Controversies in the Prevention and Treatment of Infection in Adults: A Narrative Review

Overview

Journal Microorganisms

Specialty Microbiology

Date 2023 Feb 25

PMID 36838352

Authors

Taryn B Bainum

Kelly R Reveles

Ronald G Hall 2nd

Kelli Cornell

Carlos A Alvarez

Affiliations

Soon will be listed here.

Abstract

remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.

Citing Articles

Higher disease activity of inflammatory bowel disease predisposes to infection.

Vitikainen K, Kase M, Meriranta L, Molander P, Af Bjorkesten C, Anttila V Therap Adv Gastroenterol. 2025; 18:17562848251318292.

PMID: 39963249 PMC: 11831662. DOI: 10.1177/17562848251318292.

Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.

Chen S, Zhang D, Li D, Zeng F, Chen C, Bai F Medicine (Baltimore). 2025; 104(4):e41262.

PMID: 39854760 PMC: 11771716. DOI: 10.1097/MD.0000000000041262.

Therapeutics involved in managing initial and recurrent infection: An updated literature review.

Nagesh V, Tran H, Elias D, Kianifar Aguilar I, Sethi T, Menon A World J Gastrointest Pharmacol Ther. 2024; 15(5):95467.

PMID: 39281262 PMC: 11401021. DOI: 10.4292/wjgpt.v15.i5.95467.

Protective Effects of Huo Xiang Zheng Qi Liquid on Infection on C57BL/6 Mice.

Chen M, Zhai L, Schonning K, Alpizar-Alpizar W, Larum O, Andersen L Microorganisms. 2024; 12(8).

PMID: 39203444 PMC: 11356083. DOI: 10.3390/microorganisms12081602.

PhosphoLipidome Alteration Induced by Toxin B in Enteric Glial Cells.

Buratta S, Urbanelli L, Pellegrino R, Alabed H, Latella R, Cerrotti G Cells. 2024; 13(13.

PMID: 38994956 PMC: 11240607. DOI: 10.3390/cells13131103.

References

Chen J, Gong C, Hitchcock M, Holubar M, Deresinski S, Hay J . Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection. Clin Microbiol Infect. 2021; 27(10):1448-1454. PMC: 9478885. DOI: 10.1016/j.cmi.2021.04.004. View

Maraolo A, Mazzitelli M, Zappulo E, Scotto R, Granata G, Andini R . Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis. Antibiotics (Basel). 2022; 11(2). PMC: 8868369. DOI: 10.3390/antibiotics11020183. View

Khanna S, Assi M, Lee C, Yoho D, Louie T, Knapple W . Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs. 2022; 82(15):1527-1538. PMC: 9607700. DOI: 10.1007/s40265-022-01797-x. View

Takahashi M, Mori N, Bito S . Multi-institution case-control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan. BMJ Open. 2014; 4(9):e005665. PMC: 4158213. DOI: 10.1136/bmjopen-2014-005665. View

Fischer M, Sipe B, Cheng Y, Phelps E, Rogers N, Sagi S . Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: A promising treatment approach. Gut Microbes. 2016; 8(3):289-302. PMC: 5479393. DOI: 10.1080/19490976.2016.1273998. View

Cornely O, Vehreschild M, Adomakoh N, Georgopali A, Karas A, Kazeem G . Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses. Eur J Clin Microbiol Infect Dis. 2019; 38(6):1187-1194. PMC: 6520315. DOI: 10.1007/s10096-019-03525-y. View

Giancola S, Williams 2nd R, Gentry C . Prevalence of the Clostridium difficile BI/NAP1/027 strain across the United States Veterans Health Administration. Clin Microbiol Infect. 2017; 24(8):877-881. DOI: 10.1016/j.cmi.2017.11.011. View

Popa D, Neamtu B, Mihalache M, Boicean A, Banciu A, Banciu D . Fecal Microbiota Transplant in Severe and Non-Severe Infection. Is There a Role of FMT in Primary Severe CDI?. J Clin Med. 2021; 10(24). PMC: 8707415. DOI: 10.3390/jcm10245822. View

Cornely O, Crook D, Esposito R, Poirier A, Somero M, Weiss K . 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; 12(4):281-9. DOI: 10.1016/S1473-3099(11)70374-7. View

10.

Youngster I, Russell G, Pindar C, Ziv-Baran T, Sauk J, Hohmann E . Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014; 312(17):1772-8. DOI: 10.1001/jama.2014.13875. View

11.

Polivkova S, Krutova M, capek V, Sykorova B, Benes J . Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study. Int J Infect Dis. 2020; 103:226-233. DOI: 10.1016/j.ijid.2020.11.004. View

12.

Moayyedi P, Eikelboom J, Bosch J, Connolly S, Dyal L, Shestakovska O . Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019; 157(3):682-691.e2. DOI: 10.1053/j.gastro.2019.05.056. View

13.

Mikamo H, Tateda K, Yanagihara K, Kusachi S, Takesue Y, Miki T . 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. 2018; 24(9):744-752. DOI: 10.1016/j.jiac.2018.05.010. View

14.

Escudero-Sanchez R, Muriel Garcia A, Garcia Fernandez S, Valencia Alijo A, Tasias Pitarch M, Merino de Lucas E . Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study. J Antimicrob Chemother. 2022; 77(7):1996-2002. DOI: 10.1093/jac/dkac106. View

15.

Olsen M, Yan Y, Reske K, Zilberberg M, Dubberke E . Recurrent Clostridium difficile infection is associated with increased mortality. Clin Microbiol Infect. 2015; 21(2):164-70. DOI: 10.1016/j.cmi.2014.08.017. View

16.

Preidis G, Weizman A, Kashyap P, Morgan R . AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020; 159(2):708-738.e4. PMC: 8018518. DOI: 10.1053/j.gastro.2020.05.060. View

17.

Okumura H, Fukushima A, Taieb V, Shoji S, English M . Fidaxomicin compared with vancomycin and metronidazole for the treatment of Clostridioides (Clostridium) difficile infection: A network meta-analysis. J Infect Chemother. 2019; 26(1):43-50. DOI: 10.1016/j.jiac.2019.07.005. View

18.

Hempel S, Newberry S, Ruelaz A, Wang Z, Miles J, Suttorp M . Safety of probiotics used to reduce risk and prevent or treat disease. Evid Rep Technol Assess (Full Rep). 2012; (200):1-645. PMC: 4780970. View

19.

Mullane K, Winston D, Nooka A, Morris M, Stiff P, Dugan M . A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2018; 68(2):196-203. PMC: 6321849. DOI: 10.1093/cid/ciy484. View

20.

Shen N, Maw A, Tmanova L, Pino A, Ancy K, Crawford C . Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis. Gastroenterology. 2017; 152(8):1889-1900.e9. DOI: 10.1053/j.gastro.2017.02.003. View