F1-2039. Comparisons of Methods for Finafloxacin MIC Testing at Acidic and Neutral pH
Session: Poster Session: New Topoisomerase Inhibitors
Monday, October 27, 2008: 12:00 AM
Room: Hall C
Background: Finafloxacin (FIN) is a novel 8-cyano fluoroquinolone (FQ) that exhibits optimal activity at slightly acidic conditions (pH 5-6) where other FQs lose activity. FIN is intended for therapy of bacterial infections associated with an acidic environment such as H. pylori eradication and UTI. MIC testing of aerobic bacteria with FIN at acidic and neutral pH was studied by comparing Etest, CLSI agar (AD) and broth (BMD) dilution methods. Methods: Etest, AD and BMD methods (MIC 0.002-32 µg/mL) were used to determine the MIC of FIN at pH 5.8 and pH 7.3. Challenge strains (39) used were: E. coli (8), E. cloacae (2), A. anitratus (1), K. pneumoniae (2), P. vulgaris (1), P. rettgeri (1), P. stuartii (1), P. aeruginosa (3), S. marcescens (2), S. aureus (13), S. saprophyticus (1), S. haemolyticus (3), S. warnerii (1). Quality control (QC) results for E. coli ATCC® 25922, S. aureus ATCC 29213 and P. aeruginosa ATCC 27853 were generated and inoculum effects (100-fold) studied.
Results:
ComparatorRegression analysis% Agreement
Equationr± 1 dilution
AD vs. BMD, pH 5.8y = 0.94 x + 0.270.99100
AD vs. BMD, pH 7.3y = 0.97 x + 0.360.98100
Etest vs. AD, pH 5.8y = 1.11 x - 0.450.9787.5
Etest vs. AD, pH 7.3y = 0.99 x + 0.280.99100
Etest vs. BMD, pH 5.8y = 1.05 x - 0.270.9787.5
Etest vs. BMD, pH 7.3y = 0.97 x + 0.550.9897.9

Excellent inter-method MIC agreements were seen for results compared at the same pH. Species specific pH effects were seen and MIC values were 1-3 dilutions lower at acidic pH. QC results fell within specifications provided by the drug manufacturer. Inoculum effects on MIC values were minimal.
Conclusions: MIC testing of FIN with Etest, agar and broth dilution reference methods provides substantially equivalent results at both neutral and acidic pH, and demonstrates higher activity of FIN at slightly acidic pH. Etest with a wide concentration range (15 dilutions) comprise a useful MIC tool for drug development studies with FIN and for future studies with H. pylori.
Anette Engelhardt1, Anne Yusof2, Carolina Johansson2, Karin Sjöström1, Phion Ho2 and  A. Engelhardt,
AB BIODISK Role(s): Employee., (1)AB BIODISK, Solna, Sweden, (2)AB BIODISK


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