a Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Switzerland
b Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland
Clostridioides difficile is the most common cause of hospital-acquired diarrhoea and one of the most important causes of hospital-acquired infections. It results in significant morbidity, mortality and economic burden - especially in the context of recurrent infections. After initial antibiotic therapy of a C. difficile infection, recurrence occurs in about 20% of all patients, which increases the risk of further recurrence to about 45%.
Traditional therapeutic options for treatment of C. difficile infection include metronidazole or vancomycin. Newer therapy options such as fidaxomicin, the administration of monoclonal antibodies or faecal microbiota transplantation demonstrate significant advantages over traditional therapies, particularly regarding the reduction of the recurrence rate.
This article highlights the main differences between the recommendations of the Swiss Society for Infectious Diseases on the management of “Clostridioides difficile infection” and the IDSA/SHEA reference guideline “Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)” and discusses some important challenges in -treatment of C. difficile.
In Europe, the incidence of Clostridioides difficile infection (CDI) is not well defined, as systematic surveillance is not established uniformly and underreporting is likely. Multinational studies estimate incidence rates of four to seven cases of CDI per 100,000 patient-days across Europe, with a wide variation across countries and healthcare facilities (range 0.0 to 36.3 and 0.7 to 28.7, respectively) [1, 2]. The incidence rate in participating Swiss hospitals was within the European average (mean rate of 4.8 per 10,000 patient-days) . Older reports demonstrated lower incidence rates of 2.3 and 2.8 in Swiss hospitals [3–5], but a more recent point-prevalence study suggests a higher burden, reporting 5.7 to 11.4 cases per 10,000 patient-days, depending on the sampling period and testing methodology . In Switzerland, reporting of CDI is not mandatory, and surveillance is limited mainly to acute care hospitals. Thus, national efforts aiming at improved surveillance and management of CDI are being initiated.
In 2019, a national expert panel developed clinical guidelines for the management of CDI in Switzerland. A series of guidelines of the Swiss Society for Infectious Diseases (SSI) are being developed as part of the national strategy against antimicrobial resistance (StAR). Guidelines are based on international guidelines whenever available. For C. difficile, the 2017 IDSA Clinical Practice Guidelines for C. difficile Infection in Adults and Children  were used as reference. Here we review the treatment recommendations made for C. difficile infection in the SSI guidelines. We highlight the main differences between the Infectious Diseases Society of America (IDSA) / Society for Healthcare Epidemiology of America (SHEA) reference guideline and the Swiss recommendations, particularly regarding the following:
- The use of metronidazole for treatment of non-severe CDI
- Prolonged vancomycin therapy (pulsed or tapering regimens)
- Indications for the use of fidaxomicin
- Indications for the use of bezlotoxumab
Trends in therapy of C. difficile infection
Most clinical expertise in CDI management is derived from treatment with metronidazole and vancomycin, early randomised controlled trials demonstrating equal efficacy of both drugs [8, 9]. Because of the lower price of metronidazole and concerns of selecting resistant intestinal microorganisms, in particular vancomycin-resistant enterococci (VRE), metronidazole was given preference over vancomycin as first-choice therapy for treatment of CDI in the following years and decades, as reflected in previous guidelines . Subsequent studies could not prove a clear superiority of either of the two substances, and interpretation of existing evidence remains complex due to very heterogeneous study designs and large variation between settings, and diagnostic and antibiotic regimens compared. More recent studies on larger cohorts stratified by disease severity suggested superiority of vancomycin over metronidazole, particularly for the treatment of severe CDI [11, 12]. Pooled analyses further strengthen the benefits of vancomycin over metronidazole [13, 14], even for treatment of mild infections.
Although initial treatment response is high for both drugs, treatment failures are possibly more prevalent in patients treated with metronidazole than with vancomycin. Systematic reviews including randomized controlled trials only, as well as meta-analyses with more liberal inclusion criteria, conclude that vancomycin is superior to metronidazole regarding symptomatic cure (metronidazole 72% and vancomycin 79%  or treatment failure (22.4% for metronidazole and 14.2% for vancomycin ). However, the effect regarding recurrence rates is less clear: one meta-analysis reported recurrence rates of 27.1% and 24.0% following CDI treatment with metronidazole and vancomycin, . Nelson et al. concluded, that available data are insufficient to draw firm conclusions.
There may be a more immediate effect with vancomycin in terms of symptom duration (time to response 3.0 days for vancomycin and 4.6 days for metronidazole), and symptom persistence with metronidazole has been reported in some cases [15, 16]. However, few randomised controlled trials have focused on symptom duration, and existing data failed to show a relevant difference in time to symptom resolution for the two drugs . Fidaxomicin appears to result in more rapid symptom control (median time to resolution of diarrhoea 3.0 days with standard dosage) and sustained suppression of toxin production of the remaining bacteria in the post-treatment period [18, 19].
Strong evidence regarding eradication of C. difficile is still lacking, mainly because the microbiological resolution has not been reported consistently in the newer and larger trials . Vancomycin shows rapid killing of vegetative bacteria and a steep fall of toxin levels in gut models. With only minimal absorption when given orally, it achieves high antibiotic concentrations in stool, avoiding most of the common adverse reactions experienced with its intravenous application. Since vancomycin is only effective against vegetative bacteria, C. difficile spores remain a possible reservoir for relapses and reappearing toxin levels are frequently reported in post-treatment follow up [20, 21]. In vitro data demonstrate high activity of metronidazole against C. difficile, but its efficacy in vivo might be limited to patients with severe inflammation. In the absence of inflammation, metronidazole is readily absorbed during digestive passage and reaches only low activity levels in the colon [23–26].
The significance of metronidazole for treatment of CDI
The 2017 IDSA guidelines have made significant changes regarding the recommendation for metronidazole use. Previously considered the drug of choice for the initial episode of mild-to-moderate CDI, metronidazole is currently restricted to settings where access to vancomycin and fidaxomicin is limited [7, 10].
In Switzerland, metronidazole is still the most widely used antibiotic for initial treatment of CDI [27, 28] and the SSI guideline continues to promote the use of metronidazole for patients with non-severe CDI, presenting with a first episode. Vancomycin is a universal treatment option for all patients with a first episode or a first relapse of CDI. In severe, complicated infection or critically ill patients, vancomycin is the only antibiotic recommended and might be accompanied by intravenous metronidazole therapy.
Prolonged vancomycin therapy
The evidence base for the recommendation to administer vancomycin as a tapered or pulse regimen has been classified as low in the IDSA guideline, resulting in a weak recommendation for this treatment approach (as compared with the recommendations of fidaxomicin for treatment of a first recurrence and faecal microbiota transplantation for a second or subsequent recurrence, both based on moderate quality of evidence). Therefore, contrary to the IDSA recommendations, the SSI guidelines do not promote any treatment to be administered for more than 10 days. Approaches using vancomycin as a tapered or pulsed regimen following CDI treatment are intended to suppress the bacterial load of C. difficile while allowing restoration of the normal gut flora during antibiotic-free intervals. Microbiological studies, however, do not support this hypothesis and suggest, to the contrary, that exposure to vancomycin might even delay recovery and prolong the susceptible period in which colonisation resistance [19, 29] is reduced.
Considerations regarding vancomycin-resistant enterococci
Vancomycin is used restrictively in Switzerland, one of the concerns being its potential for promoting colonisation with vancomycin-resistant enterococci (VRE) during treatment for CDI. Such concerns seem reasonable, given the increase in selection pressure during vancomycin treatment and the shared reservoir. However, strong evidence for causality of increased VRE colonisation following vancomycin therapy is lacking. Since most patients received systemic antibiotics prior to developing C. difficile infection and therapy, this common risk factor may have already resulted in higher VRE colonis–ation rates prior to treatment, with only a small impact of the actual antibiotic chosen [30–33]. In accordance, studies of vancomycin used for eradication therapy of asymptomatic carriers showed hardly any new colonisation with VRE [34, 35]. Data suggest that fidaxomicin reduces new colonisation and inhibits overgrowth in patients with established colonisation. As fidaxomicin shows less disruption of the intestinal flora paired with in vitro activity against VRE, it might be the preferred agent in patients at high risk for VRE acquisition. A drawback, however, is the regularly observed increase in minimum inhibitory concentrations of VRE to fidaxomicin [19, 22, 36] – the benefit in terms of decreasing selection pressure potentially favouring VRE survival in the healthcare environment may outweigh such concerns by far.
Fidaxomicin is a newer oral antibiotic and a promising therapeutic option for CDI. In clinical trials, it showed higher cure rates and lower recurrence rates compared with vancomycin, representing significant improvements in important clinical endpoints [38, 39]. This effect is believed to be two-fold. With its narrower activity spectrum, fidaxomicin induces less disruption of intestinal flora, thus facilitating recovery of the microbiome. Fidaxomicin demonstrates rapid killing of vegetative C. difficile and inhibits spore recovery and toxin production [19, 22, 40]. Consequently, its use is increasingly promoted as the preferred therapy option for patients with a high risk of recurrence or in patients with multiple episodes of CDI, as reflected in the IDSA guidelines . It is not approved for severe or complicated CDI and its use in first episodes of mild and moderate CDI is limited by significantly higher costs compared with standard therapy options. Therefore, the SSI guidelines encourage the use of fidaxomicin mainly for patients with heightened risk for recurrence and in situations beyond first episode of infection.
Alternative treatment options
There are only a few treatment options available to reduce recurrence, namely antibiotic therapy with vancomycin or fidaxomicin for patients at high risk of recurrence, vancomycin tapering in patients with multiple recurrences, and faecal microbiota transplantation (in addition to antibiotic therapy) [7, 17]. The efficacy of stool transplantation in preventing recurrences has been clearly demonstrated , but many questions remain unanswered regarding implementation, especially regarding safety aspects, long-term effects by alterations of the microbiome composition, preliminary examinations and selection of the donor, and regulation.
In cases with refractory illness and lacking a faecal microbiota donor, adjunctive therapy with bezlotoxumab should be considered. Bezlotoxumab is a monoclonal antibody with high affinity to C. difficile toxin B and has been available in Switzerland since late 2017 for the prevention C. difficile relapses. Toxin B is responsible for the inflammation and cell damage caused by C. difficile and thus for the induction of colitis . Two randomised placebo-controlled trials have shown that a single dose of bezlotoxumab (10 mg/kg body weight) given concomitantly with standard therapy (vancomycin, metronidazole or fidaxomicin) for C. difficile reduced the recurrence rate by 38% over 12 weeks. Primary clinical response remained unchanged . The latter may be due to the fact that bezlotoxumab was not administered at the beginning of antibiotic therapy but instead after a median of 3 days. The favourable effect of bezlotoxumab on the recurrence rate is likely to be due to its potential reduction of epithelial damage to the intestinal mucosa while promoting the restoration of normal microbial activity , although the exact mechanism of action is not known.
The most frequent adverse event during the 12 weeks of follow up was heart failure, most likely caused by volume overload rather than a direct cardiotoxic effect of the drug [43, 45].
Although current IDSA guidelines do not take a position on the use of bezlotoxumab , the SSI panel has decided to include a recommendation for its use as an adjunctive therapy in high-risk patients. At the time of revision, bezlotoxumab was not yet available for the American market. Upcoming guideline updates will likely include a statement on the use of monoclonal antibodies for the treatment of CDI, as the substance has received approval from the US Food and Drug Administration in the meantime.
We thank all contributors of the SSI guideline on the management of C. difficile for discussions and critical input regarding the content of the guideline.
No funding was received for preparation of this manuscript.
Conflicts of interest
S. Tschudin-Sutter is a member of the Astellas and MSD Advisory Boards for C. difficile, of the Pfizer Antiinfectives Advisory Board, the Menarini and Shionogi Scientific Advisory Boards. She reports grants from the Swiss National Science Foundation (NRP 72 167060) and (197901), NCCR AntiResist (180541), the Gottfried und Julia Bangerter-Rhyner Stiftung, the Fonds zur Förderung von Lehre und Forschung der Freiwilligen Akademischen Gesellschaft Basel, and the Jubiläumsstiftung from Swiss Life.
Header image: Header image: CDC/ Antibiotic Resistance Coordination and Strategy Unit; Medical Illustrator: Jennifer Oosthuizen
Prof. Sarah Tschudin Sutter, MD, MSc
Head Division of Hospital Epidemiology
Deputy Head Division of Infectious Diseases & Hospital Epidemiology
University Hospital Basel
1. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, ECDIS Study Group. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011 Jan;377(9759):63–73. http://dx.doi.org/10.1016/S0140-6736(10)61266-4 PubMed 1474-547X
2. Davies KA, Longshaw CM, Davis GL, Bouza E, Barbut F, Barna Z Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis. 2014 Dec;14(12):1208–19. http://dx.doi.org/10.1016/S1473-3099(14)70991-0 PubMed 1474-4457
3. Fenner L, Frei R, Gregory M, Dangel M, Stranden A, Widmer AF. Epidemiology of Clostridium difficile-associated disease at University Hospital Basel including molecular characterisation of the isolates 2006-2007. Eur J Clin Microbiol Infect Dis. 2008 Dec;27(12):1201–7. http://dx.doi.org/10.1007/s10096-008-0564-9 PubMed 1435-4373
4. Kohler P, Bregenzer-Witteck A, Rafeiner P, Schlegel M. Presumably hospital-transmitted Clostridium difficile infections based on epidemiological linkage. Swiss Med Wkly. 2013 Jul;143:w13824. http://dx.doi.org/10.4414/smw.2013.13824 PubMed 1424-3997
5. Vernaz N, Sax H, Pittet D, Bonnabry P, Schrenzel J, Harbarth S. Temporal effects of antibiotic use and hand rub consumption on the incidence of MRSA and Clostridium difficile. J Antimicrob Chemother. 2008 Sep;62(3):601–7. http://dx.doi.org/10.1093/jac/dkn199 PubMed 1460-2091
6. Widmer AF, Frei R, Kuijper EJ, Wilcox MH, Schindler R, Spaniol V Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland. Emerg Infect Dis. 2020 Oct;26(10):2370–7. http://dx.doi.org/10.3201/eid2610.190804 PubMed 1080-6059
7. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar;66(7):e1–48. http://dx.doi.org/10.1093/cid/cix1085 PubMed 1537-6591
8. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov;2(8358):1043–6. http://dx.doi.org/10.1016/S0140-6736(83)91036-X PubMed 0140-6736
9. Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996 May;22(5):813–8. http://dx.doi.org/10.1093/clinids/22.5.813 PubMed 1058-4838
10. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Society for Healthcare Epidemiology of America, Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May;31(5):431–55. http://dx.doi.org/10.1086/651706 PubMed 1559-6834
11. Johnson S, Louie TJ, Gerding DN, Cornely OA, Chasan-Taber S, Fitts D, Polymer Alternative for CDI Treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug;59(3):345–54. http://dx.doi.org/10.1093/cid/ciu313 PubMed 1537-6591
12. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007 Aug;45(3):302–7. http://dx.doi.org/10.1086/519265 PubMed 1537-6591
13. Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev. 2017 Mar;3:CD004610. PubMed 1469-493X
14. Vardakas KZ, Polyzos KA, Patouni K, Rafailidis PI, Samonis G, Falagas ME. Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence. Int J Antimicrob Agents. 2012 Jul;40(1):1–8. http://dx.doi.org/10.1016/j.ijantimicag.2012.01.004 PubMed 1872-7913
15. Al-Nassir WN, Sethi AK, Nerandzic MM, Bobulsky GS, Jump RL, Donskey CJ. Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis. 2008 Jul;47(1):56–62. http://dx.doi.org/10.1086/588293 PubMed 1537-6591
16. Wilcox MH, Howe R. Diarrhoea caused by Clostridium difficile: response time for treatment with metronidazole and vancomycin. J Antimicrob Chemother. 1995 Oct;36(4):673–9. http://dx.doi.org/10.1093/jac/36.4.673 PubMed 0305-7453
17. Debast SB, Bauer MP, Kuijper EJ, European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014 Mar;20 Suppl 2:1–26. http://dx.doi.org/10.1111/1469-0691.12418 PubMed 1469-0691
18. Louie T, Miller M, Donskey C, Mullane K, Goldstein EJ. Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection. Antimicrob Agents Chemother. 2009 Jan;53(1):223–8. http://dx.doi.org/10.1128/AAC.01442-07 PubMed 1098-6596
19. Louie TJ, Cannon K, Byrne B, Emery J, Ward L, Eyben M Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012 Aug;55 Suppl 2:S132–42. http://dx.doi.org/10.1093/cid/cis338 PubMed 1537-6591
20. Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med. 1992 Aug;117(4):297–302. http://dx.doi.org/10.7326/0003-4819-117-4-297 PubMed 0003-4819
21. Baines SD, O’Connor R, Saxton K, Freeman J, Wilcox MH. Activity of vancomycin against epidemic Clostridium difficile strains in a human gut model. J Antimicrob Chemother. 2009 Mar;63(3):520–5. http://dx.doi.org/10.1093/jac/dkn502 PubMed 1460-2091
22. Deshpande A, Hurless K, Cadnum JL, Chesnel L, Gao L, Chan L Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice. Antimicrob Agents Chemother. 2016 Jun;60(7):3988–93. http://dx.doi.org/10.1128/AAC.02590-15 PubMed 1098-6596
23. Freeman J, Baines SD, Saxton K, Wilcox MH. Effect of metronidazole on growth and toxin production by epidemic Clostridium difficile PCR ribotypes 001 and 027 in a human gut model. J Antimicrob Chemother. 2007 Jul;60(1):83–91. http://dx.doi.org/10.1093/jac/dkm113 PubMed 0305-7453
24. Freeman J, Vernon J, Pilling S, Morris K, Nicolson S, Shearman S, Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes’ Study Group. Five-year Pan-European, longitudinal surveillance of Clostridium difficile ribotype prevalence and antimicrobial resistance: the extended ClosER study. Eur J Clin Microbiol Infect Dis. 2020 Jan;39(1):169–77. http://dx.doi.org/10.1007/s10096-019-03708-7 PubMed 1435-4373
25. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut. 1986 Oct;27(10):1169–72. http://dx.doi.org/10.1136/gut.27.10.1169 PubMed 0017-5749
26. Cherian PT, Wu X, Yang L, Scarborough JS, Singh AP, Alam ZA Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model of Clostridium difficile infection. J Antimicrob Chemother. 2015 Nov;70(11):3061–9. http://dx.doi.org/10.1093/jac/dkv231 PubMed 1460-2091
27. Widmer AF, Frei R, Erb S, Stranden A, Kuijper EJ, Knetsch CW Transmissibility of Clostridium difficile Without Contact Isolation: Results From a Prospective Observational Study With 451 Patients. Clin Infect Dis. 2017 Feb;64(4):393–400. PubMed 1537-6591
28. Cusini A, Béguelin C, Stampf S, Boggian K, Garzoni C, Koller M, Swiss Transplant Cohort Study. Clostridium difficile infection is associated with graft loss in solid organ transplant recipients. Am J Transplant. 2018 Jul;18(7):1745–54. http://dx.doi.org/10.1111/ajt.14640 PubMed 1600-6143
29. Tomas ME, Mana TS, Wilson BM, Nerandzic MM, Joussef-Piña S, Quiñones-Mateu ME Tapering Courses of Oral Vancomycin Induce Persistent Disruption of the Microbiota That Provide Colonization Resistance to Clostridium difficile and Vancomycin-Resistant Enterococci in Mice. Antimicrob Agents Chemother. 2018 Apr;62(5):e02237-17. http://dx.doi.org/10.1128/AAC.02237-17 PubMed 1098-6596
30. Sethi AK, Al-Nassir WN, Nerandzic MM, Donskey CJ. Skin and environmental contamination with vancomycin-resistant Enterococci in patients receiving oral metronidazole or oral vancomycin treatment for Clostridium difficile-associated disease. Infect Control Hosp Epidemiol. 2009 Jan;30(1):13–7. http://dx.doi.org/10.1086/592710 PubMed 1559-6834
31. Al-Nassir WN, Sethi AK, Li Y, Pultz MJ, Riggs MM, Donskey CJ. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother. 2008 Jul;52(7):2403–6. http://dx.doi.org/10.1128/AAC.00090-08 PubMed 1098-6596
32. Miller M, Bernard L, Thompson M, Grima D, Pepin J. Lack of increased colonization with vancomycin-resistant enterococci during preferential use of vancomycin for treatment during an outbreak of healthcare-associated Clostridium difficile infection. Infect Control Hosp Epidemiol. 2010 Jul;31(7):710–5. http://dx.doi.org/10.1086/653613 PubMed 1559-6834
33. Stevens VW, <span class="docsum-authors full-authors">Khader K, Echevarria K, Nelson RE, Zhang Y, Jones M</span> Use of oral vancomycin for Clostridioides difficile Infection (CDI) and the risk of vancomycin-resistant Enterococci (VRE). Clin Infect Dis. 2020;71(3):645-51.1058-4838
34. Johnson SW, Brown SV, Priest DH. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clin Infect Dis. 2019. http://dx.doi.org/10.1093/cid/ciz966 PubMed 1058-4838
35. Morrisette T, Van Matre AG, Miller MA, Mueller SW, Bajrovic V, Abidi MZ Oral Vancomycin Prophylaxis as Secondary Prevention Against Clostridioides difficile Infection in the Hematopoietic Stem Cell Transplantation and Hematologic Malignancy Population. Biol Blood Marrow Transplant. 2019 Oct;25(10):2091–7. http://dx.doi.org/10.1016/j.bbmt.2019.06.021 PubMed 1523-6536
36. Nerandzic MM, Mullane K, Miller MA, Babakhani F, Donskey CJ. Reduced acquisition and overgrowth of vancomycin-resistant enterococci and Candida species in patients treated with fidaxomicin versus vancomycin for Clostridium difficile infection. Clin Infect Dis. 2012 Aug;55 Suppl 2:S121–6. http://dx.doi.org/10.1093/cid/cis440 PubMed 1537-6591
37. Deshpande A, Hurless K, Cadnum JL, Chesnel L, Gao L, Chan L Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice. Antimicrob Agents Chemother. 2016 May;60(6):3333–9. http://dx.doi.org/10.1128/AAC.02904-15 PubMed 1098-6596
38. Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, OPT-80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012 Apr;12(4):281–9. http://dx.doi.org/10.1016/S1473-3099(11)70374-7 PubMed 1474-4457
39. Cornely OA, Miller MA, Louie TJ, Crook DW, Gorbach SL. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012 Aug;55 Suppl 2:S154–61. http://dx.doi.org/10.1093/cid/cis462 PubMed 1537-6591
40. Louie TJ, Emery J, Krulicki W, Byrne B, Mah M. OPT-80 eliminates Clostridium difficile and is sparing of bacteroides species during treatment of C. difficile infection. Antimicrob Agents Chemother. 2009 Jan;53(1):261–3. http://dx.doi.org/10.1128/AAC.01443-07 PubMed 1098-6596
41. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan;368(5):407–15. http://dx.doi.org/10.1056/NEJMoa1205037 PubMed 1533-4406
43. Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, MODIFY I and MODIFY II Investigators. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017 Jan;376(4):305–17. http://dx.doi.org/10.1056/NEJMoa1602615 PubMed 1533-4406
45. Gerding DN, Kelly CP, Rahav G, Lee C, Dubberke ER, Kumar PN Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018 Aug;67(5):649–56. http://dx.doi.org/10.1093/cid/ciy171 PubMed 1537-6591
Published under the copyright license CC BY-NC-SA: This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.