Severe Clostridium Difficile Infection Research Articles

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.

Prevalence of Clostridium difficile infection among hospitalized inflammatory bowel disease patients in Greece.

Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), which is associated significantly with disease severity. We aimed to determine the rates of CDI among hospitalized IBD patients in major tertiary referral hospitals in Greece. A retrospective analysis was carried out of stool cultures from hospitalized patients investigated for diarrhea, during 2016, tested for CDI with glutamate dehydrogenase (GDH) and toxins A and B. In total, 6932 patients were tested for CDI; 894 were positive for GDH (12.89%) and 339 were also positive for C. difficile toxin (4.89%). The prevalence of CDI among all hospitalized patients was 1.6/1000 patient-days. Among these, there were 401 IBD patients, and 62 were positive for GDH (15.46%) and 30 were also positive for C. difficile toxin (7.48%). The prevalence of CDI in IBD patients was 2.5/1000 patient-days, significantly higher than in non-IBD hospitalized patients (30/401 vs. 309/6531, P=0.013). Among the 30 IBD patients (ulcerative colitis=18, Crohn's disease=12) with CDI, six were receiving biologics, three were on corticosteroids [one combined with azathioprine (AZA) and one combined with 5-ASA], nine were on AZA monotherapy and 12 were on 5-ASA monotherapy. The prevalence of CDI among patients receiving AZA monotherapy was significantly higher than in patients receiving other medications (9/68 vs. 21/333, P=0.047). Mild CDI (n=28) was treated with metronidazole and/or vancomycin, whereas severe CDI (n=2) was treated with vancomycin. The prevalence of CDI is higher in hospitalized IBD patients than those without IBD and AZA monotherapy increases the risk of CDI.

Proton pump inhibitors and 180-day mortality in the elderly after Clostridium difficile treatment

BackgroundThere is a reported association between proton pump inhibitor (PPI) exposure and increased risk of Clostridium difficile infection (CDI), but less is known about how this class of medications taken during treatment might influence mortality after CDI. Here we examine 180-day mortality rates in a cohort of CDI elders and its association with exposure to PPIs. We conducted a retrospective cohort study of elderly patients (> 65 years of age) diagnosed and treated for CDI in the years 2014–2016 (n = 874) in the Umass Memorial Health Care system, which represents both academic and community healthcare. Patient characteristics and medication use was extracted from the electronic medical record (EMR) and 6 month mortality data was obtained via the Center for Disease Control National Death Index. A Cox proportional hazards model was used to estimate hazard ratios associated with medication exposures and other relevant variables.ResultsOf the 874 elderly adults treated for CDI, 180-day all-cause mortality was 12.4%. Exposure to a PPI was associated with a 55% reduced risk of mortality (adjusted hazard ratio (aHR) 0.45; 95% confidence interval (CI) 0.28–0.72). In our Cox model, increasing age (aHR 1.45; 95% CI 1.14–1.84), those with severe CDI infections (aHR 1.87; 95% CI 1.22–2.88), and those with hospital acquired CDI (aHR 3.01; 95% CI 1.81–4.99) also had increased 180 day mortality risk. There were similar associations noted with both 90 day and 1-year mortality.ConclusionUse of PPIs during CDI treatment in elderly patients is associated with decreased 180-day mortality. Although use of PPIs has been associated with an increased risk of CDI, it appears to be protective against mortality when used during the treatment phase.

Impact of Clostridium difficile infection on gastrointestinal malignancies.

e15586 Background: According to the Centers for Disease Control and Prevention, there were half a million documented cases with 83,000 re-infections and 29,000 deaths due to Clostridium Difficile Infection(CDI) in the year 2011. The influence of CDI on outcomes in gastrointestinal(GI) malignancies is not well described, although the incidence is known to be higher in this subgroup of patients. Methods: National Inpatient Sample 1999-2014 was analyzed to identify adult admissions (>18 years of age) using ICD-9-CM codes with a primary diagnosis of esophageal(EC), Gastric(GC), Colorectal(CRC), Small intestinal(SIC), Hepatobiliary(HCC) and Pancreatic(PC) cancers. ICD-9 code 00845 was used to stratify these for the presence of CDI. We performed Chi-Square test to determine the in-hospital mortality percentage, and Cox Proportional Hazard model to control for confounders and determine the Hazard Ratio(HR) of death within 30 days of admission during hospitalization in patients with and without CDI. Results: See Table. Conclusions: Despite controlling for potential confounders, patients with GI cancers and CDI are at an increased risk of death compared to those without CDI. Taking the more detrimental effects of CDI in this subgroup of patients into consideration, healthcare professionals should strive to avoid the inordinate use of antibiotics and strictly maintain current guidelines designed to prevent spread. It may be prudent to treat these patients as severe CDI, even if current criteria are not met. More scientific research is warranted in analyzing the specific outcomes of CDI in GI cancer patients and if more aggressive therapy for CDI is warranted, considering the limitations of this study. [Table: see text]

Clostridium difficile Infection\u2013Daily Symptoms (CDI-DaySyms\u2122) questionnaire: psychometric characteristics and responder thresholds

BackgroundThe purpose of the current study was to determine the final content validation, psychometric characteristics, clinically meaningful improvement, and responder thresholds of the Clostridium difficile infection (CDI)–Daily Symptoms (CDI-DaySyms™) patient-reported outcome (PRO) questionnaire.MethodsThis validation study was part of two phase III studies (NCT01987895 and NCT01983683) conducted in patients with mild-to-moderate or severe CDI who completed the CDI-DaySyms™ daily throughout the treatment period. The questionnaire was evaluated in three stages: final PRO item content validation (Stage I); psychometric evaluation of reliability and construct validity (Stage II); and determination of clinically meaningful improvement and responder thresholds using distribution-based methods (Stage III).ResultsThe analysis included 168 patients. Most patients were female and Caucasian with mild-to-moderate CDI. The mean age was 57.1 years. Initial item analysis supported by confirmatory factor analysis demonstrated the relevance of 10 items grouped into three distinct domains (Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms). Domain scores demonstrated acceptable internal consistency and test-retest reliability, were sensitive to change, and correlated in expected directions with other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of − 1.00, − 0.80, and − 0.70 in the Diarrhea Symptoms, Abdominal Symptoms, and Systemic/Other Symptoms domains, respectively.ConclusionsThe CDI-DaySyms™ is a valid measure of patient-reported CDI symptoms, with good measurement properties, which supports its utility as an endpoint in clinical studies. Further studies confirming responder thresholds based on anchor-based methods are required.Trial registrationNCT01987895, registered November 20, 2013; NCT01983683, registered November 14, 2013.

Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines.

In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective. We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy. Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.

Colitis-Induced Th17 Cells Increase the Risk for Severe Subsequent Clostridium difficile Infection

Clostridium difficile infection (CDI) is the number one hospital-acquired infection in the United States. CDI is more common and severe in inflammatory bowel disease patients. Here, we studied the mechanism by which prior colitis exacerbates CDI. Mice were given dextran sulfate sodium (DSS) colitis, recovered for 2weeks, and then were infected with C.difficile. Mortality and CDI severity were increased in DSS-treated mice compared to controls. Severe CDI is dependent on CD4+ Tcells, which persist after colitis-associated inflammation subsides. Adoptive transfer of Th17 cells to naive mice is sufficient to increase CDI-associated mortality through elevated IL-17 production. Finally, in humans, the Th17 cytokines IL-6 and IL-23 associate with severe CDI, and patients with high serum IL-6 are 7.6 times more likely to die post infection. These findings establish a central role for Th17 cells in CDI pathogenesis following colitis and identify them as a potential target for preventing severe disease.

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses

Poor outcomes following Clostridium difficile infection (CDI) have been associated with advanced age, presence of cancer and C. difficile PCR-ribotype 027. The impact of baseline risk factors on clinical outcomes was evaluated using data from the EXTEND study, in which rate of sustained clinical cure (SCC) in the overall population was significantly higher with an extended-pulsed fidaxomicin (EPFX) regimen than with vancomycin. Patients aged ≥ 60 years received EPFX (fidaxomicin 200 mg twice daily, days 1–5; once daily on alternate days, days 7–25) or vancomycin (125 mg four times daily, days 1–10). We analysed outcomes by advanced age, cancer diagnosis, CDI severity, prior CDI occurrence and infection with PCR-ribotype 027. The primary endpoint was SCC 30 days after end of treatment (EOT; clinical response at test-of-cure with no subsequent recurrence). SCC rates 30 days after EOT did not differ significantly between EPFX (124/177, 70.1%) and vancomycin (106/179, 59.2%) regardless of age, cancer diagnosis, CDI severity and prior CDI. In patients with PCR-ribotype 027, SCC rate 30 days after EOT was significantly higher with EPFX (20/25, 80%) than with vancomycin (9/22, 40.9%) (treatment difference, 39.1%; 95% CI, 13.2–64.9; P = 0.006). Subgroup analyses from the EXTEND study suggest that EPFX is efficacious as a potential treatment for CDI regardless of age, cancer diagnosis, infection with PCR-ribotype 027, CDI severity or prior CDI. ClinicalTrials.gov identifier: NCT02254967.

PCR based detection of tcdCΔ117 in Clostridium difficile infection identifies patients at risk for recurrence – A hospital-based prospective observational study

ObjectivesIncreasing incidence and severity of Clostridium difficile infection (CDI) in the last decades has been attributed to the emergence of hypervirulent C. difficile strain PCR-ribotype 027 (RT027). Commercial multiplex real-time PCR tests allow the presumptive identification of RT027 by detecting a single-base deletion at nt117 in the tcdC gene (tcdCΔ117). The clinical usefulness of the detection of tcdCΔ117 is unclear.Therefore, we evaluated test performance and clinical association of the detection of tcdCΔ117 in patients with CDI in a prospective observational study conducted in a tertiary care hospital in Germany. MethodsFrom June to October 2015, stool from all patients with suspected CDI was tested for C. difficile according to ESCMID guidelines. C. difficile was cultured from positive samples and ribotyping was performed. Clinical data were collected prospectively from all C. difficile positive patients. ResultsFrom 1121 tested stool samples 107 patients with CDI were included in the study. TcdCΔ117 was detected in 18 (16.8%) of these patients. Multivariable logistic regression analysis revealed an independent association of detection of tcdCΔ117 with a further episode of CDI (OR 14.6; 95% CI 3.6–58.3; p < 0.001) and death within 30 days of the positive test (OR 5.1; 95% CI 1.0–25.7; p = 0.046). As follow up data are limited, it remains unclear, whether the further episode of CDI was due to tcdCΔ117 (recurrence) or another type. ConclusionIn our setting, PCR-based detection of tcdCΔ117 identified patients at risk for recurrent CDI and increased mortality and thus may guide therapeutic choices in CDI patients at the time of diagnosis.

P072 NOVEL RISK FACTORS AND OUTCOMES IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH CLOSTRIDIUM DIFFICILE INFECTION

Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridium difficile infection (CDI). CDI in IBD is associated with increased in-hospital mortality, IBD treatment failure, re-hospitalization and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited; however, a recent study demonstrated that corticosteroid escalation for IBD during CDI was a positive predictor of colon surgery within 1 year. We evaluated four potentially modifiable novel risk factors (BMI, statin use, opioid use, and antidepressant use) on the risk and outcomes of CDI in patients with IBD. CDI disease severity and other clinical outcomes, including colon surgery, CDI recurrence, CDI-related hospitalization, IBD exacerbations, and mortality were abstracted using the electronic medical record. Additionally, variables including BMI, statin use, opioid use, and antidepressant use at the time of CDI were abstracted from records for patients with IBD and CDI from 2008 and 2013. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses. There were 137 patients with IBD and CDI included in this study: 70 with ulcerative colitis (51%), 63 with Crohn’s disease (46%), and 4 with indeterminate colitis (3%). The median age was 46 years, and 55% were female. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe complicated CDI, compared to 22% of patients in the underweight/normal BMI (OR, 2.85, p=0.02) and 19% in the obese category (OR, 3.95, p=0.04). Statin use was associated with severe or severe complicated CDI when controlling for age and BMI (OR, 5.66, p=0.01). On multivariate analysis controlling for age and CDI severity, there was no association between statin use and post-CDI IBD exacerbations. Opioid and antidepressant use were not associated with CDI disease severity or IBD exacerbations. BMI category, statin use, opioid use, and antidepressant use were not associated with colon surgery, CDI recurrence, CDI-related hospitalizations, or mortality at 1 year. An overweight BMI and statin use were associated with severe or severe complicated CDI. There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Further studies are needed to better understand how these results could impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of CDI.

2,4-Disubstituted 5-Nitroimidazoles Potent against Clostridium difficile.

Metronidazole is one of the first-line treatments for non-severe Clostridium difficile infections (CDI). However, resistance limits its use in cases of severe and complicated CDI. Structure-activity relationships previously described for the 5-nitroimidazole series have shown that functionalization at the 2- and 4-positions can impart better activity against parasites and anaerobic bacteria than metronidazole. Herein we report the synthesis of new 2,4-disubstituted 5-nitroimidazole compounds that show potent antibacterial activity against C. difficile. We used a vicarious nucleophilic substitution of hydrogen (VNS) reaction to introduce a phenylmethylsulfone at the 4-position and a unimolecular radical nucleophilic substitution (SRN 1) reaction to introduce an ethylenic function at the 2-position of the 5-nitroimidazole scaffold.

Impact of clostridium difficile infection on gastrointestinal malignancies.

170 Background: According to the Centers for Disease Control and Prevention, there were half a million documented cases with 83,000 re-infections and 29,000 deaths due to Clostridium Difficile Infection(CDI) in the year 2011. The influence of CDI on outcomes in gastrointestinal(GI) malignancies is not well described, although the incidence is known to be higher in this subgroup of patients. Methods: National Inpatient Sample 1999-2014 was analyzed to identify adult admissions (&gt;18 years of age) using ICD-9-CM codes with a primary diagnosis of esophageal(EC), Gastric(GC), Colorectal(CRC), Small intestinal(SIC), Hepatobiliary(HCC) and Pancreatic(PC) cancers. ICD-9 code 00845 was used to stratify these for the presence of CDI. We performed Chi-Square test to determine the in-hospital mortality percentage, and Cox Proportional Hazard model to control for confounders and determine the Hazard Ratio(HR) of death within 30 days of admission during hospitalization in patients with and without CDI. Results: See table. Conclusions: Despite controlling for potential confounders, patients with GI cancers and CDI are at an increased risk of death compared to those without CDI. Taking the more detrimental effects of CDI in this subgroup of patients into consideration, healthcare professionals should strive to avoid the inordinate use of antibiotics and strictly maintain current guidelines designed to prevent spread. It may be prudent to treat these patients as severe CDI, even if current criteria are not met. More scientific research is warranted in analyzing the specific outcomes of CDI in GI cancer patients and if more aggressive therapy for CDI is warranted, considering the limitations of this study. [Table: see text]

Prolonged non-operative management of clostridium difficile colitis is associated with increased mortality, complications, and cost

BackgroundWe aim to investigate the effects of delaying surgery on outcomes and cost in patients admitted with severe clostridium difficile infection (CDI). MethodsThe Vizient database was queried for patients with CDI who underwent open total abdominal colectomy (TAC). Patients operated on the day of admission were excluded. Chi-square, Fisher's exact, student T-test, and logistic regression were performed with α = 0.05. ResultsLogistic regression analyses using days from admission to surgery (DATO), age, race, and gender demonstrated that increased DATO was associated with higher 30-day mortality (OR 1.022, 95% CI 1.001–1.044, p = 0.040), overall complications (OR 1.034, 95% CI 1.014–1.054, p = 0.001), and infectious complications (OR 1.040, 95% CI 1.018–1.062, p < 0.001) compared to age for all three outcomes. Total length of stay (LOS), intensive care unit LOS, and direct cost increased in conjunction with DATO (p < 0.001). ConclusionsEarly surgical intervention in appropriately selected patients should be considered when there is a high suspicion for prolonged non-operative treatment.

Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate Clostridium difficile Colitis while Dysregulating the Inflammatory Response.

Clostridium difficile infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes. Here, we found that treatment with the NSAID indomethacin prior to infection altered the microbiota and dramatically increased mortality and the intestinal pathology associated with CDI in mice. We demonstrated that in C. difficile-infected animals, indomethacin treatment led to PG deregulation, an altered proinflammatory transcriptional and protein profile, and perturbed epithelial cell junctions. These effects were paralleled by increased recruitment of intestinal neutrophils and CD4+ cells and also by a perturbation of the gut microbiota. Together, these data implicate NSAIDs in the disruption of protective COX-mediated PG production during CDI, resulting in altered epithelial integrity and associated immune responses.IMPORTANCEClostridium difficile infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.

Effect of using fidaxomicin on recurrent Clostridium difficile infection

Fidaxomicin is a macrocyclic antibiotic licensed for treating Clostridium difficile infection (CDI). In the UK, fidaxomicin is often reserved for severe CDI or recurrences. At Queen Elizabeth Hospital Birmingham, all courses of fidaxomicin during 2017/2018 were reviewed. Thirty-eight patients received fidaxomicin, of which 64% responded to treatment when fidaxomicin was given during the first episode of mild CDI. Conversely, all patients with recurrent CDI failed treatment with fidaxomicin. There were mixed results for the use of fidaxomicin for severe CDI, with only 42% of patients responding. These results suggest that fidaxomicin is best suited as a treatment for mild CDI during a patient's first episode.

Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.

Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.

Prevention of Clostridium difficile Infection in Critically Ill Adults.

The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.

Recurrent Clostridium difficile infection is associated with treatment failure and prolonged illness in cancer patients

Cancer patients are susceptible to recurrent Clostridium difficile infection (CDI) that is increasing globally, necessitating new approaches to prevent fatal consequences. We examined the clinical characteristics of cancer patients with recurrent CDI (RCDI). A retrospective review of cancer patients with C. difficile-positive test between January 2015 and May 2017 was carried out. CDI was defined as diarrhea and toxigenic C. difficile detection in the stool by nucleic acid amplification test and enzyme immunoassay. Patients having two CDI episodes were categorized as single recurrent CDI (SRCDI), and those having three or more CDI episodes were categorized as multiple recurrent CDI (MRCDI). Treatment failure was defined as the requirement of antimicrobial alteration or repetition. We included 170 patients having 270 CDI episodes; 85 patients had non-RCDI, and 85 had RCDI; 14 of them had MRCDI. Previous hospitalization and immunosuppressant use were more frequent in MRCDI group than in SRCDI group (P=0.009 and 0.002, respectively). Physicians treated more SRCDI episodes than MRCDI episodes with metronidazole alone (P=0.017), whereas, more MRCDI episodes needed combination antimicrobials (P=0.072). The mean duration of CDI treatment was longer in the MRCDI group than in the SRCDI group (P=0.030). MRCDI was associated with treatment failure more than SRCDI (P=0.021). The risk for a recurrent episode of CDI was increased in patients who had the following features of the first CDI episode: previous use of antibiotic, NSAID, immunosuppressant, chemotherapy, comorbidities, CDI treatment failure, and severe CDI (P<0.05). Risk factors for RCDI in cancer patients are similar to those without cancer, with the exception of chemotherapy that is only given to cancer patients. Long CDI treatment and CDI treatment failure are associated with MRCDI.

Metronidazole therapy as initial treatment of Clostridium difficile infection in patients with chronic kidney disease in Korea.

The risk of metronidazole treatment failure in Clostridium difficile infection (CDI) patients with chronic kidney disease (CKD) or end-stage renal disease in Korea has not been established. We evaluated 481 patients who had been admitted to two secondary hospitals with a diagnosis of, and treatment for, CDI during 2010-2016. CDI patients were divided into three groups according to CKD status: non-CKD (n = 363), CKD (n = 55) and those requiring dialysis (n = 63). Logistic regression analyses were performed to examine the association of CKD status with treatment failure. CDI patients receiving dialysis tended to have increased odds of metronidazole and overall treatment failure compared to non-CKD patients; adjusted odds ratios and 95% confidence intervals were 2.09 (1.03-4.21) and 2.18 (1.11-4.32) for metronidazole and overall treatment failure, respectively. However, CKD patients did not have increased odds of metronidazole or overall treatment failure compared to non-CKD patients, even where severe CDI was more prevalent in CKD patients. The incidence of symptomatic ileus or toxic megacolon did not differ among groups. Our results suggest that initial metronidazole therapy may be considered in CDI patients with non-dialysis CKD, but should not be considered in CDI patients undergoing dialysis.

Safety of fecal microbiota transplantation in Chinese children: A single-center retrospective study.

BACKGROUNDFecal microbiota transplantation (FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient’s digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection (CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects.AIMTo investigate the safety of FMT in children.METHODSA retrospective study was conducted on 49 patients who underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events (AEs) related to FMT were divided into short-term (48 h post-FMT) and long-term (3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis.RESULTSForty-nine patients (mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32% (30/114). The most common short-term AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age (P = 0.006) and immune state (P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo (P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence (P = 0.035), and the risk ratio in immunodeficient patients was 3.105 (95%CI: 1.080-8.923).CONCLUSIONAlthough FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children’s long-term health is unpredictable.