Context: The relationship between drug exposure and the time course of antimicrobial effect at the primary infection site for acute maxillary sinusitis has not previously been explored. Purpose. To quantify the time course of sinus sterilization, describe gatifloxacin exposure at the infection site, and to pose the hypothesis that the use of continuous and quantitative time-related endpoints would allow for better characterization of drug effect.
Methods: Single-center, open-label pilot study. Patients. 12 patients with a radiologically confirmed clinical diagnosis of acute maxillary sinusitis. Main Outcome Measures. Time to microbiological eradication of pathogenic organisms from the sinus. Results. Sinus catheters were inserted into the maxillary sinus with minimal discomfort and were well tolerated. Of the 12 enrolled patients, 10 were clinically evaluable, from whom 7 pathogens were isolated: S. pneumoniae (4), staphylococci (2), and E. aerogenes (1). The median predicted 24-hour AUC (mg*hr/L) in plasma and sinus aspirate was 30.1 and 54.7, respectively. The median 24-hr AUC sinus:plasma ratio was 1.51 (range 0.88, 2.23). The median time to sinus sterilization was 53 hours (95% CI 43, 91). The median time to resolution of each sign and symptom of infection ranged between 1 and 3 days with 87% (69/79) of total signs and symptoms resolving by the end of 5 days of therapy.
Conclusions: Exposure of organisms to gatifloxacin was associated with rapid sinus sterilization. The serial sinus aspirate sampling approach for quantifying the time course of sinus sterilization and describing drug exposure at the infection site provides more robust
information than standard approaches used for evaluating antimicrobial therapies of acute maxillary sinusitis. The collection of pharmacokinetic data from the site of infection may allow for better pharmacodynamic characterization of antimicrobial agents for the treatment of acute maxillary sinusitis. This model may be useful to evaluate the efficacy of antimicrobial agents with fewer patients.
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, Illinois, September 2003
By Paul G. Ambrose, Ronald N. Jones, Scott Van Wart, Joel S. Owen, Sujata M. Bhavnani, Mary Eileen McPhee, Chris Costanzo, and Jack B. Anon