Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients

Min Dai, Yafei Liu, Wei Chen, Heena Buch, Yi Shan, Liuhui Chang, Yong Bai, Chen Shen, Xiaoyin Zhang, Yufeng Huo, Dian Huang, Zhou Yang, Zhihang Hu, Xuwei He, Junyu Pan, Lili Hu, Xinfang Pan, Xiangtao Wu, Bin Deng, Zhifeng Li, Bota Cui, Faming Zhang, Min Dai, Yafei Liu, Wei Chen, Heena Buch, Yi Shan, Liuhui Chang, Yong Bai, Chen Shen, Xiaoyin Zhang, Yufeng Huo, Dian Huang, Zhou Yang, Zhihang Hu, Xuwei He, Junyu Pan, Lili Hu, Xinfang Pan, Xiangtao Wu, Bin Deng, Zhifeng Li, Bota Cui, Faming Zhang

Abstract

Background: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients.

Methods: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed.

Results: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU.

Conclusion: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU.

Trial registration: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).

Keywords: Antibiotic-associated diarrhea; Clostridium difficile; Critical care; Fecal microbiota transplantation; Infections; Intensive care unit; Multidrug resistance; Rescue therapy.

Conflict of interest statement

Faming Zhang invented the concept of GenFMTer and related devices. Other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart and reasons for rescue FMT failure
Fig. 2
Fig. 2
Types and duration of antibiotic use before rescue FMT (n = 18)
Fig. 3
Fig. 3
Abdominal symptoms and laboratory markers of inflammation. a Frequency of patients with abdominal symptoms pre-FMT and post-FMT (n = 18). b Frequency of diarrhea of patients who were responsive to rescue FMT within 1 week post the first FMT (n = 13). c–e Level of WBC count, CRP, and PCT (p = 0.0005) pre-FMT and 1 week post the first FMT (n = 18)

References

    1. Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med. 2002;346(5):334–339. doi: 10.1056/NEJMcp011603.
    1. Viswanathan VK, Mallozzi MJ, Vedantam G. Clostridium difficile infection: an overview of the disease and its pathogenesis, epidemiology and interventions. Gut Microbes. 2010;1(4):234–242. doi: 10.4161/gmic.1.4.12706.
    1. Zahar JR, Schwebel C, Adrie C, Garrouste-Orgeas M, Francais A, Vesin A, Nguile-Makao M, Tabah A, Laupland K, Le-Monnier A, et al. Outcome of ICU patients with Clostridium difficile infection. Crit Care. 2012;16(6):R215. doi: 10.1186/cc11852.
    1. Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959–1969. doi: 10.1001/jama.2012.3507.
    1. Mullish BH, Quraishi MN, Segal JP, McCune VL, Baxter M, Marsden GL, Moore DJ, Colville A, Bhala N, Iqbal TH, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. 2018;67(11):1920–1941. doi: 10.1136/gutjnl-2018-316818.
    1. Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, Weese JS, Collins S, Moayyedi P, Crowther M, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2016;315(2):142–149. doi: 10.1001/jama.2015.18098.
    1. Kao D, Roach B, Silva M, Beck P, Rioux K, Kaplan GG, Chang HJ, Coward S, Goodman KJ, Xu H, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2017;318(20):1985–1993. doi: 10.1001/jama.2017.17077.
    1. Cammarota G, Masucci L, Ianiro G, Bibbo S, Dinoi G, Costamagna G, Sanguinetti M, Gasbarrini A. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41(9):835–843. doi: 10.1111/apt.13144.
    1. Kelly CR, Khoruts A, Staley C, Sadowsky MJ, Abd M, Alani M, Bakow B, Curran P, McKenney J, Tisch A, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609–616. doi: 10.7326/M16-0271.
    1. Dinh A, Fessi H, Duran C, Batista R, Michelon H, Bouchand F, Lepeule R, Vittecoq D, Escaut L, Sobhani I, et al. Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study. J Hosp Infect. 2018;99(4):481–486. doi: 10.1016/j.jhin.2018.02.018.
    1. Saha S., Tariq R., Tosh P.K., Pardi D.S., Khanna S. Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review. Clinical Microbiology and Infection. 2019;25(8):958–963. doi: 10.1016/j.cmi.2019.04.006.
    1. Huttner BD, de Lastours V, Wassenberg M, Maharshak N, Mauris A, Galperine T, Zanichelli V, Kapel N, Bellanger A, Olearo F, et al. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019;25(7):830-8.
    1. Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014;109(7):1065–1071. doi: 10.1038/ajg.2014.133.
    1. Battipaglia Giorgia, Malard Florent, Rubio Marie Therèse, Ruggeri Annalisa, Mamez Anne Claire, Brissot Eolia, Giannotti Federica, Dulery Remy, Joly Anne Christine, Baylatry Minh Tam, Kossmann Marie Jeanne, Tankovic Jacques, Beaugerie Laurent, Sokol Harry, Mohty Mohamad. Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria. Haematologica. 2019;104(8):1682–1688. doi: 10.3324/haematol.2018.198549.
    1. Wang H, Cui B, Li Q, Ding X, Li P, Zhang T, Yang X, Ji G, Zhang F. The safety of fecal microbiota transplantation for Crohn’s disease: findings from a long-term study. Adv Ther. 2018;35(11):1935–1944. doi: 10.1007/s12325-018-0800-3.
    1. Ding X, Li Q, Li P, Zhang T, Cui B, Ji G, Lu X, Zhang F. Long-term safety and efficacy of fecal microbiota transplant in active ulcerative colitis. Drug Saf. 2019;42(7):869–880. doi: 10.1007/s40264-019-00809-2.
    1. Cui B, Li P, Xu L, Zhao Y, Wang H, Peng Z, Xu H, Xiang J, He Z, Zhang T, et al. Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med. 2015;13:298. doi: 10.1186/s12967-015-0646-2.
    1. Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, Katsikeros R, Makanyanga J, Campaniello MA, Mavrangelos C, et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA. 2019;321(2):156–164. doi: 10.1001/jama.2018.20046.
    1. Zhou Y, Mao L, Yu J, Lin Q, Luo Y, Zhu X, Sun Z. Epidemiology of Clostridium difficile infection in hospitalized adults and the first isolation of C. difficile PCR ribotype 027 in Central China. BMC Infect Dis. 2019;19(1):232. doi: 10.1186/s12879-019-3841-6.
    1. Xu H, Tang H, Xu T, Xiao M, Li J, Tan B, Yang H, Lv H, Li Y, Qian J. Retrospective analysis of Clostridium difficile infection in patients with ulcerative colitis in a tertiary hospital in China. BMC Gastroenterol. 2019;19(1):3. doi: 10.1186/s12876-018-0920-x.
    1. Li C, Li Y, Huai Y, Liu S, Meng X, Duan J, Klena JD, Rainey JJ, Wu A, Rao CY. Incidence and outbreak of healthcare-onset healthcare-associated Clostridioides difficile infections among intensive care patients in a large teaching hospital in China. Front Microbiol. 2018;9:566. doi: 10.3389/fmicb.2018.00566.
    1. Liao F, Li W, Gu W, Zhang W, Liu X, Fu X, Xu W, Wu Y, Lu J. A retrospective study of community-acquired Clostridium difficile infection in Southwest China. Sci Rep. 2018;8(1):3992. doi: 10.1038/s41598-018-21762-7.
    1. Cui B, Feng Q, Wang H, Wang M, Peng Z, Li P, Huang G, Liu Z, Wu P, Fan Z, et al. Fecal microbiota transplantation through mid-gut for refractory Crohn’s disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol. 2015;30(1):51–58. doi: 10.1111/jgh.12727.
    1. Kelly CR, Kunde SS, Khoruts A. Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies. Clin Gastroenterol Hepatol. 2014;12(2):283–288. doi: 10.1016/j.cgh.2013.09.060.
    1. Klingensmith NJ, Coopersmith CM. Fecal microbiota transplantation for multiple organ dysfunction syndrome. Crit Care. 2016;20(1):398. doi: 10.1186/s13054-016-1567-z.
    1. Alagna L, Haak BW, Gori A. Fecal microbiota transplantation in the ICU: perspectives on future implementations. Intensive Care Med. 2019;45(7):998–1001. doi: 10.1007/s00134-019-05645-7.
    1. Li Q, Wang C, Tang C, He Q, Zhao X, Li N, Li J. Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report. Crit Care. 2015;19:37. doi: 10.1186/s13054-015-0738-7.
    1. Schulz-Stubner S, Textor Z, Anetseder M. Fecal microbiota therapy as rescue therapy for life-threatening Clostridium difficile infection in the critically ill: a small case series. Infect Control Hosp Epidemiol. 2016;37(9):1129–1131. doi: 10.1017/ice.2016.158.
    1. Wei Y, Yang J, Wang J, Yang Y, Huang J, Gong H, Cui H, Chen D. Successful treatment with fecal microbiota transplantation in patients with multiple organ dysfunction syndrome and diarrhea following severe sepsis. Crit Care. 2016;20(1):332. doi: 10.1186/s13054-016-1491-2.
    1. Alukal Joseph, Dutta Sudhir K, Surapaneni Balarama Krishna, Le Michelle, Tabbaa Obada, Phillips Laila, Mattar Mark C. Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy. Journal of Digestive Diseases. 2019;20(6):301–307. doi: 10.1111/1751-2980.12750.
    1. Wurm P, Spindelboeck W, Krause R, Plank J, Fuchs G, Bashir M, Petritsch W, Halwachs B, Langner C, Hogenauer C, et al. Antibiotic-associated apoptotic enterocolitis in the absence of a defined pathogen: the role of intestinal microbiota depletion. Crit Care Med. 2017;45(6):e600–e606. doi: 10.1097/CCM.0000000000002310.
    1. Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66(4):569–580. doi: 10.1136/gutjnl-2016-313017.
    1. Zhang F, Cui B, He X, Nie Y, Wu K, Fan D, Group FM-sS Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018;9(5):462–473. doi: 10.1007/s13238-018-0541-8.
    1. Zhang F, Zhang T, Zhu H, Borody TJ. Evolution of fecal microbiota transplantation in methodology and ethical issues. Curr Opin Pharmacol. 2019;49:11–16. doi: 10.1016/j.coph.2019.04.004.
    1. Marsh HM, Krishan I, Naessens JM, Strickland RA, Gracey DR, Campion ME, Nobrega FT, Southorn PA, McMichan JC, Kelly MP. Assessment of prediction of mortality by using the APACHE II scoring system in intensive-care units. Mayo Clin Proc. 1990;65(12):1549–1557. doi: 10.1016/S0025-6196(12)62188-0.
    1. Li Q, Wang C, Tang C, He Q, Zhao X, Li N, Li J. Therapeutic modulation and reestablishment of the intestinal microbiota with fecal microbiota transplantation resolves sepsis and diarrhea in a patient. Am J Gastroenterol. 2014;109(11):1832–1834. doi: 10.1038/ajg.2014.299.
    1. Singh R, de Groot PF, Geerlings SE, Hodiamont CJ, Belzer C, Berge I, de Vos WM, Bemelman FJ, Nieuwdorp M. Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study. BMC Res Notes. 2018;11(1):190. doi: 10.1186/s13104-018-3293-x.
    1. Limketkai BN, Hendler S, Ting PS, Parian AM. Fecal microbiota transplantation for the critically ill patient. Nutr Clin Pract. 2019;34(1):73–79. doi: 10.1002/ncp.10228.
    1. Fischer M, Sipe BW, Rogers NA, Cook GK, Robb BW, Vuppalanchi R, Rex DK. Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate. Aliment Pharmacol Ther. 2015;42(4):470–476. doi: 10.1111/apt.13290.
    1. Cui B, Li P, Xu L, Peng Z, Xiang J, He Z, Zhang T, Ji G, Nie Y, Wu K, et al. Step-up fecal microbiota transplantation (FMT) strategy. Gut Microbes. 2016;7(4):323–328. doi: 10.1080/19490976.2016.1151608.
    1. Alberda Cathy, Marcushamer Sam, Hewer Tayne, Journault Nicole, Kutsogiannis Demetrios. Feasibility of a Lactobacillus casei Drink in the Intensive Care Unit for Prevention of Antibiotic Associated Diarrhea and Clostridium difficile. Nutrients. 2018;10(5):539. doi: 10.3390/nu10050539.
    1. Jafarnejad S, Shab-Bidar S, Speakman JR, Parastui K, Daneshi-Maskooni M, Djafarian K. Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18-64 years) but not the elderly (>65 years): a meta-analysis. Nutr Clin Pract. 2016;31(4):502–513. doi: 10.1177/0884533616639399.
    1. Pozzoni P, Riva A, Bellatorre AG, Amigoni M, Redaelli E, Ronchetti A, Stefani M, Tironi R, Molteni EE, Conte D, et al. Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol. 2012;107(6):922–931. doi: 10.1038/ajg.2012.56.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera