ru-66647 and Tonsillitis

Topics: Anti-Bacterial Agents; Bronchitis; Clinical Trials as Topic; Humans; Ketolides; Macrolides; Pharyngitis; Pneumonia, Bacterial; Respiratory Tract Infections; Sinusitis; Tonsillitis

A pooled analysis of two double-blind, multicentre, Phase III studies compared oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus; GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS tonsillopharyngitis were randomised to receive telithromycin (n = 430), penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S. pyogenes (n = 590) obtained from throat swab samples on study entry were tested for their in-vitro susceptibility to telithromycin, clarithromycin and azithromycin. Telithromycin demonstrated in-vitro activity against the clinical isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively), including erythromycin-resistant strains. At the post-therapy/test of cure (TOC) visit (days 16-23), satisfactory bacteriological outcome was demonstrated for 88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated patients, respectively (per-protocol population). Overall, GABHS eradication rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6% (248/265) and 90.9% (220/242) for telithromycin and pooled comparators, respectively. Telithromycin was generally well-tolerated. Most adverse events considered to be possibly related to study medication were gastrointestinal and of mild intensity. Discontinuations as a result of adverse events were few in both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days was as effective as penicillin V or clarithromycin for 10 days in the treatment of GABHS tonsillopharyngitis.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Clarithromycin; Female; Humans; Infant; Ketolides; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin V; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

Telithromycin, a ketolide antibacterial, has been developed for the treatment of community-acquired respiratory infections.. This study compared the efficacy and tolerability of 5-day, once-daily telithromycin with 10-day, twice-daily clarithromycin in adolescents and adults with acute tonsillitis/pharyngitis caused by group A beta-hemolytic streptococci ([GABHS] Streptococcus pyogenes).. In this multicenter, randomized, double-blind, parallel-group study, adolescent (aged > or = 13 years) and adult patients with a diagnosis of GABHS tonsillitis/pharyngitis received once-daily telithromycin 800 mg for 5 days (followed by placebo for 5 days) or twice-daily clarithromycin 250 mg for 10 days. Bacteriologic and clinical outcomes were assessed at a test-of-cure visit (days 16 to 23) and a late posttherapy visit (days 31 to 45).. A total of 526 patients were enrolled in the study, of which 463 (288 females, 175 males) were randomized to receive treatment (telithromycin, n = 232; clarithromycin, n = 231). The mean age of the telithromycin group was 30.9 years; in the clarithromycin group, it was 30.0 years. Bacterial eradication was achieved in 91.3% of telithromycin-treated patients and 88.1% of clarithromycin recipients (difference, 3.2%; 95% CI, -4.5 to 11.0). Clinical cure was achieved in 92.7% of telithromycin recipients and 91.1% of clarithromycin-treated patients (difference, 1.6%; 95% CI, -5.5 to 8.6). Bacteriologic and clinical cures for the 2 treatment groups also were similar at the late posttherapy visit. Treatment-related adverse events occurred more frequently in the telithromycin group than the clarithromycin group (67.2% vs 57.5%, respectively); diarrhea, nausea, and vomiting were significantly more common with telithromycin than with clarithromycin (P = 0.004, 0.010, and 0.001, respectively). Adverse events were generally mild.. This study demonstrates that telithromycin 800 mg once daily for 5 days was an effective and generally well-tolerated treatment for tonsillitis/pharyngitis caused by GABHS, providing similar bacteriologic and clinical efficacy to clarithromycin 250 mg twice daily for 10 days in the per-protocol population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clarithromycin; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Ketolides; Macrolides; Male; Middle Aged; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

This study compared the resolution of symptoms in patients with group A beta-hemolytic streptococcus tonsillopharyngitis treated with 5 d of telithromycin 800 mg once daily, or 10 d of penicillin V 500 mg 3 times daily. At days 3-5 of treatment, the mean improvement in total symptom score was greater with telithromycin than with penicillin V (p = 0.042). Thus, telithromycin provided faster symptom relief than penicillin V.

Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Ketolides; Macrolides; Male; Patient Satisfaction; Penicillin V; Pharyngitis; Probability; Severity of Illness Index; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

This randomized, double-blind study compared the efficacy and safety of a 5-d course of the new ketolide antimicrobial, telithromycin, with those of a standard 10-d course of penicillin V (phenoxymethylpenicillin) in patients with group A beta-hemolytic streptococci (GABHS) pharyngitis/tonsillitis. Patients aged 15-65 y (n = 395) with clinical signs and symptoms of pharyngitis/tonsillitis and a positive streptococcal antigen test or throat culture for GABHS were randomized to receive either telithromycin 800 mg once daily for 5 d (n = 198) or penicillin V 500 mg three times daily for 10 d (n = 197). Clinical and bacteriologic outcomes were assessed at post-therapy, test-of-cure (Days 16-20) and late post-therapy (Days 38-45) visits. Telithromycin for 5 d was equivalent to 10 d of penicillin V in terms of bacteriologic and clinical outcome (per-protocol): at post-therapy, test-of-cure visit, bacteriologic outcome was satisfactory in 84.3% and 89.1% of patients in the telithromycin and penicillin V groups, respectively, while clinical cure was achieved in 94.8% and 94.1% of patients, respectively. At late post-therapy, 82.4% of patients treated with telithromycin achieved a satisfactory bacteriologic outcome, compared with 84.7% of penicillin V recipients. The GABHS eradication rates for telithromycin and penicillin post-therapy were 85.2% and 89.1%, respectively, and 86.1% and 86.5%, respectively at late post-therapy. Both treatments were well tolerated, with a similar overall incidence of treatment-emergent adverse events. Short-course (5 d) therapy with telithromycin 800 mg once daily is comparable to a standard 10 d course of penicillin V for the treatment of GABHS pharyngitis/tonsillitis in adults and adolescents.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Double-Blind Method; Europe; Female; Humans; Ketolides; Macrolides; Male; Middle Aged; Penicillin V; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Treatment Outcome

Since the late 1990s, the prevalence of erythromycin-resistant Streptococcus pyogenes has significantly increased in several European countries. Between January 1999 and December 2002, 1,577 isolates of S. pyogenes were recovered from children with tonsillopharyngitis living in various areas of Western Greece. Erythromycin resistance was observed in 379 (24%) of the 1,577 isolates. All erythromycin-resistant strains along with 153 randomly selected erythromycin-susceptible S. pyogenes isolates were tested for their antimicrobial susceptibility, resistance phenotypes, and genotypes. Representative isolates underwent emm gene sequence typing. Isolates with reduced susceptibility to telithromycin (MIC, > or = 2 microg/ml) were studied for multilocus sequence type, L22, L4, and 23S rRNA mutations. Of the total 379 erythromycin-resistant isolates, 193 (50.9%) harbored the mef(A) gene, 163 (43%) erm(A), 1 (0.3%) mef(A) plus erm(A), and 22 (5.8%) the erm(B) gene. Among the erythromycin-susceptible isolates, emm 1 (25%), emm 2 (12.5%), and emm 77 (12.5%) predominated. Furthermore, among the erythromycin-resistant isolates, emm 4 (30.6%), emm 28 (22.2%), and emm 77 (12.5%) prevailed. Resistance to telithromycin was observed in 22 (5.8%) of the erythromycin-resistant isolates. Sixteen (72.7%) of the 22 isolates appeared to be clonally related, since all of them belonged to emm type 28 and multilocus sequence type 52. One of the well-known mutations (T2166C) in 23S rRNA, as well as a new one (T2136C), was detected in erythromycin- and telithromycin-resistant isolates. High incidence of macrolide resistance and clonal spread of telithromycin resistance were the characteristics of the Greek S. pyogenes isolates obtained from 1999 to 2002.

Topics: Acute Disease; Child; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Genotype; Greece; Humans; Ketolides; Pharyngitis; Phenotype; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis