TAM VH, LOUIE A, DEZIEL MR, LIU W, GRASELA D, MILLER MH, DRUSANO GL; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-443.
Albany Med Coll and NYSDOH, Albany, NY
BACKGROUND: B is a novel fluoroquinolone with promising in-vitro activity. In order to explore the clinical utility of B, we compared B and C in terms of cell kill and resistance selection against PA and KP in a HFS. METHODS: HFS inoculated with approximately 5=10[8] cfu/mL of bacteria in late log-growth phase were exposed to B with escalating AUC/MIC, simulating the unbound human PK of B given once every 24 hours. PA and KP were also exposed to C, simulating free drug human PK of AUC/MIC 66 and 1400 respectively. Serial samples were obtained for drug concentrations, quantification of total population and resistant (>3x MIC) sub-populations to B and C over 48 hours. RESULTS: Against PA, AUC/MIC of B >/= 100 and C resulted in an initial drop in total population, but gradually were replaced by the resistant sub-population. For KP, AUC/MIC of B of >/= 75 did not affect the total population, but selected for resistant sub-population to both B and C. Decrease in total population was achieved with AUC/MIC of B >/= 100 and C. Cross-resistance between B and C was apparent for both bacteria. In order prevent emergence of resistance at 48 hours, AUC/MIC >/= 200 and 100 was necessary for PA ad KP respectively. CONCLUSIONS: B is active against PA and KP in our infection model and AUC/MIC targets of 200 (PA) and 100 (KP) were identified for cell kill and resistance suppression.
Publication Types:
Keywords:
- Area Under Curve
- Bacteria
- Chromosomes
- Ciprofloxacin
- Fluoroquinolones
- Humans
- Klebsiella pneumoniae
- Microbial Sensitivity Tests
- Pseudomonas aeruginosa
- garenoxacin
- genetics
- p-Aminosalicylic Acid
- pharmacokinetics
- pharmacology
Other ID:
UI: 102269097
From Meeting Abstracts