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A randomized controlled trial of Lactobacillus rhamnosus GG on antimicrobial-resistant organism colonization

Published online by Cambridge University Press:  06 April 2021

Adriana M. Rauseo
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Tiffany Hink
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Kimberly A. Reske
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Sondra M. Seiler
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Kerry M. Bommarito
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Victoria J. Fraser
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
Carey-Ann D. Burnham
Affiliation:
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri
Erik R. Dubberke*
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri
*
Author for correspondence: Erik Dubberke, E-mail: edubberk@wustl.edu

Abstract

Objective:

Alteration of the colonic microbiota following antimicrobial exposure allows colonization by antimicrobial-resistant organisms (AROs). Ingestion of a probiotic, such as Lactobacillus rhamnosus GG (LGG), could prevent colonization or infection with AROs by promoting healthy colonic microbiota. The purpose of this trial was to determine the effect of LGG administration on ARO colonization in hospitalized patients receiving antibiotics.

Design:

Prospective, double-blinded, randomized controlled trial of LGG versus placebo among patients receiving broad-spectrum antibiotics.

Setting:

Tertiary care center.

Patients:

In total, 88 inpatients receiving broad-spectrum antibiotics were enrolled.

Intervention:

Patients were randomized to receive 1 capsule containing 1×1010 cells of LGG twice daily (n = 44) or placebo (n = 44), stratified by ward type. Stool or rectal-swab specimens were collected for culture at enrollment, during admission, and at discharge. Using selective media, specimens were cultured for Clostridioides difficile, vancomycin-resistant Enterococcus spp (VRE), and antibiotic-resistant gram-negative bacteria. The primary outcome was any ARO acquisition. Secondary outcomes included loss of any ARO if colonized at enrollment, and acquisition or loss of individual ARO.

Results:

ARO colonization prevalence at study enrollment was similar (LGG 39% vs placebo 39%). We detected no difference in any ARO acquisition (LGG 30% vs placebo 33%; OR,1.19; 95% CI, 0.38–3.75) nor for any individual ARO acquisition. There was no difference in the loss of any ARO (LGG 18% vs placebo 24%; OR, 1.44; 95% CI, 0.27–7.68) nor for any individual ARO.

Conclusion:

LGG administration neither prevented acquisition of ARO nor accelerated loss of ARO colonization.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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Footnotes

PREVIOUS PRESENTATION. Preliminary data from this study were presented in abstract (no. 2570) form at IDWeek 2019 on October 5, 2019, in Washington, DC.

References

Antimicrobial resistance: global report on surveillance 2014 summary. World Health Organization website. https://apps.who.int/iris/bitstream/handle/10665/112647/WHO_HSE_PED_AIP_2014.2_eng.pdf?sequence=1. Published 2014. Accessed January 26, 2020.Google Scholar
Biggest threats and data: antibiotic/antimicrobial resistance. Centers for Disease Control and Prevention website. https://www.cdc.gov/drugresistance/biggest-threats.html/ Published 2019. Accessed November 25, 2019.Google Scholar
Caetano, L, Antunes, M, Han, J, et al. Effect of antibiotic treatment on the intestinal metabolome. Antimicrob Agents Chemother 2011;55:14941503.Google Scholar
Donskey, CJ. The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis 2004;39:219226.CrossRefGoogle ScholarPubMed
Kwon, JH, Bommarito, KM, Reske, KA, et al. Randomized controlled trial to determine the impact of probiotic administration on colonization with multidrug-resistant organisms in critically ill patients. Infect Control Hosp Epidemiol 2015;36:14511454.CrossRefGoogle ScholarPubMed
Doron, S, Hibberd, PL, Goldin, B, Thorpe, C, McDermott, L, Snydman, DR. Effect of Lactobacillus rhamnosus GG administration on vancomycin-resistant Enterococcus colonization in adults with comorbidities. Antimicrob Agents Chemother 2015;59:45934599.CrossRefGoogle ScholarPubMed
Allen, SJ, Wareham, K, Wang, D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013;382:12491257.CrossRefGoogle ScholarPubMed
Freedman, SB, Williamson-Urquhart, S, Farion, KJ, et al. multicenter trial of a combination probiotic for children with gastroenteritis. N Engl J Med 2018;379:20152026.CrossRefGoogle ScholarPubMed
Schnadower, D, Tarr, PI, Casper, TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med 2018;379:20022014.CrossRefGoogle ScholarPubMed
Goldstein, EJC, Johnson, SJ, Maziade, P-J, et al. Probiotics and prevention of Clostridium difficile infection. Anaerobe 2017;45:114119.CrossRefGoogle ScholarPubMed
Eggers, S, Barker, AK, Valentine, S, Hess, T, Duster, M, Safdar, N. Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study. BMC Infect Dis 2018;18(1). doi: 10.1186/s12879-018-3028-6 CrossRefGoogle ScholarPubMed
Hink, T, Burnham, C-AD, Dubberke, ER. A systematic evaluation of methods to optimize culture-based recovery of Clostridium difficile from stool specimens. Anaerobe 2013;19:3943.CrossRefGoogle ScholarPubMed
Mills, JP, Rao, K, Young, VB. Probiotics for prevention of Clostridium difficile infection. Curr Opin Gastroenterol 2018;34:310.CrossRefGoogle ScholarPubMed
McFarland, L V, Ship, N, Auclair, J, Millette, M. Primary prevention of Clostridium difficile infections with a specific probiotic combining Lactobacillus acidophilus, L. casei, and L. rhamnosus strains: assessing the evidence. J Hosp Infect 2018;99:443452.CrossRefGoogle ScholarPubMed
Gopalsamy, SN, Woodworth, MH, Wang, T, et al. The Use of microbiome restoration therapeutics to eliminate intestinal colonization with multidrug-resistant organisms. Am J Med Sci 2018;356:433440.CrossRefGoogle ScholarPubMed
Palleja, A, Mikkelsen, KH, Forslund, SK, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol 2018;3:12551265.CrossRefGoogle ScholarPubMed
Burdet, C, Nguyen, TT, Duval, X, et al. Impact of Antibiotic gut exposure on the temporal changes in microbiome diversity. Antimicrob Agents Chemother 2019;63(10):111.CrossRefGoogle ScholarPubMed
Suez, J, Zmora, N, Zilberman-Schapira, G, et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 2018;174:14061423.CrossRefGoogle ScholarPubMed
Kho, ZY, Lal, SK. The human gut microbiome—a potential controller of wellness and disease. Front Microbiol 2018;9:1835.CrossRefGoogle Scholar
Tannock, GW, Tiong, IS, Priest, P, et al. Testing probiotic strain Escherichia coli Nissle 1917 (Mutaflor) for its ability to reduce carriage of multidrug-resistant E. coli by elderly residents in long-term care facilities. J Med Microbiol 2011;60:366370.CrossRefGoogle ScholarPubMed
Salomão, MCC, Heluany-Filho, MA, Menegueti, MG, de Kraker, MEA, Martinez, R, Bellissimo-Rodrigues, F. A randomized clinical trial on the effectiveness of a symbiotic product to decolonize patients harboring multidrug-resistant gram-negative bacilli. Rev Soc Bras Med Trop 2016;49:559566.CrossRefGoogle ScholarPubMed
Woodworth, MH, Hayden, MK, Young, VB, Kwon, JH. The role of fecal microbiota transplantation in reducing intestinal colonization with antibiotic-resistant organisms: the current landscape and future directions. Open Forum Infect Dis 2019;6(7). doi: 10.1093/ofid/ofz288 Google ScholarPubMed
Singh, R, van Nood, E, Nieuwdorp, M, et al. Donor feces infusion for eradication of extended-spectrum β-lactamase–producing Escherichia coli in a patient with end-stage renal disease. Clin Microbiol Infect 2014;20(11):O977O978.CrossRefGoogle Scholar
Stripling, J, Kumar, R, Baddley, JW, et al. Loss of vancomycin-resistant Enterococcus fecal dominance in an organ transplant patient with Clostridium difficile colitis after fecal microbiota transplant. Open forum Infect Dis 2015;2(2):ofv078.CrossRefGoogle Scholar
Crum-Cianflone, NF, Sullivan, E, Ballon-Landa, G, Onderdonk, AB. Fecal microbiota transplantation and successful resolution of multidrug-resistant–organism colonization. J Clin Microbiol 2015;53:19861989.CrossRefGoogle ScholarPubMed
Singh, R, de Groot, PF, Geerlings, SE, et al. Fecal microbiota transplantation against intestinal colonization by extended spectrum β-lactamase–producing Enterobacteriaceae: a proof of principle study. BMC Res Notes 2018;11(1):190.CrossRefGoogle ScholarPubMed
Davido, B, Batista, R, Michelon, H, et al. Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage? J Hosp Infect 2017;95:433437.CrossRefGoogle ScholarPubMed
Dubberke, ER, Mullane, KM, Gerding, DN, et al. Clearance of vancomycin-resistant Enterococcus concomitant with administration of a microbiota-based drug targeted at recurrent Clostridium difficile infection. Open Forum Infect Dis 2016;3(3):ofw133.CrossRefGoogle ScholarPubMed
Kwak, S, Choi, J, Hink, T, et al. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome 2020;8(1):125.CrossRefGoogle ScholarPubMed
Tariq, R, Pardi, DS, Tosh, PK, Walker, RC, Razonable, RR, Khanna, S. Fecal microbiota transplantation for recurrent Clostridium difficile infection reduces recurrent urinary tract infection frequency. Clin Infect Dis 2017;65:17451747.CrossRefGoogle ScholarPubMed
Keen, EC, Tasoff, P, Hink, T, et al. Microbiome restoration by RBX2660 does not preclude recurrence of multidrug-resistant urinary tract infection following subsequent antibiotic exposure: a case report. Open Forum Infect Dis 2020;7(3):ofaa042.CrossRefGoogle Scholar
Hempel, S, Newberry, S, Ruelaz, A, et al. Safety of Probiotics to Reduce Risk and Prevent or Treat Disease. Rockville, MD: Agency for Healthcare Research and Quality; 2011.Google ScholarPubMed