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P.D. Hedlin, J.M. Blondeau; Comparative Minimal Inhibitory and Mutant Prevention Concentration (MPC) Of Gatifloxacin (GA) and Other Compounds Against Gram–Positive Ocular Pathogens . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4920.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Minimal inhibitory concentration (MIC) determines the in vitro susceptibility of drug against pathogenic bacteria based on a standardized inoculum of 105 colony forming units per milliliter (cfu/ml). The MPC is a novel in vitro measurement which has been used to determine the propensity of fluoroquinolone (FQ) compounds to select for antimicrobial resistance. For MPC testing, >109 organisms are applied to agar plates containing drug. We were interested in determining both MIC and MPC values for FQs against clinical ocular isolates of Streptococcus pneumoniae (SP) and Staphylococcus aureus (SA). Methods: MIC testing was performed by broth microdilution utilizing an inoculum of 105 cfu/ml while MPC testing was by agar dilution and based on an inoculum of >109 cells. Cultures were incubated in the presence or absence of C02 at 35°C for 18–24 and 24 and 48 hours respectively and screened for growth. The lowest concentration preventing growth was either the MIC or MPC. Todd–Hewitt broth was used for SP and Mueller–Hinton for SA. Results: To date, 42 isolates have been fully characterized. For SP, MIC90 (µg/ml) were as follows: Gatifloxacin (GA) 0.25/0.25, ciprofloxacin (C) 1/2, ofloxacin (O) 2/6, levofloxacin (L) 0.5/1. The MPC (µg/ml) values were respectively 1/1, 4/8, 4/8, 2/4. For SA MIC50/90 values were respectively 0.063/0.063, 0.25/0.5, 0.25/0.25, 0.125/0.125 compared to the MPC values of GA 0.063/0.063, C 1/2, O 1/2. DNA sequence data of organisms with high MPC values to the older compounds confirmed the presence of mutations known to confer resistance to quinolones. Conclusion: MPC is a novel approach to comparing the propensity of FQs for selecting resistance. The lower the MPC value, the more likely it can be achieved and maintained throughout the dosing interval. Against SP and SA, GA by MIC and MPC was more active than C, L, and O by both MIC and MPC testing. The data suggests that the newer agent, GA is more active than the older agents C, O, and L against gram–positive pathogens and is less likely to induce resistance.
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