Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients-A Systematic Review and Meta-Analysis

Sara Blaabjerg, Daniel Maribo Artzi, Rune Aabenhus, Sara Blaabjerg, Daniel Maribo Artzi, Rune Aabenhus

Abstract

A common adverse effect of antibiotic use is diarrhea. Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The objective of this systematic review was to assess the benefits and harms of probiotics used for the prevention of AAD in an outpatient setting. A search of the PubMed database was conducted and yielded a total of 17 RCTs with 3631 participants to be included in the review. A meta-analysis was conducted for the primary outcome: the incidence of AAD. The pooled results found that AAD was present in 8.0% of the probiotic group compared to 17.7% in the control group (RR 0.49, 95% CI 0.36 to 0.66; I² = 58%), and the species-specific results were similar regarding the probiotic strains L. rhamnosus GG and S. boulardii. However, the overall quality of the included studies was moderate. A meta-analysis of the ten trials reporting adverse events demonstrated no statistically significant differences in the incidence of adverse events between the intervention and control group (RD 0.00, 95% CI -0.02 to 0.02, 2.363 participants). The results suggests that probiotic use may be beneficial in the prevention of AAD among outpatients. Furthermore, the use of probiotics appears safe.

Keywords: Bifidobacterium; Lactobacillus; Saccharomyces; antibiotic-associated diarrhea; primary care; probiotics.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Risk of bias summary.
Figure 2
Figure 2
Funnel plot.
Figure 3
Figure 3
Efficacy results of probiotic use: eight RCTs by three probiotic subgroups (outcome: incidence of antibiotic-associated diarrhea (AAD)).
Figure 4
Figure 4
Efficacy results of probiotic use by study (secondary outcome: incidence of AAD using the criteria defined by WHO).
Figure 5
Figure 5
Adverse events.

References

    1. McFarland L.V. Epidemiology, risk factors and treatments for antibiotic-associated diarrhea. Dig. Dis. (Basel Switz.) 1998;16:292–307. doi: 10.1159/000016879.
    1. Wistrom J., Norrby S.R., Myhre E.B., Eriksson S., Granstrom G., Lagergren L., Englund G., Nord C.E., Svenungsson B. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: A prospective study. J. Antimicrob. Chemother. 2001;47:43–50. doi: 10.1093/jac/47.1.43.
    1. Goossens H., Ferech M., Vander Stichele R., Elseviers M. Outpatient antibiotic use in Europe and association with resistance: A cross-national database study. Lancet (Lond. Engl.) 2005;365:579–587. doi: 10.1016/S0140-6736(05)70799-6.
    1. Food and Agriculture Organization of the United Nation/World Health Organization . Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food. FAO/WHO; London, ON, Canada: 2002.
    1. Rolfe R.D. The role of probiotic cultures in the control of gastrointestinal health. J. Nutr. 2000;130:396s–402s.
    1. Goldenberg J.Z., Lytvyn L., Steurich J., Parkin P., Mahant S., Johnston B.C. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst. Rev. 2015:Cd004827. doi: 10.1002/14651858.CD004827.
    1. Tankanow R.M., Ross M.B., Ertel I.J., Dickinson D.G., McCormick L.S., Garfinkel J.F. A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea. DICP. 1990;24:382–384. doi: 10.1177/106002809002400408.
    1. Vanderhoof J.A., Whitney D.B., Antonson D.L., Hanner T.L., Lupo J.V., Young R.J. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J. Pediatr. 1999;135:564–568. doi: 10.1016/S0022-3476(99)70053-3.
    1. Arvola T., Laiho K., Torkkeli S., Mykkanen H., Salminen S., Maunula L., Isolauri E. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: A randomized study. Pediatrics. 1999;104:e64. doi: 10.1542/peds.104.5.e64.
    1. Erdeve O., Tiras U., Dallar Y. The probiotic effect of Saccharomyces boulardii in a pediatric age group. J. Trop. Pediatr. 2004;50:234–236. doi: 10.1093/tropej/50.4.234.
    1. Duman D.G., Bor S., Ozutemiz O., Sahin T., Oguz D., Istan F., Vural T., Sandkci M., Işksal F., Simşek I., et al. Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacterpylori eradication. Eur. J. Gastroenterol. Hepatol. 2005;17:1357–1361. doi: 10.1097/00042737-200512000-00015.
    1. Park S.K., Park D.I., Choi J.S., Kang M.S., Park J.H., Kim H.J., Cho Y.K., Sohn C.I., Jeon W.K., Kim B.I. The effect of probiotics on Helicobacter pylori eradication. Hepatogastroenterology. 2007;54:2032–2036.
    1. Cindoruk M., Erkan G., Karakan T., Dursun A., Unal S. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: A prospective randomized placebo-controlled double-blind study. Helicobacter. 2007;12:309–316. doi: 10.1111/j.1523-5378.2007.00516.x.
    1. Conway S., Hart A., Clark A., Harvey I. Does eating yogurt prevent antibiotic-associated diarrhoea? A placebo-controlled randomised controlled trial in general practice. Br. J. Gen. Pract. 2007;57:953–959. doi: 10.3399/096016407782604811.
    1. Imase K., Takahashi M., Tanaka A., Tokunaga K., Sugano H., Tanaka M., Ishida H., Kamiya S., Takahashi S. Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota. Microbiol. Immunol. 2008;52:156–161. doi: 10.1111/j.1348-0421.2008.00026.x.
    1. Kim M.N., Kim N., Lee S.H., Park Y.S., Hwang J.H., Kim J.W., Jeong S.H., Lee D.H., Kim J.S., Jung H.C., et al. The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication. Helicobacter. 2008;13:261–268. doi: 10.1111/j.1523-5378.2008.00601.x.
    1. Merenstein D.J., Foster J., D’Amico F. A randomized clinical trial measuring the influence of kefir on antibiotic-associated diarrhea: The measuring the influence of Kefir (MILK) Study. Arch. Pediatr. Adolesc. Med. 2009;163:750–754. doi: 10.1001/archpediatrics.2009.119.
    1. De Vrese M., Kristen H., Rautenberg P., Laue C., Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a fermented milk product with added fruit preparation reduce antibiotic associated diarrhea and Helicobacter pylori activity. J. Dairy Res. 2011;78:396–403. doi: 10.1017/S002202991100063X.
    1. Ojetti V., Bruno G., Ainora M.E., Gigante G., Rizzo G., Roccarina D., Gasbarrini A. Impact of Lactobacillus reuteri Supplementation on Anti-Helicobacter pylori Levofloxacin-Based Second-Line Therapy. Gastroenterol. Res. Pract. 2012;2012:740381. doi: 10.1155/2012/740381.
    1. Chatterjee S., Kar P., Das T., Ray S., Gangulyt S., Rajendiran C., Mitra M. Randomised placebo-controlled double blind multicentric trial on efficacy and safety of Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 for prevention of antibiotic-associated diarrhoea. J. Assoc. Phys. India. 2013;61:708–712.
    1. Zojaji H., Ghobakhlou M., Rajabalinia H., Ataei E., Jahani Sherafat S., Moghimi-Dehkordi B., Bahreiny R. The efficacy and safety of adding the probiotic Saccharomyces boulardiito standard triple therapy for eradication of H.pylori: A randomized controlled trial. Gastroenterol. Hepatol. Bed. Bench. 2013;6:S99–S104.
    1. Fox M.J., Ahuja K.D., Robertson I.K., Ball M.J., Eri R.D. Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study. BMJ Open. 2015;5:e006474. doi: 10.1136/bmjopen-2014-006474.
    1. Olek A., Woynarowski M., Ahren I.L., Kierkus J., Socha P., Larsson N., Önning G. Efficacy and Safety of Lactobacillus plantarum DSM 9843 (LP299V) in the Prevention of Antibiotic-Associated Gastrointestinal Symptoms in Children-Randomized, Double-Blind, Placebo-Controlled Study. J. Pediatr. 2017;186:82–86. doi: 10.1016/j.jpeds.2017.03.047.
    1. WHO Diarrhoeal Disease. [(accessed on 1 June 2017)]; Available online:
    1. Ouwehand A.C. A review of dose-responses of probiotics in human studies. Benef. Microbes. 2016;8:143–151. doi: 10.3920/BM2016.0140.
    1. Hempel S., Newberry S.J., Maher A.R., Wang Z., Miles J.N., Shanman R., Johnsen B., Shekelle P.G. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: A systematic review and meta-analysis. JAMA. 2012;307:1959–1969.
    1. Petersen I., Hayward A.C. Antibacterial prescribing in primary care. J. Antimicrob. Chemother. 2007;60:i43–i47. doi: 10.1093/jac/dkm156.
    1. Hempel S., Newberry S., Ruelaz A., Wang Z., Miles J.N., Suttorp M.J., Johnsen B., Shanman R., Slusser W., Fu N., et al. Safety of Probiotics Used to Reduce Risk and Prevent or Treat Disease. Agency for Healthcare Research and Quality; Rockville, MD, USA: 2011. Evidence Report/Technology Assessment No. 200.
    1. WHO . Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean Care Is Safer Care. World Health Organization; Geneva, Switzerland: 2009. [(accessed on 1 June 2017)]. Appendix 1, Definitions of health-care settings and other related terms. Available online:
    1. Higgins J.P.T. In: Cochrane Handbook for Systematic Reviews of Interventions, Chapter 8: Assessing Risk of Bias in Included Studies. Higgins J.P.T., Green S., editors. John Wiley & Sons; Chichester, UK: 2008.
    1. The GRADE Working Group . In: GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. Schünemann H., Brożek J., Guyatt G., Oxman A., editors. The GRADE Working Group; 2013. [(accessed on 1 June 2017)]. Updated October 2013. Available online: .
    1. McMaster University; 2015. [(accessed on 5 October 2017)]. GRADEpro GDT: GRADEpro Guideline Development Tool [Software] (Developed by Evidence Prime, Inc.) Available online:
    1. Review Manager (RevMan) [Computer program]. Version 5.3. The Nordic Cochrane Centre; The Cochrane Collaboration; Copenhagen, Denmark: 2014.
    1. Higgins J.P.T., Green S., editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Updated March 2011] The Cochrane Collaboration; Copenhagen, Denmark: 2011. [(accessed on 1 June 2017)]. Available online: .

Source: PubMed

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