Use of intravenous immunoglobulin for the treatment of severe clostridium difficile colitis

Hassoun, Ali; Ibrahim, Farrah

doi:10.1016/j.amjopharm.2007.03.001

Cited by 30 publications

(19 citation statements)

References 16 publications

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“…The definition of severe CDI varied between reports, making comparison difficult. However, the various inclusion criteria included pancolitis on CT scan either with or without megacolon [36,48,50], thumbprinting on CT scan [36], and a scale described by Rubin et al [49,59]. The most recent study, by Abougergi et al, provided two scales for inclusion: One based on extent of colonic disease and the other based on the APACHE II score to assess severity of systemic involvement [56].…”

Section: Ivig For Severe CDImentioning

confidence: 97%

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Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

Abougergi

Kwon

2010

Dig Dis Sci

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Clostridium difficile infection (CDI) has increased sharply in incidence, mortality rate, and burden on the healthcare system over the past decade. Therefore, novel treatment modalities have been developed, including intravenous immunoglobulin (IVIG). The level of immune response to Clostridium difficile colonization is the major determinant of the magnitude and duration of clinical manifestations. This effect is mediated predominantly by serum IgG anti-toxin A antibodies. Based on this finding, anti-toxin A and B antibodies were successfully used in multiple in vitro and in vivo experimental settings to passively immunize hamsters in CDI models. In humans, IVIG was used as the source of those antibodies. Fifteen small, mostly retrospective and non-randomized reports documented IVIG's success in the treatment of protracted, recurrent, or severe CDI. Diarrhea resolution rates were higher in the former patient group, but the recurrence rates were similar. IVIG mechanism of action is neutralization of mainly toxin A through IgG anti-toxin A antibodies. Purified anti-toxin A and B antibodies were successfully used to decrease CDI recurrence rates among patients with no or one previous CDI episodes. In conclusion, the efficacy of IVIG for CDI treatment in animal models has been convincingly demonstrated. However, only few small non-randomized, mostly uncontrolled reports have been published on human subjects. A phase II trial results support the use of purified anti-toxin A and B antibodies to decrease CDI recurrence rates. Therefore, IVIG should currently only be used as adjunct therapy until results from large, randomized controlled trials are available.

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Section: Ivig For Severe CDImentioning

confidence: 97%

“…Its use for severe CDI was reported 7 years later [36]. Since then, a total of 15 reports have been published on IVIG for either relapsing or severe CDI treatment [25,[35][36][37][47][48][49][50][51][52][53][54][55][56][57].…”

Section: Ivig For Clostridium Difficile Infection: Outcome In Clinicamentioning

confidence: 99%

Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

Abougergi

Kwon

2010

Dig Dis Sci

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“…Beales (2002) reported successful treatment of 4 cases of refractory recurrent CDI with IVIG 400 mg/kg given twice, 21 days apart along with a tapering dose of vancomycin (Beales 2002). Several other individual case reports also reported successful treatment with varying regimens involving IVIG (Salcedo et al 1997;Murphy et al 2006;Hassoun and Ibrahim 2007).…”

Section: Immune Globulinmentioning

confidence: 97%

New advances in the treatment of <em>Clostridium difficile</em> infection (CDI)

Hedge

Strain²,

Heins³

et al. 2008

TCRM

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Clostridium diffi cile infections (CDI) have increased in frequency throughout the world. In addition to an increase in frequency, recent CDI epidemics have been linked to a hypervirulent C. diffi cile strain resulting in greater severity of disease. Although most mild to moderate cases of CDI continue to respond to metronidazole or vancomycin, refractory and recurrent cases of CDI may require alternative therapies. This review provides a brief overview of CDI and summarizes studies involving alternative antibiotics, toxin binders, probiotics, and immunological therapies that can be considered for treatment of acute and recurrent CDI in severe and refractory situations.

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“…Evidence that toxin blockade may also be protective in human patients originates from studies showing that high titers of antitoxin antibodies correlate with lower rates of primary and recurrent CDI in humans (27)(28)(29)(30)(31). Furthermore, intravenous immunoglobulin treatment is sometimes used to treat severe CDI under the assumption that such immunoglobulin preparations contain significant levels of antitoxin antibodies (32)(33)(34)(35)(36). These data clearly demonstrate that administration of neutralizing antitoxin antibodies is a viable approach to the treatment and prevention of CDI.…”

mentioning

confidence: 88%

Mechanisms of Protection against Clostridium difficile Infection by the Monoclonal Antitoxin Antibodies Actoxumab and Bezlotoxumab

et al. 2015

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dClostridium difficile infection (CDI) represents the most prevalent cause of antibiotic-associated gastrointestinal infections in health care facilities in the developed world. Disease symptoms are caused by the two homologous exotoxins, TcdA and TcdB. Standard therapy for CDI involves administration of antibiotics that are associated with a high rate of disease recurrence, highlighting the need for novel treatment paradigms that target the toxins rather than the organism itself. A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics. However, the exact mechanism of antibodymediated protection is poorly understood. In this study, we show that the antitoxin antibodies are protective in multiple murine models of CDI, including systemic and local (gut) toxin challenge models, as well as primary and recurrent models of infection in mice. Systemically administered actoxumab-bezlotoxumab prevents both the damage to the gut wall and the inflammatory response, which are associated with C. difficile in these models, including in mice challenged with a strain of the hypervirulent ribotype 027. Furthermore, mutant antibodies (N297Q) that do not bind to Fc␥ receptors provide a level of protection similar to that of wild-type antibodies, demonstrating that the mechanism of protection is through direct neutralization of the toxins and does not involve host effector functions. These data provide a mechanistic basis for the prevention of recurrent disease observed in CDI patients in clinical trials. Clostridium difficile is an anaerobic, spore-forming, Gram-positive bacterium that causes infections in the lumen of the colon and is the most frequent cause of nosocomial diarrhea in the developed world (1, 2). C. difficile infections (CDI) contribute to thousands of deaths and are associated with over $1 billion in health care-related costs in the United States each year (3-5). The symptoms of CDI range from asymptomatic carriage or mild diarrhea to fatal pseudomembranous colitis, colonic rupture, and death (6, 7). The disease occurs mainly in patients undergoing (or who have recently undergone) a course of broad-spectrum antibiotics; in such patients, composition of the gut microbiota is altered, disrupting the body's natural defense against C. difficile infections. Clinical management of CDI consists of discontinuation of the offending antibiotic and treatment with either metronidazole, vancomycin, or the newly approved fidaxomicin (8). A major concern with CDI is that even when treatment of a primary infection is successful, 20 to 30% of patients experience a recurrence of the disease within days or weeks of symptom resolution. Disease recurrence results from continued disruption of the gut microbiota by standard-of-care antibiotics (9) combined with persistence of resistant C. difficile spores (relapse) or reacquisition of new spores from the environment (rein...

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Use of intravenous immunoglobulin for the treatment of severe clostridium difficile colitis

Cited by 30 publications

References 16 publications

Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

New advances in the treatment of <em>Clostridium difficile</em> infection (CDI)

Mechanisms of Protection against Clostridium difficile Infection by the Monoclonal Antitoxin Antibodies Actoxumab and Bezlotoxumab

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