Clostridium Difficile Infection in Inflammatory Bowel Disease Patients

Abdulmajeed    A.    Albarrak; Bhupinder    S.   Romana; Suleyman       Uraz; Mohamad    H.   Yousef; Alhareth    A.   Juboori; Veysel       Tahan

doi:10.2174/1871530319666190301120558

Abstract

Background: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI.

Objective: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone.

Methods: Here, we provide an up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results.

Results: Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant.

Conclusion: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.

Keywords: Clostridium difficile, inflammatory bowel disease, treatment, management, pathogenesis, biologic therapy.

« Previous Next »

Graphical Abstract

[1] 
Bartlett, J.G.; Chang, T.W.; Gurwith, M.; Gorbach, S.L.; Onderdonk, A.B. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N. Engl. J. Med.,  1978, 298(10), 531-534.
[http://dx.doi.org/10.1056/NEJM197803092981003] [PMID:  625309] 
[2] 
Hall, A.J.; Curns, A.T.; McDonald, L.C.; Parashar, U.D.; Lopman, B.A. The roles of Clostridium difficile and norovirus among gastroenteritis-associated deaths in the United States, 1999-2007. Clin. Infect. Dis.,  2012, 55(2), 216-223.
[http://dx.doi.org/10.1093/cid/cis386] [PMID:  22491338] 
[3] 
Lessa, F.C.; Mu, Y.; Bamberg, W.M.; Beldavs, Z.G.; Dumyati, G.K.; Dunn, J.R.; Farley, M.M.; Holzbauer, S.M.; Meek, J.I.; Phipps, E.C.; Wilson, L.E.; Winston, L.G.; Cohen, J.A.; Limbago, B.M.; Fridkin, S.K.; Gerding, D.N.; McDonald, L.C. Burden of Clostridium difficile infection in the United States. N. Engl. J. Med.,  2015, 372(9), 825-834.
[http://dx.doi.org/10.1056/NEJMoa1408913] [PMID:  25714160] 
[4] 
Warny, M.; Pepin, J.; Fang, A.; Killgore, G.; Thompson, A.; Brazier, J.; Frost, E.; McDonald, L.C. 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.
[http://dx.doi.org/10.1016/S0140-6736(05)67420-X] [PMID:  16182895] 
[5] 
McDonald, L.C.; Killgore, G.E.; Thompson, A.; Owens, R.C., Jr; Kazakova, S.V.; Sambol, S.P.; Johnson, S.; Gerding, D.N. An epidemic, toxin gene-variant strain of Clostridium difficile. N. Engl. J. Med.,  2005, 353(23), 2433-2441.
[http://dx.doi.org/10.1056/NEJMoa051590] [PMID:  16322603] 
[6] 
O’Connor, J.R.; Johnson, S.; Gerding, D.N. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology,  2009, 136(6), 1913-1924.
[http://dx.doi.org/10.1053/j.gastro.2009.02.073] [PMID:  19457419] 
[7] 
Carter, G.P.; Rood, J.I.; Lyras, D. The role of toxin A and toxin B in the virulence of Clostridium difficile. Trends Microbiol.,  2012, 20(1), 21-29.
[http://dx.doi.org/10.1016/j.tim.2011.11.003] [PMID:  22154163] 
[8] 
Rodemann, J. F.; Dubberke, E. R.; Reske, K. A.; Seo, D. H.; Stone, C. D. Incidence of Clostridium difficile infection in inflammatory
bowel disease. Clinical gastroenterology and hepatology : the official
clinical practice journal of the American Gastroenterological
Association., 2007, 5(3), 339-344. 
[http://dx.doi.org/10.1016/j.cgh.2006.12.027] 
[9] 
Issa, M.; Vijayapal, A.; Graham, M. B.; Beaulieu, D. B.; Otterson, M. F.; Lundeen, S.; Skaros, S.; Weber, L. R.; Komorowski, R. A.; Knox, J. F.; Emmons, J.; Bajaj, J. S.; Binion, D. G. Impact of Clostridium
difficile on inflammatory bowel disease. Clinical gastroenterology
and hepatology : the official clinical practice journal of
the American Gastroenterological Association., 2007, 5(3), 345-
351. 
[http://dx.doi.org/10.1016/j.cgh.2006.12.028] 
[10] 
Barber, G.E.; Hendler, S.; Okafor, P.; Limsui, D.; Limketkai, B.N. Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis. Inflamm. Bowel Dis.,  2018, 24(8), 1849-1856.
[http://dx.doi.org/10.1093/ibd/izy086] [PMID:  29722832] 
[11] 
Razik, R.; Rumman, A.; Bahreini, Z.; McGeer, A.; Nguyen, G.C. Recurrence of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease: The RECIDIVISM Study. Am. J. Gastroenterol.,  2016, 111(8), 1141-1146.
[http://dx.doi.org/10.1038/ajg.2016.187] [PMID:  27215924] 
[12] 
Braun, V.; Hundsberger, T.; Leukel, P.; Sauerborn, M.; von Eichel-Streiber, C. Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene,  1996, 181(1-2), 29-38.
[http://dx.doi.org/10.1016/S0378-1119(96)00398-8] [PMID:  8973304] 
[13] 
Voth, D.E.; Ballard, J.D. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev.,  2005, 18(2), 247-263.
[http://dx.doi.org/10.1128/CMR.18.2.247-263.2005] [PMID:  15831824] 
[14] 
Pothoulakis, C. Effects of Clostridium difficile toxins on epithelial cell barrier. Ann. N. Y. Acad. Sci.,  2000, 915, 347-356.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05263.x] [PMID:  11193598] 
[15] 
Schwan, C.; Stecher, B.; Tzivelekidis, T.; van Ham, M.; Rohde, M.; Hardt, W-D.; 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
[http://dx.doi.org/10.1371/journal.ppat.1000626] [PMID:  19834554] 
[16] 
Kelly, C.P.; Becker, S.; Linevsky, J.K.; Joshi, M.A.; O’Keane, J.C.; Dickey, B.F.; LaMont, J.T.; Pothoulakis, C. Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit. J. Clin. Invest.,  1994, 93(3), 1257-1265.
[http://dx.doi.org/10.1172/JCI117080] [PMID:  7907603] 
[17] 
Flegel, W.A.; Müller, F.; Däubener, W.; Fischer, H.G.; Hadding, U.; Northoff, H. Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B. Infect. Immun.,  1991, 59(10), 3659-3666.
[PMID:  1910012] 
[18] 
Sun, X.; He, X.; Tzipori, S.; Gerhard, R.; Feng, H. Essential role of the glucosyltransferase activity in Clostridium difficile toxin-induced secretion of TNF-alpha by macrophages. Microb. Pathog.,  2009, 46(6), 298-305.
[http://dx.doi.org/10.1016/j.micpath.2009.03.002] [PMID:  19324080] 
[19] 
Kim, J.M.; Kim, J.S.; Jun, H.C.; Oh, Y.K.; Song, I.S.; Kim, C.Y. Differential expression and polarized secretion of CXC and CC chemokines by human intestinal epithelial cancer cell lines in response to Clostridium difficile toxin A. Microbiol. Immunol.,  2002, 46(5), 333-342.
[http://dx.doi.org/10.1111/j.1348-0421.2002.tb02704.x] [PMID:  12139393] 
[20] 
Savidge, T.C.; Pan, W.H.; Newman, P.; O’brien, M.; Anton, P.M.; Pothoulakis, C. Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine. Gastroenterology,  2003, 125(2), 413-420.
[http://dx.doi.org/10.1016/S0016-5085(03)00902-8] [PMID:  12891543] 
[21] 
Ng, E.K.; Panesar, N.; Longo, W.E.; Shapiro, M.J.; Kaminski, D.L.; Tolman, K.C.; Mazuski, J.E. Human intestinal epithelial and smooth muscle cells are potent producers of IL-6. Mediators Inflamm.,  2003, 12(1), 3-8.
[http://dx.doi.org/10.1080/0962935031000096917] [PMID:  12745542] 
[22] 
Eastwood, K.; Else, P.; Charlett, A.; Wilcox, M. Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J. Clin. Microbiol.,  2009, 47(10), 3211-3217.
[http://dx.doi.org/10.1128/JCM.01082-09] [PMID:  19710274] 
[23] 
Planche, T.; Wilcox, M. Reference assays for Clostridium difficile infection: one or two gold standards? J. Clin. Pathol.,  2011, 64(1), 1-5.
[http://dx.doi.org/10.1136/jcp.2010.080135] [PMID:  21118850] 
[24] 
Shetty, N.; Wren, M.W.; Coen, P.G. The role of glutamate dehydrogenase for the detection of Clostridium difficile in faecal samples: a meta-analysis. J. Hosp. Infect.,  2011, 77(1), 1-6.
[http://dx.doi.org/10.1016/j.jhin.2010.07.024] [PMID:  21145132] 
[25] 
Martínez-Meléndez, A.; Camacho-Ortiz, A.; Morfin-Otero, R.; Maldonado-Garza, H.J.; Villarreal-Treviño, L.; Garza-González, E. Current knowledge on the laboratory diagnosis of Clostridium difficile infection. World J. Gastroenterol.,  2017, 23(9), 1552-1567.
[http://dx.doi.org/10.3748/wjg.v23.i9.1552] [PMID:  28321156] 
[26] 
Planche, T.; Aghaizu, A.; Holliman, R.; Riley, P.; Poloniecki, J.; Breathnach, A.; Krishna, S. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect. Dis.,  2008, 8(12), 777-784.
[http://dx.doi.org/10.1016/S1473-3099(08)70233-0] [PMID:  18977696] 
[27] 
Johnson, S.; Kent, S.A.; O’Leary, K.J.; Merrigan, M.M.; Sambol, S.P.; Peterson, L.R.; Gerding, D.N. Fatal pseudomembranous colitis associated with a variant clostridium difficile strain not detected by toxin A immunoassay. Ann. Intern. Med.,  2001, 135(6), 434-438.
[http://dx.doi.org/10.7326/0003-4819-135-6-200109180-00012] [PMID:  11560456] 
[28] 
Deshpande, A.; Pasupuleti, V.; Rolston, D.D.; Jain, A.; Deshpande, N.; Pant, C.; Hernandez, A.V. Diagnostic accuracy of real-time polymerase chain reaction in detection of Clostridium difficile in the stool samples of patients with suspected Clostridium difficile Infection: a meta-analysis. Clin. Infect. Dis.,  2011, 53(7), e81-e90.
[http://dx.doi.org/10.1093/cid/cir505] [PMID:  21890762] 
[29] 
Korman, T.M. Diagnosis and management of Clostridium difficile infection. Semin. Respir. Crit. Care Med.,  2015, 36(1), 31-43.
[http://dx.doi.org/10.1055/s-0034-1398741] [PMID:  25643269] 
[30] 
Surawicz, C.M.; Brandt, L.J.; Binion, D.G.; Ananthakrishnan, A.N.; Curry, S.R.; Gilligan, P.H.; McFarland, L.V.; Mellow, M.; Zuckerbraun, B.S. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am. J. Gastroenterol.,  2013, 108(4), 478-498.
[http://dx.doi.org/10.1038/ajg.2013.4] [PMID:  23439232] 
[31] 
Sokol, H.; Lalande, V.; Landman, C.; Bourrier, A.; Nion-Larmurier, I.; Rajca, S.; Kirchgesner, J.; Seksik, P.; Cosnes, J.; Barbut, F.; Beaugerie, L. Clostridium difficile infection in acute flares of inflammatory bowel disease: A prospective study. Dig. Liver Dis., 2017.
[http://dx.doi.org/10.1016/j.dld.2017.01.162] 
[32] 
Polage, C.R.; Gyorke, C.E.; Kennedy, M.A.; Leslie, J.L.; Chin, D.L.; Wang, S.; Nguyen, H.H.; Huang, B.; Tang, Y.W.; Lee, L.W.; Kim, K.; Taylor, S.; Romano, P.S.; Panacek, E.A.; Goodell, P.B.; Solnick, J.V.; Cohen, S.H. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era. JAMA Intern. Med.,  2015, 175(11), 1792-1801.
[http://dx.doi.org/10.1001/jamainternmed.2015.4114] [PMID:  26348734] 
[33] 
Leekha, S.; Aronhalt, K.C.; Sloan, L.M.; Patel, R.; Orenstein, R. Asymptomatic Clostridium difficile colonization in a tertiary care hospital: admission prevalence and risk factors. Am. J. Infect. Control,  2013, 41(5), 390-393.
[http://dx.doi.org/10.1016/j.ajic.2012.09.023] [PMID:  23622704] 
[34] 
Gerding, D.N.; Olson, M.M.; Peterson, L.R.; Teasley, D.G.; Gebhard, R.L.; Schwartz, M.L.; Lee, J.T., Jr Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study. Arch. Intern. Med.,  1986, 146(1), 95-100.
[http://dx.doi.org/10.1001/archinte.1986.00360130117016] [PMID:  3942469] 
[35] 
Khanna, S.; Shin, A.; Kelly, C. P.  Management of Clostridium
difficile Infection in Inflammatory Bowel Disease: Expert Review
from the Clinical Practice Updates Committee of the AGA Institute.
Clinical gastroenterology and hepatology : the official clinical
practice journal of the American Gastroenterological Association.,
2017, 15(2), 166-174.
[36] 
Johnson, S.; Louie, T.J.; Gerding, D.N.; Cornely, O.A.; Chasan-Taber, S.; Fitts, D.; Gelone, S.P.; Broom, C.; Davidson, D.M. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin. Infect. Dis.,  2014, 59(3), 345-354.
[http://dx.doi.org/10.1093/cid/ciu313] [PMID:  24799326] 
[37] 
Lee, C.; Louie, T.J.; Weiss, K.; Valiquette, L.; Gerson, M.; Arnott, W.; Gorbach, S.L. Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes. The Canadian journal of infectious diseases & medical microbiology =. Can. J. Infect. Dis. Med. Microbiol., 2016.20168048757
[http://dx.doi.org/10.1155/2016/8048757] [PMID:  27366179] 
[38] 
Kapoor, K.; Chandra, M.; Nag, D.; Paliwal, J.K.; Gupta, R.C.; Saxena, R.C. Evaluation of metronidazole toxicity: a prospective study. Int. J. Clin. Pharmacol. Res.,  1999, 19(3), 83-88.
[PMID:  10761537] 
[39] 
Cohen, S.H.; Gerding, D.N.; Johnson, S.; Kelly, C.P.; Loo, V.G.; McDonald, L.C.; Pepin, J.; Wilcox, M.H. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect. Control Hosp. Epidemiol.,  2010, 31(5), 431-455.
[http://dx.doi.org/10.1086/651706] [PMID:  20307191] 
[40] 
Garey, K.W.; Ghantoji, S.S.; Shah, D.N.; Habib, M.; Arora, V.; Jiang, Z.D.; DuPont, H.L. A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection. J. Antimicrob. Chemother.,  2011, 66(12), 2850-2855.
[http://dx.doi.org/10.1093/jac/dkr377] [PMID:  21948965] 
[41] 
Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity of the human intestinal microbial flora. Science,  2005, 308(5728), 1635-1638.
[http://dx.doi.org/10.1126/science.1110591] [PMID:  15831718] 
[42] 
Petersen, C.; Round, J.L. Defining dysbiosis and its influence on host immunity and disease. Cell. Microbiol.,  2014, 16(7), 1024-1033.
[http://dx.doi.org/10.1111/cmi.12308] [PMID:  24798552] 
[43] 
Dalal, S.R.; Chang, E.B. The microbial basis of inflammatory bowel diseases. J. Clin. Invest.,  2014, 124(10), 4190-4196.
[http://dx.doi.org/10.1172/JCI72330] [PMID:  25083986] 
[44] 
Theriot, C.M.; Young, V.B. Interactions Between the Gastrointestinal Microbiome and Clostridium difficile. Annu. Rev. Microbiol.,  2015, 69, 445-461.
[http://dx.doi.org/10.1146/annurev-micro-091014-104115] [PMID:  26488281] 
[45] 
Hold, G.L.; Smith, M.; Grange, C.; Watt, E.R.; El-Omar, E.M.; Mukhopadhya, I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World J. Gastroenterol.,  2014, 20(5), 1192-1210.
[http://dx.doi.org/10.3748/wjg.v20.i5.1192] [PMID:  24574795] 
[46] 
Brandt, L.J. American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection. Am. J. Gastroenterol.,  2013, 108(2), 177-185.
[http://dx.doi.org/10.1038/ajg.2012.450] [PMID:  23318479] 
[47] 
Eiseman, B.; Silen, W.; Bascom, G.S.; Kauvar, A.J. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery,  1958, 44(5), 854-859.
[PMID:  13592638] 
[48] 
Kassam, Z.; Lee, C.H.; Yuan, Y.; Hunt, R.H. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am. J. Gastroenterol.,  2013, 108(4), 500-508.
[http://dx.doi.org/10.1038/ajg.2013.59] [PMID:  23511459] 
[49] 
Gough, E.; Shaikh, H.; Manges, A.R. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin. Infect. Dis.,  2011, 53(10), 994-1002.
[http://dx.doi.org/10.1093/cid/cir632] [PMID:  22002980] 
[50] 
Fischer, M.; Kao, D.; Kelly, C.; Kuchipudi, A.; Jafri, S.M.; Blumenkehl, M.; Rex, D.; Mellow, M.; Kaur, N.; Sokol, H.; Cook, G.; Hamilton, M.J.; Phelps, E.; Sipe, B.; Xu, H.; Allegretti, J.R. Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Inflamm. Bowel Dis.,  2016, 22(10), 2402-2409.
[http://dx.doi.org/10.1097/MIB.0000000000000908] [PMID:  27580384] 
[51] 
Fischer, M.; Kao, D.; Mehta, S.R.; Martin, T.; Dimitry, J.; Keshteli, A.H.; Cook, G.K.; Phelps, E.; Sipe, B.W.; Xu, H.; Kelly, C.R. Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study. Am. J. Gastroenterol.,  2016, 111(7), 1024-1031.
[http://dx.doi.org/10.1038/ajg.2016.180] [PMID:  27185076] 
[52] 
Saffouri, G.; Gupta, A.; Loftus, E.V., Jr; Baddour, L.M.; Pardi, D.S.; Khanna, S. The incidence and outcomes from Clostridium difficile infection in hospitalized adults with inflammatory bowel disease. Scand. J. Gastroenterol.,  2017, 52(11), 1240-1247.
[http://dx.doi.org/10.1080/00365521.2017.1362466] [PMID:  28782372] 
[53] 
Romana, B.S.; Albarrak, A.A.; Yousef, M.H.; Tahan, V. Infliximab use in ulcerative colitis flare with clostridium difficile infection: A report of two cases and literature review. North. Clin. Istanb.,  2018, 5(3), 256-260.
[PMID:  30688931] 
[54] 
Rahier, J.F.; Magro, F.; Abreu, C.; Armuzzi, A.; Ben-Horin, S.; Chowers, Y.; Cottone, M.; de Ridder, L.; Doherty, G.; Ehehalt, R.; Esteve, M.; Katsanos, K.; Lees, C.W.; Macmahon, E.; Moreels, T.; Reinisch, W.; Tilg, H.; Tremblay, L.; Veereman-Wauters, G.; Viget, N.; Yazdanpanah, Y.; Eliakim, R.; Colombel, J.F. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J. Crohn’s Colitis,  2014, 8(6), 443-468.
[http://dx.doi.org/10.1016/j.crohns.2013.12.013] [PMID:  24613021] 
[55] 
Ben-Horin, S.; Margalit, M.; Bossuyt, P.; Maul, J.; Shapira, Y.; Bojic, D.; Chermesh, I.; Al-Rifai, A.; Schoepfer, A.; Bosani, M.; Allez, M.; Lakatos, P.L.; Bossa, F.; Eser, A.; Stefanelli, T.; Carbonnel, F.; Katsanos, K.; Checchin, D.; Miera, I.S.; Chowers, Y.; Moran, G.W. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection. Clin. Gastroenterol. Hepatol.,  2009, 7(9), 981-987.
[http://dx.doi.org/10.1016/j.cgh.2009.05.031] [PMID:  19523534] 
[56] 
Ananthakrishnan, A.N.; Guzman-Perez, R.; Gainer, V.; Cai, T.; Churchill, S.; Kohane, I.; Plenge, R.M.; Murphy, S. Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther.,  2012, 35(7), 789-795.
[http://dx.doi.org/10.1111/j.1365-2036.2012.05022.x] [PMID:  22360370] 
[57] 
Seicean, A.; Moldovan-Pop, A.; Seicean, R. Ulcerative colitis worsened after Clostridium difficile infection: efficacy of infliximab. World J. Gastroenterol.,  2014, 20(17), 5135-5140.
[http://dx.doi.org/10.3748/wjg.v20.i17.5135] [PMID:  24803831] 

Rights & Permissions Print Cite

Article Metrics

37

5

1

2

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1871530319666190301120558	Print ISSN 1871-5303
Publisher Name Bentham Science Publisher	Online ISSN 2212-3873

Endocrine, Metabolic & Immune Disorders - Drug Targets

Clostridium Difficile Infection in Inflammatory Bowel Disease Patients

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract