A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium djffcile-associated diarrhea (CDAD) was performed.Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. dfficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%o) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%o) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11). Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P = 0.059) appeared not to be cleared of C. diffcile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed.
A total of 108 volunteers undergoing an elective surgical procedure were randomly given a single 2-g intravenous prophylactic dose of either a cephalosporin or mezlocillin. Stool samples were cultured for Clostridium difficile the day before the operation and later on postoperative days 4, 7, and 14. C. difficile was detected in 23.0% of patients who received a cephalosporin (cefoxitin, 8.3%; cefazolin, 14.3%; cefotetan, 20.0%; ceftriaxone, 25.0%; cefoperazone, 43.7%), in 3.3% of patients given mezlocillin, and in none of 15 control volunteers given no antimicrobial agent. No patient experienced diarrhea.
Pegylated interferon (Peg-IFN) plus ribavirin is the standard treatment for patients with chronic hepatitis C. In a multicenter open trial, we assessed the efficacy and tolerability of this treatment in 78 HIV negative hemophiliacs (age: 20–64 years) with persistently high transaminase values. Sixty-four were naïve and 14 were relapsers to IFN monotherapy. Cirrhosis was clinically detected in 12 patients (15%). HCV genotype was 1 in 69%, 2a/c in 14%, 3a in 14% and 4 in 3%. Peg-IFN alpha-2b was given subcutaneously at doses of 1.5 mcg/Kg/week for 48 weeks in genotypes 1 and 4 and for 24 weeks in genotypes 2 and 3; oral ribavirin at 800–1200 mg/day based on body weight. Treatment was stopped in patients with polymerase chain reaction positive HCV-RNA at month 6. Results: 11 patients (14%) withdrew for side effects (4) or non-compliance (7). Neutropenia (<500 cells/mmc), decompensated diabetes, ALT flares, and vomiting not responding to antiemetic drugs were reasons for treatment discontinuation. The median fall in hemoglobin levels was 3.1 g/dL. Weight loss (38%), fatigue (33%) and cephalalgia (15%) were frequent side effects. Thirty-two patients (41%) required dose reduction of ribavirin (23, 29%) or Peg-IFN (20, 26%). At the end of the 6-month follow-up, sustained virological response (SVR) was achieved in 43 patients (55%): 40/64 naïve (63%) and 3/14 relapsers (21%, p = 0.007). Five patients (6%), all relapsers to IFN monotherapy, had a virological breakthrough during treatment and 4 (5%) relapsed during the post-treatment follow-up period. SVR was obtained in 86% genotypes 2/3 and 43% genotypes 1/4 (p = 0.001). Predictors of SVR were evaluated by univariate analysis in the 64 naïve patients. SVR was significantly associated with HCV infection type 2 and 3 (86% vs 50% in HCV type 1 and 4; p = 0.008), absence of cirrhosis (97.5% vs 75% in non-responders; p = 0.02) and higher pre-treatment serum ALT levels (111 vs 75 IU/L in non-responders; p = 0.02). SVR rates did not differ in relation to patient’s age, pretreatment HCV viremia, median disease duration and compliance to full-dose treatment. Conclusions: combination therapy with Peg-IFN plus ribavirin is the recommended therapeutic option for hemophiliacs with hepatitis C chronic infection. Relapsers to IFN monotherapy may benefit of re-treatment with Peg-IFN plus ribavirin achieving at least 20% SVR. Genotype 2 and 3 infection is the most significant predictor of SVR.
A combination of clarithromycin, ciprofloxacin, and amikacin for the treatment of Mycobacterium avium-Mycobacterium intracellulare bacteremia was evaluated in 12 AIDS patients. Mycobacteremia cleared in all patients by 2 to 8 weeks of treatment, and symptoms resolved. Four patients died; all had negative blood cultures until death, and disseminated M. avium-M. intracellulare complex infection was not considered the primary cause of death.Mycobacterium avium-Mycobactenium intracellulare complex (MAC) infection is one of the most common systemic bacterial infections complicating AIDS. It has been cultured during life from as many as 34% of AIDS patients (8), and according to recent studies, 40 to 50% of all patients with AIDS appear to be infected (6). Moreover, many studies show that disseminated MAC infection is a major cause of illness and makes a substantial contribution to the death of these patients (3).Early reports on the effect of treatment were discouraging, with persistent bacteremia despite therapy. Recent trials with newer antimicrobial agents have met with only limited success (6,13,19), and at present, the most effective therapeutic regimen is unknown.Clarithromycin, a new macrolide antibiotic structurally related to erythromycin, has recently been found to have, in vitro, favorable activities against MAC isolates, inhibiting 90% of strains at a MIC of 1 to 8 p,g/ml (1,5,11,14,18). It has also been shown to concentrate inside macrophages and tissues (4,5,(15)(16)(17) and to be more acid stable than erythromycin. For these reasons, concentrations lower than the MIC might in vivo be as effective as the higher ones. It is, moreover, possible that clarithromycin, though more active in vitro at a physiologic pH than at an acid pH (18), would remain active for a long period of time in the acid environment of the phagolysosome.Clinical experience with clarithromycin in MAC-infected AIDS patients is lacking. A prospective, double-blind, placebo-controlled trial in disseminated MAC infection has recently been reported by Dautzenberg et al. (2). In this study MAC disappeared from the blood cultures of seven of eight clarithromycin-treated patients. Five of these patients were cleared of mycobacteria after 2 weeks of treatment, and the other two were cleared after 4 weeks. By contrast, MAC increased in the five patients who received the placebo.According to some authors, another two compounds, ciprofloxacin and amikacin, have nowadays been recognized * Corresponding author. to have a good anti-MAC activity both in vitro and in experimental infection (7, 9-11).We report the results of a pilot study on the value of a triple combination of clarithromycin, ciprofloxacin, and amikacin in the treatment of AIDS patients with persistent MAC bacteremia.In the period from October 1989 to July 1990 patients admitted to the Infectious Diseases Departments of Vicenza and Pavia Hospitals were included in the study if (i) human immunodeficiency virus antibodies and at least two pretherapy MAC cultures from blood were positiv...
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