Symptomatic Clostridium Difficile Infection Research Articles

A55: Clostridium difficile Infection‐Associated Reactive Arthritis in a Pediatric Cohort

Background/Purpose:Clostridium difficile infection (CDI) has increased among children and is associated with significant morbidity and mortality. CDI‐associated reactive arthritis (CDIAReA) has been described in adults and a few pediatric case reports, but little is known about CDIAReA in pediatric patients.Methods:Children ages 2–20 with CDIAReA in 2004–2013 were identified within a multistate pediatric care network's electronic medical record. Administrative data were used to identify cases defined by: 1) a diagnosis code for arthritis and 2) the CDI diagnosis code and/or positive C. difficile test in any setting (ambulatory or inpatient). Records were reviewed to confirm presence of symptomatic CDI and acute arthritis and/or tenosynovitis that met the following inclusion criteria: 1) occurrence between 4 weeks before and 12 weeks after CDI diagnosis, 2) documentation by a physicianlevel provider or imaging, 3) no other cause identified, and 4) negative synovial fluid cultures (if obtained).Results:111 patients were identified for record review, and 13 met the inclusion criteria. Median age of confirmed cases was 13.2 years [range 3.4, 19.3], with similar sex distribution (6 females, 7 males). Approximately half (46%) of cases had chronic medical conditions, including 3 (23%) with autoimmune diseases, whose underlying condition did not explain their acute arthritis. Among subjects with CDIAReA, all CDIs were community‐associated and mild, except for 1 subject with preexisting lupus nephritis. Arthritis was most often migratory (85%) and polyarticular (54%) involving large and small joints, with a median of 6 affected joints [range 2, 15]. The most commonly involved joints were knees (69%) and ankles (69%) followed by wrists (62%) and elbows (54%). Eight patients (62%) experienced concurrent fever, and 9 (69%) had rash. Over half (62%) were hospitalized due to joint pain. Of these, 5 (38%) were suspected to have septic arthritis and 2 (15%) underwent surgical drainage procedures for presumed septic hip arthritis with purulent effusions (both culture‐negative). Median time from onset of gastrointestinal symptoms to resolution of joint symptoms was 30 days [range 8,76]. Symptoms generally resolved with treatment of underlying CDI and, in 69%, NSAID use. Three subjects (23%) without prior arthritis had subsequent recurrent episodes of migratory joint pain not associated with documented CDI. Aside from the primary physician, 85% were evaluated by emergency physicians, 69% by rheumatologists, 54% by inpatient pediatricians, and 46% by orthopedists. Of confirmed cases, 5 (38% [95% CI 14, 68%]) were never diagnosed with CDIAReA by their treating providers.Conclusion:CDIAReA is an under‐recognized pediatric condition characterized by a painful, migratory, often polyarticular arthritis of large and small joints in the setting of CDI. Though a self‐limited condition in this cohort, its acuity led to considerable morbidity and resource utilization, in some cases due to confusion with septic arthritis. Further research is needed to determine the incidence and risk factors for pediatric CDIAReA.

Clinical Characteristics of SymptomaticClostridium difficileInfection in Children: Conditions as Infection Risks and Whether Probiotics Is Effective

PurposeThis study investigated the clinical presentations of symptomatic Clostridium difficile infection (CDI) in children.MethodsWe reviewed the medical records of 43 children aged <20 years who showed either positive C. difficile culture or C. difficile toxin test results between June 2010 and April 2014.ResultsOf the 43 patients (mean age 6.7 years), 22 were boys. Sixteen patients (37.2%) showed both positive C. difficile culture and toxin test results. Seventeen out of 43 children (39.5%) had preexisting gastrointestinal diseases, and 26 children had other medical conditions that were risk factors for CDI. Twenty-eight children had a history of antibiotic treatment for >3 days, and the most frequently prescribed antibiotic was amoxicillin-clavulanate (35.7%). Twenty-eight patients were diagnosed with CDI despite taking probiotic supplements, most commonly Lactobacillus acidophilus (53.6%). The most common symptom was diarrhea (72.1%) at the time CDI was diagnosed. C. difficile was eradicated in 11 patients (25.6%) after treatment with oral metronidazole for 10-14 days, and in the two patients (4.6%) who required two courses of oral metronidazole. Sixteen patients (37.2%) showed clinical improvement without any treatment.ConclusionThis study showed the various clinical characteristics of CDI in children and that preexisting clinical conditions favored the development of CDI. In addition, CDI was found to occur in a number of patients even after probiotic prophylaxis given in conjunction with antibiotic therapy.

Evolutionary history of the Clostridium difficile pathogenicity locus.

The symptoms of Clostridium difficile infection are caused by toxins expressed from its 19 kb pathogenicity locus (PaLoc). Stable integration of the PaLoc is suggested by its single chromosomal location and the clade specificity of its different genetic variants. However, the PaLoc is variably present, even among closely related strains, and thus resembles a mobile genetic element. Our aim was to explain these apparently conflicting observations by reconstructing the evolutionary history of the PaLoc. Phylogenetic analyses and annotation of the regions spanning the PaLoc were performed using C. difficile population-representative genomes chosen from a collection of 1,693 toxigenic (PaLoc present) and nontoxigenic (PaLoc absent) isolates. Comparison of the core genome and PaLoc phylogenies demonstrated an eventful evolutionary history, with distinct PaLoc variants acquired clade specifically after divergence. In particular, our data suggest a relatively recent PaLoc acquisition in clade 4. Exchanges and losses of the PaLoc DNA have also occurred, via long homologous recombination events involving flanking chromosomal sequences. The most recent loss event occurred ∼30 years ago within a clade 1 genotype. The genetic organization of the clade 3 PaLoc was unique in containing a stably integrated novel transposon (designated Tn6218), variants of which were found at multiple chromosomal locations. Tn6218 elements were Tn916-related but nonconjugative and occasionally contained genes conferring resistance to clinically relevant antibiotics. The evolutionary histories of two contrasting but clinically important genetic elements were thus characterized: the PaLoc, mobilized rarely via homologous recombination, and Tn6218, mobilized frequently through transposition.

Intestinal Inflammatory Biomarkers and Outcome in Pediatric Clostridium difficile Infections

To identify specific fecal biomarkers for symptomatic Clostridium difficile infection and predictors of poor outcomes. We enrolled 65 children with positive C difficile testing (cases) and 37 symptomatic controls. We also analyzed stool samples from colonized and non-colonized asymptomatic children. We performed enzyme immunoassays to determine fecal interleukin (IL)-8, lactoferrin, and phosphorylated-p38 protein concentrations, and quantitative polymerase chain reaction to determine IL-8 and chemokine ligand (CXCL)-5 RNA relative transcript abundances, and C difficile bacterial burden. Of 68 asymptomatic controls, 16 were colonized with C difficile. Phosphorylated-p38 was specific for C difficile infection but lacked sensitivity. Fecal cytokines were elevated in samples from symptomatic children, whether cases or controls. In children with C difficile infection, fecal CXCL-5 and IL-8 messenger RNA abundances at diagnosis correlated with persistent diarrhea after 5 days of C difficile infection therapy and with treatment with vancomycin. When children with concomitant viral gastroenteritis were excluded, these correlations persisted. Time-to-diarrhea resolution was significantly longer in patients with elevated fecal cytokines at diagnosis. A logistic regression model identified high CXCL-5 messenger RNA abundance as the only predictor of persistent diarrhea. Conversely, fecal C difficile bacterial burden was not different in symptomatic and asymptomatic children and did not correlate with any clinical outcome measure. Fecal inflammatory cytokines may be useful in distinguishing C difficile colonization from disease and identifying children with C difficile infection likely to have prolonged diarrhea.

Novel Strategy for Preventing CDI

Spore germination is necessary for the development of symptomatic Clostridium difficile infection (CDI). Recent investigations have yielded novel nonantibiotic agents that inhibit spore germination mediated by taurocholate, a bile salt. To determine whether CamSA — a taurocholate analog that inhibits germination in vitro — might prevent CDIs, researchers conducted experiments using a mouse model. Mice received an antibiotic “cocktail” in their drinking water for 3 …

Predictors ofClostridium difficileinfection severity in patients hospitalised in medical intensive care

To describe and analyse factors associated with Clostridium difficile infection (CDI) severity in hospitalised medical intensive care unit patients. We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit (MICU) at a French university hospital. We include patients hospitalised between January 1, 2007 and December 31, 2011. Data on demographics characteristics, past medical history, CDI description was collected. Exposure to risk factors associated with CDI within 8 wk before CDI was recorded, including previous hospitalisation, nursing home residency, antibiotics, antisecretory drugs, and surgical procedures. All included cases had their first episode of CDI. The mean incidence rate was 12.94 cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31 respectively per 1000 admitted patients annually from 2007 to 2011. Median age was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women. Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones, 3(rd) generation cephalosporins, coamoxiclav and tazocillin were prescribed most frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired. Fifteen patients had severe CDI. The crude mortality rate within 30 d after diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044], rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021), and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P = 0.036) were independently associated with severe CDI. We report predictors of severe CDI not dependent on time of assessment. Such factors could help in the development of a quantitative score in ICU's patients.

Community-Acquired Clostridium Difficile Infection: Awareness and Clinical Implications

The epidemiology of Clostridium difficile infection (CDI) is changing. CDI, usually depicted as a nosocomial infection in the elderly, is now occurring in community-dwelling persons who are younger and otherwise dissimilar. A more virulent isolate, North American Pulsed Field type 1, associated with increased morbidity and mortality, has been identified. In 2005, similar strains were associated with severe disease in community-dwelling patients at a rate of 7.6/100,000. Screening patients with potential CDI symptoms and implementing preventive measures, including judicious use of antibiotics, can reduce disease burden.

Fidaxomicin Preserves the Intestinal Microbiome During and After Treatment of Clostridium difficile Infection (CDI) and Reduces Both Toxin Reexpression and Recurrence of CDI

The microflora-sparing properties of fidaxomicin were examined during the conduct of a randomized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of Clostridium difficile infection (CDI). Fecal samples were obtained from 89 patients (45 received fidaxomicin, and 44 received vancomycin) at study entry and on days 4, 10, 14, 21, 28, and 38 for quantitative cultures for C. difficile and cytotoxin B fecal filtrate concentrations. Additionally, samples from 10 patients, each receiving vancomycin or fidaxomicin, and 10 samples from healthy controls were analyzed by quantitative real-time polymerase chain reaction with multiple group-specific primers to evaluate the impact of antibiotic treatment on the microbiome. Compared with controls, patients with CDI at study entry had counts of major microbiome components that were 2–3-log10 colony-forming units (CFU)/g lower. In patients with CDI, fidaxomicin allowed the major components to persist, whereas vancomycin was associated with a further 2–4-log10 CFU reduction of Bacteroides/Prevotella group organisms, which persisted to day 28 of the study, and shorter term and temporary suppression of both Clostridium coccoides and Clostridium leptum group organisms. In the posttreatment period, C. difficile counts similarly persisted in both study populations, but reappearance of toxin in fecal filtrates was observed in 28% of vancomycin-treated patient samples (29 of 94), compared with 14% of fidaxomicin-treated patient samples (13 of 91; P = .03). Similarly, 23% of vancomycin-treated patients (10 of 44) and 11% of fidaxomicin-treated patients (5 of 44) had recurrence of CDI. Whereas vancomycin and fidaxomicin are equally effective in resolving CDI symptoms, preservation of the microflora by fidaxomicin is associated with a lower likelihood of CDI recurrence.Clinical Trials Registration. NTC00314951.

ASID/AICA position statement – Infection control guidelines for patients with Clostridium difficile infection in healthcare settings

Since 2000 there has been an increase in the rates of Clostridium difficile infection (CDI) in many healthcare facilities in the United States, Canada and Europe. This increase is associated with an epidemic strain of C. difficile and this strain (PCR ribotype 027) has recently been identified in Australia. All healthcare services should have in place an optimal evidence-based programfor CDI prevention and control. Management principles include the following. • All healthcare organisations, including residential aged care facilities, must give CDI prevention and control the highest priority, even if the prevailing incidence of CDI is low. • Surveillance should be integrated into quality improvement programs to optimise prevention, control and clinical care of CDI. • Antimicrobial stewardship programs aimed at minimising the frequency and duration of antibiotic use and promoting a narrow spectrum antibiotic policy should be implemented. • Emphasis should be placed on compliance with hand disinfection using alcohol-based hand rub and glove use for CDI patient care to minimise spore contamination. • Contact precautions should be in place for symptomatic CDI patients, including the donning of gowns/aprons and gloves on entry to patient rooms. • The use of sporocidal environmental cleaning and disinfection in high-risk areas such as toilets, bathrooms, and CDI patient rooms should be implemented. There should be the limination of other potential fomites by either using disposable equipment or ensuring that equipment is adequately cleaned and disinfected before re-use. • Education of all healthcare staff, patients and visitors about C. difficile disease, its prevention and management should be implemented.

Outcomes of Patients Who Develop Symptomatic Clostridium difficile Infection After Solid Organ Transplantation

Clostridium difficile–associated diarrhea is the most common cause of hospital-associated diarrhea in the UK. Infection can produce a spectrum of manifestations from mild diarrhea to toxic megacolon, colonic perforation, and death. The aim of this study was to evaluate the outcomes of patients who developed symptomatic Clostridium difficile infection (CDI) within the first year after solid organ transplantation. Between 2004 and 2007, we performed 682 transplantation: 433 from deceased-donor kidney, 143 live-donor kidney, 18 pancreas-only, and 88 simultaneous kidney and pancreas transplants. Within the first year of transplantation, 24 patients developed symptomatic CDI. No single risk factor or antimicrobial agent was associated with acquiring infection. Among this group, 2 patients developed toxic megacolon requiring subtotal colectomy and recovered. Although 5 patients who developed CDI died within the first year, CDI was not the primary cause of death. The overall mortality of patients who developed CDI within the first year of transplantation accounted for 0.7% of all transplanted patients. Increased awareness of CDI and barrier nursing can minimize the impact of CDI on the morbidity and mortality associated with transplantation. Patients should be informed of the risk of CDI during consenting for transplantation, because the 3.5% incidence is more common than that of graft loss due to thrombosis.

Randomized Clinical Trial in Clostridium difficile Infection Confirms Superiority of Fidaxomicin Over Vancomycin

The usual treatments of Clostridium difficile infection (CDI), metronidazole, or vancomycin (VAN), have cure rates of 80%–90% but 20%–30% of patients experience a relapse. This phase III, randomized, controlled trial (RCT) compared fidaxomicin (FDX), a first-in-class bacteriocidal macrocyclic antibiotic, with VAN in treatment of CDI. Eligible patients had acute CDI symptoms and a positive stool toxin test. Patients received oral FDX (200 mg twice daily) or oral VAN (125 mg 4 times daily) for 10 days. The primary end point was clinical cure. Secondary end points were CDI recurrence (diarrhea and positive stool toxin test within 4 weeks after treatment), and global cure (clinical cure with no recurrence). This RCT comprised 535 subjects with 524 available for safety, 509 for modified intent-to-treat (mITT), and 451 for per-protocol (PP) analyses. Europe (39%), the United States (30%), and Canada (31%) contributed subjects from 100 clinical sites. All data are given for the PP population; the mITT population was similar in all instances. The primary noninferiority end point of cure was met with 91.7% cured vs 90.6% (FDX vs VAN, respectively). Recurrence was seen in 12.8% vs 25.3% (FDX vs VAN, respectively; P = .002). Global cure was noted in 79.6% vs 65.5% (FDX vs VAN, respectively; P < .001). Concomitant antibiotics (CAs) to treat infections other than CDI were given to 59% of patients during CDI treatment. Those who received CAs had a lower cure rate (86.1% with CAs vs 98.4% without; P ≤ .001), a higher recurrence rate (23.9% with CAs vs 8.1% without; P ≤ .001), and lower global cure rate (59.8% with CAs vs 90.3% without; P ≤ .001). For those given CAs, FDX treatment was associated with lower recurrences (17.6% FDX vs 29.5% VAN; P = .027) and higher global cures (67.5% FDX vs 53.4% VAN; P = .020), but no difference in cures. FDX was well tolerated with an adverse event profile similar to that of VAN. This RCT found equivalent cure rates with FDX and VAN, but significantly fewer relapses and higher global cures. A previously reported RCT of identical design revealed the same findings. CAs had a deleterious effect on lowering cures and global cures and increasing relapses; however, FDX therapy significantly improved the relapse rate and global cures in the CA group. A total of 1100 CDI subjects in 2 RCTs have established the potential benefits of FDX in CDI treatment, even when CAs are administered.

Fidaxomicin (OPT-80) for the treatment of Clostridium difficile infection

Importance of the field: Clostridium difficile infection (CDI) has become an increasingly important healthcare-associated complication in many countries. CDI outbreaks, a new ‘hypervirulent’ form and increased worldwide rates have underscored four urgent unmet needs for this disease: i) effective prevention of CDI; ii) therapies to produce faster resolution of CDI symptoms; iii) therapies to treat severe CDI more effectively and reduce its mortality; and iv) therapies to reduce the CDI recurrence rate following treatment.Areas covered in this review: Fidaxomicin, a new macrocyclic antibiotic, has demonstrated potent in vitro activity against C. difficile with limited or no activity against normal fecal flora. It is minimally absorbed from the intestinal tract, even in the presence of intestinal inflammation. When tested against oral vancomycin in clinical studies of CDI therapy, it has equivalent efficacy for curing CDI at end of treatment and a comparable safety profile to that agent. However, fidaxomicin therapy of CDI is associated with significantly fewer CDI recurrences in the 28 days following treatment. Symptom resolution is also slightly quicker in some CDI patients. Additional fecal flora analysis in the CDI trials showed that fewer individuals developed intestinal colonization with vancomycin-resistant enterococci (VRE) among the fidaxomicin-treated group. This new molecule, which has just completed two large Phase III multicenter studies, successfully addresses two of the four urgent and unmet needs for dealing with CDI.What the reader will gain: Fidaxomicin is as effective and as safe as vancomycin therapy for treating CDI but is associated with far fewer recurrences post-treatment and a decreased risk of VRE acquisition.Take home message: Fidaxomicin is a potential new therapy for CDI which has the capacity to substantially decrease post-treatment recurrences and is as safe and well-tolerated as standard vancomycin treatment.

Use of International Classification of Diseases, Ninth Revision Clinical Modification Codes and Medication Use Data to Identify Nosocomial Clostridium difficile Infection

The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for Clostridium difficile infection (CDI) is used for surveillance of CDI. However, the ICD-9-CM code alone cannot separate nosocomial cases from cases acquired outside the institution. The purpose of this study was to determine whether combining the ICD-9-CM code with medication treatment data for CDI in hospitalized patients could enable us to distinguish between patients with nosocomial CDI and patients who were admitted with CDI. The primary objective was to compare the sensitivity, specificity, and predictive value of using the combination of ICD-9-CM code for CDI and CDI treatment records to identify cases of nosocomial CDI with the sensitivity, specificity, and predictive value of using the ICD-9-CM code alone. Validation sample cross-sectional study. Academic health center. Administrative claims data from July 1, 2004, to June 30, 2005, were queried to identify adults discharged with an ICD-9-CM code for CDI and to find documentation of CDI therapy with oral vancomycin or metronidazole. Laboratory and medical records were queried to identify symptomatic CDI toxin-positive adult patients with nosocomial CDI and were compared with records of patients whose cases were predicted to be nosocomial by means of ICD-9-CM code and CDI therapy data. Of 23,920 adult patients discharged from the hospital, 62 had nosocomial CDI according to symptoms and toxin assay. The sensitivity of the ICD-9-CM code alone for identifying nosocomial CDI was 96.8%, the specificity was 99.6%, the positive predictive value was 40.8%, and the negative predictive value was 100%. When CDI drug therapy was included with the ICD-9-CM code, the sensitivity ranged from 58.1% to 85.5%, specificity was virtually unchanged, and the range in positive predictive value was 37.9%-80.0%. Combining the ICD-9-CM code for CDI with drug therapy information increased the positive predictive value for nosocomial CDI but decreased the sensitivity.

Clostridium difficile Strain NAP-1 Is Not Associated With Severe Disease in a Nonepidemic Setting

Recent outbreaks of Clostridium difficile infection (CDI) in North America and in Europe with very high case-fatality rates have been associated with infection by North American Pulsed Field Type I (NAP-1) isolates. This study examined whether NAP-1 strains are associated with worse outcomes of CDI in a nonepidemic, nosocomial setting. All cases of CDI that occurred over a 13-month period at a tertiary medical center were examined for risk factors associated with increased severity of CDI and other outcomes. Stool samples from each patient were cultured for C difficile and the resulting isolates were strain-typed by pulsed-field gel electrophoresis. Strain types were obtained from 236 of 272 CDI samples; the NAP-1 strain was identified in 59 (25%). In this inpatient cohort of patients with CDI, the incidence of in hospital death was 12.1% and of death caused by CDI was 4.0%. Of the patients with CDI, 22.1% met the combined outcome end point of severe CDI. In both univariate and multivariate analyses, patients infected with the NAP-1 strain did not have worse outcomes compared with those infected with non-NAP-1 strains. Infection with the NAP-1 strain was correlated with admission from outside health care facilities regardless of whether symptoms of CDI began before or after admission to the study hospital. The NAP-1 strain of C difficile was found to cause 25% of cases of CDI in the hospital where the study was performed. However, compared with non-NAP-1 strains, CDI was not associated with increased severity of disease in this nonepidemic setting.

Impact of Clostridium difficile Infection on Pediatric Inflammatory Bowel Disease

To determine the prevalence of and explore possible differences in the risk for and symptoms of Clostridium difficile infection between patients with and without inflammatory bowel disease (IBD). Stool specimens from subjects with and without IBD were evaluated for the presence of C difficile toxins. Demographic information, diagnosis, anatomic location, disease activity, IBD therapy, hospitalizations, and antibiotic and proton pump inhibitor (PPI) exposures were recorded. A total of 193 specimens were collected from 81 patients with IBD and 112 patients without IBD. The prevalence of C difficile infection was significantly greater in the patients with IBD than in those without IBD (P = .004; chi2 = 0.003; odds ratio = 3.3; 95% confidence interval = 1.5 to 7.6). In the patients with IBD, the prevalence of active disease was significantly greater in the C difficile-infected patients than in the uninfected patients (P < .0001). Colonic involvement was found in all patients with IBD. The specific type of IBD, IBD therapy, and antibiotic and PPI exposures that predisposed patients with IBD to C difficile infection were not identified, whereas hospitalization was significantly more frequent in the patients without IBD (P = .025). Our findings indicate that in children, IBD is associated with an increased prevalence of C difficile infection. The specific risk factors reported in adults were not identified in these children, suggesting the possible involvement of other mechanisms for acquiring the pathogen.

Nitazoxanide versus Vancomycin inClostridium difficileInfection: A Randomized, Double‐Blind Study

Vancomycin is the only US Food and Drug Administration-approved drug for treatment of Clostridium difficile infection (CDI). Metronidazole has been widely used for this purpose but may be inferior to vancomycin, especially for hospitalized patients with severe disease. We report a prospective, double-blind, randomized controlled trial comparing nitazoxanide with vancomycin for treatment of CDI. Fifty patients with CDI were randomized to receive vancomycin or nitazoxanide for 10 days. An initial response was considered to be the absence of all CDI symptoms between days 11 and 13, and a final response was considered to be lack of symptom recurrence by day 31. One patient fulfilled an exclusion criterion and was removed from the study. Twenty-seven patients received vancomycin, and 23 received nitazoxanide; 23 and 18 patients, respectively, completed the full course of treatment. Initial responses occurred in 20 (74%) of 27 patients treated with vancomycin and in 17 (77%) of 22 patients treated with nitazoxanide (95% confidence interval, -24% to +28%). In those who completed therapy, response rates were 87% (20 of 23 patients) in the vancomycin group and 94% (17 of 18 patients) in the nitazoxanide group (95% confidence interval, -18% to +30%). Times to complete resolution of symptoms were similar in the 2 groups (P = .55). Two patients in the vancomycin group and 1 patient in the nitazoxanide group experienced relapse within 31 days after beginning treatment. Sustained response rates were 78% (18 of 23 patients) for the vancomycin group, and 89% (16 of 18 patients) for the nitazoxanide group (95% confidence interval, -18% to +35%). The small sample precludes conclusions about noninferiority of nitazoxanide to vancomycin. Nevertheless, this is the first recent randomized controlled trial to compare any antimicrobial agent other than metronidazole with vancomycin. Results suggest that nitazoxanide may be as effective as vancomycin in treating CDI. ClinicalTrials.gov identifier: NCT00384527.