Clostridium difficile Infections in an Emergency Surgical Unit from North-East Romania.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the 'Saint Spiridon' Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

Clostridium difficile colitis following geriatric hip fracture surgery: incidence, trends, and risk factors from 45,910 patients.

PURPOSE: Clostridium difficile colitis is a serious complication in elderly patients undergoing surgery. The objectives of this study were: (1) to use a nationwide sample of patients to report the incidence and timing of C. difficile colitis in geriatric patients who underwent surgery for hip fractures, (2) to identify preoperative factors associated with developing C. difficile colitis and mortality. METHODS: This was a retrospective evaluation of the 2016-2019 ACS Targeted Hip Fracture database merged with the ACS-NSQIP database. Patients undergoing surgery for hip fracture were included. Outcomes studied were incidence, preoperative, and postoperative risk factors for occurrence of C. difficile infection and mortality. Chi-squared tests were used to compare demographics between the patients infected (study) and not infected (control). Logistic regression models were utilized to compute the odds ratios (OR) testing for the association of independent factors on developing C. difficile infection postoperatively and mortality. A statistical threshold was set at p < 0.008. RESULTS: The incidence of C. difficile infection within 30 days of hip fracture surgery was 0.81%. Fifty percent of infections were diagnosed within 9 days postoperatively. Preoperative and hospital-associated factors associated with development of C. difficile infection were ≥ 2 days until operation (OR 1.88 [95% CI 1.39-2.55], p < 0.001) and dependent functional status (OR 1.43 [95% CI 1.14-1.79], p = 0.002). After adjusting for multiple comorbidities, increased age, male sex, COPD, CHF, dependent functional status, and C. difficile infection were associated with increased mortality within 30 days of surgery (all p < 0.001). CONCLUSION: Clostridium difficile colitis is a serious infection after hip fracture surgery in geriatric patients with an incidence of about 1%. Patients at increased risk should be targeted with preventative measures to prevent the morbidity from this complication.

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

BACKGROUND: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood. AIM: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes. METHODS: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection. CONCLUSIONS: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection.

Unique Clindamycin-Resistant Clostridioides difficile Strain Related to Fluoroquinolone-Resistant Epidemic BI/RT027 Strain.

During a surveillance study of patients in a long-term care facility and the affiliated acute care hospital in the United States, we identified a Clostridioides difficile strain related to the epidemic PCR ribotype (RT) 027 strain associated with hospital outbreaks of severe disease. Fifteen patients were infected with this strain, characterized as restriction endonuclease analysis group DQ and RT591. Like RT027, DQ/RT591 contained genes for toxin B and binary toxin CDT and a tcdC gene of identical sequence. Whole-genome sequencing and multilocus sequence typing showed that DQ/RT591 is a member of the same multilocus sequence typing clade 2 as RT027 but in a separate cluster. DQ/RT591 produced a similar cytopathic effect as RT027 but showed delayed toxin production in vitro. DQ/RT591 was susceptible to moxifloxacin but highly resistant to clindamycin. Continued surveillance is warranted for this clindamycin-resistant strain that is related to the fluoroquinolone-resistant epidemic RT027 strain.

Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy.

Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.

Five-year Pan-European, longitudinal surveillance of Clostridium difficile ribotype prevalence and antimicrobial resistance: the extended ClosER study.

Clostridium difficile infection (CDI) has been primarily treated with metronidazole or vancomycin. High recurrence rates, the emergence of epidemic PCR ribotypes (RTs) and the introduction of fidaxomicin in Europe in 2011 necessitate surveillance of antimicrobial resistance and CDI epidemiology. The ClosER study monitored antimicrobial susceptibility and geographical distribution of C. difficile RTs pre- and post-fidaxomicin introduction. From 2011 to 2016, 28 European countries submitted isolates or faecal samples for determination of PCR ribotype, toxin status and minimal inhibitory concentrations (MICs) of metronidazole, vancomycin, rifampicin, fidaxomicin, moxifloxacin, clindamycin, imipenem, chloramphenicol and tigecycline. RT diversity scores for each country were calculated and mean MIC results used to generate cumulative resistant scores (CRSs) for each isolate and country. From 40 sites, 3499 isolates were analysed, of which 95% (3338/3499) were toxin positive. The most common of the 264 RTs isolated was RT027 (mean prevalence 11.4%); however, RT prevalence varied greatly between countries and between years. The fidaxomicin geometric mean MIC for years 1-5 was 0.04 mg/L; only one fidaxomicin-resistant isolate (RT344) was submitted (MIC ≥ 4 mg/L). Metronidazole and vancomycin geometric mean MICs were 0.46 mg/L and 0.70 mg/L, respectively. Of prevalent RTs, RT027, RT017 and RT012 demonstrated resistance or reduced susceptibility to multiple antimicrobials. RT diversity was inversely correlated with mean CRS for individual countries (Pearson coefficient r = - 0.57). Overall, C. difficile RT prevalence remained stable in 2011-2016. Fidaxomicin susceptibility, including in RT027, was maintained post-introduction. Reduced ribotype diversity in individual countries was associated with increased antimicrobial resistance.

Evaluation of anti-infective-related Clostridium difficile-associated colitis using the Japanese Adverse Drug Event Report database.

Clostridium difficile-associated colitis (CDAC) may cause gastrointestinal illness, ranging in severity from mild diarrhea to fulminant colitis and even mortality. The purpose of this study was to evaluate anti-infective-related CDAC profiles using the Japanese Adverse Drug Event Report (JADER) database. Methods: We selected case reports of adverse events of CDAC as specified in the Medical Dictionary for Regulatory Activities. The association between the number of administered anti-infectives and aging was evaluated using reporting odds ratio (ROR) and adjusted for covariates using multiple-logistic regression. We also evaluated anti-infective-related CDAC-onset profiles using Weibull shape parameter. Results: The JADER database contained 534 688 reports from April 2004 to June 2018. There were 1222 anti-infective related CDAC events. The top five anti-infectives were as follows: third-generation cephalosporins (Anatomical Therapeutic Chemical (ATC) code: J01DD, 313 cases), fluoroquinolones (ATC code: J01MA, 201 cases), macrolides (ATC code: J01FA, 146 cases), carbapenems (ATC code: J01DH, 143 cases), and penicillins with extended spectrum (ATC code: J01CA, 103 cases). The adjusted RORs (95% confidence interval) in individuals using 1, 2, and ≥ 3 anti-infectives were 8.88 (7.05-11.18), 9.77 (6.89-13.86), and 18.39 (11.85-28.54), respectively. Moreover, 47.2% of CDACs occurred within 7 days of anti-infective therapy initiation. The adjusted ROR of interaction terms of ≥ 70 years × 1 drug was 21.81 (14.56-32.68). Conclusion: Our results suggest that the number of administered anti-infectives and patient age are associated with CDAC. These data may be particularly beneficial to prescribers and would contribute to improving the management of CDAC.

Growing consumption of antibiotics and epidemiology of Clostridioides difficile infections in Poland: A need to develop new solutions.

Clostridioides (formerly Clostridium) difficile infections (CDIs) are becoming more common and more serious. C. difficile is the etiologic agent of antibiotic-associated diarrhea, pseudomembranous enterocolitis, and toxic megacolon while CDIs recur in 7.9% of patients. About 42.9 CDI cases/10,000 patient-days are diagnosed each day in Europe, whereas in Poland 5.6 CDI cases/10,000 patient-days are reported; however, the median for European countries is 2.9 CDI cases/10,000 patient-days. Epidemiology of CDIs has changed in recent years and risk of developing the disease has doubled in the past decade that is largely determined by use of antibiotics. Studies show that rate of antibiotic consumption in the non-hospital sector in Poland is much higher than the European average (27 vs. 21.8 DDD/1,000 patient-days), and this value has increased in recent years. Antibiotic consumption has also increased in the hospital sector, especially in the intensive care units - 1,520 DDD/1,000 patient-days (ranging from 620 to 3,960 DDD/1,000 patient-days) - and was significantly higher than in Germany 1,305 (ranging from 463 to 2,216 DDD/1,000 patient-days) or in Sweden 1,147 (ranging from 605 to 2,134 DDD/1,000 patient-days). The recent rise in CDI incidence has prompted a search for alternative treatments. Great hope is placed in probiotics, bacteriocins, monoclonal antibodies, bacteriophages, and developing new vaccines.

A Prospective Program to Reduce the Clinical Incidence of Clostridium difficile Colitis Infection after Cystectomy.

PURPOSE: The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of C. difficile and assessed its impact on clinical C. difficile infection rates compared to historical matched controls. MATERIALS AND METHODS: Prospective C. difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients who underwent cystectomy before the initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Patients who screened positive were placed in contact isolation and treated prophylactically with metronidazole. Multivariable models were built on an intent to screen basis and an effectiveness of screening basis to determine whether screening reduced the rate of symptomatic C. difficile infection postoperatively. RESULTS: With the implementation of the screening protocol the C. difficile infection rate declined from 9.4% to 5.5% (OR 0.52, p = 0.0268) in patients on the intent to screen protocol and from 9.2% to 4.9% in those on the effectiveness of screening protocol (OR 0.46, p = 0.0174). CONCLUSIONS: C. difficile screening prior to cystectomy is associated with a significant decrease in the rate of clinically symptomatic infection postoperatively. These results should be confirmed in a randomized controlled trial.

Long-term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic.

CLINICAL QUESTION/SCENARIO: Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course? BACKGROUND: Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks. METHODS: We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin. RESULTS/IDENTIFIED EVIDENCE: The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited. DISCUSSION AND RECOMMENDATION FOR CLINICAL CARE: The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.

Gastrointestinal disease burden and mortality: A public hospital-based study from 2005 to 2014.

BACKGROUND AND AIM: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and health care utilization. This public hospital-based study assessed the incidence and time trend of hospitalization and mortality of major GI diseases over one decade. METHODS: We conducted an observational study using population-wide database managed by the Hong Kong Hospital Authority with a principal diagnosis of GI diseases defined by International Classification of Disease, 9th Revision, Clinical Modification coding. We measured age-standardized incidence of hospitalization, emergency admissions, multiple admissions, and in-hospital mortality from 2005 to 2014 using Poisson regression. RESULTS: The annual incidence of hospitalization for GI diseases increased from 4713 to 5241 per 100 000 discharges (incidence rate ratio [IRR] = 1.004; 95% confidence interval [CI]: 1.003-1.005). GI infections and cancers showed the highest rates of hospitalization in 2014. Hospitalization for GI cancers (IRR = 1.014; 95% CI: 1.013-1.016) and non-infectious enterocolitis (IRR = 1.058; 95% CI: 1.055-1.061) increased, whereas peptic ulcer disease has decreased. Hospitalization for Crohn's disease showed the most significant rise (126%). Annual incidence of hospitalization for Clostridium difficile infections increased by fivefold (IRR = 1.221; 95% CI: 1.178-1.266), while a 66% reduction was observed for peptic ulcer bleeding (IRR = 0.894; 95% CI: 0.889-0.899). GI cancers had the highest in-hospital mortality rate in 2014, especially colorectal cancer and gastric cancer. CONCLUSIONS: This study showed an increased hospitalization burden of GI cancers and Crohn's disease, and a reduction in overall mortality for GI diseases. These data provide insight into epidemiological changes of GI diseases in the 21st century and implications for hospital burden and need of resource re-allocation.

Proton-pump inhibitors and the risk of Clostridium difficile-associated diarrhea in high-risk antibiotics users: A population-based case-crossover study.

PURPOSE: Given the severity and high-costs demand of Clostridium difficile-associated diarrhea (CDAD), management of risk factors is very important. Although the association between proton-pump inhibitors (PPIs) and CDAD has been established, little is known among high-risk antibiotics users. This study aimed to identify the association between PPIs and CDAD in high-risk antibiotics users by using a case-crossover design. METHODS: We conducted a case-crossover study using a nationwide population-based cohort in South Korea. Participants who developed CDAD from 1 January 2003 to 31 December 2013 and had prior prescription records of both PPIs and high-risk antibiotics were included. The hazard period was 49 days, and the three prior control periods had the same duration as the hazard period. The status of exposure to PPIs was assessed during the hazard and control periods in each patient and discordant pairs of exposure were used to estimate the matched odds ratio (OR). RESULTS: In total, 200 participants with CDAD who had histories of both PPIs and high-risk antibiotics use were included. A twofold increased risk for CDAD due to PPI use was observed (OR = 2.0; 95% confidence interval, 1.2-3.2). The time-invariant variables including age group, sex, and comorbidities were proven not to modify the association between PPIs and CDAD. CONCLUSIONS: Our study suggested that PPIs increase the risk of developing CDAD in high-risk antibiotics users. Thus, PPIs should be used cautiously in patients requiring high-risk antibiotics in the situation of medical treatment to prevent further incidence of CDAD.

Clostridium difficile Colitis Following Revision Total Knee Arthroplasty: Incidence and Risk Factors.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is associated with adverse events and financial liability. As institutions continue to adopt CDAD rates as a quality control metric, it is important to identify patients at risk before surgery, including revision total knee arthroplasty (rTKA). This study was conducted to (1) determine the incidence of CDAD within 30 days of rTKA and (2) identify perioperative risk factors for CDAD following rTKA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried to identify 6023 rTKA procedures from 2015-2016. Preoperative and perioperative variables, including patient demographics, lab values, comorbidities, operative time, procedure type, presence of postoperative infections, and rates of CDAD were collected. Chi-square and Fisher's exact tests were used to detect differences between categorical variables, and t-tests were used to compare continuous variables. A stepwise logistic regression model was used to identify the risk factors for CDAD. RESULTS: The rate of CDAD within 30 days of rTKA was found to be 0.4% (24/6024). The CDAD rate following aseptic revision was 0.2% (12/4893), while the incidence of CDAD after septic revision was 1.1% (12/1130). Preoperative functional dependence (odds ratio [OR] = 5.14; P = .002), septic revision (OR = 2.77; P = .026), and cancer (OR = 14.26; P = .016) were statistically significant independent risk factors for CDAD after rTKA. CONCLUSION: The incidence of CDAD after rTKA is approximately 0.4% in the United States. Independent risk factors for CDAD include septic revision, preoperative functional dependence, and cancer. Prevention of CDAD in these higher risk patients must be considered before surgery and antibiotic selection for other infections should be managed judiciously.

Clostridium difficile infection in the USA: incidence and associated factors in revision total knee arthroplasty patients.

INTRODUCTION: Revision total knee arthroplasty (TKA) procedures performed secondary to periprosthetic joint infection (PJI) are associated with significant morbidity and mortality. These poor outcomes may be further complicated by postoperative infection requiring antibiotics. However, antibiotic overuse may suppress patients' bacterial flora, leading to Clostridium difficile infection (CDI). Therefore, we aimed to study the: (1) incidence; (2) costs; and (3) risk factors associated with CDI in revision TKA patients. METHODS: The National Inpatient Sample database was queried for individuals diagnosed with PJI who underwent revision TKA between 2009 and 2013 (n = 83,806). Patients who developed CDI during their inpatient stay were identified (n = 799). Logistic regression analysis was conducted to assess the association between hospital- and patient-specific characteristics and the development of CDI. RESULTS: The incidence of CDI after revision TKA was 1.0%. These patients were older (mean age 69.05 vs. 65.52 years), had greater LOS (median 11 vs. 5 days) and greater costs ($30,612.93 vs. 18,873.75), and experienced higher in-hospital mortality (3.6 vs. 0.5%; p < 0.001 for all) compared to those without infection. Patients with CDI were more likely to be treated in urban, not-for-profit, medium/large hospitals in the Northeast or Midwest (p < 0.05 for all) and to have underlying depression (OR 4.267; p = 0.007) or fluid/electrolyte disorders (OR 3.48; p = 0.001). CONCLUSION: Although CDI is rare following revision TKA, it can have detrimental consequences. We demonstrate that CDI is associated with longer LOS, higher costs, and greater in-hospital mortality. With increased legislative pressure to lower healthcare expenditures, it is crucial to identify means of preventing costly complications.

Low Risk of Primary Clostridium difficile Infection With Tetracyclines: A Systematic Review and Metaanalysis.

Background: The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics. Methods: We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale. Results: Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Conclusions: Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use.

Imipenem Resistance in Clostridium difficile Ribotype 017, Portugal.

We describe imipenem-resistant and imipenem-susceptible clinical isolates of Clostridium difficile ribotype 017 in Portugal. All ribotype 017 isolates carried an extra penicillin-binding protein gene, pbp5, and the imipenem-resistant isolates had additional substitutions near the transpeptidase active sites of pbp1 and pbp3. These clones could disseminate and contribute to imipenem resistance.

Higher Incidence of Clostridium difficile Infection Among Individuals With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Studies of Clostridium difficile infections (CDIs) among individuals with inflammatory bowel disease (IBD) have used data from single centers or CDI administrative data codes of limited diagnostic accuracy. We determined the incidence, risk factors, and outcomes after CDI in a population-based cohort of patients with IBD and laboratory confirmation diagnoses of CDI. METHODS: We searched the University of Manitoba IBD Epidemiology Database and Manitoba Health CDI databases to identify individuals with CDI, with or without IBD, from July 1, 2005 through March 31, 2014. Time trends of incidence were assessed using joinpoint regression. Multivariable Cox regression analyses were performed to assess differences in CDI incidence rates and mortality after CDI between individuals with and without IBD. Conditional logistic regression was performed to determine predictors of CDI among individuals with IBD. RESULTS: Individuals with IBD had a 4.8-fold increase in risk of CDI than individuals without IBD; we found no difference between individuals with ulcerative colitis vs Crohn's disease. There was no increase in CDI incidence over the study time period in either group. Among individuals with IBD, exposure to corticosteroids, infliximab or adalimumab, metronidazole, hospitalizations, higher ambulatory care visits, shorter duration of IBD, and higher comorbidities were associated with an increased risk of CDI. Although CDI increased mortality among individuals with and without IBD, there was lower mortality after CDI among individuals with IBD than without IBD (hazard ratio, 0.65; 95% confidence interval, 0.44-0.96). CONCLUSIONS: CDI incidence is no longer increasing among individuals with IBD. We identified unique risk factors for CDI in patients with IBD. CDI is associated with a greater increase in mortality among individuals without IBD than with IBD.

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.

Asymptomatic Carriers Contribute to Nosocomial Clostridium difficile Infection: A Cohort Study of 4508 Patients.

BACKGROUND & AIMS: Nosocomial infections with Clostridium difficile present a considerable problem despite numerous attempts by health care workers to reduce risk of transmission. Asymptomatic carriers of C difficile can spread their infection to other patients. We investigated the effects of asymptomatic carriers on nosocomial C difficile infections. METHODS: We performed a population-based prospective cohort study at 2 university hospitals in Denmark, screening all patients for toxigenic C difficile in the intestine upon admittance, from October 1, 2012, to January 31, 2013. Screening results were blinded to patients, staff, and researchers. Patients were followed during their hospital stay by daily registration of wards and patient rooms. The primary outcomes were rate of C difficile infection in exposed and unexposed patients and factors associated with transmission. RESULTS: C difficile infection was detected in 2.6% of patients not exposed to carriers and in 4.6% of patients exposed to asymptomatic carriers at the ward level (odds ratio for infection if exposed to carrier, 1.79; 95% confidence interval, 1.16-2.76). Amount of exposure correlated with risk of C difficile infection, from 2.2% in the lowest quartile to 4.2% in the highest quartile of exposed patients (P = .026). Combining the load of exposure to carriers and length of stay seemed to have an additive effect on the risk of contracting C difficile. CONCLUSIONS: In a population-based prospective cohort study in Denmark, we found that asymptomatic carriers of toxigenic C difficile in hospitals increase risk of infection in other patients.

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon.

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area.