Bezlotoxumab prevents extraintestinal organ damage induced by Clostridioides difficile infection

References

• Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2(1):16020. doi:10.1038/nrdp.2016.20.
   PubMedGoogle Scholar
• Snydman DR, McDermott LA, Jacobus NV, Thorpe C, Stone S, Jenkins SG, Goldstein EJC, Patel R, Forbes BA, Mirrett S, et al. U.S.-based national sentinel surveillance study for the epidemiology of Clostridium difficile-associated diarrheal isolates and their susceptibility to fidaxomicin. Antimicrob Agents Chemother. 2015;59(10):6437–18. doi:10.1128/AAC.00845-15.
   PubMed Web of Science ®Google Scholar
• Gerding DN, Johnson S, Rupnik M, Aktories K. Clostridium difficile binary toxin CDT. Gut Microbes. 2014;5(1):15–27. doi:10.4161/gmic.26854.
   PubMed Web of Science ®Google Scholar
• Cowardin CA, Buonomo EL, Saleh MM, Wilson MG, Burgess SL, Kuehne SA, Schwan C, Eichhoff AM, Koch-Nolte F, Lyras D, et al. The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. Nat Microbiol. 2016;1(8):16108. doi:10.1038/nmicrobiol.2016.108.
   PubMed Web of Science ®Google Scholar
• Schwan C, Stecher B, Tzivelekidis T, van Ham M, Rohde M, Hardt WD, Wehland J, Aktories K. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. PLoS Pathog. 2009;5(10):e1000626. doi:10.1371/journal.ppat.1000626.
   PubMed Web of Science ®Google Scholar
• Lewis BB, Carter RA, Ling L, Leiner I, Taur Y, Kamboj M, Dubberke ER, Xavier J, Pamer EG. Pathogenicity locus, core genome, and accessory gene contributions to Clostridium difficile virulence. MBio. 2017;8(4):e00885–17. doi:10.1128/mBio.00885-17.
   PubMed Web of Science ®Google Scholar
• Kim J, Kim Y, Pai H, Popoff MR. Clinical characteristics and treatment outcomes of Clostridium difficile infections by PCR ribotype 017 and 018 strains. PloS one. 2016;11(12):e0168849. doi:10.1371/journal.pone.0168849.
   PubMed Web of Science ®Google Scholar
• Cairns MD, Preston MD, Lawley TD, Clark TG, Stabler RA, Wren BW. Genomic epidemiology of a protracted hospital outbreak caused by a toxin A-negative Clostridium difficile sublineage PCR ribotype 017 strain in London, England. England. J Clin Microbiol. 2015;53(10):1148–1154. doi:10.1128/JCM.00648-15.
   Web of Science ®Google Scholar
• Hung YP, Huang IH, Lin HJ, Tsai BY, Liu HC, Liu HC, Lee JC, Wu YH, Tsai PJ, Ko WC, et al. Predominance of Clostridium difficile ribotypes 017 and 078 among toxigenic clinical isolates in southern Taiwan. PloS one. 2016;11(11):e0166159. doi:10.1371/journal.pone.0166159.
   PubMed Web of Science ®Google Scholar
• Shin BM, Kuak EY, Yoo SJ, Shin WC, Yoo HM. Emerging toxin A−B+ variant strain of Clostridium difficile responsible for pseudomembranous colitis at a tertiary care hospital in Korea. Diagn Microbiol Infect Dis. 2008;60(4):333–337. doi:10.1016/j.diagmicrobio.2007.10.022.
   PubMed Web of Science ®Google Scholar
• Lim SK, Stuart RL, Mackin KE, Carter GP, Kotsanas D, Francis MJ, Easton M, Dimovski K, Elliott B, Riley TV, et al. Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain. Clin Infect Dis. 2014;58(12):1723–1730. doi:10.1093/cid/ciu203.
   PubMed Web of Science ®Google Scholar
• Stabler RA, Dawson LF, Valiente E, Cairns MD, Martin MJ, Donahue EH, Riley TV, Songer JG, Kuijper EJ, Dingle KE, et al. Macro and micro diversity of Clostridium difficile isolates from diverse sources and geographical locations. PloS one. 2012;7(3):e31559. doi:10.1371/journal.pone.0031559.
   PubMed Web of Science ®Google Scholar
• Lanis JM, Barua S, Ballard JD, Gilmore MS. Variations in TcdB activity and the hypervirulence of emerging strains of Clostridium difficile. PLoS Pathog. 2010;6(8):e1001061. doi:10.1371/journal.ppat.1001061.
   PubMed Web of Science ®Google Scholar
• Libby DB, Bearman G. Bacteremia due to Clostridium difficile —review of the literature. Int J Infect Dis. 2009;13(5):e305–e9. doi:10.1016/j.ijid.2009.01.014.
   PubMed Web of Science ®Google Scholar
• Garcia-Lechuz JM, Hernangomez S, Juan RS, Pelaez T, Alcala L, Bouza E. Extra-intestinal infections caused by Clostridium difficile. Clin Microbiol Infect. 2001;7(8):453–457. doi:10.1046/j.1469-0691.2001.00313.x.
   PubMed Web of Science ®Google Scholar
• Mattila E, Arkkila P, Mattila PS, Tarkka E, Tissari P, Anttila VJ. Extraintestinal Clostridium difficile infections. Clin Infect Dis. 2013;57(6):e148–53. doi:10.1093/cid/cit392.
   PubMed Web of Science ®Google Scholar
• Steele J, Chen K, Sun X, Zhang Y, Wang H, Tzipori S, Feng H. Systemic dissemination of Clostridium difficile toxins A and B is associated with severe, fatal disease in animal models. J Infect Dis. 2012;205(3):384–391. doi:10.1093/infdis/jir748.
   PubMed Web of Science ®Google Scholar
• Yu H, Chen K, Wu J, Yang Z, Shi L, Barlow LL, Aronoff DM, Garey KW, Savidge TC, von Rosenvinge EC, et al. Identification of toxemia in patients with Clostridium difficile infection. PloS one. 2015;10(4):e0124235. doi:10.1371/journal.pone.0124235.
   PubMed Web of Science ®Google Scholar
• Vaishnavi C. Translocation of gut flora and its role in sepsis. Indian J Med Microbiol. 2013;31(4):334–342. doi:10.4103/0255-0857.118870.
   PubMed Web of Science ®Google Scholar
• Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the intestinal mucosa during sepsis. Front Immunol. 2019;10:10. doi:10.3389/fimmu.2019.00010.
   PubMed Web of Science ®Google Scholar
• Szeto CC, McIntyre CW, Li PK. Circulating bacterial fragments as cardiovascular risk factors in CKD. J Am Soc Nephrol. 2018;29(6):1601–1608. doi:10.1681/ASN.2018010068.
   PubMed Web of Science ®Google Scholar
• Li J, Moturi KR, Wang L, Zhang K, Yu C. Gut derived-endotoxin contributes to inflammation in severe ischemic acute kidney injury. BMC Nephrol. 2019;20(1):16. doi:10.1186/s12882-018-1199-4.
   PubMedGoogle Scholar
• Thongprayoon C, Cheungpasitporn W, Phatharacharukul P, Mahaparn P, Bruminhent J. High mortality risk in chronic kidney disease and end stage kidney disease patients with Clostridium difficile infection: a systematic review and meta-analysis. J Nat Sci. 2015;1(4):e85.
   PubMedGoogle Scholar
• Lemaire A, Dombrovskiy V, Batsides G, Scholz P, Solina A, Brownstone N, Spotnitz A, Lee LY. The effect of Clostridium difficile infection on cardiac surgery outcomes. Surg Infect (Larchmt). 2015;16(1):24–28. doi:10.1089/sur.2013.097.
   PubMed Web of Science ®Google Scholar
• Henrich TJ, Krakower D, Bitton A, Yokoe DS. Clinical risk factors for severe Clostridium difficile –associated disease. Emerg Infect Dis. 2009;15(3):415–422. doi:10.3201/eid1503.080312.
   PubMed Web of Science ®Google Scholar
• Dobson G, Hickey C, Trinder J. Clostridium difficile colitis causing toxic megacolon, severe sepsis and multiple organ dysfunction syndrome. Intensive Care Med. 2003;29(6):1030. doi:10.1007/s00134-003-1754-7.
   PubMed Web of Science ®Google Scholar
• Carter GP, Chakravorty A, Pham Nguyen TA, Mileto S, Schreiber F, Li L, Howarth P, Clare S, Cunningham B, Sambol SP, et al. Defining the roles of TcdA and TcdB in localized gastrointestinal disease, systemic organ damage, and the host response during Clostridium difficile infections. mBio. 2015;6(3):e00551–15.
   PubMed Web of Science ®Google Scholar
• Autenrieth DM, Baumgart DC. Toxic megacolon. Inflamm Bowel Dis. 2011;18(3):584–591. doi:10.1002/ibd.21847.
   Web of Science ®Google Scholar
• Hung YP, Lin HJ, Tsai BY, Liu HC, Liu HC, Lee JC, Wu Y-H, Wilcox MH, Fawley WN, Hsueh P-R, et al. Clostridium difficile ribotype 126 in southern Taiwan: a cluster of three symptomatic cases. Anaerobe. 2014;30:188–192. doi:10.1016/j.anaerobe.2014.06.005.
   PubMed Web of Science ®Google Scholar
• Mileto SJ, Jarde T, Childress KO, Jensen JL, Rogers AP, Kerr G, Hutton ML, Sheedlo MJ, Bloch SC, Shupe JA, et al. Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease. Proc Natl Acad Sci U S A. 2020;117(14):8064–8073. doi:10.1073/pnas.1915255117.
   PubMed Web of Science ®Google Scholar
• Shrum B, Anantha RV, Xu SX, Donnelly M, Haeryfar SM, McCormick JK, Mele T. A robust scoring system to evaluate sepsis severity in an animal model. BMC Res Notes. 2014;7(1):233. doi:10.1186/1756-0500-7-233.
   PubMedGoogle Scholar
• Botros M, Sikaris KA. The de ritis ratio: the test of time. Clin Biochem Rev. 2013;34:117–130.
   PubMedGoogle Scholar
• Waltz P, Carchman E, Gomez H, Zuckerbraun B. Sepsis results in an altered renal metabolic and osmolyte profile. J Surg Res. 2016;202(1):8–12. doi:10.1016/j.jss.2015.12.011.
   PubMed Web of Science ®Google Scholar
• Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, Kellum JA. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014;41(1):3–11. doi:10.1097/SHK.0000000000000052.
   PubMed Web of Science ®Google Scholar
• Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369(26):2525–2534. doi:10.1056/NEJMra1208937.
   PubMed Web of Science ®Google Scholar
• Alamgir S, Volkova NB, Peterson MW. Prognostic value of low blood glucose at the presentation of E. coli bacteremia. Am J Med. 2006;119(11):952–957. doi:10.1016/j.amjmed.2006.03.035.
   PubMed Web of Science ®Google Scholar
• Jan IS, Tsai TH, Chen JM, Jerng JS, Hsu HF, Hung PL, Hsueh P-R, Lee L-N. Hypoglycemia associated with bacteremic pneumococcal infections. Int J Infect Dis. 2009;13(5):570–576. doi:10.1016/j.ijid.2008.08.026.
   PubMed Web of Science ®Google Scholar
• Majumdar S, Deobagkar-Lele M, Adiga V, Raghavan A, Wadhwa N, Ahmed SM, Rananaware SR, Chakraborty S, Joy O, Nandi D, et al. Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma. Sci Rep. 2017;7(1):40793. doi:10.1038/srep40793.
   PubMedGoogle Scholar
• Perez AR, Roggero E, Nicora A, Palazzi J, Besedovsky HO, Del Rey A, Bottasso OA. Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance. Brain Behav Immun. 2007;21(7):890–900. doi:10.1016/j.bbi.2007.02.004.
   PubMed Web of Science ®Google Scholar
• Seixas E, Ostler D. Plasmodium chabaudi chabaudi (AS): differential cellular responses to infection in resistant and susceptible mice. Exp Parasitol. 2005;110(4):394–405. doi:10.1016/j.exppara.2005.03.024.
   PubMed Web of Science ®Google Scholar
• Savino W, Dardenne M, Marche C, Trophilme D, Dupuy JM, Pekovic D, Lapointe N, Bach, JF. Thymic epithelium in AIDS. An immunohistologic study. Am J Pathol. 1986;122(2):302–307.
   PubMed Web of Science ®Google Scholar
• Marcovistz R, Bertho AL, Matos DC. Relationship between apoptosis and thymocyte depletion in rabies-infected mice. Braz J Med Biol Res. 1994;27:1599–1603.
   PubMed Web of Science ®Google Scholar
• Watson SR, Redington TJ, Miller TB, Bullock WE. Flow microfluorometry analysis of alterations in T-lymphocyte subsets during murine listeriosis. Infect Immun. 1984;45(2):372–377. doi:10.1128/iai.45.2.372-377.1984.
   PubMed Web of Science ®Google Scholar
• Leite-de-Moraes MC, Hontebeyrie-Joskowicz M, Dardenne M, Savino W. Modulation of thymocyte subsets during acute and chronic phases of experimental Trypanosoma cruzi infection. Immunology. 1992;77:95–98.
   PubMed Web of Science ®Google Scholar
• Dieterle MG, Young VB. Reducing recurrence of C. difficile infection. Cell. 2017;169(3):375. doi:10.1016/j.cell.2017.03.039.
   PubMed Web of Science ®Google Scholar
• Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, Cornely OA, Rahav G, Bouza E, Lee C, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305–317. doi:10.1056/NEJMoa1602615.
   PubMed Web of Science ®Google Scholar
• Mikamo H, Aoyama N, Sawata M, Fujimoto G, Dorr MB, Yoshinari T. The effect of bezlotoxumab for prevention of recurrent Clostridium difficile infection (CDI) in Japanese patients. J Infect Chemother. 2018;24(2):123–129. doi:10.1016/j.jiac.2017.10.005.
   PubMed Web of Science ®Google Scholar
• Steele J, Mukherjee J, Parry N, Tzipori S. Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease. J Infect Dis. 2013;207(2):323–330. doi:10.1093/infdis/jis669.
   PubMed Web of Science ®Google Scholar
• Chen W, Kuolee R, Austin JW, Shen H, Che Y, Conlan JW. Low dose aerosol infection of mice with virulent type A Francisella tularensis induces severe thymus atrophy and CD4+CD8+ thymocyte depletion. Microb Pathog. 2005;39:189–196.
   PubMed Web of Science ®Google Scholar
• Deobagkar-Lele M, Chacko SK, Victor ES, Kadthur JC, Nandi D. Interferon-γ- and glucocorticoid-mediated pathways synergize to enhance death of CD4 + CD8 + thymocytes during Salmonella enterica serovar Typhimurium infection. Immunology. 2013;138(4):307–321. doi:10.1111/imm.12047.
   PubMed Web of Science ®Google Scholar
• Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 2006;6(2):127–135. doi:10.1038/nri1781.
   PubMed Web of Science ®Google Scholar
• Steele J, Feng H, Parry N, Tzipori S. Piglet models of acute or chronic Clostridium difficile illness. J Infect Dis. 2010;201(3):428–434. doi:10.1086/649799.
   PubMed Web of Science ®Google Scholar
• Awad MM, Hutton ML, Quek AJ, Klare WP, Mileto SJ, Mackin K, Ly D, Oorschot V, Bosnjak M, Jenkin G, et al. Human plasminogen exacerbates Clostridioides difficile enteric disease and alters the spore surface. Gastroenterology. 2020;159(4):1431–1443.e6. doi:10.1053/j.gastro.2020.06.032.
   PubMed Web of Science ®Google Scholar
• Coskun M. Intestinal epithelium in inflammatory bowel disease. Front Med (Lausanne). 2014;1:24. doi:10.3389/fmed.2014.00024.
   PubMedGoogle Scholar
• Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011;7:235–241.
   PubMedGoogle Scholar
• Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–1371. doi:10.1038/nm1511.
   PubMed Web of Science ®Google Scholar
• Borges M, Barreira-Silva P, Florido M, Jordan MB, Correia-Neves M, Appelberg R. Molecular and cellular mechanisms of Mycobacterium avium -induced thymic atrophy. J Immunol. 2012;189(7):3600–3608. doi:10.4049/jimmunol.1201525.
   PubMed Web of Science ®Google Scholar
• Yang Z, Ramsey J, Hamza T, Zhang Y, Li S, Yfantis HG, Lee D, Hernandez LD, Seghezzi W, Furneisen JM, et al. Mechanisms of protection against Clostridium difficile infection by the monoclonal antitoxin antibodies actoxumab and bezlotoxumab. Infect Immun. 2015;83(2):822–831. doi:10.1128/IAI.02897-14.
   PubMed Web of Science ®Google Scholar
• Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14(1):24–35. doi:10.1038/nri3567.
   PubMed Web of Science ®Google Scholar
• Kurosaki T, Kometani K, Ise W. Memory B cells. Nat Rev Immunol. 2015;15(3):149–159. doi:10.1038/nri3802.
   PubMed Web of Science ®Google Scholar
• Douek DC, Betts MR, Hill BJ, Little SJ, Lempicki R, Metcalf JA, Casazza J, Yoder C, Adelsberger JW, Stevens RA, et al. Evidence for increased T cell turnover and decreased thymic output in HIV infection. J Immunol. 2001;167(11):6663–6668. doi:10.4049/jimmunol.167.11.6663.
   PubMed Web of Science ®Google Scholar
• Morrot A, Terra-Granado E, Pérez AR, Silva-Barbosa SD, Milićević NM, Farias-de-Oliveira DA, Berbert LR, De Meis J, Takiya CM, Beloscar J, et al. Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease. PLoS Negl Trop Dis. 2011;5(8):e1268. doi:10.1371/journal.pntd.0001268.
   PubMed Web of Science ®Google Scholar
• Francelin C, Paulino LC, Gameiro J, Verinaud L. Effects of Plasmodium berghei on thymus: high levels of apoptosis and premature egress of CD4+CD8+ thymocytes in experimentally infected mice. Immunobiology. 2011;216(10):1148–1154. doi:10.1016/j.imbio.2011.03.009.
   PubMed Web of Science ®Google Scholar
• Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357(9251):189–193. doi:10.1016/S0140-6736(00)03592-3.
   PubMed Web of Science ®Google Scholar
• Drudy D, Calabi E, Kyne L, Sougioultzis S, Kelly E, Fairweather N, Kelly CP. Human antibody response to surface layer proteins in Clostridium difficile infection. FEMS Immunol Med Microbiol. 2004;41(3):237–242. doi:10.1016/j.femsim.2004.03.007.
   PubMedGoogle Scholar
• Eisen HN. Affinity enhancement of antibodies: how low-affinity antibodies produced early in immune responses are followed by high-affinity antibodies later and in memory B-cell responses. Cancer Immunol Res. 2014;2(5):381–392. doi:10.1158/2326-6066.CIR-14-0029.
   PubMed Web of Science ®Google Scholar
• Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(6):21–27. doi:10.1111/1469-0691.12046.
   PubMedGoogle Scholar
• Feuerstadt P, Nelson WW, Drozd EM, Dreyfus J, Dahdal DN, Wong AC, Mohammadi I, Teigland C, Amin A. Mortality, health care use, and costs of Clostridioides difficile infections in older adults. J Am Med Dir Assoc. 2022. doi:10.1016/j.jamda.2022.01.075.
   PubMed Web of Science ®Google Scholar
• Avni T, Hammud H, Itzhaki O, Gafter-Gvili A, Rozen-Zvi B, Ben-Zvi H, Bishara J, Atamna A. The significance of acute kidney injury in Clostridioides difficile infection. Int J Clin Pract. 2020;75(3):e13785. doi:10.1111/ijcp.13785.
   PubMed Web of Science ®Google Scholar
• O’Horo J, Safdar N. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review. Int J Infect Dis. 2009;13(6):663–667. doi:10.1016/j.ijid.2008.11.012.
   PubMed Web of Science ®Google Scholar
• Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, et al. Trends in U.S. Burden of Clostridioides difficile infection and outcomes. N Engl J Med. 2020;382(14):1320–1330. doi:10.1056/NEJMoa1910215.
   PubMed Web of Science ®Google Scholar