Single-Dose Azithromycin Microsphere Formulation for Acute Exacerbation of Chronic Bronchitis

Speaker: Marcus J. Zervos, MD, Infectious Diseases Specialist, William Beaumont Hospital, Royal Oak, Michigan, and Wayne State University School of Medicine, Detroit, Michigan

A single dose of a novel formulation of azithromycin micro-spheres (Pfizer) has proved to be as effective as a seven-day course of levofloxacin (Generic Levaquin, Ortho-McNeil) for the treatment of an acute exacerbation of chronic bronchitis (AECB). This advance has made it possible to administer an entire regimen as a single oral dose while maintaining tolerabil-ity and efficacy.

In a multicenter, randomized, double-blind, double-dummy clinical trial, 551 patients with AECB were randomly assigned to receive azithromycin microspheres as a 2-g single dose or levofloxacin 500 mg once daily for seven days. The primary and secondary endpoints were clinical and bacteriological responses, respectively, in patients with a baseline pathogen at the test-of-cure (TOC) visit between days 14 and 21.

A total of 438 patients—220 receiving azithromycin microspheres and 218 receiving levofloxacin—met the criteria for the clinical-per-protocol (CPP) population at the TOC visit. The CPP cure rates were comparable in the two treatment groups: 93.6% for azithromycin microspheres and 92.7% for levofloxacin.

The bacteriological-per-protocol (BPP) population consisted of 247 patients: 123 received azithromycin microspheres and 124 received levofloxacin. The overall bacteriological eradication rates at the TOC visit were 91.9% for azithromycin microspheres and 94.4% for levofloxacin.

Because many patients were unable to produce sputum at the TOC visit, most of the pathogens were assigned a bacterial response of presumed eradication according to an assessment of the clinical response. The clinical cure rates for patients with Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, isolated at baseline, were similar in the azithromycin patients (95.0%, 94.7%, and 92.0%, respectively) and in the canadian levofloxacin patients (100%, 90.5%, and 81.3%, respectively).

Both drugs were well tolerated. Because azithromycin therapy can be administered as a single dose, the rate of compliance was 100% in patients following this regimen. In contrast, 14 of 279 patients in the original levofloxacin group (5%) did not complete the entire seven-day course of active treatment.

Moxifloxacin Once-Daily Regimen for Complicated Intra-abdominal Infections

Speaker: Mark A. Malangoni, MD, Chairperson, Department of Surgery, MetroHealth Medical Center and Professor of Surgery and Vice President, Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio

Sequential intravenous (IV)/oral (PO) monotherapy with moxifloxacin HCl (Avelox drug, Bayer) once daily for complicated intra-abdominal infections was as effective as IV pipacillin-tazobactam (Zosyn®, Wyeth) four times daily, followed by oral amoxicillin-clavulanate (Augmentin drug, Glaxo-SmithKline) twice daily, a widely used therapy for this type of infection.

A total of 681 patients were enrolled into a prospective, double-blind, phase 3 trial. Of these, 656 patients were included in the safety population (328 receiving moxifloxacin and 328 receiving comparator therapy), and 379 patients were included in the efficacy population (182 receiving moxifloxacin and 197 receiving comparator therapy).

After the patients were ranked according to disease severity, they were randomly assigned to receive IV followed by oral moxifloxacin 400 mg every 24 hours or IV piperacillin-tazobac-tam 3.0/0.375 g every six hours followed by oral amoxicillin-clavulanate 800 mg/114 mg every 12 hours for five to 14 days. Clinical cure and bacteriological eradication rates were recorded at the test-of-cure visit at 25 to 50 days after therapy.

In the patients who were evaluable for efficacy, clinical cure rates were similar for moxifloxacin (79.7%) and comparator therapy (78.2%), as were bacteriological eradication rates, at 77.9% and 77.4%, respectively. Higher clinical cure rates were recorded in the moxifloxacin patients (85.4%) than in the patients receiving comparator therapy (72%) when the infection was acquired in a hospital.

Higher cure rates were also observed with moxifloxacin (85.4%) than with comparator therapy (72.%) in infections caused by Bacillus fragilis. Outcomes were similar in the two treatment groups in patients with intra-abdominal abscesses, community-acquired infections, and infections caused by Escherichia coli.

Adverse drug events (ADEs) were similar in both groups. The three most common ADEs were diarrhea, nausea, and elevated gamma glutamyl transferase levels.