Comparative Study of Azithromycin and AmoxiciUin/Clavulanic Acid in the Treatment of Lower Respiratory Tract Infections R B a l m e s l , G. Clerc 2, B. D u p o n t 3, C. L a b r a m 4, R. P a r i e n t e 5, R. Poirier 6
Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 rag/ day on days 2-5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillinJclavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92 % and 87 % of patients respectively, bacteriological cure in 89 % and 86 %, with 91% and 89 % of pathogens eliminated. Minor side effects occurred in 6 % and 12 % of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group.
Azithromycin is a new azalide antibiotic being developed for the treatment of a wide range of infections. Derived chemically from erythromycin, it differs structurally by the insertion of a methylsubstituted nitrogen at position 9a in the lactone ring (1). This modification gives a significant improvement in potency against gram-negative bacteria, including Haemophilus influenzae, compared with erythromycin, while retaining the gram-positive activity of the latter (2). Although serum concentrations of azithromycin are relatively low, high and persistent concentrations of the drug are achieved in a wide variety of tissues (3, 4). These properties suggested that a short COurse of treatment with relatively infrequent adl Service de Pneumologie,Centre Hospitalier Regional et Universitaire, 5 rue Hoche, 30006 Nimes, France. zCentre Hospitalier Sp6cialis6, 50170 Pontorson, France. 3Service de Maladies Infeetieuses,H6pital Pasteur, 75015 Paris, France. 4Service de M6dicine Interne, Centre Hospitalier, 51005 Chalons sur Marne, France. SServicc de Pneumologie et Rdanimation, H6pital Beaujon, 92110 Clichy,France. Service de Pneumologlc, Centre Hospitalier~ 13616 Aixen-Provence, France.
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ministration would be useful in the treatment of respiratory tract infections, and this paper reports the results of an open, comparative, multicentre (six participants) study carried out in France in 1988/1989.
Patients and Methods. The study protocol specified the inclusion of male or female (other than those pregnant or lactating) patients aged 18 years or more, who had given informed consent and who presented with acute bacterial bronchial or bronchopulmonary infection accompanied by the production of purulent sputum. Patients with cystic fibrosis, infectious mononucleosis, or chronic or obstructive pulmonary disease without an acute infection were specifically excluded, as were those who had received anti biotic treatment within 48 hours prior to the start of the study or who had a known hypersensitivity to macrolides or penicillins. Patients were re-examined during the 48 hours immediately after the last dose of study drug and again 5 to 10 days (azithromycin) or 0 to 5 days (amoxicillin/clavulanic acid) after this last dose. Clinical efficacy was evaluated by changes, compared with pre-treatment, in the total and differential leucocyte count, body temperature, frequency and severity of cough, amount and purulence of sputum, dyspnoea and abnormal chest sounds. The clinical response was classified after completion of therapy as cure, improvement or failure based on the investigator's overall summary assessment of the patient's response to treatment. Cure was defined as complete resolution of all signs and symptoms at the final assessment visit, improvement as incomplete resolution of signs and symptoms at the final assessment visit. Clinical failure was defined as any of the following: persistence or progression of all signs and symptoms; development of new clinical findings consistent with active infection; death from the primary diagnosis; or inability to complete the study because of adverse effects. The bacteriological response was determined by the presence of pathogens in sputum recorded at baseline and after treatment, based on a repeat culture. If no sputum sample could be produced post-treatment, bacteriological cure was assumed. All bacteriological assessments were carried out blind. Sensitivity of isolated pathogens to azithromycin and (amoxicillin/clavulanic acid) discs, and a range of standard antibiotics was determined by a routine laboratory antibiogram. Each pathogen was defined as being either resistant or susceptible to the drugs. For azithromycin, resistant or-
ganisms were defined as those with a zone size of _