Fundamental and clinical studies on Ceftazidime in paranasal sinusitis

Abstract

To objectively evaluate the clinical efficacy and safety of Ceftazidime (CAZ) in treating paranasal sinusitis, a standard protocol was designed and carried out in a multi-center clinical study. CAZ was examined for its sensitivity distribution against different clinical isolates, and its transfer into the tissue membranes of the maxillary antrum. The results are as follows: 1. The MIC₈₀, of CAZ was 1.56μg/ml for 23 strains of Gram-positive bacteria and 0.39μg/ml for 9 strains of Gram-negative bacteria. These strains were all isolated from patients with paranasal sinusitis. Among all the antibiotics tested (cefpiramide, cefotiam, cefazolin, and ceftazidime), CAZ showed the most potent antibacterial activity against Gram-negative bacteria. 2. The mean tissue concentration in the membranes of the maxillary antrum were 31-32μg/g for the interval 30 to 90 minutes after intravenous administration of 1g CAZ. Although the tissue levels gradually declined with the passage of time, the concentration was still 8.6μg/g at 180 minutes after administration. The ratio of tissue level to serum level of CAZ tended to increase with the passage of time. 3. A total of 43 patients received CAZ for clinical evaluation. Clinical effectiveness was evaluated in 39 cases, clinical usefulness in 40 and safety in all 43 cases. The majority of the patients were given a dose of 1 g, twice daily (28 patients, 65.1%) for longer than 5 days, but not exceeding 7 days (21 patients, 48.8%). 4. Both the Efficacy Assessment Committee and the doctors in charge evaluated the efficacy rate (“Excellent” and “Good”) of CAZ to be 74.4% (29/ 39). However, the percentage of “Excellent” cases was higher in the committee evaluation (53.8%). In the assessment by the Committee, the efficacy rate for each type of disease was 86.4% (22 cases) in acute paranasal sinusitis, 69.2% (13 cases) in acute exacerbation of chronic paranasal sinusitis and 25.0% (4 cases) in chronic paranasal sinusitis. 5. When the bacteriological effects were evaluated by case, bacteria were eliminated in all the cases, except for one case with polymicrobial infection (23 cases were assessed). When the evaluation was done by strain (25 strains were assessed), bacteria were eliminated, except for one strain of _{S. intermedius}. The bacterial elimination rates in the above assessments were 95.7% and 96.0%, respectively. 6. Clinically adverse events were observed in 3 cases out of 43 (One each of eruption, loose stool, and palpitation). As for abnormal laboratory findings, one case of increased platelet counts and one case of elevated GPT levels were noted. None of the above adverse events or abnormal laboratory findings were considered to be serious. From the above results, CAZ is considered to be highly useful drug in the treatment of paranasal sinusitis.