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Biomedical subjects

R Fekety

Publications and source records attributed to R Fekety.

At least 37 records · Page 2Linked to original sources

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↗

Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomycin and rifampin.

Seven patients with multiple bacteriologic and symptomatic relapses of Clostridium difficile-associated diarrhea and/or colitis were treated with vancomycin and rifampin in combination. Diarrhea and abdominal pain promptly resolved in all, and neither C. difficile nor its toxin could be recovered from their stools shortly after therapy. However, stools of all patients subsequently became culture-positive for C. difficile and occasionally had demonstrable cytotoxin. Except in one instance following oral antibiotic use, all patients remained free of symptoms. Resistance to either vancomycin or rifampin was not encountered. Biotyping of isolates with clostridial bacteriophages and bacteriocins suggested true relapse with the same organism in all patients studied, rather than reinfection with another strain. Vancomycin and rifampin in combination appear to be useful in the therapy of relapsing antibiotic-associated diarrhea due to C. difficile.

Adult↗

Ciprofloxacin versus vancomycin in the therapy of experimental methicillin-resistant Staphylococcus aureus endocarditis.

We compared the efficacy of ciprofloxacin with that of vancomycin by using the rabbit model of methicillin-resistant Staphylococcus aureus endocarditis. Endocarditis was treated with ciprofloxacin (25 mg/kg [body weight] intravenously every 8 h) or vancomycin (17.5 mg/kg intravenously every 6 h) for 3 days. Vancomycin and ciprofloxacin were equally efficacious in clearing bacteremia. Both reduced vegetation bacterial counts by 5 log10 CFU/g and renal and splenic bacterial counts by more than 3 log10 CFU/g as compared with untreated control rabbits after 26 h of infection (P less than 0.001). Both antimicrobial agents were able to eradicate the infectious process in an equivalent proportion of animals. No methicillin-resistant S. aureus that was recovered from ciprofloxacin-treated rabbits developed resistance to ciprofloxacin during therapy. Peak concentrations of ciprofloxacin in the sera of rabbits with endocarditis were significantly higher than those predicted by single-dose studies in uninfected rabbits. This finding was likely due to changes in the pharmacokinetics of the drug with multiple dosing and in infected versus uninfected rabbits. This study demonstrated that intravenously administered ciprofloxacin is as efficacious as vancomycin is in an in vivo model of a serious systemic methicillin-resistant S. aureus infection.

Animals↗

Altered pharmacokinetic disposition of ciprofloxacin and vancomycin after single and multiple doses in rabbits.

The pharmacokinetic disposition of vancomycin and ciprofloxacin was assessed in rabbits before the efficacy of these compounds in experimental staphylococcal endocarditis was compared. Ciprofloxacin was given in single intravenous bolus doses of 25 and 35 mg/kg and also in a multiple-dose regimen of 35 mg/kg every 6 h. Vancomycin was given in a similar manner in single doses of 17.5 and 25 mg/kg and in a multiple-dose regimen of 17.5 mg/kg every 6 h. Serum was sampled frequently after injections and analyzed by microbiologic assay for drug concentration. The pharmacokinetic parameters of clearance and steady-state volume of distribution were calculated by compartment-independent methods. These studies revealed that clearance of ciprofloxacin was reduced significantly after multiple doses (7.42 +/- 0.85 [standard deviation] versus 6.09 +/- 0.71 liters/h, P less than 0.01). Although the half-life and volume of distribution increased after multiple dosing, the differences were not statistically significant. The disposition of vancomycin following single doses was significantly altered after the 25-mg/kg dose compared with the 17.5-mg/kg dose. Half-life, clearance, and volume of distribution changed from 1.27 +/- 0.2 to 1.60 +/- 0.21 h (P less than 0.05), 0.54 +/- 0.05 to 0.39 +/- 0.04 liters/h (P less than 0.01), and 0.37 +/- 0.04 to 0.31 +/- 0.03 liters/kg (P less than 0.05), respectively. The disposition of ciprofloxacin was not altered with increases in dose size, and the disposition of vancomycin was not altered after multiple doses. If such alterations in the pharmacokinetic disposition of antimicrobial agents are unanticipated, the higher and more prolonged than expected serum concentrations may have an effect on the outcome of experimental infections.

Animals↗

Effects of topical clindamycin on intestinal microflora in patients with acne.

Thirty-two patients with acne completed a randomized, double-blind study using topical 1% clindamycin phosphate or its vehicle applied twice daily for 8 weeks for a study of its effects on the intestinal microflora. Two clindamycin patients and one vehicle patient had Clostridium difficile in stools prior to therapy. Of the remaining twenty-nine patients, four of nineteen patients who used clindamycin and none of ten patients who used vehicle had C. difficile detected during treatment; the difference was not statistically significant. There was no diarrhea in the clindamycin group, even though clostridial cytotoxin was found transiently in two patients. Self-limited diarrhea occurred in one vehicle-treated patient, whose stool culture was negative but whose stool specimen showed a positive reaction for C. difficile cytotoxin. With the use of a bioassay, clindamycin was not detected in urine or stool of any patient. No significant changes in Bacteroides fragilis counts in stools were observed in either group.

Acne Vulgaris↗

Persistent staphylococcal bacteremia in an intravenous drug abuser.

A patient with methicillin-resistant Staphylococcus aureus bacteremia received vancomycin (MIC = 0.8 microgram/ml, MBC = 15 micrograms/ml) and heparin simultaneously through the same intravenous line to treat a septic deep venous thrombosis. Bacteremia persisted for 7 days. Bacteremia terminated when the simultaneous infusion of heparin and vancomycin through the same line was stopped. This suggested that an interaction between vancomycin and heparin may have occurred, which resulted in a reduction in vancomycin activity. To test for such an interaction, mixtures of heparin and vancomycin in various concentrations were made and tested for antimicrobial activity against the organisms in the patient. A precipitate formed at the concentrations achieved in the intravenous lines, and when the vancomycin concentrations were measured by bioassay, a 50 to 60% reduction in activity was noted. In contrast, when these solutions were prepared and mixed at microgram concentrations, a precipitate was no longer observed, and antimicrobial activity was not reduced. Heparin appeared to interact unfavorably with vancomycin at the concentrations in the intravenous lines when these drugs were administered simultaneously to patients. This may be the cause of poor therapeutic responses to vancomycin in some patients, especially those infected with tolerant organisms.

Adult↗

In-vitro activity of Sch 34343 against nosocomial pathogens: methicillin-resistant staphylococci, gentamicin-susceptible and -resistant Streptococcus faecalis, Clostridium difficile and Bacteroides fragilis.

The in-vitro activity of Sch 34343, a new beta-lactam antimicrobial, was studied in vitro by quantitative broth dilution methods. It was found to have good antibacterial activity against four emerging problem pathogens: methicillin-resistant Staphylococcus aureus, Streptococcus faecalis isolates showing high level resistance to gentamicin (and other aminoglycosides), Clostridium difficile (the cause of pseudomembranous colitis), and Bacteroides fragilis. On the basis of these promising results, Sch 34343 merits further in-vitro and in-vivo study to define its potential usefulness in treatment of infections with these pathogens in humans.

Anti-Bacterial Agents↗

Effect of adding sodium taurocholate to selective media on the recovery of Clostridium difficile from environmental surfaces.

The recovery of Clostridium difficile on a medium containing cefoxitin, cycloserine, fructose, and egg yolk was compared with that on media containing one of three preparations of sodium taurocholate. In aerobic environments contaminated with C. difficile, media containing either crude taurocholate from Mann Research Laboratories, New York, N.Y., or pure taurocholate from Sigma Chemical Co., St. Louis, Mo., recovered organisms significantly more often than did cefoxitin-cycloserine-fructose-egg yolk agar.

Clostridium↗

Epidemiology of colitis induced by Clostridium difficile in hamsters: application of a bacteriophage and bacteriocin typing system.

The epidemiology of colitis induced by Clostridium difficile in hamsters was studied with a new bacteriophage and bacteriocin typing system. Fatal enterocolitis was induced by administration of N-formimidoyl thienamycin. Environmental cultures were obtained repeatedly throughout the experiments. Thirteen percent of 90 healthy hamsters were already colonized with C difficile on arrival from the supplier. Mortality from enterocolitis after antibiotic administration was 75% and was not diminished by use of a laminar-flow facility. The same uncommon bacteriocin type (83/1309/2329) of toxigenic C difficile that colonized hamsters on arrival was recovered from the cecal contents of all hamsters dying with enterocolitis and from most environmental isolates. Previously uncolonized , antibiotic-treated hamsters placed into cages where animals had died from enterocolitis also developed enterocolitis with the same bacteriocin type (83/1309/2329), an outcome suggesting acquisition of C difficile from the environment.

Animals↗

Effect of therapy with latamoxef (moxalactam) on carriage of Clostridium difficile.

Twenty-seven patients receiving latamoxef (moxalactam) as a single antimicrobial agent were studied prospectively for Clostridium difficile carriage and development of diarrhoea or colitis. Stools were available prior to therapy from only seven patients, one of whom (14.3%) was an asymptomatic carrier. None of twelve patients studied during therapy were carriers. Seven of 27 patients (25.9%) were colonized with Cl. difficile after completion of latamoxef therapy, and three patients had cytotoxin positive stools. Two patients with cytotoxin grew Cl difficile from stools and one patient was culture negative. Only one patient, who had both culture and cytotoxin positive stools, had profuse diarrhoea. Cl. difficile clinical isolates were only moderately susceptible to latamoxef in vitro. Hamsters given moxalactam developed caecitis. Patients receiving latamoxef, or third generation cephalosporins, may be at increased risk of development of Cl. difficile associated diarrhoea and should be followed closely for this complication, especially after therapy has been discontinued.

Animals↗

Treatment of antibiotic-associated colitis with vancomycin.

Sixty-five patients were treated with oral vancomycin for Clostridium difficile colitis associated with treatment of infection by antibiotics. Colitis was confirmed by endoscopy in patients with diarrhoea and positive tests on diarrhoeal stools for Cl. difficile and/or its cytotoxin or, if endoscopy could not be performed, by the presence of fever and peripheral or faecal leucocytosis. Vancomycin dosage ranged from 125 to 500 mg four times daily for an average of about ten days. The mean duration of diarrhoea after starting therapy was four days; abdominal pain and fever usually resolved in two or three days. Post-treatment carriage of Cl. difficile was common. Eighteen per cent of patients developed a recurrence of colitis after treatment was discontinued, but responded to treatment with oral vancomycin, metronidazole, or bacitracin. After comparison of our results with those reported by others we concluded that vancomycin remains the treatment of choice for patients who are acutely and severely ill with Cl. difficile.

Adult↗

Factors affecting survival in prosthetic valve endocarditis. Review of the effectiveness of prophylaxis.

We review factors affecting survival of 44 episodes of prosthetic valve endocarditis occurring in 39 patients from 1965 to 1982. The mortality was 31.8 percent (14/44), and 21.6 percent (8/37) if the fungal cases are excluded. The development of a new murmur of valvular regurgitation in 18 patients led to valve replacement or death in every patient. Streptococcal endocarditis in 11 patients resulted in no deaths and only two valve replacements; staphylococcal infections had a mortality of 27.1 percent (6/22). Length of medical therapy before valve replacement did not relate to a successful outcome. Eight cases of early staphylococcal endocarditis occurred in which the organism was susceptible to the prophylactic antibiotic therapy. Changes in prophylaxis have led to no cases of early endocarditis over the past three years in 261 valve replacements.

Adult↗