Table 4 Regional and geographic variation in endemic ﬂuoroquinolone resistance (%) among ocular pathogens Region Fluoroquinolone Ciproﬂoxacin Gatiﬂoxacin Moxiﬂoxacin Number of Isolates Time Period Europe 12.4 5.5 ND 532 July 2001–Dec 2002 France 12.4 5.6 ND Germany 4.6 1.5 ND Italy 19.9 4.6 ND Spain 15.9 9.8 ND Sweden 2.0 0 ND UK 8.3 8.3 ND USA (Northeast) 28.3 13.7 20 350 1993–2005 16.7 11.9 23.3 11.9 431 183 2000–2006 2002–2004 Moxiﬂoxacin hydrochloride ophthalmic solution Reference Morrissey et al 2004 Mather et al 2002; Kowlaski et al 2003; Kowalski et al 2005 Miller 2006 (unpublished) Oliveira et al 2007 USA (South Florida) 30.1 Brazil 14.2 ND=Not done. Spencer et al 2005; Matieli et al 2006). Treatment strategies include amikacin and clarithromycin (Wilhelmus 2003). The antifungal activities of the 8-methoxyﬂuoroquino- lones have been investigated. There is both in vitro and in vivo evidence for some efﬁcacy of the 8 methoyl ﬂuoroqui- nolones to reduce fungal loads in the lab and for patients with contact lens associated fungal keratitis. Additional studies need to be done (Ozdek et al 2006; Munir et al 2007) Pharmacokinetics Direct application of topical antimicrobial to conjunctival and corneal tissues can initially provide very high local and aqueous chamber concentrations. Final or sustained concen- trations are altered by rapid tear ﬁlm dissipation, underlying tissue health and dosing frequency (Robertson et al 2005; Stroman et al 2005). Penetration of moxifoxacin has been studied in ocular tissues and ﬂuids in both humans and animals. Human studies have revealed wide variation in drug concentrations. Recorded concentrations are impacted by route of administration, dosing frequency, site of infection, presence or absence of epithelial defect and underlying disease. The recommended dosing frequency for the treatment of bacterial conjunctivitis is one drop 3 times a day for 5 days. (Vigamox 2004; Alfonso and Crider 2005; Robertson et al 2005; Stroman et al 2005) In general, moxiﬂoxacin’s high concentration formula- tion, enhanced bioavailability, and solubility have allowed for levels 2- to 4-fold higher ocular tissues levels than gatiﬂoxacin (Zymar®, Allergan, Irvine CA), ciproﬂoxacin (Ciloxacin®, Alcon, Ft. Worth, TX), levoﬂoxacin (Quixin®, Vistakon Pharmaceuticals, USA), or oﬂoxacin (Ocuﬂox®, Allergan, Irvine, CA) (Cekic et al 1999a; Cekic et al 1999b; Clinical Ophthalmology 2008:2(1) Garcia-Saenz et al 2001; Smith et al 2001; Donnenfeld et al 2004; Hwang 2004; Mah 2004; Koch et al 2005; Robertson et al 2005; Chang Lin and Welty 2006; O’Brien 2006) Table 5 summarizes studies evaluating the penetration of moxiﬂoxacin, gatiﬂoxacin and ciproﬂoxacin into the aqueous and vitreous chambers by topical and oral routes of administration. Topical dosing protocols that mimic pre and post dosing frequencies for cataract and refractive surgeries of 4 times a day, pulsing dosing or a combination of the two, report concentration levels in the aqueous chamber that ranged from 0.38 ± 0.32 μg/mL to 2.28 ± 1.23 μg/mL. Resultant concentration in the vitreous ranged from 0.011 ± 0.008 μg/mL to 0.11 ± 0.05 μg/mL. Vitreal concentrations were 20- to 40-fold lower than those obtained in the aqueous. (Donnenfeld et al 2004; Hariprasad et al 2005; Hariprasad et al 2005; Katz et al 2005; Kim et al 2005a; Kim et al 2005b; Solomon et al 2005; Costello et al 2006; McCulley et al 2006; Ong-Tone 2007). Concentration levels in the aqueous and the vitreous were usually 2-fold higher for moxiﬂoxacin compared to gatifoxacin or ciloxacin. Oral administration of 400–800 mg of moxiﬂoxacin ranged from 0.21 ± 0.21 μg/mL to 2.33 μg/mL ± 0.85 and produced concentrations that were comparable to topical administration in the aqueous chamber. Drug levels were negligible in the vitreous (Garcia-Saenz et al 2001; Kampougeris et al 2005; Hariprasad et al 2006; Vedantham et al 2006; Fuller et al 2007; Walter et al 2007). Pharmacodynamics The therapeutic success or potency of an antibacterial agent is a complex interrelationship between drug and its ability to reach the target site (pharmacokinetics), the microbial pathogen and susceptibility to the selective drug 83