Multiple Relapses of Clostridium difficile-Associated Diarrhea in a Cancer Patient Successful Control with Long-Term Cholestyramine Therapy

Moncino, Mark D.; Falletta, John M.

doi:10.1097/00043426-199211000-00015

Cited by 44 publications

(13 citation statements)

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“…Case reports and animal studies suggested that CSM binds and enhances elimination rates of many organic toxins including Kepone (28,29), DDE (30), other organochlorine pesticides (31), polychlorinated biphenyl compounds (32), Clostridum difficile toxin (33,34), Escheria coli and Vibrio cholera toxins (35,36), a cytotoxin(s) from an unidentified gastrointestinal microorganism(s) (37,38), the mycotoxins ochratoxin A (39,40) and fumonisin B1 (41), the cyanobacterial toxin microcystin LR (42), the fusarium toxin zearalenone (43), and a toxin from the Chinese herbal product Jin Bu Huan (44). Toxins that circulate systemically were thought to enter the small intestine with bile and become bound by CSM, thereby interrupting enterohepatic recirculation and preventing systemic recirculation.…”

Section: Discussionmentioning

confidence: 99%

Possible estuary-associated syndrome: symptoms, vision, and treatment.

Shoemaker

Hudnell

2001

Environ Health Perspect

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The human illness designated as possible estuarine-associated syndrome (PEAS) by the Centers for Disease Control and Prevention (CDC) has been associated with exposure to estuaries inhabited by toxin-forming dinoflagellates, including members of the fish-killing toxic Pfiesteria complex (TPC), Pfiesteria piscicida and Pfiesteria shumwayae. Humans may be exposed through direct contact with estuarine water or by inhalation of aerosolized or volatilized toxin(s). The five cases reported here demonstrate the full spectrum of symptoms experienced during acute and chronic stages of this suspected neurotoxin-mediated illness. The nonspecific symptoms most commonly reported are cough, secretory diarrhea, headache, fatigue, memory impairment, rash, difficulty in concentrating, light sensitivity, burning skin upon water contact, muscle ache, and abdominal pain. Less frequently encountered symptoms are upper airway obstruction, shortness of breath, confusion, red or tearing eyes, weakness, and vertigo. Some patients experience as few as four of these symptoms. The discovery that an indicator of visual pattern-detection ability, visual contrast sensitivity (VCS), is sharply reduced in affected individuals has provided an objective indicator that is useful in diagnosing and monitoring PEAS. VCS deficits are present in both acute and chronic PEAS, and VCS recovers during cholestyramine treatment coincident with symptom abatement. Although PEAS cannot yet be definitively associated with TPC exposure, resolution with cholestyramine treatment suggests a neurotoxin-mediated illness.

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Section: Discussionmentioning

confidence: 99%

Possible estuary-associated syndrome: symptoms, vision, and treatment.

Shoemaker

Hudnell

2001

Environ Health Perspect

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“…The theoretical basis for CSM use in the PEAS cases was that toxin elimination rates can be enhanced through anion-exchange or other binding of CSM with toxins, thereby interrupting the enterohepatic recirculation process through which toxins concentrated in bile are reabsorbed and systemically distributed, leading to toxin elimination. CSM has been used previously for detoxification in case studies or animal models of toxicity, including kepone (21,22), DDE (23), other organochlorine pesticides (24), polychlorinated biphenyl compounds (25), Clostridium dificile toxin (26,27), Escherichia coli and Vibrio cholera toxins (28,29), one or more cytotoxins from at least one unidentified gastrointestinal microorganism (30,31), the mycotoxins ochratoxin A (32,33) and fumonisin B 1 (34), the Fusarium toxin zearalenone (35), the cyanobacterial toxin microcystin LR (36), and a toxin from the Chinese herbal product Jin Bu Huan (37). The plasma halflife of M1, the active metabolite of Arava Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Residential and recreational acquisition of possible estuary-associated syndrome: a new approach to successful diagnosis and treatment.

Shoemaker

2001

Environ Health Perspect

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Evidence suggests that the estuarine dinoflagellates, Pfiesteria piscicida Steidinger & Burkholder and P. shumwayae Glasgow & Burkholder, members of the toxic Pfiesteria complex (TPC), may release one or more toxins that kill fish and adversely affect human health. In the current study we investigated the potential for undiagnosed cases of possible estuary-associated syndrome (PEAS), as termed by the Centers for Disease Control and Prevention (CDC), in a population that had residential and/or recreational exposure to TPC-affected estuaries, but that did not have direct contact with fish kills or lesioned fish. Age-adjusted visual contrast sensitivity (VCS) was significantly lower and the presence of PEAS-associated symptoms was much higher in the estuary cohort (n = 77) than in combined-control cohorts (n = 87), one without exposure to bodies of water (n = 53) and one with exposure to marine waters (n = 34). In the estuary cohort, 37 individuals met the CDC case definition for PEAS and had significantly lower VCS than non-PEAS cases. The VCS improved and symptoms abated after 2 weeks of treatment with cholestyramine. Cholestyramine, the original drug approved for treatment of hypercholesterolemia, has previously been reported to enhance the elimination rates of a variety of toxins, presumably by interruption of enterohepatic recirculation through toxin entrapment in its polymeric structure and/or anion-exchange process. Control studies showed that repeated VCS testing alone did not improve VCS scores and that cholestyramine treatment did not affect VCS in patients with elevated cholesterol levels. These results suggested that a) susceptible individuals may acquire PEAS through residential and/or recreational contact with TPC-affected estuaries in the absence of an active fish kill; b) VCS is a useful indicator in PEAS diagnosis and treatment monitoring; and c) PEAS can be effectively treated with cholestyramine. Because the study did not use population sampling techniques, the results do not indicate PEAS prevalence. Furthermore, definitive diagnosis of PEAS and association with TPC toxin(s) must await identification of, and a serologic test for, the putative TPC toxin(s).

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“…53 Cholestyramine, an anion-exchange resin that was thought to bind C. difficile toxins, has also been used as an adjunct to conventional antibiotic therapy for CDI. Although early case studies 54,55 found that extended courses of cholestyramine were effective in controlling recurrent CDI in children and a cancer patient, the potential affinity of cholestyramine for vancomycin and the relative lack of affinity for C. difficile toxins translate into limited clinical efficacy. During an early study comparing tolevamer with cholestyramine, tolevamer (a novel non-antibiotic toxin binder) exhibited a 16-fold greater ability to block toxin Aemediated enterotoxic activity in rats, and tolevamer was also significantly more effective than cholestyramine in protecting hamsters from C. difficile-related death.…”

Section: Current Interim Recommendationsmentioning

confidence: 99%