Biomedical subjects
Publications and source records attributed to C M Surawicz.
Chronic diarrhea can be seen in association with specific pathogens, usually parasites and occasionally some bacteria. This article reviews pathogens causing chronic diarrhea in immunocompetent individuals and provides a rational diagnostic approach.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.
Between 1980 and 1993, collagenous colitis was diagnosed in 56 patients at UCLA. These authors evaluated the histology of almost 300 biopsies from these patients to further clarify the relationship between diagnostic histology and site of biopsy. As expected, their patients were predominately women (71%), with a mean age at diagnosis of 59 yr. Chronicity of diarrheal symptoms ranged from 3 months to 15 yr. Diagnostic subepithelial collagen thickness was variable throughout the colon. The highest yield was in transverse colon (83%), right colon (70%), and lowest in rectosigmoid (66%). Diagnostic collagen thickness was >15 microm in most biopsies, but was detected most readily when >30 microm--a threshold the authors suggest increases the diagnostic com-fort level. They recommend flexible sigmoidoscopy as adequate for diagnosis of most patients with collagenous colitis, noting colonoscopy is often used to clarify diagnosis, i.e., when only mild or focal colitis is seen distally.
Explore the source record for details and available documents.
Clostridium difficile is the most common nosocomial infection of the gastrointestinal tract. Most cases are associated with antibiotic therapy that alters the fecal flora, allowing overgrowth of C difficile with production of its toxins. Diagnosis is made by detection of the organism or toxin in the stools. A variety of different tests can be used, but none is perfect. A stool culture can be positive in someone without diarrhea, ie, a carrier. While the cytotoxin is the gold standard, it is expensive, and there is a delay before results are available. Thus, many laboratories use the enzyme-linked immunoassay tests to detect toxin of C difficile because they are a more rapid screen. Depending on the specific test used, they can detect toxin A, toxin B or occasionally both. Sensitivity and specificity rates vary. First line therapy for C difficile disease should be metronidazole 250 mg qid for 10 days. Vancomycin should be reserved for severe cases where metronidazole has failed or where metronidazole cannot be tolerated or is contraindicated. Recurrent C difficile disease is a particularly vexing clinical problem. A variety of biotherapeutic approaches have been used. Retreatment with antibiotics is almost always necessary. In addition, the nonpathogenic yeast Saccharomyces boulardii has been showed to be of benefit as an adjunct in preventing further recurrences.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations of Saccharomyces boulardii in a patient population with Clostridium difficile disease (CDD) and correlates stool concentrations with efficacy. METHODS: Patients with recurrent CDD all received a 10-day standard antibiotic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. boulardii. RESULTS: The mean concentration of S. boulardii of patients who recurred was 2.5 x 104 CFU/g compared to 1 x 106 CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% had positive stools 3 days after stopping dosing. CONCLUSIONS: After chronic dosing of S. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.
Explore the source record for details and available documents.
OBJECTIVE: To describe the epidemiology, diagnosis, risk factors, patient impact, and treatment strategies for recurrent Clostridium difficile-associated disease (CDAD). DESIGN: Data were collected as part of a blinded, placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD. Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review. Prospective data on the current CDAD episode, risk factors, and recurrence rates were collected during a 2-month follow-up. SETTINGS: National referral study. PARTICIPANTS: Patients with recurrent CDAD. INTERVENTIONS: Treatment with a 10-day course of low-dose (500 mg/d) or high-dose (2 g/d) vancomycin or metronidazole (1 g/d). RESULTS: Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea, abdominal cramping, nausea, and fever. CDAD may recur over several years despite frequent treatment with antibiotics. Recurrence rates were similar regardless of the choice or dose of antibiotic. Recurrent CDAD is not a trivial disease: patients may have multiple episodes (as many as 14), may require hospitalization, and the mean lifetime cost of direct medical care was $10,970 per patient. Fortunately, the disease does not become progressively more severe as the number of episodes increase. Two risk factors predictive for recurrent CDAD were found: increasing age and a decreased quality-of-life score at enrollment. CONCLUSIONS: Recurrent CDAD is a persistent disease that may result in prolonged hospital stays, additional medical costs, and rare serious complications.
Explore the source record for details and available documents.
A possible etiologic role for mycobacteria in Crohn's disease has been the subject of much investigation. This paper critically reviews the literature exploring 4 major areas: (1) attempts to culture mycobacteria from intestinal specimens; (2) indirect detection of organisms in intestinal specimens by techniques including immunohistochemistry, nucleic acid hybridization and polymerase chain reaction; (3) detection of serum antibodies to mycobacteria, and (4) results of antimycobacterial drug trials in treating patients with Crohn's disease. While the evidence does not support an etiologic role for mycobacteria in Crohn's disease, newer techniques may change this conclusion.
OBJECTIVE: To identify risk factors for the detection of prevalent and incident anal human papillomavirus (HPV) infection, and HPV persistence among HIV-seropositive and seronegative homosexual men. DESIGN: Longitudinal study of 287 HIV-seronegative and 322 HIV-seropositive men attending a community-based clinic. METHODS: Subjects underwent an interview and examination; specimens were collected for HIV serology and assessment of anal HPV and HIV DNA. RESULTS: Anal HPV DNA was detected at study entry in 91.6% of HIV-infected men, and 65.9% of men not infected with HIV. HPV detection was associated with lifetime number of sexual partners and recent receptive anal intercourse (HIV-seronegative men), decreased CD4+ lymphocyte count (HIV-seropositive men), and anal warts (all men). Among men negative for HPV at study entry, subsequent detection of HPV was associated with HIV, unprotected receptive anal intercourse, and any sexual contact since the last visit. Among men positive for HPV at study entry, subsequent detection of additional HPV types was more common among HIV-seropositive men. Becoming HPV negative during follow-up was less common among men with HIV or high HPV levels at study entry. Among those with HIV, HPV persistence was associated with presence of anal HIV DNA, but not with CD4+ lymphocyte count. CONCLUSIONS: Risk of anal HPV infection appears to increase with sexual exposure, epithelial trauma, HIV infection and immune deficiency. Incident infection may result from recent sexual exposure or reactivation of latent infection. Further studies are needed to elucidate the mechanism by which HIV DNA in the anal canal increases the risk of HPV persistence.
Explore the source record for details and available documents.
Clostridium difficile is the most common nosocomial pathogen of the gastrointestinal tract. Disease is usually a consequence of antibiotic therapy, but sporadic cases do occur. Cytotoxin assay for toxin B remains the gold standard for confirming diagnosis. Several rapid enzyme immunoassay tests are available, but specificity and sensitivity vary; a negative test may not exclude disease. Oral metronidazole 250 to 500 mg four times a day is the recommended first-line therapy; vancomycin (125 mg four times a day) should be reserved for patients who cannot tolerate metronidazole, who do not respond to this drug, or who should not take it for various reasons (i.e., pregnancy). Recurrent C. difficile disease is a difficult problem. The nonpathogenic yeast Saccharomyces boulardii has been shown in controlled trials to be effective in reducing recurrences when given as an adjunct to standard therapy. Prevention of epidemics relies on careful hand washing and environmental decontamination.
Recurrent Clostridium difficile diarrhea (RCDD) occurs in 20% of patients after they have received standard antibiotic treatment with vancomycin or metronidazole, but the reasons for the recurrences are largely unknown. Patients receiving vancomycin or metronidazole for active C. difficile diarrhea (CDD) were referred to our study centers for treatment and a 2-month follow-up as part of a randomized placebo-controlled trial. Sixty patients had RCDD (median number of episodes, 3.0; range, 2-9 episodes) and 64 were having their first episode of CDD. Patients with RCDD had more-severe abdominal pain and were more likely to have fever but initially responded well to antibiotic therapy. Data on sequential episodes showed no progression in disease severity. Five factors were associated with a higher risk of RCDD: the number of previous CDD episodes, onset of the initial disease in the spring, exposure to additional antibiotics for treatment of other infections, infection with immunoblot type 1 or 2 strains of C. difficile, and female gender. These factors may help to identify patients who are more likely to develop RCDD and require careful medical supervision.