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Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis

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Abstract

Background

Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic.

Methods

Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)—classified as either high, moderate, low, or very low.

Results

Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96–1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07–1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01–2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96–1.14; moderate-certainty evidence).

Conclusions

Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.

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Data availability

Our data has been uploaded to the Open Science Framework database for viewing. https://osf.io/dt6y4/. The DOI identifier for this account is 10.17605/OSF.IO/DT6Y4.

References

  1. Guh AY, Mu Y, Winston LG et al (2020) Trends in U.S. burden of clostridioides difficile infection and outcomes. N Engl J Med 382(14):1320–1330. https://doi.org/10.1056/NEJMoa1910215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Centers for Disease Control and Prevention, National Center for Health Statistics. Underlying Cause of Death 1999–2020 on CDC WONDER Online Database, released in 2021. Data are from the Multiple Cause of Death Files, 1999–2020, as compiled from data provided by the 57 vital statistics jurisdictions through the vital statistics cooperative program. at http://wonder.cdc.gov/ucd-icd10.html. Accessed 1 Mar 2022

  3. Goyal H, Perisetti A, Rehman MR, Singla U (2018) New and emerging therapies in treatment of Clostridium difficile infection. Eur J Gastroenterol Hepatol 30(6):589–597. https://doi.org/10.1097/MEG.0000000000001103

    Article  CAS  PubMed  Google Scholar 

  4. Petrosillo N, Granata G, Cataldo MA (2018) Novel antimicrobials for the treatment of Clostridium difficile infection. Front Med 5:96. https://doi.org/10.3389/fmed.2018.00096

    Article  Google Scholar 

  5. Ooijevaar RE, van Beurden YH, Terveer EM et al (2018) Update of treatment algorithms for Clostridium difficile infection. Clin Microbiol Infect 24(5):452–462. https://doi.org/10.1016/j.cmi.2017.12.022

    Article  CAS  PubMed  Google Scholar 

  6. Higgins JPT, Altman DG, Sterne JAC (2011) Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration. http://www.cochrane-handbook.org

  7. Burke JF, Sussman JB, Kent DM, Hayward RA (2015) Three simple rules to ensure reasonably credible subgroup analyses. BMJ 4(351):h5651. https://doi.org/10.1136/bmj.h5651

    Article  Google Scholar 

  8. Guyatt GH, Oxman AD, Kunz R et al (2008) What is “quality of evidence” and why is it important to clinicians? BMJ 336(7651):995–998. https://doi.org/10.1136/bmj.39490.551019.BE

    Article  PubMed  PubMed Central  Google Scholar 

Excluded studies

  1. Lee CH, Patino H, Stevens C et al (2016) Surotomycin versus vancomycin for Clostridium difficile infection: phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother 71(10):2964–2971. https://doi.org/10.1093/jac/dkw246

    Article  CAS  PubMed  Google Scholar 

  2. Louie TJ, Miller MA, Mullane KM et al (2011) Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 364(5):422–431. https://doi.org/10.1056/NEJMoa0910812

    Article  CAS  PubMed  Google Scholar 

  3. Cornely OA, Crook DW, Esposito R et al (2012) 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 12(4):281–289. https://doi.org/10.1016/S1473-3099(11)70374-7

    Article  CAS  PubMed  Google Scholar 

  4. Louie T, Nord CE, Talbot GH et al (2015) Multicenter, double-blind, randomized, phase 2 Study evaluating the novel antibiotic cadazolid in patients with Clostridium difficile infection. Antimicrob Agents Chemother 59(10):6266–6273. https://doi.org/10.1128/AAC.00504-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Boix V, Fedorak RN, Mullane KM et al (2017) Primary outcomes from a phase 3, randomized, double-blind, active-controlled trial of surotomycin in subjects with Clostridium difficile infection. Open Forum Infect Dis 4(1):ofw275. https://doi.org/10.1093/ofid/ofw275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Daley P, Louie T, Lutz JE et al (2017) Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, phase 3 trial. J Antimicrob Chemother 72(12):3462–3470. https://doi.org/10.1093/jac/dkx299

    Article  CAS  PubMed  Google Scholar 

  7. Gerding DN, Cornely OA, Grill S et al (2019) Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis 19(3):265–274. https://doi.org/10.1016/S1473-3099(18)30614-5

    Article  CAS  PubMed  Google Scholar 

  8. Guery B, Menichetti F, Anttila VJ et al (2018) Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis 18(3):296–307. https://doi.org/10.1016/S1473-3099(17)30751-X

    Article  CAS  PubMed  Google Scholar 

  9. Hvas CL, Dahl Jørgensen SM, Jørgensen SP et al (2019) Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection. Gastroenterology 156(5):1324-1332.e3. https://doi.org/10.1053/j.gastro.2018.12.019

    Article  PubMed  Google Scholar 

  10. Mikamo H, Tateda K, Yanagihara K et al (2018) Efficacy and safety of fidaxomicin for the treatment of Clostridioides (Clostridium) difficile infection in a randomized, double-blind, comparative phase III study in Japan. J Infect Chemother 24(9):744–752. https://doi.org/10.1016/j.jiac.2018.05.010

    Article  CAS  PubMed  Google Scholar 

  11. Thabit AK, Alam MJ, Khaleduzzaman M, Garey KW, Nicolau DP (2016) A pilot study to assess bacterial and toxin reduction in patients with Clostridium difficile infection given fidaxomicin or vancomycin. Ann Clin Microbiol Antimicrob 15(1):22. https://doi.org/10.1186/s12941-016-0140-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vickers RJ, Tillotson GS, Nathan R et al (2017) Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Lancet Infect Dis 17(7):735–744. https://doi.org/10.1016/S1473-3099(17)30235-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wolf J, Kalocsai K, Fortuny C et al (2020) Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis 71(10):2581–2588. https://doi.org/10.1093/cid/ciz1149

    Article  CAS  PubMed  Google Scholar 

  14. Housman ST, Thabit AK, Kuti JL, Qsuintiliani R, Nicolau DP (2016) Assessment of Clostridium difficile burden in patients over time with first episode Infection following fidaxomicin or vancomycin. Infect Control Hosp Epidemiol 37(2):215–218. https://doi.org/10.1017/ice.2015.270

    Article  PubMed  Google Scholar 

  15. Louie T, Miller M, Donskey C, Mullane K, Goldstein EJ (2009) Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection. Antimicrob Agents Chemother 53(1):223–228. https://doi.org/10.1128/AAC.01442-07

    Article  CAS  PubMed  Google Scholar 

Included studies

  1. Dubberke ER, Gerding DN, Kelly CP et al (2020) Efficacy of bezlotoxumab in participants receiving metronidazole, vancomycin, or fidaxomicin for treatment of Clostridioides (Clostridium) difficile infection. Open Forum Infect Dis 7(6):ofaa157. https://doi.org/10.1093/ofid/ofaa157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gawronska A, Banasiuk M, Lachowicz D, Pituch H, Albrecht P, Banaszkiewicz A (2017) Metronidazole or rifaximin for treatment of Clostridium difficile in pediatric patients with inflammatory bowel disease: a randomized clinical trial. Inflamm Bowel Dis 23(12):2209–2214. https://doi.org/10.1097/MIB.0000000000001249

    Article  PubMed  Google Scholar 

  3. Fabre V, Dzintars K, Avdic E, Cosgrove SE (2018) Role of metronidazole in mild Clostridium difficile infections. Clin Infect Dis 67(12):1956–1958. https://doi.org/10.1093/cid/ciy474

    Article  PubMed  Google Scholar 

  4. Appaneal HJ, Caffrey AR, LaPlante KL (2019) What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of veterans with initial mild disease. Clin Infect Dis 69(8):1288–1295. https://doi.org/10.1093/cid/ciy1077

    Article  CAS  PubMed  Google Scholar 

  5. Frelick M. C Diff recurrence drops with highly targeted ridinilazole. https://www.medscape.com/viewarticle/98297

Further citations

  1. https://en.wikipedia.org/wiki/Surotomycin

  2. Nelson RL, Suda KJ, Evans CT (2017) Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev 3(3):CD004610. https://doi.org/10.1002/14651858.CD004610

    Article  PubMed  Google Scholar 

  3. Zhang VRY, Woo ASJ, Scaduto C et al (2021) Systematic review on the definition and predictors of severe Clostridiodes difficile infection. J Gastroenterol Hepatol 36(1):89–104. https://doi.org/10.1111/jgh.15102

    Article  PubMed  Google Scholar 

  4. (2021) Treatment of Clostridioides difficile infection. Med Lett Drugs Ther 63(1632):137–141

  5. Kim J, Kim J, Kim B, Pai H (2022) Which is the preferred regimen for non-severe Clostridioides difficile infection in Korea, vancomycin or metronidazole? Infect Chemother 54(2):213–219. https://doi.org/10.3947/ic.2022.0027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Assmann SF, Pocock SJ, Enos LE, Kasten LE (2000) Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 355:1064–1069

    Article  CAS  PubMed  Google Scholar 

  7. Montedori A, Bonacini MI, Casazza G et al (2011) Modified versus standard intention-to-treat reporting: are there differences in methodological quality, sponsorship, and findings in randomized trials? A cross-sectional study. Trials 28(12):58. https://doi.org/10.1186/1745-6215-12-58

    Article  Google Scholar 

  8. Liao JX, Appaneal HJ, Vicent ML, Vyas A, LaPlante KL (2022) Path of least recurrence: a systematic review and meta-analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection. Pharmacotherapy 42(11):810–827. https://doi.org/10.1002/phar.2734

    Article  CAS  PubMed  Google Scholar 

  9. Tashiro S, Mihara T, Sasaki M et al (2022) Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials. J Infect Chemother 28(11):1536–1545. https://doi.org/10.1016/j.jiac.2022.08.008

    Article  CAS  PubMed  Google Scholar 

  10. Dai J, Gong J, Guo R (2022) Real-world comparison of fidaxomicin versus vancomycin or metronidazole in the treatment of Clostridium difficile infection: asystematic review and meta-analysis. Eur J Clin Pharmacol 78(11):1727–1737. https://doi.org/10.1007/s00228-022-03376-1

    Article  CAS  PubMed  Google Scholar 

  11. Muhammad A, Simcha W, Rawish F et al (2019) Cadazolid vs. vancomycin for treatment of Clostridioides difficile infection: systematic review with meta-analysis. Am J Gastroenterol 114:S118–S119. https://doi.org/10.14309/01.ajg.0000590308.97510.e1

    Article  Google Scholar 

  12. Muhammad A, Madhav D, Rawish F et al (2019) Surotomycin (a novel cyclic lipopeptide) vs vancomycin for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis. Curr Clin Pharmacol 14:1–9

    Article  CAS  Google Scholar 

  13. Johnson S, Lavergne V, Skinner AM et al (2021) Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of clostridioides difficile infection in adults. Clin Microbiol Infect 27(Suppl 2):S1–S21. https://doi.org/10.1016/j.cmi.2021.09.038

    Article  CAS  Google Scholar 

  14. van Prehn J, Reigadas E, Vogelzang EH et al (2021) European Society of Clinical Microbiology and Infectious Diseases: European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect 27(Suppl 2):S1–S21. https://doi.org/10.1016/j.cmi.2021.09.038

    Article  CAS  PubMed  Google Scholar 

  15. Guery B, Galperine T, Barbut F (2019) Clostridioides difficile: diagnosis and treatments. BMJ 20(366):l4609. https://doi.org/10.1136/bmj.l4609

    Article  Google Scholar 

  16. Gnocchi M, Gagliardi M, Gismondi P, Gaiani F, de Angelis GL, Esposito S (2020) Updated management guidelines for Clostridioides difficile in paediatrics. Pathogens 9(4):291. https://doi.org/10.3390/pathogens9040291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. NICE guideline: Clostridioides difficile infection: antimicrobial prescribing NICE guideline: evidence review Published 23 July 2021. https://www.nice.org.uk/guidance/ng199/evidence/evidence-review-pdf-9194637853. Accessed 7 Jun 2023

  18. Nicholas S, Araadhna MS, Anthony B, Helen S, Gordon S, Sophia Ceder, Mark HW (2023) A cost-utility analysis of two Clostridioides difficile infection guideline treatment pathways. Clin Microbiol Infect 29(10):1291–1297. https://doi.org/10.1016/j.cmi.2023.06.018

    Article  Google Scholar 

  19. Harbrecht BG (2019) Limitations of the Infectious Disease Society of America/Society for Hospital Epidemiologists of America 2017 update of guidelines for the treatment of Clostridium difficile colitis. Dis Colon Rectum 62(10):1147–1149. https://doi.org/10.1097/DCR.0000000000001469

    Article  PubMed  Google Scholar 

  20. Beinortas T, Burr NE, Wilcox MH, Subramanian V (2018) Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis. Lancet Infect Dis 18(9):1035–1044. https://doi.org/10.1016/S1473-3099(18)30285-8

    Article  CAS  PubMed  Google Scholar 

  21. Baker SG, Kramer BS (2002) The transitive fallacy for randomized trials: if A bests B and B bests C in separate trials, is A better than C? BMC Med Res Methodol 13(2):13.

    Article  Google Scholar 

  22. Clancy CJ, Buehrle D, Vu M, Wagener MM, Nguyen MH (2021) Impact of revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America clinical practice guidelines on the treatment of Clostridium difficile infections in the United States. Clin Infect Dis 72(11):1944–1949. https://doi.org/10.1093/cid/ciaa484

    Article  CAS  PubMed  Google Scholar 

  23. Gøtzsche PC (2006) Lessons from and cautions about noninferiority and equivalence randomized trials. JAMA 295(10):1172–1174. https://doi.org/10.1001/jama.295.10.1172

    Article  PubMed  Google Scholar 

  24. DiNubile MJ (2016) Noninferior antibiotics: when is “not bad” “good enough”? Open Forum Infect Di 3(3):ofw110. https://doi.org/10.1093/ofid/ofw110

    Article  Google Scholar 

  25. Mostazir M, Taylor G, Henley WE, Watkins ER, Taylor RS (2021) Per-Protocol analyses produced larger treatment effect sizes than intention to treat: a meta-epidemiological study. J Clin Epidemiol 138:12–21. https://doi.org/10.1016/j.jclinepi.2021.06.010

    Article  PubMed  Google Scholar 

  26. Morlock R, Rose J, Powers JH 3rd (2023) Perspectives of US adults on antimicrobial trials with noninferiority designs. JAMA Netw Open 6(5):e2316297. https://doi.org/10.1001/jamanetworkopen.2023.16297

    Article  PubMed  PubMed Central  Google Scholar 

  27. Johnson S, Gerding DN, Li X et al (2022) Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): a randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence. Contemp Clin Trials 116:106756. https://doi.org/10.1016/j.cct.2022.106756

    Article  PubMed  Google Scholar 

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Funding

No funding was obtained for this study.

Author information

Authors and Affiliations

  1. Poznan University of Medical Sciences, Poznan, Poland

    A. M. Kravets

  2. Library of the Health Sciences-Chicago, University of Illinois at Chicago, Chicago, IL, USA

    R. Hanneke

  3. Epidemiology/Biometry Division, School of Public Health, University of Illinois, Chicago, IL, USA

    R. L. Nelson

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  1. A. M. Kravets
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Correspondence to R. L. Nelson.

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Appendix: search strategy

Appendix: search strategy

Adapted from [33] Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev 2017 Mar3;3(3):CD004610. https://doi.org/10.1002/14651858.CD004610.pub5

Ovid MEDLINE

  1. 1.

    exp “Anti-Bacterial Agents”/

  2. 2.

    exp Aminoglycosides/

  3. 3.

    exp Cephalosporins/

  4. 4.

    (Vancomycin or Metronidazole or Fusidic acid or Nitazoxanide or Teicoplanin or Rifampicin or Rifaximin or Bacitracin or Fidaxomicin or Amoxicillin or Azithromycin or Cadazolid or Cephalosporin* or Cephalexin or Ciprofloxacin or Clarithromycin or Clindamycin or Doxycycline or Erythromycin or Flouroquinolone* or Levofloxacin or Macrolide* or Nitrofurantoin or Penicillin or Ridinilazole or Surotomycin or Tetracycline or Trimethoprim or antibiotic* or anti‐bacterial* or anti bacterial* or antibacterial* or bacteriocid* or bactericid* or antimicrobial* or anti‐microbial*).mp.

  5. 5.

    1 or 2 or 3 or 4

  6. 6.

    exp Clostridium difficile/

  7. 7.

    exp Clostridium Infections/

  8. 8.

    exp Diarrhea/dt [Drug Therapy]

  9. 9.

    exp Enterocolitis, Pseudomembranous/dt [Drug Therapy]

  10. 10.

    (Clostridium difficile or difficile or pseudomembranous enterocolitis).mp.

  11. 11.

    6 or 7 or 8 or 9 or 10

  12. 12.

    5 and 11

  13. 13.

    randomized controlled trial.pt.

  14. 14.

    controlled clinical trial.pt.

  15. 15.

    randomized.ab.

  16. 16.

    placebo.ab.

  17. 17.

    clinical trial.sh.

  18. 18.

    randomly.ab.

  19. 19.

    trial.ti.

  20. 20.

    13 or 14 or 15 or 16 or 17 or 18 or 19

  21. 21.

    Humans.sh.

  22. 22.

    20 and 21

  23. 23.

    12 and 22

Embase.com

  1. 1.

    ‘antiinfective agent’/mj

  2. 2.

    vancomycin:ti OR metronidazole:ti OR ‘fusidic acid’:ti OR nitazoxanide:ti OR teicoplanin:ti OR rifampicin:ti OR rifaximin:ti OR bacitracin:ti OR fidaxomicin:ti OR amoxicillin:ti OR azithromycin:ti OR cephalosporin*:ti OR cephalexin:ti OR ciprofloxacin:ti OR clarithromycin:ti OR clindamycin:ti OR doxycycline:ti OR erythromycin:ti OR flouroquinolone*:ti OR levofloxacin:ti OR macrolide*:ti OR nitrofurantoin:ti OR penicillin:ti OR tetracycline:ti OR trimethoprim:ti OR antibiotic*:ti OR ‘anti bacterial*’:ti OR antibacterial*:ti OR bacteriocid*:ti OR bactericid*:ti OR antimicrobial*:ti OR ‘anti microbial’:ti

  3. 3.

    #1 OR #2

  4. 4.

    ‘Clostridioides difficile’/mj

  5. 5.

    ‘Clostridium difficile infection’/mj

  6. 6.

    ‘diarrhea’/mj/dm_dt

  7. 7.

    ‘pseudomembranous colitis’/mj/dm_dt

  8. 8.

    (‘Clostridium difficile’ OR difficile OR ‘pseudomembranous enterocolitis’):ti,ab,kw

  9. 9.

    #4 OR #5 OR #6 OR #7 OR #8

  10. 10.

    #3 AND #9

  11. 11.

    ‘randomized controlled trial’:de

  12. 12.

    ‘randomization’:de

  13. 13.

    ‘controlled study’:de

  14. 14.

    ‘multicenter study’:de

  15. 15.

    ‘phase 3 clinical trial’:de

  16. 16.

    ‘phase 4 clinical trial’:de

  17. 17.

    ‘double blind procedure’:de

  18. 18.

    ‘single blind procedure’:de

  19. 19.

    ((singl* OR doubl* OR trebl* OR tripl*) NEAR/1 (blind* OR mask*)):ti,ab

  20. 20.

    (random* OR cross-over* OR factorial* OR placebo* OR volunteer*):ti,ab

  21. 21.

    #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20

  22. 22.

    ‘human*’:ti,ab

  23. 23.

    (animal* OR nonhuman*):ti,ab

  24. 24.

    #23 AND #22

  25. 25.

    #23 NOT #24

  26. 26.

    #21 NOT #25

  27. 27.

    #10 AND #26

Central

  1. 1.

    MeSH descriptor Anti‐Bacterial Agents explode all trees

  2. 2.

    MeSH descriptor Aminoglycosides explode all trees

  3. 3.

    MeSH descriptor Cephalosporins explode all trees

  4. 4.

    (Vancomycin or Metronidazole or Fusidic acid or Nitazoxanide or Teicoplanin or Ridinilazole or Rifampicin or Rifaximin or Bacitracin or Fidaxomicin or Amoxicillin or Azithromycin or Cadazolid or Cephalosporin* or Cephalexin or Ciprofloxacin or Clarithromycin or Clindamycin or Doxycycline or Erythromycin or Flouroquinolone* or Levofloxacin or Macrolide* or Nitrofurantoin or Penicillin or Surotomycin or Tetracycline or Trimethoprim or antibiotic* or anti‐bacterial* or anti bacterial* or antibacterial* or bacteriocid* or bactericid* or antimicrobial* or anti‐microbial*):ti,ab,kw

  5. 5.

    (#1 OR #2 OR #3 OR #4)

  6. 6.

    MeSH descriptor Clostridium difficile explode all trees

  7. 7.

    MeSH descriptor Clostridium Infections explode all trees

  8. 8.

    MeSH descriptor Diarrhea explode all trees with qualifier: DT

  9. 9.

    MeSH descriptor Enterocolitis, Pseudomembranous explode all trees with qualifier: DT

  10. 10.

    (Clostridium difficile or difficile or pseudomembranous enterocolitis):ti,ab,kw

  11. 11.

    (#6 OR #7 OR #8 OR #9 OR #10)

  12. 12.

    (#5 AND #11)

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Kravets, A.M., Hanneke, R. & Nelson, R.L. Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis. Tech Coloproctol 28, 20 (2024). https://doi.org/10.1007/s10151-023-02878-z

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