CLINICAL EFFICACY OF ROXITHROMYCIN IN THE TREATMENT OF ADULTS WITH UPPER AND LOWER RESPIRATORY-TRACT INFECTION DUE TO HAEMOPHILUS-INFLUENZAE - A METAANALYSIS OF 12 CLINICAL-STUDIES

12 clinical studies on the use of roxithromycin 300mg daily in adult r espiratory tract infection were subject to meta-analysis. Nine of the studies were comparative and 5 were from the published literature. Aud itable individual patient data were reviewed for 11 of the 12 studies. 4297 patients with respiratory tract infection were enrolled in these studies and 384 (8.9%) had Haemophilus influenzae identified as a cau sative pathogen. Of these patients, 331 were treated with roxithromyci n: 268 with 150mg twice daily and 63 with 300mg once daily. 53 patient s were treated with comparator antibiotics. The primary analysis was u ndertaken on 300 cases where H. influenzae was the sole pathogen ident ified: 253 of these cases were treated with roxithromycin and 47 with comparator antibiotics. On a 'per protocol' (PPA) basis, the overall s atisfactory clinical and bacteriological response for all roxithromyci n regimens was 87% [95% confidence interval (CI), 82 to 92%] and 83%, respectively. Clinical response on an 'intention-to-treat' (ITT) basis was 80% (CI: 75 to 85%) excluding studies enrolling only hospitalised patients, and 78% (CI: 73 to 83%) for all cases. Clinical response (I TT) was marginally lower at 76% (CI: 72 to 82%) if mixed infections we re included. Comparator antibiotics were amoxicillin/clavulanic acid, cefaclor, doxycycline, erythromycin and cotrimoxazole. A satisfactory clinical response (ITT) was obtained in 70% of cases treated with comp arator antibiotics (CI: 57 to 83%). Roxithromycin demonstrated a respo nse rate similar to that of amoxicillin/clavulanic acid and significan tly better than erythromycin (p = 0.03). Although the numbers were sma ll, roxithromycin was significantly more effective for the treatment o f pneumonia in the directly comparative studies, with 93% success, com pared with only 53% for the comparator antibiotics (p = 0.02). The res ponse rate was similar to that reported for clarithromycin. Current mi nimum inhibitory concentration and disc zone susceptibility breakpoint s of less-than-or-equal-to 1 mg/L and greater-than-or-equal-to 22mm un derestimate the clinical efficacy of roxithromycin against H. influenz ae. A disc zone diameter susceptibility breakpoint of greater-than-or- equal-to 10mm is predictive of a successful outcome in 78% of cases (9 5% CI: 71 to 85%). This correlates well with recent recommendations to adopt susceptibility breakpoints of greater-than-or-equal-to 10mm and less-than-or-equal-to 16 mg/L when using National Committee for Clini cal Laboratory Standards (NCCLS) methodology. The results of this anal ysis support the empirical use of roxithromycin in respiratory tract i nfections where H. influenzae is a potential pathogen. Future clinical studies of respiratory tract infection with roxithromycin should eval uate these new breakpoints.