***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Background Although the incidence of Clostridium difficile infection ( CDI ) is increasing , available CDI treatment options are limited in terms of sustained response after treatment . This phase 3 trial assessed the efficacy and safety of surotomycin , a novel bactericidal cyclic lipopeptide , versus oral vancomycin in subjects with CDI . Methods In this r and omized , double-blind , active-controlled , multicenter , international trial , subjects with CDI confirmed by a positive toxin result were r and omized to receive surotomycin ( 250 mg twice daily ) or vancomycin ( 125 mg 4 times daily ) orally for 10 days . The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety . The key secondary endpoints were clinical response over time and sustained clinical response through a 30- to 40-day follow-up period . Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed . Results In total , 570 subjects were r and omized and had confirmed CDI ; 290 subjects received surotomycin and 280 subjects received vancomycin . Surotomycin clinical cure rates at end of treatment ( surotomycin/vancomycin : 79.0%/83.6 % ; difference of −4.6 % ; 95 % confidence interval , −11.0 to 1.9 ] ) , clinical response over time ( stratified log-rank test , P = .832 ) , and sustained clinical response at end of trial ( Day 40–50 ) ( 60.6%/61.4 % ; difference of −0.8 % ; 95 % CI , −8.8 to 7.1 ) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin . Both treatments were generally well tolerated . Conclusions Surotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial Background The available treatment options for Clostridium difficile infection ( CDI ) are limited by high recurrence rates . Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial . Objectives To assess surotomycin  safety and clinical response ( non-inferiority versus vancomycin ) at the end of treatment ( EOT ) of CDI . Additionally , to assess surotomycin  response over time and sustained response at 30 - 40 days post-EOT ( superiority versus vancomycin ) . Patients and methods Patients with CDI were r and omized ( 1:1 ) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3 , double-blind , multicentre , international trial . Clinical response over time and sustained clinical response were monitored until the end of the trial , through a follow-up period of 30 - 40 days . Clinical Trial Registration : NCT01598311 . Results A total of 285 and 292 patients with confirmed CDI were r and omized to receive surotomycin and vancomycin , respectively .  Surotomycin-associated clinical response at EOT was non-inferior to vancomycin ( surotomycin/vancomycin : 83.4%/82.1 % ; difference 1.4 % , 95 % CI - 4.9 , 7.6 ) . Following treatment with surotomycin , both clinical response over time ( stratified log-rank test , P = 0.277 ) and sustained clinical response ( 63.3%/59.0 % ; difference 4.3 % , 95 % CI - 3.6 , 12.2 ) did not demonstrate superiority versus vancomycin at end of trial . Both treatments were generally well tolerated . Conclusions Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT . Surotomycin did not demonstrate superiority to  vancomycin  for clinical response over time or sustained clinical response rate IMPORTANCE Clostridium difficile infection ( CDI ) is a major burden in health care and community setting s. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues . Fecal microbiota transplantation ( FMT ) is a promising , but not readily available , intervention . OBJECTIVE To determine whether frozen- and -thawed ( frozen , experimental ) FMT is noninferior to fresh ( st and ard ) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , noninferiority trial enrolling 232 adults with recurrent or refractory CDI , conducted between July 2012 and September 2014 at 6 academic medical centers in Canada . INTERVENTIONS Patients were r and omly allocated to receive frozen ( n = 114 ) or fresh ( n = 118 ) FMT via enema . MAIN OUTCOMES AND MEASURES The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events . Noninferiority margin was set at 15 % . RESULTS A total of 219 patients ( n = 108 in the frozen FMT group and n = 111 in the fresh FMT group ) were included in the modified intention-to-treat ( mITT ) population and 178 ( frozen FMT : n = 91 , fresh FMT : n = 87 ) in the per- protocol population . In the per- protocol population , the proportion of patients with clinical resolution was 83.5 % for the frozen FMT group and 85.1 % for the fresh FMT group ( difference , -1.6 % [ 95 % CI , -10.5 % to ∞ ] ; P = .01 for noninferiority ) . In the mITT population the clinical resolution was 75.0 % for the frozen FMT group and 70.3 % for the fresh FMT group ( difference , 4.7 % [ 95 % CI , -5.2 % to ∞ ] ; P < .001 for noninferiority ) . There were no differences in the proportion of adverse or serious adverse events between the treatment groups . CONCLUSIONS AND RELEVANCE Among adults with recurrent or refractory CDI , the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea . Given the potential advantages of providing frozen FMT , its use is a reasonable option in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01398969 BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 . Recurrence of Clostridium difficile infection ( CDI ) occurs in approximately 25 % of successfully treated patients . Two phase 3 r and omized , double-blind trials were conducted at 154 sites in the United States , Canada , and Europe to compare fidaxomicin vs vancomycin in treating CDI . Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days . The primary end point was clinical cure of CDI at end of treatment , and a secondary end point was recurrence during the 28 days following clinical cure . In all , 1164 subjects were enrolled , of which a subgroup of 128 in the per- protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment . In the analysis of this subgroup , initial response to therapy was similar for both drugs ( > 90 % cure ) . However , recurrence within 28 days occurred in 35.5 % of patients treated with vancomycin and 19.7 % of patients treated with fidaxomicin ( −15.8 % difference ; 95 % confidence interval , −30.4 % to −0.3 % ; P = .045 ) . Early recurrence ( within 14 days ) was reported in 27 % of patients treated with vancomycin and 8 % of patients treated with fidaxomicin ( P = .003 ) . In patients with a first recurrence of CDI , fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days . Clinical Trials Registration . NCT00314951 and NCT00468728 Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection ( CDI ) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days . Strains originated from patients who had been entered into two phase 3 r and omized clinical trials of fidaxomicin versus vancomycin .  Isolates of C. difficile from the initial and recurrent episodes within 28 ( ±2 ) days of cure of CDI were compared using restriction endonuclease analysis ( REA ) typing . Paired isolates were available from 90 of 194 ( 46 % ) patients with recurrent CDI . Patients with isolates available were significantly younger ( P = .008 ) and more likely to be from Canadian sites ( P = .0001 ) , compared with patients without isolates . In 75 of 90 subjects ( 83.3 % ) , the identical REA type strain was identified at recurrence and the initial episode ( putative relapse ) . Early recurrences ( 0–14 days after treatment completion ) were relapses in 86.7 % and a new strain ( reinfection ) in 13.3 % . Later recurrences ( 15–31 days after treatment ) were relapses in 76.7 % and reinfections in 23.3 % . Mean time ( ± st and ard deviation ) to recurrence was 12.2 ( ±6.4 ) days for relapses and 14.7 ( ±6.8 ) days for reinfections ( P = .177 ) . The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain ( relapse ) , compared with the other REA groups ( 39 of 42 [ 93 % ] vs 36 of 48 [ 75 % ] , respectively ; P = .023 ) . We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode , a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains , such as groups BI and J , for which relapse rates may be higher than for other REA groups . Caution in generalizing these observations is required , because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates . Clinical Trials Registration . NCT00314951 and NCT00468728 Background Clostridium difficile infection ( CDI ) is a leading cause of diarrhoea in health care setting s with symptoms ranging from m 
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CONTENT Meta-analyses and systematic review s have shown that CDI and rCDI risk factors are similar .
C. difficile spore germination can be influenced by gut environmental factors result ing from dysbiosis , and spore outgrowth may be affected stage by some antimicrobials ( e.g. fidaxomicin , ramoplanin , oritavancin ) .