title: Use of pharmacodynamic end points in the evaluation of gatifloxacin for the treatment of acute maxillary sinusitis.
abstract: 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 x h/L and 30.1 mg x 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.
authors.affiliation: Division of Infectious Diseases, Cognigen Corporation, Buffalo, New York 14221, USA. PGAmbrose@aol.com
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ambrose
authors.forename: Jack B
authors.initials: JB
authors.lastname: Anon
authors.forename: Joel S
authors.initials: JS
authors.lastname: Owen
authors.forename: Scott
authors.initials: S
authors.lastname: Van Wart
authors.forename: Mary Eileen
authors.initials: ME
authors.lastname: McPhee
authors.forename: Sujata M
authors.initials: SM
authors.lastname: Bhavnani
authors.forename: Marion
authors.initials: M
authors.lastname: Piedmonte
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D003030:Coagulase; D021902:Enterobacter aerogenes / Q000187:drug effects / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D015523:Maxillary Sinusitis / Q000188:drug therapy* / Q000382:microbiology*; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000175:diagnosis / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy; D013210:Staphylococcus / Q000187:drug effects / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003030:Coagulase; D024841:Fluoroquinolones; D000077734:Gatifloxacin