Moxiﬂoxacin hydrochloride ophthalmic solution Antimicrobial outcome Pharmacokinetics Pharmacodynamics Patient Microorganism Pathogenicity/virulence Figure 4 Factors affecting favorable outcomes during antimicrobial therapy. and MIC distribution. The third partner in this complex relationship is what both the drug and the pathogen do to the patient. This interplay is described by the patient’s age, genetic background, underlying disease and prior antimicrobial exposure. The ratio of peak concentration (Cmax) to the MIC and the area under the concentration curve (AUC) are the pharmaco- dynamic indices that correlate most favorable with clinical outcomes for concentration-dependent anti-infectives. Main- taining adequate concentration of an antibiotic above a certain level known as the mutant prevention concentration (MPC) can also reduce the probability of selecting resistant subpopu- lations and increasing a favorable clinical outcome. Antibiotic penetration into ocular tissues and ﬂuids must not only reach but exceed the minimal inhibitory concentration (MIC) sufﬁciently to meet the targeted phar- macodynamic indices (Cmax: MIC or MPC) by a factor of 10. A Cmax:MIC ratio or MPC values greater than 10 have been documented to eradicate pathogens and suppress emergence of resistance in patients treated with ﬂuoroqui- nolones (Allen et al 2004; Metzler et al 2004; Smith et al 2004; Hermsen et al 2005). Wilhelmus (Wilhelmus 2003; Wilhelmus et al 2003) conﬁrmed the application and utility of pharmacodynamic indices to predict clinical outcome in patients with bacterial keratitis. The pharmacodynamic indices (PDI): Cmax:MIC and AUC:MIC were use to correlate clinical outcome for 391 patients with bacterial keratitis. Clinical improvement was associated with a Cmax:MIC ratio greater than 8 and an AUC:MIC ratio greater than 152. Corneal pathogens included S. aureus (21%), P. aeruginosa (12%), S. pneumoniae (7%), Clinical Ophthalmology 2008:2(1) Streptococcus viridans (5%), other gram-positive isolates (44%), and other gram-negative isolates (11%). Table 6 displays calculated pharmacodynamic indices (PDI) for moxiﬂoxacin and gatiﬂoxacin using reported aque- ous concentrations and MIC50s/MIC90s values for coagulase negative staphylococci recovered from endophthalmitis (Mather et al 2002; Miller et al 2006) Targeted PDIs ranged from less than or equal to 0.038 μg/mL to 0.228 μg/mL for moxiﬂoxacin and less than or equal to 0.048–0.094 μg/mL for gatiﬂoxacin. Obtainable moxiﬂoxacin concentrations exceeded the MIC and met the PDI factor of 10 for 89% (8/9) and 78% (7/9) of the isolates when using the MIC50. None of the moxiﬂoxacin concentrations were sufﬁcient to provide coverage for ﬂuo- roquinolone resistant coagulase negative staphylococci for reported MIC90s. Gatiﬂoxacin concentrations met the PDI factor of 10 for 28% (2/7) of the isolates at the MIC50 value of 0.09 μg/mL. None of the obtainable Zymar concentrations met the PDI factor of 10 for ﬂuoroquinolone resistant isolates at values reported by Miller et al (2006). In a more recent report from the same Institution, Harper and colleagues (Harper et al 2007) conﬁrmed the low peak concentration:mic ratios for both gatiﬂoxacin and moxiﬂoxa- cin using reported intraocular levels against 59 coagulase negative staphylococci isolates collected between 1993 and 2006. Moxiﬂoxacin ratios (Cmax:MIC90) were higher than gatiﬂoxacin (0.05 μg/mL vs 0.02 μg/mL) but lower than vancomycin (0.45 μg/mL) for reported mean (1.66 μg/mL) aqueous concentrations. A signiﬁcant difference in the PDI parameter was observed for moxiﬂoxacin when the MIC50 85