An Open-Label, Non-Comparative Phase IIIb Study of Oral Gatifloxacin in the Treatment of Acute, Uncomplicated Bacterial Sinusitis in Thai Patients

Abstract

This was an open-label, non-comparative phase IIIb study of oral gatifloxacin in the treatment of acute, uncomplicated bacterial sinusitis in Thai patients. The study was conducted at three otolaryngologic centers in Thailand, i.e. Siriraj Hospital, Srinakarind Hospital, and Bhumipol Hospital, during the period of November 1999 through October 2000. Thirty patients with symptoms and signs of acute maxillary sinusitis, which were confirmed by abnormal radiological findings, were included. Documentation of infection was made by pre- and post-therapy culture and susceptibility testing. All patients received gatifloxacin 400 mg tablet orally once daily for 10 days. Symptoms and signs were evaluated on four occasions, i.e. before treatment started (day 0, V1), day 3-5 (V2), the third (V3) on day 11-14 (V3), and day 21-28 (V4). Primary outcome measures were the changes in the percentage of patients who had general clinical symptoms (i.e. fever, malaise, chill, sore throat, headache, cough, and halitosis), and also the clinical symptoms and signs of sinusitis (i.e. sinus pain, sinus tenderness, purulent nasal discharge, facial pressure, nasal congestion, postnasal drip, and anosmia). The clinical responses were classified as cure, improvement, relapse or failure at the end of treatment (V3) and at follow up (V4). Treatment success was defined as cure or improvement. The safety of gatifloxacin was assessed from vital signs, general physical examination, hemato-biochemical parameters, and adverse events reported.
   There were 13 males and 17 females, with a mean age of 34.7 ± 12.2 years (range 21-70). The mean duration of symptoms was 2.4 ± 8.8 weeks. At V1,23 patients (76.7%) had headache, 19 patients (63.3%) had cough, and 14 patients (46.7%) had halitosis. At V3 and V4 all these symptoms had resolved, except in 1 patients who still had cough. The percentages of patients who had symptoms and sign of sinusitis at V1 were as follows : purulent nasal discharge 90%, nasal congestion 86.7%, postnasal drip 86.7%, sinus pain 80%, facial pain 66.7%, and sinus tenderness 63.6%. After 3-5 days of treatment (V2), the percentages of patients who had symptoms and signs of sinusitis decreased significantly for every symptom and sign. The same was true at V3 and V4.
   The total percent improvement in radiological findings was 83.4% (41.7% resolution, 41.7% improvement). Pretreatment cultures were positive in 23 out of 30 patients (76.7%). The most common pathogens were Hemophilus influenzae (18.4%), Streptococcus pneumoniae (9.4%), other Streptococcus species (9.4%), Klebsiella pneumoniae (6.3%) and coagulase negative Staphylococcus (6.3%). The anaerobes found were Peptostreptococcus prevotii (9.4%), Fusobacterium nucleatum (9.4%), Bacteroides species (6.1%) and Prevotella species (3.1%). Bacteriological responses at V3 were 30.4% eradication, 65.2% presumed eradication, and 4.4% persistence. Clinical responses at V4 were 88.9% cured, 7.4% relapsed, and 3.7% failed. Adverse events were found in 4 patients (13.3%) which were transient and resolved spontaneously. Adverse events found were nausea, vomiting, dry mouth, constipation, agitation and tremor.
   This study showed the efficacy and safety of a 10-day course of oral gatifloxacin 400 mg once daily in the treatment of acute uncomplicated bacterial sinusitis. 88.9% of patients experienced a cure, and bacteriological eradication was achieved in 95.6%. The excellent profile of gatifloxacin makes it suitable for the treatment of community acquired acute bacterial sinusitis. The once daily regimen enhances patient compliance.