Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

BACKGROUND & AIMS: Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. METHODS: We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. RESULTS: We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I2 = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I2 = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I2 = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. CONCLUSIONS: In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.

Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study.

OBJECTIVES: Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent or refractory Clostridium difficile infection (CDI); however, 10-20% of patients fail to achieve cure after a single FMT. The aim of this study was to identify risk factors associated with FMT failure and to develop and validate a prediction model for FMT failure. METHODS: Patient characteristics, CDI history, FMT characteristics, and outcomes data for patients treated between 2011 and 2015 at three academic tertiary referral centers were prospectively collected. Early FMT failure was defined as non-response or recurrence of diarrhea associated with positive stool C. difficile toxin or PCR within 1 month of FMT. Late FMT failure was defined as recurrence of diarrhea associated with positive stool C. difficile toxin or PCR between 1 and 3 months of the FMT. Patient data from two centers were used to determine independent predictors of FMT failure and to build a prediction model. A risk index was constructed based on coefficients of final predictors. The patient cohort from the third center was used to validate the prediction model. RESULTS: Of 328 patients in the developmental cohort, 73.5% (N=241) were females with a mean age of 61.4±19.3 years; 19.2% (N=63) had inflammatory bowel disease (IBD), and 23.5% (N=77) were immunocompromised. The indication for FMT was recurrent CDI in 87.2% (N=286) and severe or severe-complicated in 12.8% (N=42). FMT was performed as an inpatient in 16.7% (N=54). The stool source was patient-directed donors in 40% (N=130) of cases. The early FMT failure rate was 18.6%, and the late failure rate was 2.7%. In the multivariable analysis, predictors of early FMT failure included severe or severe-complicated CDI (odds ratio (OR) 5.95, 95% confidence interval (CI): 2.26-15.62), inpatient status during FMT (OR 3.78, 95% CI: 1.55-9.24), and previous CDI-related hospitalization (OR 1.43, 95% CI: 1.18-1.75); with each additional hospitalization, the odds of failure increased by 43%. Risk scores ranged from 0 to 13, with 0 indicating low risk, 1-2 indicating moderate risk, and ≥3 indicating high risk. In the developmental cohort, early FMT failure rates were 5.6% for low risk, 12.7% for moderate risk, and 41% for high-risk patients. Of 134 patients in the validation cohort, 57% (N=77) were females with a mean age of 66±18.1 years; 9.7% (N=13) had IBD, and 17.9% (N=24) were immunocompromised. The early FMT failure rate at 1 month was 19.4%, with an additional 3% failing by 3 months. In the validation cohort, FMT failure rates were 2.1% for low risk, 16.1% for moderate risk, and 35.7% for high risk patients. The area under the receiver operating characteristic curve (AUROC) for FMT failure was 0.81 in the developmental cohort and 0.84 in the validation cohort. CONCLUSIONS: Severe and severe-complicated indication, inpatient status during FMT, and the number of previous CDI-related hospitalizations are strongly associated with early failure of a single FMT for CDI. The novel prediction model has good discriminative power at identifying individuals who are at high risk of failure after FMT therapy and may assist the treating physician in subsequent management plans.

Clostridium difficile Infection in Production Animals and Avian Species: A Review.

Clostridium difficile is the leading cause of antibiotic-associated diarrhea and colitis in hospitalized humans. Recently, C. difficile infection (CDI) has been increasingly recognized as a cause of neonatal enteritis in food animals such as pigs, resulting in stunted growth, delays in weaning, and mortality, as well as colitis in large birds such as ostriches. C. difficile is a strictly anaerobic spore-forming bacterium, which produces two toxins A (TcdA) and B (TcdB) as its main virulence factors. The majority of strains isolated from animals produce an additional binary toxin (C. difficile transferase) that is associated with increased virulence. C. difficile is ubiquitous in the environment and has a wide host range. This review summarizes the epidemiology, clinical presentations, risk factors, and laboratory diagnosis of CDI in animals. Increased awareness by veterinarians and animal owners of the significance of clinical disease caused by C. difficile in livestock and avians is needed. Finally, this review provides an overview on methods for controlling environmental contamination and potential therapeutics available.

Adverse reactions associated with oral and parenteral use of cephalosporins: A retrospective population-based analysis.

BACKGROUND: Few studies have provided population-based, route-specific data on allergy to cephalosporin or incidence of serious adverse drug reactions (ADRs). OBJECTIVE: We investigated the incidence of new reports of cephalosporin-associated "allergy" and serious ADRs. METHODS: We identified all members of the Kaiser Permanente Southern California health plan given cephalosporins (from January 1, 2010, through December 31, 2012), all new reports of cephalosporin-associated allergy, and all serious ADRs. RESULTS: There were 622,456 health plan members exposed to 901,908 courses of oral cephalosporins and 326,867 members exposed to 487,630 courses of parenteral cephalosporins over the 3-year study period. New reports of allergy to cephalosporin were more frequent among women (0.56%; 95% CI, 0.54% to 0.57%) than among men (0.43%; 95% CI, 0.41% to 0.44%) per course (P < .0001). The most frequent serious cephalosporin-associated ADRs were Clostridium difficile infection within 90 days (0.91%), nephropathy within 30 days (0.15%), and all-cause death within 1 day (0.10%). None correlated with history of drug allergy. Physician-documented cephalosporin-associated anaphylaxis occurred with 5 oral exposures (95% CI, 1/1,428,571-1/96,154) and 8 parenteral exposures (95% CI, 1/200,000-1/35,971) (P = .0761). There were 3 documented cephalosporin-associated serious cutaneous adverse reactions (95% CI, 0-1 in 217,291). All were associated with the use of another antibiotic at the same time as cephalosporin. CONCLUSIONS: Cephalosporins are widely and safely used, even in individuals with a history of penicillin allergy. Physician-documented cephalosporin-associated anaphylaxis and serious cutaneous adverse reactions are rare compared with C difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day.

[Relationship between Clostridium difficile ITS-PCR Type and Pathogenicity].

Clostridium difficile (C. difficile) causes antibiotic-associated diarrhea and nosocomial infection. The PCR of internal transcribed spacer regions (ITS) is easily conductible in a relatively short time. The purpose of the current study is to classify C. difficile by PCR electrophoresis pattern of ITS (ITS-PCR type) and estimate the relationship of the ITS-PCR type of C. difficile with its pathogenicity. We examined 77 strains which were obtained in our hospital from March 2012 to August 2013. Toxin genes were detected by PCR using toxin gene specific primers. Antimicrobial sensitivities were measured by E-test. Pseudomembrane formation and severity of the illness in clinical patients were investigated based on the medical records. The strains were classified into the 33 ITS-PCR types. Among them, most of strains in 18 PCR types were not associated with any toxin genes. Strains with toxin A(+)/B(+)genes were classified into 14PCR types. The 3 strains with toxin B (+) strains and the two strains with toxin A(+)/B(+)/binary toxin(+) genes were classified into 1 PCR type, type 17, and type 16, respectively. 6 strains in 13 strains of type 33, and 5 strains in 11 strains of type 2 were detected from the same ward, presuming nosocomial infection. Minimum inhibitory concentrations (MICs) of vancomycin and metronidazole were ≤ 2 µg/mL, distribution of MICs were not correlated with ITS-PCR type. The pseudomembrane forming and severity of the illness were not obviously related to ITS-PCR pattern. Thus, the typing of C. difficile by ITS-PCR pattern is considered to be useful for early detection of nosocomial infection, and assessment of toxigenicity.

Clostridium difficile enteritis: a new role for an old foe.

BACKGROUND: Small bowel involvement of Clostridium difficile is increasingly encountered. Data on many management aspects are lacking. AIM: To synthesis existing reports and assess the frequency, pathophysiology, outcomes, risk factors, diagnosis and management of C. difficle enteritis. METHODS: A systematic review of the literature was conducted to evaluate evidence regarding frequency, pathophysiology, risk factors, optimal diagnosis, management and outcomes for C. difficle enteritis. Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The review included original articles reporting C. difficle enteritis from January 1950 to December 2012. RESULTS: C. difficle enteritis is rare but increasingly encountered. Presentation is variable and distinct predisposing factors include emergency surgery, white race and increased age. Diagnosis generally involves a sensitive but often non specific screening test for C. difficile antigens. Oral metronidazole represents first line therapy and surgery may be required for complications. Outcomes are inconsistent but may be improving. CONCLUSIONS: A high index of clinical suspicion, early diagnosis and treatment are vital. Further prospective studies are needed to determine the significance of asymptomatic small bowel C. difficile infections.

Novel management strategies in the treatment of severe Clostridium difficile infection.

CDI is increasing in incidence and severity. Clinicians must have a low threshold to consider the diagnosis and to treat patients with the clinical syndrome and risk factors before laboratory confirmation of the diagnosis. In patients who have signs of advanced disease, escalation of care with antimicrobial strategies and multidisciplinary care including surgical consultation is necessary. Furthermore, lowering the threshold for surgery compared with traditional approaches likely results in improved survival. Novel surgical approaches may obviate total abdominal colectomy and the associated immediate and long-term morbidity in this often fragile patient population, thus allowing clinicians to embrace surgical therapy earlier in the course of severe, complicated disease.

Clostridium difficile infection in an endemic setting in the Netherlands.

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case-control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high.

Clostridium difficile-associated disease acquired in the neurocritical care unit.

BACKGROUND: Clostridium difficile is an important cause of nosocomial infection on the intensive care unit. Little is known about infection rates on the neurocritical care unit (NICU). The purpose of this study was to determine the prevalence, severity, and outcome associated with Clostridium difficile-associated disease (CDAD) acquired on the NICU. METHODS: Patients on NICU with a positive stool Clostridium difficile toxin assay, from August 2004 to February 2008, were identified by the Department of Microbiology. Each patient's medical notes and charts were reviewed in turn. Patients with a positive assay within 48 h of NICU admission were excluded. RESULTS: Twenty-one (0.6%) NICU patients developed CDAD. All were emergency admissions, 18 (86.0%) were neurosurgical. Subarachnoid hemorrhage was the most common diagnosis, 5 (23.8%) patients. Median age and APACHE II score on admission were 55 (IQR 40-66) and 21 (IQR 16-24), respectively. Thirteen (61.9%) patients were female. Median interval between NICU admission and diarrhea onset and CDAD diagnosis were 5 (3-8) days and 7 (4-12) days, respectively. At the time of diagnosis most, 11 (52.4%) patients, had moderate CDAD. Previously identified risk factors for ICU-acquired CDAD comprised: age > 65 (6), antibiotics (21), and medical device requirements (21). Five (23.8%) patients deteriorated clinically as a result of CDAD. The overall in-hospital mortality for those with NICU acquired CDAD was 19%. CONCLUSIONS: Although CDAD is rarely acquired on the NICU, up to one quarter of affected patients may experience complications. Prospective validation of severity definitions and treatment guidelines may help to reduce the complication rates.

[Clostridium-difficile-associated infections]. / Infections à Clostridium difficile.

C. difficile is a spore-forming anaerobic enteropathogen. This bacillus is responsible for virtually all cases of pseudomembranous colitis and for 15 to 25% of cases of antibiotic-associated diarrhoea. Clostridium difficile associated-infections (CDI) have a wide range of clinical features which vary from mild uncomplicated diarrhoea to severe debilitating disease, paralytic ileus, toxic megacolon, or even perforation and sometimes death. Risk factors for CDI include age > 65 years, previous hospitalization and recent antibiotic therapy. Main virulence factors for this pathogen are toxins A and B. A third toxin, the binary toxin, has been found in up to 10% of strains from infected patients. For some years, a new hypervirulent strain has emerged. This epidemic strain belongs to PCR-ribotype 027 and is responsible for outbreaks with increased mortality and severity in North America and Europe. The most effective antibiotics for treatment are oral metronidazole and vancomycin. Control of CDI needs to prevent the emergence of CDI by minimizing the number of patients exposed to antimicrobials and to limit cross transmission.

Clinical risk factors for severe Clostridium difficile-associated disease.

Identifying patients who are at high risk for severe Clostridium difficile-associated disease (CDAD) early in the course of their infection may help clinicians improve outcomes. Therefore, we compared clinical features associated with severe versus nonsevere CDAD by retrospectively reviewing records of hospitalized patients whose fecal assays were positive for C. difficile toxin. Of 336 patients, 12.2% had severe disease and 10.1% died from all causes. Regression modeling showed the following to be significantly associated with severe CDAD (p< or =0.05): age >70 years (odds ratio [OR] 3.35), maximum leukocyte count >20,000 cells/mL (OR 2.77), minimum albumin level <2.5 g/dL (OR 3.44), maximum creatinine level >2 mg/dL (OR 2.47), small bowel obstruction or ileus (OR 3.06), and computed tomography scan showing colorectal inflammation (OR 13.54). These clinical and laboratory markers for severe disease may be useful for identifying patients at risk for serious outcomes or death.

Unexpected serum level of vancomycin after oral administration in a patient with severe colitis and renal insufficiency.

OBJECTIVE: To report a case in which the serum concentration of vancomycin (VCM) reached the supratherapeutic range following oral administration in a patient with severe pseudomembranous colitis and renal insufficiency. CASE SUMMARY: A 65-year-old, 70 kg weighing man with severe acute pancreatitis and acute renal failure was subjected to continuous hemodiafiltration (CHDF). CHDF could only be performed intermittently because of the unstable circulation dynamic of this patient. After admission, intravenous VCM therapy was initiated. Thereafter, oral VCM administration was begun (0.5 g every 6 h). Despite the discontinuation of intravenous VCM after the first 2 days of oral VCM, the serum VCM concentration increased gradually to 49.8 mg/l over a period of 2 weeks from the initiation of oral administration (34.4 mg/l). Based on pharmacokinetic analysis, the bioavailability of VCM was estimated to over 33%. Autopsy findings indicated broadly distributed necrosis on the lamina propria of the mucosa throughout all parts of the intestine below the duodenum. DISCUSSION: This case indicates necessity of the careful monitoring after oral high-dose VCM administration in a patient with a broadly distributed necrosis and renal insufficiency. CONCLUSIONS: TDM should be considered according to renal function, the severity of enteritis and the total dosage of oral VCM administration.

Laboratory diagnosis of clostridium difficile infection. An evaluation of tests for faecal toxin, glutamate dehydrogenase, lactoferrin and toxigenic culture in the diagnostic laboratory.

Faecal samples from 1007 patients suspected of having diarrhoea caused by Clostridium difficile infection are investigated for the presence of toxins A and B and for the presence of C. difficile-specific glutamate dehydrogenase (GDH). Toxigenic culture is performed on all samples and is used as the 'gold standard' for the purpose of the study. A marker for intestinal inflammation, faecal lactoferrin, is used on any samples that give a positive result in any of the above tests. Part of the study also involves an assessment of six commercial toxin kits to detect the presence of C. difficile toxins in faecal samples. This study revealed that the commercial toxin detection kits used can give rise to false-positive and false-negative results and that all demonstrated poor sensitivity when compared to the gold standard of toxigenic culture. Testing of faecal samples for GDH can be useful as a negative screening method as the results of this test show high correlation with culture. Faecal toxin testing can then be performed on all GDH-positive samples (GDH positivity is independent of toxigenicity in strains of C. difficile). The combined use of GDH and toxin testing, coupled with toxigenic culture, revealed that some patients with diarrhoea who harboured toxigenic strains of C. difficile were faecal toxin-negative. Lactoferrin appears to be a useful marker for the presence of inflammatory diarrhoea.

Development and validation of a clinical risk calculator for mortality after colectomy for fulminant Clostridium difficile colitis.

BACKGROUND: Clostridium difficile colitis is an increasingly important cause of morbidity and mortality. Fulminant C. difficile colitis (FCDC) is a severe form of the colitis driven by a significant systemic inflammatory response, and managed with a total abdominal colectomy. Despite surgery, postoperative mortality rates remain high. The aim of this study was to develop a bedside calculator to predict the risk of 30-day postoperative mortality for patients with FCDC. METHODS: After institutional review board approval, the American College of Surgeons National Surgical Quality Improvement Program database (2005-2015) was used to include adult patients who underwent emergency surgery for FCDC. A priori preoperative predictors of mortality were selected from the literature: age, immunosuppression, preoperative shock, intubation, and laboratory values. The predictive accuracy of different logistic regression models was measured by calculating the area under the receiver-operating characteristic curve. A cohort of 124 patients from Québec was used to validate the developed mortality calculator. RESULTS: A total of 557 patients met the inclusion criteria, and the overall mortality was 44%. After developing the calculator, no statistically significant differences were found in comparison with the American College of Surgeons National Surgical Quality Improvement Program probability of mortality available in the database (area under the receiver operating curve, 75.61 vs. 75.14; p = 0.79). External validation with the cohort of patients from Quebec showed an area under the curve of 74.0% (95% confidence interval, 65.0-82.9). CONCLUSION: A clinically applicable calculator using preoperative variables to predict postoperative mortality for patients with FCDC was developed and externally validated. This calculator may help guide preoperative decision making. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Historical perspectives on studies of Clostridium difficile and C. difficile infection.

The initial period of studies on Clostridium difficile (published during 1978-1980) appeared to provide a nearly complete portfolio of criteria for diagnosing and treating C. difficile infection (CDI). The putative pathogenic role of C. difficile was established using Koch's postulates, risk factors were well-defined, use of a cell cytotoxicity assay as the diagnostic test provided accurate results, and treatment with oral vancomycin was highly effective and rapidly incorporated into practice. During the next 10 years, enzyme immunoassays (EIAs) were introduced as diagnostic tests and became the standard for most laboratories. This was not because EIAs were as good as the cell cytotoxicity assay; rather, EIAs were inexpensive and yielded results quickly. Similarly, metronidazole became the favored treatment because it was less expensive and quelled fears of colonization with vancomycin-resistant organisms, not because it was better than vancomycin therapy. Cephalosporins replaced clindamycin as the major inducers of CDI because they were so extensively used, rather than because they incurred the same risk. Some serious issues remained unresolved during this period: the major challenges were to determine ways to treat seriously ill patients for whom it was not possible to get vancomycin into the colon and to find methods that stop persistent relapses. These concerns persist today.

Clinical recognition and diagnosis of Clostridium difficile infection.

Prompt and precise diagnosis is an important aspect of effective management of Clostridium difficile infection (CDI). CDI causes 15%-25% of all cases of antibiotic-associated diarrhea, the severity of which ranges from mild diarrhea to fulminant pseudomembranous colitis. Several factors, especially advanced age and hospitalization, should be considered in the diagnosis of CDI. In particular, nosocomial diarrhea arising >72 hours after admission among patients receiving antibiotics is highly likely to have resulted from CDI. Testing of stool for the presence of C. difficile toxin confirms the diagnosis of CDI. However, performance of an enzyme immunoassay is the usual method by which CDI is confirmed, but this test appears to be relatively insensitive, compared with the cell cytotoxicity assay and stool culture for toxigenic C. difficile on selective medium. Endoscopy and computed tomography are less sensitive than stool toxin assays but may be useful when immediate results are important or other confounding conditions rank high in the differential diagnosis. Often overlooked aspects of this diagnosis are high white blood cell counts (which are sometimes in the leukemoid range) and hypoalbuminemia.

Tolevamer, an orally administered, toxin-binding polymer for Clostridium difficile-associated diarrhea.

Genzyme Corp is developing tolevamer, an anionic toxin-binding polymer that binds and neutralizes the Clostridium difficile A and B toxins, for the potential treatment of C difficile-associated diarrhea (CDAD). Two phase III clinical trials of tolevamer in patients with CDAD have been completed and results from the second trial are expected to be released imminently.

Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile.

Previous studies have shown conflicting results concerning mortality related to Clostridium difficile infection. The objective of this study was to determine the impact of C. difficile infection on short- and long-term mortality in hospitalised patients with antibiotic-associated diarrhoea. We therefore undertook a prospective case-control study of 217 hospitalised patients who received antibiotics, developed diarrhoea and underwent stool enzyme immunoassay for C. difficile TOX A/B. The Kaplan-Meier and the log-rank test were used to determine univariate survival analysis and a Cox regression model for multivariate analysis of 28 day and long-term mortality. Fifty-two (24%) of the 217 patients who met the study criteria were positive for C. difficile TOX A/B. The crude 28 day and long-term mortality rates of the entire cohort were 12.4% and 56%, respectively. On Cox regression analysis, hypoalbuminaemia, impaired functional capacity and elevated serum urea levels were found to be the only independent and statistically significant variables associated with long-term mortality. C. difficile toxin positivity per se was not associated with increased short- or long-term mortality rates. In conclusion, hypoalbuminaemia, renal failure, and impaired function capacity predict mortality due to antibiotic-associated diarrhoea, but C. difficile involvement by itself does not further increase the risk of death in these patients.

Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation.

BACKGROUND: Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile-associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known. METHODS: We reviewed the medical files of all CF patients who presented with symptomatic C. difficile infection from January 1998 to December 2004 and compared the incidence, clinical aspects, severity of disease, and clinical outcome between non-transplanted and transplanted CF patients. RESULTS: Between 1998 and 2004, 106 adult CF patients were followed at our clinic. Forty-nine patients underwent lung transplantation; 15 before 1998 and 34 after 1998. The incidence density of CDAD was higher in transplanted CF patients as compared with non-transplanted CF patients (24.2 vs. 9.5 episodes/100,000 patient-days; risk ratio: 2.93 [1.41-6.08]; P=0.0044). Diarrhea was a very frequent feature, but was notably absent in 20% of the cases. Rates of moderate and severe colitis were similar in both groups. However, only transplanted patients developed complicated colitis. CT scan and endoscopy were performed more frequently in the transplant group. Two transplant recipients died because of CDAD. CONCLUSION: CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.