Determination of Minimal Inhibitory Concentration (MIC) and Mutant Prevention Concentration (MPC) of Ocular Isolates of Pseudomonas aeruginosa (PA) and Haemophilus influenzae (HI) to 5 Fluorquinolone (FQ) Antimicrobial Agents (AA).

Abstract

Abstract: : Purpose: Gram–negative eye infection requires prompt therapy. Emerging antimicrobial resistance has compromised the use of various AAs. The MPC is a novel parameter that represents a drug concentration threshold above which an organism would require 2 simultaneous mutations for growth in the presence of the drug. We were interested in determining both MIC and MPC values for ocular isolates of PA and HI. Methods: To date, 22 PA and 31 HI isolates have been tested. For MICs, 10⁵ cfu/ml were tested by microbroth dilution based on 18–24 hours incubation at 35–37^oC with or without CO₂. For MPC testing, >10⁹ organisms were inoculated to agar plates, incubated as described and screened at 24 and 48 hours for growth. The lowest concentration preventing growth was either the MIC or MPC respectively. Results: The following MIC_50/90 (µg/ml) values were recorded for PA respectively against ciprofloxacin (C), gatifloxacin (G), levofloxacin (L), moxifloxacin (M) and ofloxacin (O) 0.25/1, 1/4, 1/4, 1/8, 2/8. For HI, all FQs have MIC_50/90 (µg/ml) values of <0.016/0.031. The following MPC_50/90 (µg/ml) values respectively were recorded for the PA isolates: 2/4, 8/8, 8/8, 16/32, 16/16. For HI, all FQs had MPC_50/90 values of <=0.25/0.5 µg/ml. Conclusion: All FQs had low MIC and MPC values against HI isolates. For PA isolates, the rank order of potency by MIC and MPC were as follows: C > G = L > M = O and C > G = L > O > M. Dosing to achieve MIC results in favourable clinical outcomes and dosing to achieve MPC has the added benefit of reducing the likelihood of selecting for resistance.

Keywords: bacterial disease • antibiotics/antifungals/antiparasitics • Pseudomonas