Use of pharmacodynamic end points in the evaluation of gatifloxacin for the treatment of acute maxillary sinusitis.
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.
Ambrose
Paul G
PG
Division of Infectious Diseases, Cognigen Corporation, Buffalo, New York 14221, USA. PGAmbrose@aol.com
Anon
Jack B
JB
Owen
Joel S
JS
Van Wart
Scott
S
McPhee
Mary Eileen
ME
Bhavnani
Sujata M
SM
Piedmonte
Marion
M
Jones
Ronald N
RN
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
D000900:Anti-Bacterial Agents; D003030:Coagulase; D024841:Fluoroquinolones; D000077734:Gatifloxacin