Use of Pharmacodynamic End Points in the Evaluation of Gatifloxacin for the Treatment of Acute Maxillary Sinusitis

• Published in: Clinical infectious diseases 2004-06, Vol.38 (11), p.1513-1520
• Main Authors: Ambrose, Paul G., Anon, Jack B., Owen, Joel S., Van Wart, Scott, McPhee, Mary Eileen, Bhavnani, Sujata M., Piedmonte, Marion, Jones, Ronald N.
• Format: Article
• Language: English
• Subjects: Acute Disease; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antimicrobials; Bacterial diseases; Biological and medical sciences; Blood plasma; Clinical trials; Coagulase; Enterobacter aerogenes; Enterobacter aerogenes - drug effects; Enterobacter aerogenes - isolation & purification; Enterobacteriaceae Infections - diagnosis; Enterobacteriaceae Infections - drug therapy; Female; Fluoroquinolones - adverse effects; Fluoroquinolones - pharmacokinetics; Fluoroquinolones - pharmacology; Human bacterial diseases; Humans; Infections; Infectious diseases; Major Articles; Male; Maxillary sinus; Maxillary Sinusitis - drug therapy; Maxillary Sinusitis - microbiology; Medical sciences; Middle Aged; Non tumoral diseases; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacokinetics; Pneumococcal Infections - diagnosis; Pneumococcal Infections - drug therapy; Sinuses; Sinusitis; Staphylococcal Infections - diagnosis; Staphylococcal Infections - drug therapy; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus - drug effects; Staphylococcus - isolation & purification; Sterilization; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - isolation & purification; Symptoms; Treatment Outcome
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/420739

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. This single-center, open-label study quantified the time course of sinus sterilization, described gatifloxacin exposure at the infection site, and posed the hypothesis that the use of continuous and quantitative time-related end points may allow for better characterization of drug effect with fewer patients than traditional clinical trial approaches. Of the 12 enrolled patients, 10 were clinically evaluable, from whom 7 pathogens were isolated: 4 Streptococcus pneumoniae, 2 staphylococci, and 1 Enterobacter aerogenes. The median predicted 24-h area under the curve (AUC) in sinus aspirates and plasma samples was 54.7 mg × h/L and 30.1 mg × h/L, respectively. The median 24-h AUC ratio for sinus aspirates and plasma samples was 1.51 (range, 0.88-2.23). For patients infected with pneumococci, the median time to sinus sterilization was 50 h. The use of quantitative time-related end points may be useful in evaluating the efficacy of antimicrobial agents with fewer patients.