Comparison of ofloxacin, gentamicin, and tobramycin concentrations in tears and in vitro MICs for 90% of test organisms

Abstract

Concentrations of three anti-infective agents in tear film were monitored after one topical application in rabbits. Ofloxacin concentrations exceeded the MIC for 90% of the organisms tested (MIC90) (gram-negative and gram-positive organisms) for 240 min. Tobramycin concentrations exceeded the MIC90 for 10 min. Gentamicin concentrations exceeded the MIC90 for 20 min for gram-positive organisms and 120 min for gram-negative organisms.The increasing number of bacterial strains resistant to widely used antibiotics has given impetus to the search for new anti-infective agents, including drugs suitable for topical use in the treatment of ocular infection. The fluoroquinolones are a class of compounds possessing bactericidal activity against gram-negative and gram-positive organisms and some anaerobic bacteria. Ofloxacin is a fluoroquinolone that shows promise in treating ocular infections (1, 2). Ofloxacin is active against a broad spectrum of bacterial organisms (9), including many species isolated from ocular sources (4, 5, 10-15). Bacterial resistance to ofloxacin rarely arises, and ofloxacin-resistant strains are generally unable to compete with nonresistant strains (4, 7).The value of ofloxacin in treating ocular infections depends in part on the maintenance of effective concentrations in the eye for sufficient periods. The MIC against 90%o of bacterial strains tested in vitro (MIC90) of an anti-infective compound is a useful gauge of effective concentration. In this study, the durations at effective concentrations of ofloxacin and the commonly used aminoglycosides gentamicin and tobramycin were determined.(Results of this study were reported as a poster presentation at the 61st Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla., May 1989.) Drug concentrations were measured at multiple time points after a single topical application. The test formulations were 0.3% ofloxacin, 0.3% gentamicin (Genoptic Liquifilm; Allergan Pharmaceuticals, Irvine, Calif.), and 0.3% tobramycin (Tobrex Solution; Alcon Laboratories, Fort Worth, Tex.). Healthy female New Zealand albino rabbits (Vista Rabbitry, Vista, Calif.) weighing approximately 2.0 to 3.5 kg were each treated with 50 IL oftest formulation placed in the lower conjunctival cul-de-sac of the left eye with a micropipette. After drug application, the eyelids were held closed for 30 s.Tear samples were collected from the lower conjunctival cul-de-sac with a Schirmer strip before treatment and from 1 to 360 min after treatment. At each time point, tear specimens were obtained from 10 rabbits and specimen weights were recorded. The Schirmer strips containing tear samples were dried immediately under a stream of N2 and stored at -20°C until they were assayed. Ofloxacin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorometric detection. Samples were introduced into the HPLC system with an Intelligent Sample Processor (model 710B; Waters Associates, Inc., Milford, Mass.). Aqueous solvent consis...

Increasing Bacterial Resistance in Pediatric Acute Conjunctivitis (1997–1998)

“…Thus, evaluating antibiotic pharmacokinetics-by comparing concentrations in tears with current MIC 90 s-may better enable clinicians to predict efficacy for some topical antibiotics, similar to our assumptions about antibiotics for other illnesses, such as bacteremia and AOM. Despite the high concentration that topical antibiotics initially deliver to the conjunctiva, with continuous normal blinking and lacrimation, concentrations in adult tears fall below reported tobramycin, gentamicin, and ofloxacin MIC 90 s for H. influenzae after 10, 120, and 240 min, respectively (15,16). In contrast, after 240 min, ciprofloxacin tear concentrations (16.0 g/ml) remain well above the MIC 90 values for H. influenzae and S. pneumoniae (12).…”

Topical Lomefloxacin 0.3% Twice Daily versus Tobramycin 0.3% in Acute Bacterial Conjunctivitis: A Multicenter Double-Blind Phase III Study

“…In fact, lomefloxacin 0.3% ophthalmic solution resulted in supra-MIC 90 values for most pathogens for more than 8 h [10, 11]. This fact together with the postantibiotic effect of lomefloxacin, which lasts up to 1.6 h depending on bacteria and exposure, justifies the twice daily dosage regimen of this drug for the treatment of bacterial conjunctivitis; in contrast, after a single instillation, established antibiotics such as tobramycin or gentamycin need a 4–5 times dosage regimen [12]. …”

Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers

“…Moreover, changes in drug distribution following inflammation must be considered. Particularly, concentrations in tears may be of clinical relevance in the systemic treatment of ocular infections (5,32). The exposure of enoxacin and other gyrase inhibitors in tears is higher than those of most other antibiotics and has been shown to depend primarily on their lipophilicity (18,35).…”