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DOI: 10.1055/s-0041-1740973
Fulminant Clostridioides difficile Infection: A Review of Treatment Options for a Life-Threatening Infection
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Abstract
Fulminant Clostridioides difficile infection (FCDI) encompasses 3 to 5% of all CDI cases with associated mortality rates between 30 and 40%. Major treatment modalities include surgery and medical management with antibiotic and nonantibiotic therapies. However, identification of patients with CDI that will progress to FCDI is difficult and makes it challenging to direct medical management and identify those who may benefit from surgery. Furthermore, since it is difficult to study such a critically ill population, data investigating treatment options are limited. Surgical management with diverting loop ileostomy (LI) instead of a total abdominal colectomy (TAC) with end ileostomy has several appealing advantages, and studies have not consistently demonstrated a clinical benefit with this less-invasive strategy, so both LI and TAC remain acceptable surgical options. Successful medical management of FCDI is complicated by pharmacokinetic changes that occur in critically ill patients, and there is an absence of high-quality studies that included patients with FCDI. Recommendations accordingly include a combination of antibiotics administered via multiple routes to ensure adequate drug concentrations in the colon: intravenous metronidazole, high-dose oral vancomycin, and rectal vancomycin. Although fidaxomicin is now recommended as first-line therapy for non-FCDI, there are limited clinical data to support its use in FCDI. Several nonantibiotic therapies, including fecal microbiota transplantation and intravenous immunoglobulin, have shown success as adjunctive therapies, but they are unlikely to be effective alone. In this review, we aim to summarize diagnosis and treatment options for FCDI.
Keywords
colectomy - fecal microbiota transplantation - fidaxomicin - vancomycin - metronidazole - Clostridium difficilePublication History
Article published online:
16 February 2022
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References
- 1 Lessa FC, Mu Y, Bamberg WM. et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372 (09) 825-834
- 2 Guh AY, Mu Y, Winston LG. et al; Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U.S. burden of Clostridioides difficile infection and outcomes. N Engl J Med 2020; 382 (14) 1320-1330
- 3 Sailhamer EA, Carson K, Chang Y. et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg 2009; 144 (05) 433-439 , discussion 439–440
- 4 Hurley BW, Nguyen CC. The spectrum of pseudomembranous enterocolitis and antibiotic-associated diarrhea. Arch Intern Med 2002; 162 (19) 2177-2184
- 5 Loo VG, Poirier L, Miller MA. et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353 (23) 2442-2449
- 6 Juo YY, Sanaiha Y, Jabaji Z, Benharash P. Trends in diverting loop ileostomy vs total abdominal colectomy as surgical management for Clostridium difficile colitis. JAMA Surg 2019; 154 (10) 899-906
- 7 Kenneally C, Rosini JM, Skrupky LP. et al. Analysis of 30-day mortality for Clostridium difficile-associated disease in the ICU setting. Chest 2007; 132 (02) 418-424
- 8 Karanika S, Paudel S, Zervou FN, Grigoras C, Zacharioudakis IM, Mylonakis E. Prevalence and clinical outcomes of Clostridium difficile infection in the intensive care unit: a systematic review and meta-analysis. Open Forum Infect Dis 2015; 3 (01) ofv186
- 9 Dodek PM, Norena M, Ayas NT, Romney M, Wong H. Length of stay and mortality due to Clostridium difficile infection acquired in the intensive care unit. J Crit Care 2013; 28 (04) 335-340
- 10 Dallal RM, Harbrecht BG, Boujoukas AJ. et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg 2002; 235 (03) 363-372
- 11 Carlson TJ, Endres BT, Le Pham J. et al. Eosinopenia and binary toxin increase mortality in hospitalized patients with Clostridioides difficile infection. Open Forum Infect Dis 2020; 7 (01) ofz552
- 12 Cowardin CA, Buonomo EL, Saleh MM. et al. The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. Nat Microbiol 2016; 1 (08) 16108
- 13 McDonald LC, Killgore GE, Thompson A. et al. An epidemic, toxin gene-variant strain of Clostridium difficile . N Engl J Med 2005; 353 (23) 2433-2441
- 14 Warny M, Pepin J, Fang A. et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005; 366 (9491): 1079-1084
- 15 Kelly CP. Immune response to Clostridium difficile infection. Eur J Gastroenterol Hepatol 1996; 8 (11) 1048-1053
- 16 McDonald LC, Gerding DN, Johnson S. et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66 (07) 987-994
- 17 Kelly CR, Fischer M, Allegretti JR. et al. ACG Clinical Guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol 2021; 116 (06) 1124-1147
- 18 Stevens VW, Shoemaker HE, Jones MM. et al. Validation of the SHEA/IDSA severity criteria to predict poor outcomes among inpatients and outpatients with Clostridioides difficile infection. Infect Control Hosp Epidemiol 2020; 41 (05) 510-516
- 19 Rao K, Santhosh K, Mogle JA, Higgins PD, Young VB. Elevated fecal calprotectin associates with adverse outcomes from Clostridium difficile infection in older adults. Infect Dis (Lond) 2016; 48 (09) 663-669
- 20 Rao K, Walk ST, Micic D. et al. Procalcitonin levels associate with severity of Clostridium difficile infection. PLoS One 2013; 8 (03) e58265
- 21 Crook DW, Walker AS, Kean Y. et al; Study 003/004 Teams. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis 2012; 55 (Suppl. 02) S93-S103
- 22 Kulaylat AS, Buonomo EL, Scully KW. et al. Development and validation of a prediction model for mortality and adverse outcomes among patients with peripheral eosinopenia on admission for Clostridium difficile infection. JAMA Surg 2018; 153 (12) 1127-1133
- 23 Sartelli M, Malangoni MA, Abu-Zidan FM. et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World J Emerg Surg 2015; 10: 38
- 24 Kundrapu S, Sunkesula VC, Jury LA, Sethi AK, Donskey CJ. Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection. Clin Infect Dis 2012; 55 (11) 1527-1530
- 25 Surawicz CM, Brandt LJ, Binion DG. et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108 (04) 478-498 , quiz 499
- 26 Lamontagne F, Labbé AC, Haeck O. et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007; 245 (02) 267-272
- 27 Byrn JC, Maun DC, Gingold DS, Baril DT, Ozao JJ, Divino CM. Predictors of mortality after colectomy for fulminant Clostridium difficile colitis. Arch Surg 2008; 143 (02) 150-154 , discussion 155
- 28 Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P. West Midlands Research Collaborative. Systematic review and meta-analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg 2012; 99 (11) 1501-1513
- 29 Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis 2013; 15 (07) 798-804
- 30 Steele SR, McCormick J, Melton GB. et al. Practice parameters for the management of Clostridium difficile infection. Dis Colon Rectum 2015; 58 (01) 10-24
- 31 Ferrada P, Callcut R, Zielinski MD. et al; EAST Multi-Institutional Trials Committee. Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile-associated disease: an Eastern Association for the Surgery of Trauma multicenter trial. J Trauma Acute Care Surg 2017; 83 (01) 36-40
- 32 Hall BR, Leinicke JA, Armijo PR, Smith LM, Langenfeld SJ, Oleynikov D. No survival advantage exists for patients undergoing loop ileostomy for clostridium difficile colitis. Am J Surg 2019; 217 (01) 34-39
- 33 Adelman MW, Woodworth MH, Shaffer VO, Martin GS, Kraft CS. Critical care management of the patient with Clostridioides difficile . Crit Care Med 2021; 49 (01) 127-139
- 34 Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg 2011; 254 (03) 423-427 , discussion 427–429
- 35 Hall BR, Armijo PR, Leinicke JA, Langenfeld SJ, Oleynikov D. Prolonged non-operative management of Clostridium difficile colitis is associated with increased mortality, complications, and cost. Am J Surg 2019; 217 (06) 1042-1046
- 36 Ferrada P, Velopulos CG, Sultan S. et al. Timing and type of surgical treatment of Clostridium difficile-associated disease: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2014; 76 (06) 1484-1493
- 37 Seder CW, Villalba Jr MR, Robbins J. et al. Early colectomy may be associated with improved survival in fulminant Clostridium difficile colitis: an 8-year experience. Am J Surg 2009; 197 (03) 302-307
- 38 Halabi WJ, Nguyen VQ, Carmichael JC, Pigazzi A, Stamos MJ, Mills S. Clostridium difficile colitis in the United States: a decade of trends, outcomes, risk factors for colectomy, and mortality after colectomy. J Am Coll Surg 2013; 217 (05) 802-812
- 39 Markelov A, Livert D, Kohli H. Predictors of fatal outcome after colectomy for fulminant Clostridium difficile colitis: a 10-year experience. dr.markelov@gmail.com. Am Surg 2011; 77 (08) 977-980
- 40 Pepin J, Vo TT, Boutros M. et al. Risk factors for mortality following emergency colectomy for fulminant Clostridium difficile infection. Dis Colon Rectum 2009; 52 (03) 400-405
- 41 Longo WE, Mazuski JE, Virgo KS, Lee P, Bahadursingh AN, Johnson FE. Outcome after colectomy for Clostridium difficile colitis. Dis Colon Rectum 2004; 47 (10) 1620-1626
- 42 Perera AD, Akbari RP, Cowher MS. et al. Colectomy for fulminant Clostridium difficile colitis: predictors of mortality. Am Surg 2010; 76 (04) 418-421
- 43 Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 2012; 67 (03) 742-748
- 44 Kazakova SV, Baggs J, Yi SH. et al. Associations of facility-level antibiotic use and hospital-onset Clostridioides difficile infection in US acute-care hospitals, 2012-2018. Infect Control Hosp Epidemiol 2021; (epub ahead of print) DOI: 10.1017/ice.2021.151.
- 45 Louie TJ, Cannon K, Byrne B. et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis 2012; 55 (Suppl. 02) S132-S142
- 46 Thorpe CM, Kane AV, Chang J, Tai A, Vickers RJ, Snydman DR. Enhanced preservation of the human intestinal microbiota by ridinilazole, a novel Clostridium difficile-targeting antibacterial, compared to vancomycin. PLoS One 2018; 13 (08) e0199810
- 47 Guery B, Menichetti F, Anttila VJ. et al; EXTEND Clinical Study Group. 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 2018; 18 (03) 296-307
- 48 Power BM, Forbes AM, van Heerden PV, Ilett KF. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet 1998; 34 (01) 25-56
- 49 Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile . Gut 1986; 27 (10) 1169-1172
- 50 Thabit AK, Nicolau DP. Impact of vancomycin faecal concentrations on clinical and microbiological outcomes in Clostridium difficile infection. Int J Antimicrob Agents 2015; 46 (02) 205-208
- 51 Johnson S, Homann SR, Bettin KM. et al. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117 (04) 297-302
- 52 Krook A, Lindström B, Kjellander J, Järnerot G, Bodin L. Relation between concentrations of metronidazole and Bacteroides spp in faeces of patients with Crohn's disease and healthy individuals. J Clin Pathol 1981; 34 (06) 645-650
- 53 Arabi Y, Dimock F, Burdon DW, Alexander-Williams J, Keighley MR. Influence of neomycin and metronidazole on colonic microflora of volunteers. J Antimicrob Chemother 1979; 5 (05) 531-537
- 54 Edlund C, Barkholt L, Olsson-Liljequist B, Nord CE. Effect of vancomycin on intestinal flora of patients who previously received antimicrobial therapy. Clin Infect Dis 1997; 25 (03) 729-732
- 55 Gonzales M, Pepin J, Frost EH. et al. Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection. BMC Infect Dis 2010; 10: 363
- 56 Louie T, Miller M, Donskey C, Mullane K, Goldstein EJ. Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection. Antimicrob Agents Chemother 2009; 53 (01) 223-228
- 57 Louie TJ, Miller MA, Mullane KM. et al; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364 (05) 422-431
- 58 Mikamo H, Tateda K, Yanagihara K. et al. 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 (09) 744-752
- 59 Shue YK, Sears PS, Shangle S. et al. Safety, tolerance, and pharmacokinetic studies of OPT-80 in healthy volunteers following single and multiple oral doses. Antimicrob Agents Chemother 2008; 52 (04) 1391-1395
- 60 Cheng YW, Phelps E, Nemes S. et al. Fecal microbiota transplant decreases mortality in patients with refractory severe or fulminant Clostridioides difficile infection. Clin Gastroenterol Hepatol 2020; 18 (10) 2234-2243.e1
- 61 Ianiro G, Masucci L, Quaranta G. et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions. Aliment Pharmacol Ther 2018; 48 (02) 152-159
- 62 Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45 (03) 302-307
- 63 Johnson S, Louie TJ, Gerding DN. et al; Polymer Alternative for CDI Treatment (PACT) Investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis 2014; 59 (03) 345-354
- 64 Kim PK, Huh HC, Cohen HW. et al. Intracolonic vancomycin for severe Clostridium difficile colitis. Surg Infect (Larchmt) 2013; 14 (06) 532-539
- 65 Apisarnthanarak A, Razavi B, Mundy LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of the literature. Clin Infect Dis 2002; 35 (06) 690-696
- 66 Malamood M, Nellis E, Ehrlich AC, Friedenberg FK. Vancomycin enemas as adjunctive therapy for Clostridium difficile infection. J Clin Med Res 2015; 7 (06) 422-427
- 67 Olson MM, Shanholtzer CJ, Lee Jr JT, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol 1994; 15 (06) 371-381
- 68 Akamine CM, Ing MB, Jackson CS, Loo LK. The efficacy of intracolonic vancomycin for severe Clostridium difficile colitis: a case series. BMC Infect Dis 2016; 16: 316
- 69 Saffouri G, Khanna S, Estes L, Pardi D. Outcomes from rectal vancomycin therapy in patients with Clostridium difficile infection. Am J Gastroenterol 2014; 109 (06) 924-925
- 70 van Bodegraven AA, Boer RO, Lourens J, Tuynman HA, Sindram JW. Distribution of mesalazine enemas in active and quiescent ulcerative colitis. Aliment Pharmacol Ther 1996; 10 (03) 327-332
- 71 Shetler K, Nieuwenhuis R, Wren SM, Triadafilopoulos G. Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis. Surg Endosc 2001; 15 (07) 653-659
- 72 Pasic M, Jost R, Carrel T, Von Segesser L, Turina M. Intracolonic vancomycin for pseudomembranous colitis. N Engl J Med 1993; 329 (08) 583
- 73 Johnson S, Lavergne V, Skinner AM. et al. 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 Infect Dis 2021; 73 (05) e1029-e1044
- 74 Rokas KE, Johnson JW, Beardsley JR, Ohl CA, Luther VP, Williamson JC. The addition of intravenous metronidazole to oral vancomycin is associated with improved mortality in critically ill patients with Clostridium difficile infection. Clin Infect Dis 2015; 61 (06) 934-941
- 75 Wang Y, Schluger A, Li J, Gomez-Simmonds A, Salmasian H, Freedberg DE. Does Addition of intravenous metronidazole to oral vancomycin improve outcomes in Clostridioides difficile infection?. Clin Infect Dis 2020; 71 (09) 2414-2420
- 76 Vega AD, Heil EL, Blackman AL. et al. Evaluation of addition of intravenous metronidazole to oral vancomycin therapy in critically ill patients with non-fulminant severe Clostridioides difficile infection. Pharmacotherapy 2020; 40 (05) 398-407
- 77 Fekety R, Silva J, Kauffman C, Buggy B, Deery HG. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989; 86 (01) 15-19
- 78 Lam SW, Bass SN, Neuner EA, Bauer SR. Effect of vancomycin dose on treatment outcomes in severe Clostridium difficile infection. Int J Antimicrob Agents 2013; 42 (06) 553-558
- 79 Cornely OA, Crook DW, Esposito R. et al; OPT-80-004 Clinical Study Group. 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 (04) 281-289
- 80 Penziner S, Dubrovskaya Y, Press R, Safdar A. Fidaxomicin therapy in critically ill patients with Clostridium difficile infection. Antimicrob Agents Chemother 2015; 59 (03) 1776-1781
- 81 Goldstein EJ, Citron DM, Merriam CV, Warren YA, Tyrrell KL, Fernandez HT. Comparative in vitro susceptibilities of 396 unusual anaerobic strains to tigecycline and eight other antimicrobial agents. Antimicrob Agents Chemother 2006; 50 (10) 3507-3513
- 82 Rodloff AC, Dowzicky MJ. In vitro activity of tigecycline and comparators against a European collection of anaerobes collected as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2010-2016. Anaerobe 2018; 51: 78-88
- 83 Sutcliffe JA, O'Brien W, Fyfe C, Grossman TH. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother 2013; 57 (11) 5548-5558
- 84 Snydman DR, McDermott LA, Jacobus NV, Kerstein K, Grossman TH, Sutcliffe JA. Evaluation of the in vitro activity of eravacycline against a broad spectrum of recent clinical anaerobic isolates. Antimicrob Agents Chemother 2018; 62 (05) e02206-17
- 85 Bassères E, Begum K, Lancaster C. et al. In vitro activity of eravacycline against common ribotypes of Clostridioides difficile . J Antimicrob Chemother 2020; 75 (10) 2879-2884
- 86 Stapert L, Wolfe C, Shinabarger D, Marra A, Pillar C. In vitro activities of omadacycline and comparators against anaerobic bacteria. Antimicrob Agents Chemother 2018; 62 (04) e00047-18
- 87 Begum K, Bassères E, Miranda J. et al. In vitro activity of omadacycline, a new tetracycline analog, and comparators against Clostridioides difficile . Antimicrob Agents Chemother 2020; 64 (08) e00522-20
- 88 Herpers BL, Vlaminckx B, Burkhardt O. et al. Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clin Infect Dis 2009; 48 (12) 1732-1735
- 89 Britt NS, Steed ME, Potter EM, Clough LA. Tigecycline for the treatment of severe and severe complicated Clostridium difficile infection. Infect Dis Ther 2014; 3 (02) 321-331
- 90 Bishop EJ, Tiruvoipati R, Metcalfe J, Marshall C, Botha J, Kelley PG. The outcome of patients with severe and severe-complicated Clostridium difficile infection treated with tigecycline combination therapy: a retrospective observational study. Intern Med J 2018; 48 (06) 651-660
- 91 Dumitru IM, Dumitru E, Rugina S, Tuta LA. Toxic megacolon - a three case presentation. J Crit Care Med (Targu Mures) 2017; 3 (01) 39-44
- 92 Brinda BJ, Pasikhova Y, Quilitz RE, Thai CM, Greene JN. Use of tigecycline for the management of Clostridium difficile colitis in oncology patients and case series of breakthrough infections. J Hosp Infect 2017; 95 (04) 426-432
- 93 Szabo BG, Duma L, Lenart KS. et al. Characteristics and predictors of treatment failure with intravenous tigecycline monotherapy among adult patients with severe Clostridioides (Clostridium) difficile infection: a single-centre observational cohort study. Diagn Microbiol Infect Dis 2021; 99 (02) 115231
- 94 Thomas A, Khan F, Uddin N, Wallace MR. Tigecycline for severe Clostridium difficile infection. Int J Infect Dis 2014; 26: 171-172
- 95 Gergely Szabo B, Kadar B, Szidonia Lenart K. et al. Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study. Clin Microbiol Infect 2016; 22 (12) 990-995
- 96 LaSalvia MT, Branch-Elliman W, Snyder GM. et al. Does adjunctive tigecycline improve outcomes in severe-complicated, nonoperative Clostridium difficile infection?. Open Forum Infect Dis 2017; 4 (01) ofw264
- 97 Manea E, Sojo-Dorado J, Jipa RE, Benea SN, Rodríguez-Baño J, Hristea A. The role of tigecycline in the management of Clostridium difficile infection: a retrospective cohort study. Clin Microbiol Infect 2018; 24 (02) 180-184
- 98 Carlson TJG-LA. Antibiotic treatment pipeline for Clostridioides difficile infection (CDI): a wide array of narrow-spectrum agents. Curr Infect Dis Rep 2020;22(08):
- 99 Rashid MU, Dalhoff A, Bäckström T. et al. Ecological impact of MCB3837 on the normal human microbiota. Int J Antimicrob Agents 2014; 44 (02) 125-130
- 100 An exploratory, open-label, oligo-center study to evaluate the safety, efficacy, and pharmacokinetics of intravenous DNV3837 in subjects with Clostridium difficile infection. Accessed August 6, 2021 at: https://ClinicalTrials.gov/show/NCT03988855
- 101 Salcedo J, Keates S, Pothoulakis C. et al. Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 1997; 41 (03) 366-370
- 102 Negm OH, MacKenzie B, Hamed MR. et al. Protective antibodies against Clostridium difficile are present in intravenous immunoglobulin and are retained in humans following its administration. Clin Exp Immunol 2017; 188 (03) 437-443
- 103 Wilcox MH. Descriptive study of intravenous immunoglobulin for the treatment of recurrent Clostridium difficile diarrhoea. J Antimicrob Chemother 2004; 53 (05) 882-884
- 104 McPherson S, Rees CJ, Ellis R, Soo S, Panter SJ. Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea. Dis Colon Rectum 2006; 49 (05) 640-645
- 105 Abougergi MS, Broor A, Cui W, Jaar BG. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: an observational study and review of the literature. J Hosp Med 2010; 5 (01) E1-E9
- 106 Juang P, Skledar SJ, Zgheib NK. et al. Clinical outcomes of intravenous immune globulin in severe Clostridium difficile-associated diarrhea. Am J Infect Control 2007; 35 (02) 131-137
- 107 Wilcox MH, Gerding DN, Poxton IR. et al; MODIFY I and MODIFY II Investigators. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med 2017; 376 (04) 305-317
- 108 Birch T, Golan Y, Rizzardini G. et al. Efficacy of bezlotoxumab based on timing of administration relative to start of antibacterial therapy for Clostridium difficile infection. J Antimicrob Chemother 2018; 73 (09) 2524-2528
- 109 Fischer M, Sipe B, Cheng YW. et al. Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: a promising treatment approach. Gut Microbes 2017; 8 (03) 289-302
- 110 Fischer M, Sipe BW, Rogers NA. et al. 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 (04) 470-476
- 111 Hocquart M, Lagier JC, Cassir N. et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis 2018; 66 (05) 645-650
- 112 Tixier EN, Verheyen E, Ungaro RC, Grinspan AM. Faecal microbiota transplant decreases mortality in severe and fulminant Clostridioides difficile infection in critically ill patients. Aliment Pharmacol Ther 2019; 50 (10) 1094-1099
- 113 Thorpe CM, McDermott LA, Tran MK. et al. U.S.-based national surveillance for fidaxomicin susceptibility of Clostridioides difficile-associated diarrheal isolates from 2013 to 2016. Antimicrob Agents Chemother 2019; 63 (07) e00391-19
- 114 Saunders M, Jeffery J, Vincent Z, Ayling RM, Lewis S. Relationship between faecal metronidazole and lactoferrin concentrations to clinical response of patients with Clostridioides difficile . Eur J Clin Microbiol Infect Dis 2020; 39 (09) 1781-1784
- 115 Tedesco F, Markham R, Gurwith M, Christie D, Bartlett JG. Oral vancomycin for antibiotic-associated pseudomembranous colitis. Lancet 1978; 2 (8083): 226-228