ru-66647 and Maxillary-Sinusitis

To compare the efficacy and tolerability of a 5-day course of telithromycin (800 mg once daily) with a 10-day course of telithromycin or standard comparators (amoxicillin-clavulanate 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily) in patients with acute maxillary sinusitis (AMS).. Data from three randomised double blind studies were pooled. The studies included patients with clinical symptoms of AMS and sinus X-ray findings of total opacity, air-fluid levels or mucosal thickening.. Pooled analysis of results for 5-day telithromycin revealed overall clinical cure rates of 83.6% (383/458 patients) at post-therapy (days 17-24) and 78.9% (330/418 patients) at late post-therapy (days 31-45) in the per-protocol population. Clinical cure rates at post-therapy were equivalent to those observed with 10-day telithromycin (82.5% vs 81.7%) or comparator treatment (80.9% vs 77.4%). Moreover, clinical cure rates exceeded 80% in subgroups of patients of interest, including those with severe infection and those fulfilling more stringent criteria for bacterial AMS. A satisfactory bacteriological outcome was achieved in 87.6% of patients. The 5-day telithromycin regimen was well tolerated.. Telithromycin once daily for 5 days offers effective treatment for AMS and is comparable to 10-day courses of standard treatments.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefuroxime; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged

Telithromycin, the first approved ketolide antibiotic, was developed to treat community-acquired respiratory tract infections, including acute bacterial maxillary sinusitis (ABMS). A previously published study showed that a 5-day course of 800 mg telithromycin once daily is as effective as a 10-day course in the treatment of ABMS.. Data were pooled from two controlled, multinational, prospective, randomized, double-blinded ABMS trials comparing 5-day telithromycin (800 mg once daily) with 10-day amoxicillin-clavulanate (500/125 mg 3 times daily) and cefuroxime axetil (250 mg twice daily). Clinical cure and bacteriologic eradication rates were compared by means of descriptive statistics.. The clinical cure rate for telithromycin was 80.9% versus 77.4% for comparators; bacteriologic eradication rate for telithromycin was 84.9% versus 81.7% for comparators. Most adverse events were mild to moderate in intensity and, most commonly, gastrointestinal in nature.. These results support the conclusion that 5 days of treatment with telithromycin is as safe and effective in patients with ABMS as a 10-day course of treatment with amoxicillin-clavulanate or cefuroxime axetil.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefuroxime; Double-Blind Method; Drug Administration Schedule; Female; Haemophilus influenzae; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Prospective Studies; Randomized Controlled Trials as Topic; Staphylococcus aureus; Streptococcus pneumoniae

To explore the efficacy of the ketolide telithromycin compared with azithromycin in eradicating S pneumoniae from the nasopharynx of adults with acute maxillary sinusitis. The growing resistance of Streptococcus pneumoniae to penicillin and macrolides brought about the development of a new class of antibiotics-the ketolides-that are effective against resistant pneumococci.. Otolaryngology clinic.. One-hundred five patients with acute maxillary sinusitis.. Nasopharyngeal cultures were obtained before therapy and 10 to 12 days after initiation of treatment. Fifty-nine patients were treated with 500 mg of azithromycin daily for 3 days and 46 were treated with 800 mg of telithromycin daily for 5 days.. Sixty-seven potential pathogens were recovered prior to initiation of therapy in 57 patients, 32 treated with telithromycin and 25 treated with azithromycin: S pneumoniae (31 isolates), Haemophilus influenzae (non-type b) (13), Staphylococcus aureus (8), Streptococcus pyogenes (8), and Moraxella catarrhalis (7). The distribution of the pathogens was similar in both groups. The number of S pneumoniae isolates in the azithromycin group was reduced following treatment from 14 to 8 (43% reduction), and 5 of these 8 isolates were resistant to azithromycin. In contrast, the number of S pneumoniae isolates in the telithromycin group was reduced following treatment from 17 to 1 (94% reduction) (P < .01). This isolate was susceptible to azithromycin and telithromycin. No differences were noted in the eradication rate of all of the other potential pathogens, which were all susceptible to both azithromycin and telithromycin. Development of resistance to the antimicrobial agents used (defined as increase in the minimal inhibitory concentration by at least 2 tubes) was found only in 5 isolates (4 S pneumoniae and 1 H influenzae) recovered only from patients who received azithromycin (P < .05).. These data illustrate the superiority of telithromycin to azithromycin in the eradication of S pneumoniae from the nasopharynx.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Female; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Pneumococcal Infections; Streptococcus pneumoniae

Increasing resistance among the key pathogens responsible for community-acquired respiratory tract infections, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, has the potential to limit the effectiveness of the antibacterial agents available to treat these infections. Moreover, there are regional differences in the susceptibility patterns observed and, as treatment is usually empirical, choosing an effective treatment can be challenging. Telithromycin, the first ketolide to be approved for clinical use, offers an activity profile that covers the key respiratory pathogens including penicillin- and macrolide-resistant S. pneumoniae as well as beta-lactamase-producing H. influenzae and M. catarrhalis. In a pooled analysis of three large controlled clinical trials involving patients with acute maxillary sinusitis, the bacteriological efficacy of 5- or 10-day treatment with telithromycin and 10-day treatment with comparators was evaluated. Telithromycin administered as a once-daily 800 mg dose for 5 days achieved eradication rates of 91.8, 87.5 and 92.9% for S. pneumoniae, H. influenzae and M. catarrhalis, respectively. Bacteriological eradication of 8/10 and 12/14 isolates of S. pneumoniae resistant to penicillin and erythromycin, respectively, was also reported following 5-day treatment with telithromycin. The clinical efficacy of this regimen was equivalent to that of a 10-day regimen of telithromycin or standard 10-day courses of amoxicillin-clavulanic acid or cefuroxime axetil. Telithromycin 800mg given for 5 days was well tolerated, with the majority of adverse events being of mild or moderate intensity. These data suggest that telithromycin provides effective first-line therapy for use in patients with acute maxillary sinusitis in a short and convenient once-daily dosage regimen.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Cefuroxime; Drug Resistance, Bacterial; Female; Haemophilus influenzae; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Streptococcus pneumoniae

The aim of this study was to evaluate the efficacy and tolerance of 5 days of telithromycin (800 mg once a day) in the treatment of bacteriologically proven acute maxillary sinusitis (AMS).. Two hundred and sixty-three patients with a clinically diagnosed AMS and purulent rhinorrhea were included in this prospective, multicenter, non-comparative open-labeled French study. Pus was sampled from the middle meatus before inclusion. The bacterial origin of the infection was confirmed by a scientific committee (presence of leucocytes/bacteria on direct microscopic examination of pus, and positive culture).. Seven to 14 days after the end of the treatment the clinical success rate (cure and improvement) was 91% (63/69 patients) in the per protocol bacteriologically documented (PPb) population and 90% (231/257 patients) in the modified intent-to-treat population. The main strains identified in the 69 patients of PPb population were Streptococcus pneumoniae (47.8%, of which 15 strains with reduced susceptibility to penicillin and 15 erythromycin resistant strains), Haemophilus influenzae (14.5%), Branhamella catarrhalis (8.7%) and Streptococcus aureus (29.0%). Drug tolerance was assessed on 263 patients as satisfactory with mainly gastro-intestinal disorders considered to be related to the treatment in 7.6% of patients. No serious adverse event related to the study drug was reported.. The efficacy of telithromycin 800 mg once daily for 5 days is confirmed in the treatment of AMS, even for those due to S. Pneumoniae.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Infections; Female; France; Humans; Ketolides; Male; Maxillary Sinusitis; Recurrence; Reproducibility of Results; Safety

Telithromycin (HMR 3647) is a new ketolide antimicrobial that was developed for the treatment of community-acquired respiratory tract injections. We conducted a randomized, double-blind, multicenter study to compare the clinical efficacy and safety of oral telithromycin, at 800 mg once daily for 5 or 10 days, with that of amoxicillin/clavulanic acid, at 500/125 mg three times daily for 10 days, in adults with acute maxillary sinusitis (AMS). A total of 754 patients with AMS of less than 28 days' duration were randomized to receive either telithromycin for 5 days followed by placebo for 5 days, telithromycin for 10 days, or amoxicillin/clavulanic acid for 10 days. Clinical outcome was assessed at a test-of-cure (TOC) visit between days 17 and 24 and at a late post-therapy visit between days 31 and 45. Analysis of clinical outcome on a per-protocol basis (n = 434) demonstrated therapeutic equivalence among the three regimens at the TOC visit; in each treatment group, the clinical cure rate was approximately 75%. Only a few patients (3 to 5 in each group) had relapsed by the late post-therapy follow-up visit. Telithromycin was generally safe and well tolerated. The most common adverse events were mild or moderate gastrointestinal effects, which occurred with similar frequency in all three groups. We conclude that 5 or 10 days of telithromycin at 800 mg once daily is as effective clinically and as well tolerated as 10 days of treatment with amoxicillin/clavulanic acid. Telithromycin, therefore, appears to be a valuable option for the treatment of AMS.

Topics: Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Ketolides; Macrolides; Male; Maxillary Sinusitis; Middle Aged; Treatment Outcome

The efficacy and tolerability of oral telithromycin 800 mg once daily for 5 vs. 10 days were assessed in patients with acute maxillary sinusitis (AMS).. Adults (n = 341) with confirmed AMS diagnosed on clinical signs and symptoms and sinus X-ray showing total opacity or air-fluid level were randomized to receive oral telithromycin for 5 days (followed by placebo for 5 days; n = 170) or 10 days (n = 171). Causative pathogens were isolated by pretreatment sinus puncture (day 1). Clinical and bacteriologic outcomes, and safety and tolerability endpoints were assessed.. Clinical cure rates post-therapy (per-protocol; days 17-21) were comparable (91.1% in the 5-day group, n = 123; 91.0% in the 10-day group, n = 133). Bacteriologic eradication rates (per-protocol) were also similar (90.7 vs. 91.3%). Both regimens were well tolerated.. A 5-day course of telithromycin 800 mg once daily is an effective, well-tolerated treatment for adults with AMS, comparable to a 10-day regimen.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Double-Blind Method; Drug Administration Schedule; Female; Humans; Ketolides; Macrolides; Male; Maxillary Sinusitis; Middle Aged; Treatment Outcome

To evaluate the effects of subinhibitory concentrations of penicillin and telithromycin on capsular formation by Streptococcus pneumoniae.. A total of 60 isolates of S. pneumoniae, 20 susceptible, 20 intermediately resistant and 20 resistant to penicillin, were studied. All isolates were susceptible to telithromycin.. All isolates were capsulate when grown without antibiotics. Encapsulation was lower after incubation with telithromycin as compared with penicillin in isolates susceptible to penicillin (20% versus 75%), in those intermediately resistant to penicillin (25% versus 95%) and in isolates fully resistant to penicillin (15% versus 100%) (P < 0.01).. Telithromycin appears to be superior to penicillin in reducing the expression of the capsule by S. pneumoniae.

Topics: Anti-Bacterial Agents; Bacterial Capsules; Humans; Ketolides; Maxillary Sinusitis; Microbial Sensitivity Tests; Penicillin Resistance; Streptococcal Infections; Streptococcus pneumoniae

The effect on the nasopharyngeal flora of 7 days of amoxicillin-clavulanate or 5 days of 800 mg once a day was studied in 50 adults with acute sinusitis. The numbers of potential pathogens and interfering alpha-hemolytic streptococci were equally reduced after both therapies. However, the number of interfering Prevotella spp. declined more significantly after amoxicillin-clavulanate treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Female; Haemophilus influenzae; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Nasopharynx; Prevotella; Streptococcus pneumoniae

A study of the comparative in vitro activity of telithromycin, a new ketolide, against 155 aerobic and 171 anaerobic antral sinus puncture isolates showed it to be active against a broad range of sinus pathogens. All pneumococci, including erythromycin-resistant strains, were susceptible to telithromycin at < or = 0.5 microg/ml; all Haemophilus influenzae and Eikenella corrodens strains were inhibited by < or = 4 microg of telithromycin/ml; all Moraxella spp. and beta-lactamase-producing Prevotella species strains were inhibited by < or = 0.25 and 0.5 microg of telithromycin/ml, respectively. Among all anaerobes tested, 94% (160 of 171 strains) were susceptible to < or = 4 microg of telithromycin/ml; however, 8 of 17 (47%) Fusobacterium strains, 2 Veillonella strains, and 1 Peptostreptococcus micros strain required > 4 microg of telithromycin/ml for inhibition. Telithromycin may offer a therapeutic alternative for sinus infections, including those due to erythromycin-resistant pneumococci.

Topics: Adult; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Humans; Ketolides; Macrolides; Maxillary Sinusitis; Microbial Sensitivity Tests

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