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Biomedical subjects

R Fekety

Publications and source records attributed to R Fekety.

At least 19 recordsLinked to original sources

Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea.

Serum immunoglobulin G (IgG) class antibodies directed against toxins A and B of Clostridium difficile were studied using an enzyme-linked immunosorbent assay and a serum-neutralizing assay based on the MRC-5 tissue cytotoxicity assay. Of 185 individuals, 46 sera (24%) in the general population demonstrated IgG antibody, 36 (19.4%) against toxin A and 15 (8.1%) against toxin B. Antibody titer in the general population did not correlate with serum-neutralizing activity. Antibody prevalence fell with age (P = 0.58) over 50 years. Six of ten patients with acute primary episodes of C. difficile-associated diarrhea demonstrated antibody in convalescent-phase sera, predominantly directed against toxin B. Only two (28%) of seven patients with a history of relapsing C. difficile disease had demonstrable antibody.

Adolescent

Diagnosis and treatment of Clostridium difficile colitis.

Pseudomembranous colitis associated with antibiotic therapy is almost always due to an overgrowth of Clostridium difficile. If untreated, pseudomembranous colitis can lead to severe diarrhea, hypovolemic shock, toxic dilatation of the colon, cecal perforation, hemorrhage, and death. However, C difficile-associated colitis can mimic the more common "benign" antibiotic-associated diarrhea that is not caused by C difficile. An algorithm for diagnosis management of hospitalized patients with antibiotic diarrhea and C difficile colitis is presented in this review. Diagnosis depends on sigmoidoscopy and/or stool tests for C difficile toxins in all patients with antibiotic-associated diarrhea. If the results of these tests are positive, either metronidazole or vancomycin is recommended for treatment of mild illness, and vancomycin is recommended for treatment of severe illness. Oral therapy is always preferred because it is more reliable. In patients with recurrent or relapsing colitis, treatment with either metronidazole or vancomycin is effective for that episode, but novel approaches, such as the oral or rectal introduction of competing nonpathogenic organisms, may prove to be more successful in prevention of relapses.

Anti-Bacterial Agents

Evaluation of new anti-infective drugs for the treatment of acute infectious diarrhea. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline includes diarrhea causing infantile mortality in which a bacterial pathogen is recovered and for which oral rehydration therapy is an important component of care as well as traveler's diarrhea (with or without recovery of a pathogen). Diarrhea is defined as the passage of three or more unformed stools per day plus--in all patients except infants--one or more signs or symptoms of enteric infection. The preferred study design is prospective and randomized, with an active concurrent control and (when possible) blinding. Placebo-controlled trials may be performed if the severity of disease is judged by the investigator to be mild or moderate. It is desirable that both clinical and microbiological outcome be determined. Microbiological eradication is paramount.

Acute Disease

Evaluation of new anti-infective drugs for the treatment of typhoid fever. Infectious Diseases Society of America and the Food and Drug Administration.

Typhoid fever is an acute febrile illness caused by Salmonella typhi. The evidence of blood-borne infection required for study entry includes clinical signs and symptoms plus confirmation of the presence of S. typhi in blood or other tissues or body fluids. The preferred study design is prospective and randomized with an active concurrent control. It is preferred that the investigator or an evaluator be blinded to therapy. In general, treatment should be administered for 2 weeks until it is demonstrated that a shorter course is as efficacious and as safe. Follow-up cultures of specimens from sites originally shown to be infected with S. typhi should be performed unless the diagnostic procedure places the patient at unnecessary risk.

Anti-Infective Agents

Evaluation of new anti-infective drugs for the treatment of cholera. Infectious Diseases Society of America and the Food and Drug Administration.

Cholera is an acute gastrointestinal infection caused by Vibrio cholerae. It is characterized by watery diarrhea that may lead to massive fluid loss, which in turn may result in hypotension, shock, and death within hours. Key to the treatment of cholera is fluid replacement. Anti-infective therapy decreases the severity and duration of diarrhea and the duration of shedding of V. cholerae. Enrolled patients should have diarrhea that is moderate to severe and a culture that ultimately yields V. cholerae. A prospective, randomized, active-controlled clinical trial is preferred. Studies should be double-blinded or evaluator-blinded. The rapidity with which the organism is eliminated from stool may be assessed. Both clinical and microbiological outcome should be determined. Assessment of microbiological eradication is paramount, since fluid replacement may suffice for treatment of signs and symptoms.

Anti-Infective Agents

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Giardia lamblia. Infectious Diseases Society of America and the Food and Drug Administration.

Giardia lamblia is a flagellate protozoan that produces symptoms by infecting the small bowel and biliary tract in the trophozoite form. Diagnosis is currently established by microscopic visualization of the organism in appropriate intestinal contents (stool, small-bowel contents, or biopsy specimen). Adult patients with diarrhea and one or more enteric symptoms may be enrolled in clinical trials of new drugs for the treatment of giardial disease. A randomized, double-blind, active-concurrent-control design is recommended. Post hoc stratification by age, immune status, chronicity of disease, and ease of establishing diagnosis (organism load) may be performed. Microbiological assessment 48 hours to 7 days after the completion of therapy is paramount for determining final outcome.

Anti-Infective Agents

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Cryptosporidium. Infectious Diseases Society of America and the Food and Drug Administration.

Cryptosporidium is a coccidian protozoan that produces symptoms by infesting the small bowel. The illness is characterized by watery stools, anorexia, weight loss, and abdominal pain. Diagnosis is made by visualization of the organisms on microscopic examination of stool. There currently is no approved therapy for this infection. A randomized, double-blind, placebo-controlled study design is recommended. Stratification of patients by age and immune status should be considered. Two stool samples obtained 48 hours to 7 days after completion of therapy should be negative for Cryptosporidium oocysts. Assessment of microbiological outcome is paramount.

Adolescent

Evaluation of new anti-infective drugs for the treatment of diarrhea caused by Entamoeba histolytica. Infectious Diseases Society of America and the Food and Drug Administration.

Entamoeba histolytica causes colonic infection that ranges from asymptomatic carriage to invasive disease with infection of extraintestinal organs, particularly the liver. The disease occurs in both sporadic and epidemic forms. Diagnosis requires visualization of trophozoites or cysts by microscopic examination of stool, colonic scrapings, or biopsy specimens. Patients with either asymptomatic or symptomatic disease may be eligible for clinical trials. A prospective, randomized, double-blind, placebo-controlled study design is recommended for asymptomatic carriers and an active-concurrent-control study design for symptomatic patients. Final outcome should be assessed 48 hours to 7 days after completion of therapy. Assessment of microbiological outcome is paramount.

Anti-Infective Agents

Evaluation of new anti-infective drugs for the treatment of chronic carriage of Salmonella. Infectious Diseases Society of America and the Food and Drug Administration.

The chronic carriage of salmonellae is defined as the shedding of a Salmonella species for > or = 1 year, as documented by an initial positive culture of a stool sample obtained at least 1 month after resolution of the acute illness and repeated positive cultures for at least 1 year. Clinical trials of investigational anti-infective drugs for the treatment of the salmonella carrier state may be conducted with a placebo control or an active concurrent control. A crossover design also may be employed for establishing efficacy. Patients should generally receive therapy for at least 6 weeks. Outcome will be assessed only by microbiological criteria. Determination of the interval required for the suppression of salmonellae and follow-up for 6 months after completion of therapy are recommended.

Anti-Infective Agents

Evaluation of new anti-infective drugs for the treatment of antibiotic-associated colitis. Infectious Diseases Society of America and the Food and Drug Administration.

Colitis due to Clostridium difficile is diagnosed in 10%-15% of hospitalized patients who develop diarrhea after treatment with antimicrobial drugs. Diagnosis is based on the concurrence of diarrhea, one or more signs or symptoms of enteric intoxication, and stool from which toxigenic C. difficile is isolated or from which its toxins are identified. Clinical trials evaluating therapy may be placebo controlled (for mild disease) or concurrently controlled with an active drug. A randomized, double-blind study design is preferred. Outcome should be assessed by monitoring of the degree of inflammation of the bowel mucosa, the intensity and severity of diarrhea, the duration of illness, changes in stool form, and the eradication of C. difficile or its toxins from stool. Because C. difficile can be a component of the normal gastrointestinal flora, assessment of clinical outcome is paramount.

Anti-Bacterial Agents

Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Infectious Diseases Society of America and the Food and Drug Administration.

Helicobacter pylori is a gram-negative, microaerophilic, spiral bacillus. Infection by this organism is currently believed to be the major cause of type B gastritis. Inflammation and infection may persist for years in the absence of therapeutic intervention. There is currently no approved antimicrobial therapy for gastritis. Clinical investigations have shown that combination regimens including bismuth salts and antimicrobial drugs result in the relief of symptoms, the resolution of histologic evidence of gastritis, the eradication of H. pylori, high rates of ulcer healing, and lower rates of ulcer relapse than have been found with other therapies (antacids and H2 antagonists). A randomized, double-blind, placebo-controlled study design is recommended for evaluation of new therapies. Study participants should have their progress monitored by endoscopy performed at enrollment, at completion of therapy, and 3 months thereafter. Assessment of microbiological outcome is paramount for final evaluation of the patient.

Anti-Bacterial Agents

In vitro synergy studies with Clostridium difficile.

Agar dilution anaerobic susceptibility studies using rifampin, vancomycin, metronidazole, and bacitracin individually and in combination were performed with Clostridium difficile. Fifty-five strains of C. difficile were studied. Eighty-five percent of strains tested (29 of 34) were synergistically inhibited by the combination of bacitracin and rifampin (fractional inhibitory concentration, less than or equal to 0.50).

Bacitracin

Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens.

PURPOSE: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial. PATIENTS AND METHODS: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days. RESULTS: No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients. CONCLUSION: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill.

Administration, Oral

Clostridium difficile plasmid isolation as an epidemiologic tool.

A large hospital outbreak of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center (MVAMC) was studied by plasmid profile typing. Plasmids were obtained from 30 (37%) of 82 clinical isolates from MVAMC patients and 10 (67%) of 15 non-MVAMC isolates. While bacteriophage plus bacteriocin typing and polyacrylamide gel electrophoresis (PAGE) plus bacterial agglutination typing proved more universally applicable, plasmid profiles may be useful for tracing isolated epidemic outbreaks, reinfections and relapses caused by plasmid-bearing strains.

Bacteriocins

Epidemiology of Clostridium difficile colonization in newborns: results using a bacteriophage and bacteriocin typing system.

We used a typing system based on bacteriophage and bacteriocin susceptibility to study the epidemiology of Clostridium difficile colonization of newborn infants. C. difficile was found in the stools of 30 (16.0%) of 187 infants who were screened. Increased length of stay in the nursery (P less than .001) and delivery by cesarian section (P less than .001) were associated with higher rates of colonization. The isolates initially detected from the environment and the infants were strain B1811-1700. Strain B1537/Cld7 became the predominant isolate obtained from the infants; positive cultures were also obtained from the environment and the hands of personnel who worked in the nursery and had strain B1537/Cld7. Our results suggest that the infants acquired C. difficile through transfer from the hands of hospital staff.

Bacterial Proteins

Acquisition of Clostridium difficile from the hospital environment.

An outbreak of antibiotic-associated colitis that occurred on a ward of a Michigan hospital during February-April, 1984, was studied by bacteriophage-bacteriocin typing. Stools from the seven involved patients yielded Clostridium difficile isolates of types B1537 or Cld7;B1537. C. difficile was recovered from 31.4% of environmental cultures obtained on the ward, and the majority of isolates were types B1537 or Cld7;B1537. When the ward was disinfected with unbuffered hypochlorite (500 parts per million (ppm) available chlorine), surface contamination decreased to 21% of initial levels and the outbreak subsequently ended. Phosphate buffered hypochlorite (1,600 ppm available chlorine, pH 7.6) was even more effective; its use resulted in a 98% reduction in surface contamination. These findings suggest that environmental contamination with C. difficile is important in the epidemiology of antibiotic-associated colitis, and that hypochlorite is effective in eliminating C. difficile from the hospital environment.

Clostridium

The emergence of resistance to ciprofloxacin during treatment of experimental Staphylococcus aureus endocarditis.

The efficacy of ciprofloxacin was compared with that of vancomycin in the rabbit model of methicillin-susceptible Staphylococcus aureus endocarditis. Animals were treated with ciprofloxacin, 25 mg/kg iv every 8 h or vancomycin, 17.5 mg/kg iv every 6 h, for 3, 6, or 9 days. Both drugs were found to be equally effective in the therapy of this infection, but the degree of reduction in bacterial counts was less than expected on the basis of previous studies. Additionally, resistance to ciprofloxacin in the test strain of S. aureus was seen to emerge in 12.5% of animals that received the drug. This raises concern about the use of ciprofloxacin as a single agent in the therapy of humans with serious systemic S. aureus infections.

Animals