ru-66647 and Pharyngitis

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

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

Telithromycin is the first member of a new family of the macrolide-lincosamide-streptogramin-B (MLS(B)) class of antimicrobials, the ketolides. It has a good spectrum of activity against respiratory pathogens, including penicillin- and erythromycin-resistant pneumococci, as well as intracellular and atypical bacteria. Furthermore, it has a low potential to select for resistance or induce cross-resistance among other MLS(B) antimicrobials. At the recommended dosage of 800 mg orally once daily, telithromycin reaches maximal plasma concentrations of about 2 mg/L. It penetrates rapidly into bronchopulmonary, tonsillar, sinus and middle ear tissues and/or fluids and achieves high concentrations at sites of infection. It also concentrates within polymorphonuclear neutrophils. In clinical trials in patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) or pharyngitis/tonsillitis caused by group A beta-haemolytic streptococci, telithromycin 800 mg once daily achieved clinical cure rates of 86 to 95%. In acute maxillary sinusitis (AMS), cure rates were 73 to 91%. A 7- to 10-day regimen of telithromycin was as effective as a 10-day course of amoxicillin 1000 mg 3 times daily, clarithromycin 500 mg twice daily or a 7- to 10-day course of trovafloxacin 200 mg once daily for treating CAP. A 5-day regimen of telithromycin was as effective as a 10-day regimen of cefuroxime axetil 500 mg twice daily or amoxicillin/clavulanic acid 500/125 mg 3 times daily in AECB. A 5-day regimen of telithromycin was as effective as a 10-day regimen of clarithromycin 250 mg twice daily or phenoxymethylpenicillin 500 mg 3 times daily in pharyngitis/tonsillitis, or a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg 3 times daily in patients with AMS. Telithromycin was well tolerated across all patient populations. Adverse events associated with telithromycin were generally mild to moderate in intensity and seldom led to treatment discontinuation. The most frequent adverse events were diarrhoea (13.3%) and nausea (8.1%). Other adverse events included dizziness and vomiting.

Topics: Anti-Bacterial Agents; Bronchitis; Clinical Trials as Topic; Drug Interactions; Humans; Ketolides; Macrolides; Maxillary Sinusitis; Pharyngitis; Pneumonia, Bacterial