Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection

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Avila" }, { "@type": "Person", "name": "Nathaniel P. Avila" }, { "@type": "Person", "name": "Andrew W. Dupont" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/5-118", "name": "Recent Advances in the Diagnosis and Treatment of Clostridium Difficile..." } } ] } Home Browse Recent Advances in the Diagnosis and Treatment of Clostridium Difficile... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Avila MB, Avila NP and Dupont AW. Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.12688/f1000research.7109.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Review Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] Meera B. Avila 1 , Nathaniel P. Avila 1 , Andrew W. Dupont 1 Meera B. Avila 1 , Nathaniel P. Avila 1 , Andrew W. Dupont 1 PUBLISHED 29 Jan 2016 Author details Author details 1 Department of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, 77030, USA OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies. READ ALL READ LESS Keywords Clostridium Difficile, CDI, antibiotics, microbiota Corresponding Author(s) Andrew W. Dupont ( [email protected] ) Close Corresponding author: Andrew W. Dupont Competing interests: The authors declare that they have no competing interests. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2016 Avila MB et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Avila MB, Avila NP and Dupont AW. Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.12688/f1000research.7109.1 ) First published: 29 Jan 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.12688/f1000research.7109.1 ) Latest published: 29 Jan 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.12688/f1000research.7109.1 ) Introduction Clostridium difficile is an opportunistic organism that causes infection in patients with an alteration in intestinal microbiota. Microbiota is the community of organisms that inhabits a particular region of the body, and the intestine is composed of 300–500 species of bacteria. Alteration in intestinal microbiota predisposes patients to becoming infected with the spores from C. difficile via fecal-oral transmission 2 . Once a patient has C. difficile infection (CDI), outcomes can range from asymptomatic colonization to severe diarrhea. Fulminant or severe complicated CDI is characterized by inflammatory lesions and the formation of pseudomembranes in the colon, which can lead to toxic megacolon, bowel perforation, sepsis, shock, and death 2 . In addition, CDI has become nefarious for more severe disease associated with frequent recurrences despite appropriate and adequate treatment 3 , in part due to a virulent strain of CD termed NAP1/B1/027 4 . The consequences of CDI affect the patient and society alike, as more than 300,000 hospitalizations involve CDI each year. The mean cost of each hospitalization ranges from $8911 to $30,049 per patient, at a yearly cost estimated at $1.0 to $4.9 billion to the US health care system 5 , 6 . While a large portion of this cost is related to a true increase in CDI incidence, some of the cost burden can be attributed to the over-diagnosis of CDI after the introduction of molecular tests 7 – 10 . As health care costs rise, so does the importance of continued research in the detection and treatment of CDI. Update in diagnosis of CDI In the molecular era, how to best diagnose CDI in a cost-effective manner has become an area of much debate. In order to efficiently and effectively treat CDI, the diagnosis should be made rapidly based on clinical and laboratory evidence of the infection. Testing for CDI should only occur if patients have clinical risk factors for the disease along with signs and symptoms, most commonly diarrhea 11 . The most common risk factors include patients who are currently receiving antibiotics or who have received antibiotics in the past 8 weeks 12 . There are compelling data that almost all antibiotics can increase the risk of CDI, but third-generation cephalosporins, clindamycin, amoxicillin, and fluoroquinolones have been the most frequently reported 12 – 14 . In addition, patients are at greater risk if their age is greater than 65, if they are hospitalized or were recently hospitalized, or if they live in long-term care facilities 4 . Laboratory testing for CDI should be performed only on symptomatic patients and only on diarrheal stool 15 – 17 . Additionally, testing patients with CDI for “cure or clearance” or for “colonization” after treatment is not appropriate and not recommended 16 . Treated patients often shed spores for several weeks to months despite being asymptomatic, and further testing can lead to inappropriate courses of treatment 15 , 17 . There is general consensus that radiologic diagnosis of CDI is of little value 18 ; however, imaging should be done in cases of suspected toxic megacolon. Endoscopic diagnosis should be reserved for cases when a diagnosis is emergently needed, if there is delay in implementing CDI testing, if laboratory tests are negative and CDI is strongly suspected, or in cases of ileus when stool is unavailable 19 . Laboratory testing for CDI is an exciting and rapidly changing field; however, it remains an area of confusion, largely because there is no generally accepted gold standard or single best test 20 . In general, the clinical usefulness of a CDI diagnostic test is judged on its sensitivity, specificity, turnaround time (TAT), cost, and availability 21 . Currently, the five accepted tests are enzyme immunoassay (EIA) for toxin A/B, glutamate dehydrogenase (GDH), nucleic acid amplification tests (NAATs), toxigenic culture (TC), and cytotoxin neutralization (CTN) test. These tests vary widely in terms of clinical usefulness ( Table 1 ) 21 . Table 1. Properties of tests available for C. difficile infection detection. Sensitivity Turnaround Time (TAT) Cost Availability Detects gene responsible for production of Toxin NAATs 1~ *** Hours 6 **** *** Detects toxin in stool CTN 2+ *** Days *** * 7 EIA 3 toxin A/B ** Hours * **** Detects common antigen on C. difficile GDH 4 **** Hours * **** Relies on culture of C. difficile TC 5 ***** *** * 7 Days 1. NAAT: nucleic acid amplification test; 2. CTN: cytotoxin neutralization test; 3. EIA: solid-phase enzyme immunoassay; 4. glutamate dehydrogenase; 5. toxigenic culture; 6. TAT are variable and dependent on type of NAAT; 7. only available in specialty research laboratories; * indicates magnitude of characteristic, i.e. *** has a greater cost than ** Toxins A and B are the most important virulence determinants of disease and the majority of diagnostic tests target these toxins 22 . These toxins are responsible for symptoms of infection and are present in the stool of infected patients with diarrhea. The first test for detection, the CTN test, was developed in the 1970s 23 . CTN was novel in that it detected C. difficile toxins on cell culture medium. Unfortunately, CTN requires significant expertise, is time consuming, has very slow TAT, and is not widely available 21 , 24 . Subsequently, TC on selective medium was developed for the detection of C. difficile 23 . Although considered the gold standard for its time due to its very high sensitivity, it lacks specificity. Data now show a high rate of false positives in asymptomatic carriers and in certain patient populations, such as infants and patients recently exposed to antibiotics 2 . In addition, it has a very slow TAT and is not widely available, as testing requires an experienced laboratory 21 . In the early 1990s, detection of C. difficile toxins A and B through solid-phase EIAs was developed. EIAs have a rapid TAT, are widely available and inexpensive, and thus became the new standard for CDI detection in most laboratories until the early 2000s 21 . Although initially reported to have a sensitivity of as high as 98%, subsequent studies showed toxin A and B EIA had a poorer sensitivity, between 45 and 60%, respectively, but a positive predictive value between 90 and 100%, respectively 22 . Currently, the general consensus is that the EIA for toxin A and B is too insensitive and is no longer recommended as a stand-alone test 11 . In 2006, the GDH assay was marketed as a CDI detection test. GDH detects C. difficile cell-wall-associated antigen and has a reported sensitivity of 100%. To its strength, GDH has a negative predictive value approaching 100%, but with a positive predictive value of only 59% 25 . It has a rapid TAT, is widely available and affordable, and has become an effective screening tool for CDI detection 21 . GDH, however, detects all C. difficile , including nontoxigenic strains, subsequently lowering the specificity for the diagnosis of CDI 26 . Given the high specificity of toxin A/B EIAs and the sensitivity of GDH, several laboratories adopted a two-step algorithm for testing. Referred to as a multistep approach, CDI testing begins with common antigen GDH. If GDH is found to be positive, the toxin A/B assay is performed for the detection of direct toxin production 27 . GDH and EIA have subsequently been combined and marketed as a single confirmatory test for CDI. The C. Diff QUIK CHEK Complete assay (TechLab, Blacksburg, VA) combines GDH testing and toxin testing using a toxin A/B EIA 28 . This assay takes about 30 minutes to perform and has a built-in control. At least two publications demonstrate sensitivities of 100% for the GDH portion of the test 24 , 25 . The combination of the two tests together in a step-wise process is recognized as confirmation of CDI 15 , 16 . Unfortunately, testing can produce discordant results, which can be difficult to interpret, and thus confirmation requires further diagnostic testing 20 , 21 . Further advancements in detection came in 2009 when NAATs for CDI became commercially available 29 . The basis of NAATs is the detection of toxigenic C. difficile strains based on DNA extraction from the stool 21 . In general, the target of most NAATs is the gene responsible for coding toxin B ( tcdB gene) 29 , 30 . At this time, there are nine US Food and Drug Administration (FDA)-approved C. difficile NAATs. Six are polymerase chain reaction (PCR)-based assays and three are isothermal assays. The assays have sensitivities ranging from 80 to 100%, specificities ranging from 87 to 99%, and all have rapid TATs. NAATs have quickly become popular, and in many laboratories they have become a stand-alone approach for the diagnosis of CDI 21 , 29 . NAATs have also been shown to lead to a more rapid diagnosis when compared to GDH and EIA 31 . There are some data showing earlier detection has led to fewer CDI-related complications, such as intensive care unit admission, colectomy, and death 6 . However, NAATs have been criticized for being overly sensitive, and their use as a stand-alone test has been controversially linked to elevated reported incidence rates of CDI 7 , 20 , 29 . False positives can occur with NAATs, as they do not detect the presence of biologically active toxin in stool specimens and can detect only the genes responsible for potential toxin production. This has led many to believe that over-diagnosis of colonized C. difficile patients is occurring and that NAATs have increased antibiotic treatment for possible colonized states or limited infections 10 , 20 , 32 . The best standard laboratory test for the diagnosis of CDI has not yet been defined; however, recent clinical guidelines on this topic have been published by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA) 15 , the American College of Gastroenterology (ACG) 16 , and the United Kingdom National Health Service 26 . In the United States, the ACG recommends the use of the NAAT as the best test for CDI diagnosis, either as a stand-alone test or as part of a multistep testing algorithm. The ACG also states GDH testing can be used in a two- to three-step algorithm that includes subsequent toxin A/B EIA testing 16 . The IDSA recommends a two-step method that uses GDH as initial screening followed by the CTN or TC as a confirmatory test. The IDSA recognizes the potential value of NAATs; however, it does not currently recommend these tests in the diagnosis of CDI, citing more data on utility is necessary 16 . In the United Kingdom, guidelines recommend a combination of two tests, the first of which should be a NAAT or GDH followed by a toxin EIA test 33 . All guidelines make a significant contribution to clinical decision making, but recent updates should also be considered when choosing testing and treatment. Update in treatment of CDI There has recently been much research in the field of CDI treatment. New medications and novel therapy highlight the progression made. The first step in treating CDI is to stop the offending antibiotic when possible. Although it is difficult in the age of polypharmacy to accurately quantify the association between antibiotics and CDI, most studies have determined a link between prior exposure to antimicrobial agents and CDI 12 – 14 . Medical treatment of CDI varies based on a graded severity scale and whether it is the first occurrence or recurrence of the disease. Severity is usually defined by factors such as age, temperature, serum albumin, and white blood cell count. Guidelines recommend the use of metronidazole 500 mg orally three times per day for 10–14 days for initial mild to moderate disease, and vancomycin 125 mg orally four times per day for 10–14 days for initial severe disease 15 , 16 , 34 . The evidence for these guidelines is supported by Zar et al. ’s randomized, prospective, double-blind, placebo-controlled trial, showing vancomycin to be superior to metronidazole in curing severe cases of CDI (97% vs. 76% of patients respectively, p=0.02) 35 . In patients with mild disease, cure rates were similar in the two treatment groups 35 . Another study comparing treatment of CDI with vancomycin or metronidazole in patients risk-stratified by infection severity showed significantly less treatment-refractory disease after treatment with vancomycin in severe cases of CDI (32% refractory disease in pre-implementation phase vs. 15% in post-implementation phase, p=0.035) 36 . Additionally, in another randomized control trial, vancomycin was found to be superior to metronidazole in terms of clinical success and cure rates in patients with severe CDI (88% vs. 77% in the vancomycin and metronidazole groups, respectively) 37 . There is a high risk of recurrence associated with CDI. Studies show that up to 25–30% of patients appropriately treated for CDI experience at least one additional episode 15 , 34 . Recurrence comprises both episodes of relapse with infection by the current strain and reinfection by a new strain, and it remains difficult to distinguish between the two infections 37 , 38 . Treatment of the first episode of recurrence is usually with the same antibiotic used to treat the initial episode; however, treatment should also be guided by CDI severity if there is a significant change. To help combat the increasing burden of recurrence, the FDA approved fidaxomicin (FDX) for the treatment of CDI in 2011. FDX is a non-absorbed macrolide antibiotic effective against Gram-positive anaerobes but with no effect against bacteroides, a prominent constituent of the intestinal flora. Unlike metronidazole and vancomycin, which both have activity against bacteroides, FDX is thought to have some intestinal microbiota-sparing effect 34 . FDX has been shown to be superior in the prevention of recurrence of CDI 3 , 39 . A large randomized control trial comparing FDX to vancomycin demonstrated a lower rate of recurrence in the FDX group 34 , 39 . In another randomized double-blind trial comparing FDX to vancomycin, clinical response rates were similar in the treatment of a first recurrence of CDI; however, FDX was shown to be more likely to prevent a second recurrence 34 . There are concerns about the cost of FDX, as it is nearly 10-times more expensive than current standard oral vancomycin 40 . However, a recent study assessed the economic impact of treatment with FDX compared to oral vancomycin and showed an overall cost benefit in patients treated with FDX 40 . Patients treated with FDX had lower rates of recurrence, lower rates of hospital readmission, and shorter hospital stays, resulting in an overall saving of $3047 per patient treated with FDX 40 . Although this study has its limitations, it promotes further advancements in the future of CDI treatment with reduced rates of recurrence. One existing concept for the treatment of CDI that is gaining popularity is bacteriotherapy with fecal microbiota transplantation (FMT). FMT has been shown to be an effective treatment for recurrent CDI 29 . Stool from a healthy donor in the form of a liquid suspension has traditionally been transplanted into the patient’s gastrointestinal tract. This can be performed through a variety of routes including nasogastric tube, nasojejunal tube, upper endoscopy, colonoscopy, or enema, with similar success rates 41 . The rationale for FMT is to restore a healthier intestinal microbiota in patients with recurrent CDI who have disrupted intestinal flora and decreased microbiota diversity from antibiotic therapy 42 . FMT was previously considered a therapy of last resort for CDI; however, there has been significant research and interest in FMT, and it is becoming more widely practiced 41 – 43 . A case series of 12 patients with recurrent CDI treated with FMT demonstrated a 100% cure rate 44 . Another case series of 18 patients demonstrated a 94% cure rate in the 16 surviving patients 45 . A randomized control trial in 2013 compared FMT with donor feces solution transmitted via nasoduodenal tube preceded by four doses of vancomycin and bowel lavage vs. standard vancomycin with and without bowel lavage 46 . This study showed resolution of diarrhea in 81% of patients after the first FMT and in 94% of patients overall, as two patients were subsequently cured after second infusion of donor feces. Comparatively, only 31% of patients in the vancomycin alone group and 23% in the vancomycin with bowel lavage group had resolution of diarrhea 46 . Adverse events included diarrhea (94%) immediately after donor-feces infusion, as well as cramping (31%), constipation (19%), and belching (19%). No persistent adverse events related to FMT were noted. The most recent and largest systematic review with meta-analysis in 2015 of FMT studies, involving 18 observational studies with 611 patients, showed a primary cure rate of 91.2% (95% confidence interval [CI] 86.7–94.8%). The overall recurrence rate of CDI was 5.5% (95% CI 2.2–10.3%). The early recurrence rate and late recurrence rate were 2.7% (95% CI 0.7–6.0%) and 1.7% (95% CI 0.4–4.2%), respectively. Most adverse events were expected, short-lived, self-limited, and manageable 47 . These studies seem to show that FMT is a highly effective therapy for recurrent CDI. Another advancement has been the use of probiotics to prevent the development of CDI. Since antibiotics disturb the natural intestinal flora, leading to susceptibility to infection from C. difficile , a treatment which prevents alteration of the natural intestinal microbiome is theorized to help prevent CDI 48 . The use of lactobacillus has been shown to reduce diarrheal symptoms and reduce the risk of CDI in hospitalized patients on antibiotics 49 . A large meta-analysis (Cochrane review) composed of 23 randomized controlled trials with 4213 patients showed a significant relative risk reduction in the incidence of C. difficile- associated diarrhea in patients treated with probiotics 49 . In contrast, a large prospective randomized control trial composed of 3981 patients compared the incidence of antibiotic-associated diarrhea, including C. difficile -associated diarrhea, in patients receiving probiotics compared to a placebo group and found similar incidences of antibiotic-associated diarrhea in the probiotic and placebo groups 50 . Overall, strong evidence to support the use of probiotic use in the treatment or prevention of CDI is lacking. However, given the overall low cost and lack of significant side effects with probiotics, they are often used to attempt prevention of CDI in patients prescribed antibiotics. In summary, many recent efforts and advancements have been made in the diagnosis and treatment of CDI. Rapid and accurate detection of CDI has improved significantly, but possibly at the cost of over-diagnosis. There is still no uniform agreement regarding the best means of diagnosing CDI. Also, when discordant results occur with testing, this may lead to confusion regarding therapy. Future treatment of CDI seems promising, as recent advancements in newer antibiotic therapy and FMT have been shown to more effectively treat CDI, especially in terms of lowering rates of recurrence and also in the treatment of recurrent infection. With the rising burden of CDI, continued research in diagnostic testing and treatment is needed to combat this significant health care problem. Abbreviations CDI: Clostridium difficile infection CI: confidence interval CTN: cytotoxin neutralization test EIA: enzyme immunoassay FMT: fecal microbiota transplantation GDH: glutamate dehydrogenase NAAT: nucleic acid amplification test TAT: turn around time Competing interests The authors declare that they have no competing interests. Grant information The author(s) declared that no grants were involved in supporting this work. F1000 recommended References 1. Magill SS, Edwards JR, Bamberg W, et al. : Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014; 370 (13): 1198–208. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 2. Kyne L, Warny M, Qamar A, et al. : Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000; 342 (6): 390–7. PubMed Abstract | Publisher Full Text 3. 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Lancet. 2013; 382 (9900): 1249–57. PubMed Abstract | Publisher Full Text | F1000 Recommendation Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 29 Jan 2016 ADD YOUR COMMENT Comment Author details Author details 1 Department of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, 77030, USA Competing interests The authors declare that they have no competing interests. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 29 Jan 2016, 5:118 https://doi.org/10.12688/f1000research.7109.1 Copyright © 2016 Avila MB et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. 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Reviewer Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12197 ) The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12197 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Tillotson G. Reviewer Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12196 ) The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12196 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 29 Jan 2016 Glen Tillotson , Cempra Pharmaceuticals Inc, Chapel Hill, NC, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.7655.r12196 I confirm that I have read this submission and believe that I have an ... Continue reading READ ALL Competing Interests: No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Tillotson G. Reviewer Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12196 ) The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12196 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Garey K. Reviewer Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12195 ) The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12195 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 29 Jan 2016 Kevin Garey , Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.7655.r12195 I confirm that I have read this submission and believe that I have an ... Continue reading READ ALL Competing Interests: No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Garey K. Reviewer Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12195 ) The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12195 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 29 Jan 2016 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 1 29 Jan 16 read read read Kevin Garey , University of Houston College of Pharmacy, Houston, USA Glen Tillotson , Cempra Pharmaceuticals Inc, Chapel Hill, USA Vincent Young , University of Michigan, Ann Arbor, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2016 Young V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jan 2016 | for Version 1 Vincent Young , University of Michigan, Ann Arbor, MI, USA 0 Views copyright © 2016 Young V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Young V. Peer Review Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12197) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12197 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2016 Tillotson G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jan 2016 | for Version 1 Glen Tillotson , Cempra Pharmaceuticals Inc, Chapel Hill, NC, USA 0 Views copyright © 2016 Tillotson G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Tillotson G. Peer Review Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12196) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12196 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2016 Garey K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jan 2016 | for Version 1 Kevin Garey , Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA 0 Views copyright © 2016 Garey K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Garey K. Peer Review Report For: Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection [version 1; peer review: 3 approved] . F1000Research 2016, 5 (F1000 Faculty Rev):118 ( https://doi.org/10.5256/f1000research.7655.r12195) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/5-118/v1#referee-response-12195 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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