka3, M. Ramesh1,2,3 and G. Alangaden1,2,3 1
Division of Infectious Diseases, Henry Ford Health System, Detroit, MI 2 School of Medicine, Wayne State University, Detroit, MI 3 Transplant Institute, Henry Ford Health System, Detroit, MI Corresponding author: Chetan Mittal, [email protected]
Clostridium difficile infection (CDI) occurs in 3–7% of liver transplant recipients (LTR). However, few data exist on the recent epidemiology, predictors and outcomes of CDI in LTR. A cohort study was performed including LTR from 2000 to 2010 at a tertiary care hospital in Detroit. CDI was defined as diarrhea with a stool C. difficile positive test. Data analyzed included demographics, comorbidities, length of stay (LOS), severity of CDI, rates of recurrence (1.5 times the baseline, abdominal distension, low albumin, ICU treatment and CDI-related colectomy (10,11). Since several of these parameters may be abnormal in patients with end-stage liver disease and LTR, for the purposes of this study severe CDI was defined as the presence of the following—white cell count >15 000 cells/mm3 within 1 week of onset of CDI (in the absence of other cause), or CDI-related colectomy. Recurrent CDI was defined as new-onset of diarrhea and a positive stool toxin assay within 12 weeks of previous CDI. If recurrent CDI occurred within 4 weeks of prior episode of CDI, it was considered a relapse of CDI. CDI was classified by the onset of symptoms according to the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network surveillance definition (9). Community onset CDI—onset of symptoms within 72 h of hospital admission; hospital onset CDI—symptom onset after 72 h of admission; health-care facility (HCF) associated CDI—CDI in a patient discharged from an HCF within the last 12 weeks; Communityassociated CDI—disease in patients with no prior HCF stay in the previous 12 weeks (12). Cases considered as indeterminate in the CDC definition were considered HCF associated.
Results A total of 970 LTR (mean age 53.2 10.0 years, women 34.6% and white 64.5%) were identified between January 2000 and December 2010. Table 1 summarizes the baseline characteristics of the patients with post-LT CDI (cases) and those without CDI (controls).
Rates CDI occurred in 32 (3.3%) patients pretransplant (within 30 days before LT), and 162 (16.7%) patients developed CDI posttransplant. The overall prevalence of CDI in LTR was 18.9% (n ¼ 183). The incidence of CDI in LTR within 1 year of transplant (early CDI) was 12.4% (120/970) and after 1 year of transplant (late CDI) was 6.6% (63/954). Overall the median time to CDI after LT was 51 days. Of the patients with CDI, 29.1% (n ¼ 53) had severe CDI, 53 had white cell count >15 000 and 5 required a colectomy. Of the 53 patients with white cell count >15 000, 3 required a colectomy for CDI. A new rise in serum creatinine was noted in 45% (n ¼ 72). The CDI recurrence rate was 16.9%, with an average time to recurrence (mean SD) of 62.5 26.5 days. The CDI relapse rate was 9.7%. Among patients with severe CDI, 29% developed recurrence compared to 13% recurrence in patients without severe CDI. Graft loss rate was 3.6% but was not attributable to CDI. Hospital onset of infection versus community onset was 62% versus 38%, respectively. Statistical significance was detected for hospital onset of CDI predicting severe infection and mortality versus community onset (Table 2). The HCF acquired CDI rate was 77% as compared to community acquired rate of 23%. Single drug therapy was used in 32.7% (oral metronidazole), 1.2% (IV metronidazole) and 4.3% (oral vancomycin), respectively. Combination therapy was used in 15.4% (oral metronidazole and oral vancomycin), 9.3% (IV metronidazole and oral vancomycin) and 2% (oral metronidazole, IV metronidazole and oral vancomycin).
Statistical methodology Data analysis of all LTR and outcomes were stratified according to presence of CDI posttransplant. Baseline characteristics were summarized using basic frequencies to obtain descriptive information such as age, sex, race and mean pretransplant MELD scores. Continuous variables were expressed in mean standard deviation since there was minimal skewing of
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Predictors of posttransplant CDI The statistically significant predictors of posttransplant infection were year of transplant, race, MELD score and transplant LOS (Table 3). All (100%) of LTR in the study American Journal of Transplantation 2014; 14: 1901–1907
Clostridium difficile Infections in Liver Transplant Recipients Table 1: Characteristics of liver transplant recipients with and without C. difficile infection (CDI)
Variables Age in years (mean SD) Male gender White race Black race Charlson score (mean SD) Charlson score 3 No. of antibiotics
C
Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12798
Brief Communication
Clostridium difficile Infection in Liver Transplant Recipients: A Retrospective Study of Rates, Risk Factors and Outcomes C. Mittal1,*, S. Hassan1, S. Arshad1, S. Jeepalyam1, S. Bruni2, M. Miceli1, G. Jacobsen1, M. Abouljoud3, I. Bajjoka3, M. Ramesh1,2,3 and G. Alangaden1,2,3 1
Division of Infectious Diseases, Henry Ford Health System, Detroit, MI 2 School of Medicine, Wayne State University, Detroit, MI 3 Transplant Institute, Henry Ford Health System, Detroit, MI Corresponding author: Chetan Mittal, [email protected]
Clostridium difficile infection (CDI) occurs in 3–7% of liver transplant recipients (LTR). However, few data exist on the recent epidemiology, predictors and outcomes of CDI in LTR. A cohort study was performed including LTR from 2000 to 2010 at a tertiary care hospital in Detroit. CDI was defined as diarrhea with a stool C. difficile positive test. Data analyzed included demographics, comorbidities, length of stay (LOS), severity of CDI, rates of recurrence (1.5 times the baseline, abdominal distension, low albumin, ICU treatment and CDI-related colectomy (10,11). Since several of these parameters may be abnormal in patients with end-stage liver disease and LTR, for the purposes of this study severe CDI was defined as the presence of the following—white cell count >15 000 cells/mm3 within 1 week of onset of CDI (in the absence of other cause), or CDI-related colectomy. Recurrent CDI was defined as new-onset of diarrhea and a positive stool toxin assay within 12 weeks of previous CDI. If recurrent CDI occurred within 4 weeks of prior episode of CDI, it was considered a relapse of CDI. CDI was classified by the onset of symptoms according to the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network surveillance definition (9). Community onset CDI—onset of symptoms within 72 h of hospital admission; hospital onset CDI—symptom onset after 72 h of admission; health-care facility (HCF) associated CDI—CDI in a patient discharged from an HCF within the last 12 weeks; Communityassociated CDI—disease in patients with no prior HCF stay in the previous 12 weeks (12). Cases considered as indeterminate in the CDC definition were considered HCF associated.
Results A total of 970 LTR (mean age 53.2 10.0 years, women 34.6% and white 64.5%) were identified between January 2000 and December 2010. Table 1 summarizes the baseline characteristics of the patients with post-LT CDI (cases) and those without CDI (controls).
Rates CDI occurred in 32 (3.3%) patients pretransplant (within 30 days before LT), and 162 (16.7%) patients developed CDI posttransplant. The overall prevalence of CDI in LTR was 18.9% (n ¼ 183). The incidence of CDI in LTR within 1 year of transplant (early CDI) was 12.4% (120/970) and after 1 year of transplant (late CDI) was 6.6% (63/954). Overall the median time to CDI after LT was 51 days. Of the patients with CDI, 29.1% (n ¼ 53) had severe CDI, 53 had white cell count >15 000 and 5 required a colectomy. Of the 53 patients with white cell count >15 000, 3 required a colectomy for CDI. A new rise in serum creatinine was noted in 45% (n ¼ 72). The CDI recurrence rate was 16.9%, with an average time to recurrence (mean SD) of 62.5 26.5 days. The CDI relapse rate was 9.7%. Among patients with severe CDI, 29% developed recurrence compared to 13% recurrence in patients without severe CDI. Graft loss rate was 3.6% but was not attributable to CDI. Hospital onset of infection versus community onset was 62% versus 38%, respectively. Statistical significance was detected for hospital onset of CDI predicting severe infection and mortality versus community onset (Table 2). The HCF acquired CDI rate was 77% as compared to community acquired rate of 23%. Single drug therapy was used in 32.7% (oral metronidazole), 1.2% (IV metronidazole) and 4.3% (oral vancomycin), respectively. Combination therapy was used in 15.4% (oral metronidazole and oral vancomycin), 9.3% (IV metronidazole and oral vancomycin) and 2% (oral metronidazole, IV metronidazole and oral vancomycin).
Statistical methodology Data analysis of all LTR and outcomes were stratified according to presence of CDI posttransplant. Baseline characteristics were summarized using basic frequencies to obtain descriptive information such as age, sex, race and mean pretransplant MELD scores. Continuous variables were expressed in mean standard deviation since there was minimal skewing of
1902
Predictors of posttransplant CDI The statistically significant predictors of posttransplant infection were year of transplant, race, MELD score and transplant LOS (Table 3). All (100%) of LTR in the study American Journal of Transplantation 2014; 14: 1901–1907
Clostridium difficile Infections in Liver Transplant Recipients Table 1: Characteristics of liver transplant recipients with and without C. difficile infection (CDI)
Variables Age in years (mean SD) Male gender White race Black race Charlson score (mean SD) Charlson score 3 No. of antibiotics
