Antimicrobial Agents and Chemotherapy
Short-Duration Antimicrobial Therapy for AECB
Speaker: Marcus J. Zervos, MD, Clinical Professor of Medicine, Wayne State University School of Medicine, Detroit, Michigan, and William Beaumont Hospital, Royal Oak, Michigan.
Five-day therapy with oral telithromycin (Ketek, Aventis), a new ketolide antimicrobial agent, is as effective as standard 10-day treatment with comparators in adult patients with acute exacerbation of chronic bronchitis. When considered along with its convenience of once-daily dosing and tolerabili-ty, this new antibiotic becomes a first-line treatment option for patients with AECB.
To reach these conclusions, two multicenter, randomized, double-blind, two-arm, parallel group comparator studies were conduced, comparing the efficacy and safety of telithromycin 800 mg for five days with standard 10-day therapy with comparator antimicrobials (amoxicillin clavulanate 500/125 mg three times daily or generic cefuroxime axetil 500 mg twice daily). A total of 700 patients with AECB were randomized and 693 individuals were included in the modified intent-to-treat (mITT) population—342 in the telithromycin group and 351 in the comparator group. A total of 509 patients in the mITT population had no major protocol violations and were included in the per protocol (PP) population (telithromycin: 255 patients; comparator: 254 patients).
The pooled clinical cure rate in the telithromycin-treated patients was 86.3% post-therapy (days 17-24) and 78.4% late post-therapy (days 31-45), equivalent to the rate seen in the comparator group (82.7% and 75.6%, respectively), demonstrating that the shorter five-day treatment with telithromycin did not result in a greater number of relapses or reinfections compared with standard 10-day regimens. In addition, telithomycin was equally effective in elderly patients (>65 years) and in patients at increased risk for morbid sequelae.
The majority of adverse events were mild or moderate in severity in both treatment groups. Telithromycin was particularly well-tolerated, with treatment resulting in discontinuations of only 1.9% to 3.3%, compared to 10% of patients treated with generic amoxicillin/clavulanate drug and 1.6% of those treated with cefuroxime axetil.
Advanced-Generation Fluoroquinolone for Recurrent/ Non-Responsive Acute Otitis Media
Speaker: Ron Dagan, MD, Professor of Pediatrics, Pediatric Infectious Disease Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Preliminary results from an ongoing clinical study designed to demonstrate the effectiveness of fluoroquinolones in treating pediatric ear infections have shown that gatifloxacin (Tequin, Bristol-Myers Squibb) is effective against commonly found respiratory tract pathogens, particularly against resistant Streptococcus pneumoniae (S. pneumoniae). Gati-floxacin is an advanced generation, broad-spectrum fluoro-quinolone antibiotic.
In an ongoing study, 70 patients aged six to 48 months (median 11 months, 71% under one year) with recurrent/non-responsive acute otitis media (RNR-AOM) have been enrolled so far and treated with an oral suspension of gatifloxacin 10 mg/kg once daily for 10 days. Middle ear fluid was cultured by typanocentesis pre-treatment (day one) and on days four to six of treatment. Additional cultures were obtained if clinical relapse occurred. Patients were followed for up to 28 days.
A total of 58 of the 70 youngsters completed the course of treatment, with 12 patients discontinuing the study. The mean number of previous acute otitis media (AOM) episodes in this group of patients was 4.5 (range 1-12). Overall, 50 pathogens were identified in 38 (66%) of the patients, with 29 identified as Haemophilus influenzae (H. influenzae), 15 as S. pneumoniae, five as Moraxella catarrhalis (M. catarrhalis), and one identified as S. pyogenes. All 15 S. pneumoniae isolates, 13 of which were resistant to a number of other antibiotics (including penicillin), were susceptible to gatifloxacin, as were all 29 isolates of H. influenzae and five isolates of M. catarrhalis, many of which produced beta-lactamase. Bacteriologic eradication was achieved in 98% (49/50) of the pathogens and clinical improvement/cure at the end of treatment was seen in 97% (56/58) of the gatifloxacin treated patients. The drug eliminated more than 90% of all pathogens from the middle ear fluid (the site of infection in AOM patients). Clinical relapse was reported in 18 patients before day 28, and a middle ear fluid cure was reported in 16 of these youngsters, with a new pathogen found in 10. True relapse was documented in the other six patients.
