Surfactant protein D in Pseudomonas aeruginosa keratitis.

PURPOSE: To determine the importance of surfactant protein D in Pseudomonas keratitis. METHODS: The surfactant D status of wild-type and surfactant D-deficient Black Swiss mice was confirmed by PCR reactions and immunoblot assay. Mouse corneas were infected with one of three strains of P. aeruginosa. At 1, 2, 3, and 6 days postinfection, eyes were scored by slit-lamp examination and bacteria per cornea quantified. RESULTS: Infected wild-type mice had slit-lamp scores on 3 and 6 days postinfection that were significantly lower than those of surfactant D-deficient mice (p

Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection.

It is beyond doubt that the neurotrophin family of proteins plays key roles in determining the fate of the neuron, not only during embryonic development, but also in the adult brain. Neurotrophins such as NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor) can play dual roles: first, in neuronal survival and death, and, secondly, in activity-dependent plasticity. The neurotrophins manifest their effects by binding to two discrete receptor subtypes: the Trk (tropomyosin receptor kinase) family of RTKs (receptor tyrosine kinases) and the p75NTR (p75 neurotrophin receptor). The differential activation of these receptors by the mature neurotrophins and their precursors, the proneurotrophins, renders analysis of the biological functions of these receptors in the adult brain highly complex. Here, we briefly give a broad review of current knowledge of the roles of neurotrophins in the adult brain, including expression of hippocampal plasticity, neurodegeneration and exercise-induced neuroprotection.

Prevalence of pharyngeal and laryngeal abnormalities in Thoroughbreds racing in Australia, and their association with performance.

REASONS FOR PERFORMING STUDY: Little information is available regarding the prevalence of abnormalities of the upper airway and their association with performance in the general population of Thoroughbred racehorses. OBJECTIVES: To describe the prevalence of selected abnormalities of the upper airway and their association with performance in Thoroughbred racehorses in Australia. HYPOTHESIS: That abnormalities of the upper airway of Thoroughbred racehorses are associated with poor race performance. METHODS: Rhinolaryngoscopy was performed after racing and presence and characteristics of abnormalities of the larynx and pharynx were recorded in a prospective cross-sectional study of Thoroughbred horses racing in Victoria, Australia. RESULTS: Rhinolaryngoscopy was performed once on each of 744 horses over 35 months. Fifty abnormalities of the upper airway were detected in 47 horses (6.3%, 95% confidence interval [CI] 4.7-83%). Epiglottic entrapment was detected in 7 horses (0.9%, 95% CI 0.4-1.9%) and was significantly (P = 0.015) associated with superior performance. Grade 2 asymmetry (4 grade scale) of the left arytenoid cartilage was detected in 9 horses (1.2%, 95% CI 0.5-2.4%) and was also associated with superior performance (P<0.001). Ulceration or erosion of the mucosa of the axial surface of one or both arytenoids was detected in 18 horses (2.4%, 95% CI 13-3.8%) and was not associated with alterations in exercise performance (P = 0.31). CONCLUSIONS: Epiglottic entrapment, Grade 2 laryngeal asymmetry and mucosal erosions detected in Thoroughbred racehorses were not associated with impaired performance; therefore, surgical correction and concern over laryngeal function in horses with Grade 2 asymmetry may not be necessary in individuals performing to expectation.

Staphylococcus corneal virulence in a new topical model of infection.

PURPOSE: To develop a topical inoculation model of Staphylococcus aureus keratitis in which scarification, contact lenses, and spermidine are used to inhibit the host defenses and to investigate the role of alpha-toxin in this infection. METHODS: An alpha-toxin-positive parent strain (8325-4), its isogenic alpha-toxin-negative mutant (DU1090), and a genetically rescued form of the mutant (DU1090/pDU1212) were bound to rabbit-specific contact lenses, treated with spermidine (50 mM), and applied to scarified rabbit corneas. Eyes were treated topically with spermidine before and after lens application. Eyes were graded for disease by slit lamp examination (SLE) every 6 hours until 24 hours PI (PI), and erosion diameters were measured. Histopathologic changes and colony forming units (CFUs) of bacteria were determined. RESULTS: Spermidine treatment and inoculation of eyes with Staphylococcus on contact lenses resulted in significant increases in both CFUs per cornea (P = 0.0041) and SLE score (P or= 0.1959) multilog increase in CFUs over the inoculum at 24 hours PI. The alpha-toxin-producing strains, 8325-4 and DU1090/pDU1212, caused significantly more disease than the alpha-toxin-deficient mutant DU1090 at 24 hours PI (P

Lysostaphin is effective in treating methicillin-resistant Staphylococcus aureus endophthalmitis in the rabbit.

PURPOSE: To determine the effectiveness of lysostaphin treatment of experimental endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS: In one experiment, rabbits were injected in the mid-vitreous with 50 or 200 CFU of S. aureus; untreated groups and groups injected intra-vitreally at 8 or 24 hours postinfection with vehicle or lysostaphin (0.1 mg/ml) were compared in terms of CFU/ml vitreous at 24 or 48 hours postinfection. Histopathology of untreated and treated eyes was also compared. To quantify the potency of lysostaphin, additional rabbits were injected with 50 CFU of S. aureus and untreated eyes and eyes treated at 8 hours with 0.001, 0.01 or 0.05 mg/ml were compared in terms of CFU/ml vitreous at 24 hours postinfection. RESULTS: Vitreous of untreated eyes or vehicle-treated eyes injected with 50 or 200 CFU of S. aureus contained 5-10 million CFU/ml at 24 or 48 hours postinfection. All eyes treated with lysostaphin at 8 hours postinfection had less than 1 log CFU/ml in the vitreous (P >or= 0.0001). Similarly, eyes treated with lysostaphin at 24 hours postinfection had approximately 1 log of CFU/ml at 48 hours postinfection. None of the untreated eyes were sterile and 88% or 50% of the eyes treated at 8 or 24 hours postinfection, respectively, were sterile. Eyes treated with lysostaphin at 8, but not 24, hours postinfection had less pronounced pathologic changes than the untreated eyes (P = 0.002). A significant reduction in the CFU/ml vitreous at 24 hours postinfection was obtained by treating infected eyes at 8 hours postinfection with lysostaphin at concentrations of >or=0.001 mg/ml (P

Effectiveness of ciprofloxacin and ofloxacin in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic fluoroquinolone treatment against staphylococci in a rabbit keratitis model. METHODS: Prophylactic ciprofloxacin or ofloxacin was applied as one topical drop 15 minutes before infection or as one drop at three time points (19, 17, and 15 minutes) before infection. In a second experiment, rabbits were treated with two, three, or four drops of ciprofloxacin 1 hour before infection. Approximately 250 colony-forming units (CFUs) of Staphylococcus aureus were injected intrastromally, and CFUs were determined 5 hours after infection. RESULTS: The CFUs per cornea in all treatment groups were significantly less than the 5.6 +/- 0.11 log CFUs per cornea in the untreated group ( p < or = 0.0001). Rabbit eyes treated 15 minutes before infection with Ciloxan or Ocuflox had 0.96 +/- 0.48 log CFUs per cornea (three of six sterile corneas) or 1.26 +/- 0.31 log CFUs per cornea (one of six sterile corneas), respectively ( p = 0.5226). Eyes treated with Ciloxan 19, 17, and 15 minutes before infection had 0.0 +/- 0.0 log CFUs per cornea, and all eyes were sterile, whereas eyes treated with Ocuflox had 0.98 +/- 0.48 log CFUs per cornea and two of six eyes sterile ( p = 0.0435). Eyes treated 1 hour before infection with two, three, or four drops of Ciloxan had 2.61 +/- 0.69 log CFUs, 1.23 +/- 0.32 log CFUs, or 0.85 +/- 0.28 log CFUs per cornea, respectively, which was significantly less than untreated eyes ( p < or = 0.0001). CONCLUSIONS: Multiple topical drops of a fluoroquinolone administered prophylactically were effective for subsequent staphylococcal ocular infection.

Phospholipase A(2) in rabbit tears: a host defense against Staphylococcus aureus.

PURPOSE: This study analyzed rabbit tears for anti-staphylococcal activity, the role of phospholipase A(2) (PLA2) in this reaction, and the ability of enzyme inhibitors to promote bacterial survival. METHODS: Contact lenses with Staphylococcus aureus were applied to scarified rabbit eyes. The colony-forming units (CFU) per cornea or lens were determined and pathology was scored by slit-lamp examination (SLE). The bactericidal activity was measured by incubating bacteria with rabbit tears or PLA2 at 33 degrees or 37 degrees C. Radiolabeled S. aureus was incubated with PLA2 or tears to quantify the release of a membrane component that was identified by thin-layer chromatography. Inhibitors of these reactions were also analyzed. RESULTS: Application of Staphylococcus, on contact lenses, to rabbit corneas resulted in bacterial killing and limited inflammation. Incubation of tears and bacteria (1:1; v/v) in tryptic soy broth at 33 degrees C decreased CFU approximately 4 logs. Tears (> or =30 microl) or PLA2 (> or =30 U) incubated with bacteria in phosphate-buffered saline were bactericidal. PLA2 (> or =0.2 U) or tears (> or =2 microl) cleaved bacterial membranes, liberating arachidonic acid. Spermidine or tetracaine inhibited cleavage of bacterial membranes by tears or PLA2 and spermidine promoted bacterial survival and growth in tears. Tears (60 microl) killed >99% of the bacterial inoculum, whereas bacteria incubated in tears plus spermidine approximately doubled in number. CONCLUSIONS: PLA2 in rabbit tears kills Staphylococcus by hydrolyzing bacterial membranes to release arachidonic acid. Spermidine and tetracaine inhibited PLA2 activity and spermidine protected Staphylococcus from PLA2 in rabbit tears.

Pseudomonas aeruginosa LasA protease and corneal infections.

PURPOSE: A mutant strain of Pseudomonas aeruginosa deficient in LasA protease (staphylolytic protease) has been described as having reduced ocular virulence, suggesting that LasA is a major virulence factor. This study was undertaken to provide further genetic analysis of the role of P. aeruginosa LasA protease in ocular infections. METHODS: LasA protease-deficient mutants of P. aeruginosa PAO1-V and ATCC 19660 were constructed by allelic replacement. Mutants and their respective wild type parent strains were evaluated for virulence and growth in the eye using mouse scarification and rabbit intrastromal injection models of keratitis. RESULTS: LasA protease-deficient mutants of both strains were as virulent as wild type strains, growing to 4 to 6 log10 CFU/cornea and causing significant ocular pathology in the mouse (P > 0.42) and rabbit (P > 0.53). CONCLUSIONS: These data show that LasA protease is not a major corneal virulence factor, suggesting that the main mechanism of corneal damage has yet to be definitively identified.

Corneal virulence of LasA protease--deficient Pseudomonas aeruginosa PAO1.

PURPOSE: Pseudomonas aeruginosa PAO1 deficient in LasA protease was reported to be ocularly avirulent. However, the avirulence of this mutant could not attributed to the loss of LasA protease. The purpose of this study was to define the mechanism for such a mutant's inability to cause corneal disease. METHODS: A LasA protease--deficient mutant of P. aeruginosa PAO1 was constructed by allelic exchange. Virulence of this mutant in mouse and rabbit models of keratitis was assessed by scoring for ocular disease and quantitating viable bacteria from infected corneas. Adherence to scarified mouse corneal tissue was determined with an organ culture assay. RESULTS: In the mouse eye, the LasA protease--deficient mutant was not virulent, despite being as adherent as its parent strain. Virulence of the mutant was also significantly reduced in the rabbit eye. Complementation with lasA did not restore virulence in either model of infection. Neither the mutant nor the mutant complemented with lasA grew well in ocular tissue. An analysis of the mutant showed that it was auxotrophic for leucine. CONCLUSION: These data show that the mutant's avirulence in the eye is caused by poor growth in the ocular environment and not the loss of a functional lasA gene.

Pseudomonas aeruginosa protease IV enzyme assays and comparison to other Pseudomonas proteases.

Pseudomonas aeruginosa secretes multiple proteases that have been implicated as virulence factors and the detection of each specific enzyme can be difficult to determine. Unlike the three Pseudomonas enzymes that have been well characterized (elastase A, elastase B, and alkaline protease), the activity of protease IV in multiple assays has yet to be described. This study defines new assays for Pseudomonas proteases and compares protease IV activity to the activities of elastase A, elastase B, and alkaline protease. Six in vitro assays were studied: zymography, elastin congo red assay, staphylolytic assay, colorimetric peptide assay, solid-phase colorimetric peptide assay, and poly-l-lysine degradation. Casein zymography distinguished protease IV from elastase B and alkaline protease, and gelatin zymography differentiated all four proteases. The elastin congo red assay detected mainly elastase B while the staphylolytic assay was specific for elastase A. Protease IV activity was assayed specifically by the colorimetric assay and two new assays, the solid-phase colorimetric assay and degradation of poly-L-lysine in the presence of EDTA. Alkaline protease could be specifically assayed by poly-L-lysine degradation in the presence of N-alpha-p-tosyl-L-lysine chloromethyl ketone. The results identified three specific assays for protease IV, a new assay specific for alkaline protease, and showed that protease IV has a distinct enzymatic specificity relative to the three other Pseudomonas proteases.

The effectiveness of tobramycin and Ocuflox in a prophylaxis model of Staphylococcus keratitis.

PURPOSE: To determine the effectiveness of prophylactic antibiotic treatment prior to intra-corneal infection with Staphylococcus aureus. METHODS: One topical drop of Tobrex (0.3% tobramycin), tobramycin (0.3%) in the Tobrex vehicle with 0.05% dodecyl maltoside (DDM)/4.0% hydroxypropylmethycellulose (HPMC), Ocuflox (0.3% ofloxacin) or DDM/HPMC vehicle were applied to rabbit eyes at one or five hours prior to injection of bacteria. Approximately 500 colony-forming units (CFU) of S. aureus strain 8325-4 were injected into the corneal stroma. Rabbits were sacrificed five hours after infection and corneal homogenates were cultured to determine the number of colony forming units (CFU) per cornea. RESULTS: Rabbits treated at five hours prior to infection with tobramycin-DDM/HPMC reduced the bacterial load by approximately 2.4 log CFU/cornea as compared to the untreated control (3.47 +/- 0.98 vs. 5.71 +/- 0.14 log CFU/cornea, respectively; P = 0.0010); however, Ocuflox, Tobrex, or DDM/HPMC vehicle did not significantly reduce the log CFU (P >or= 0.4837). Rabbits treated at 1 hour prior to infection with Ocuflox or tobramycin-DDM/HPMC had significantly reduced CFU/cornea (1.31 +/- 0.86 and 0.48 +/- 0.31 log CFU/cornea, respectively) as compared to the untreated group (5.71 +/- 0.14 log CFU/cornea; P or= 0.2312). CONCLUSIONS: This pre-treatment model of Staphylococcus keratitis quantitatively measured the prophylactic effectiveness of topical antibiotic formulations. An important finding was that a tobramycin-DDM/HPMC formulation was highly effective as a prophylactic medication.

Prevention of diseases caused by Staphylococcus aureus using the peptide RIP.

Staphylococcus aureus causes many diseases including cellulitis, keratitis, osteomyelitis, septic arthritis and mastitis. The heptapeptide RIP has been shown to prevent cellulitis in mice, which was induced by S. aureus strain Smith diffuse. Here we show that RIP can also significantly reduce the overall pathology and delay the onset of disease symptoms in several other models of S. aureus infections, including: keratitis (tested in rabbits against S. aureus 8325-4), osteomyelitis (tested in rabbits against S. aureus MS), mastitis (tested in cows against S. aureus Newbould 305, AE-1, and environmental infections) and septic arthritis (tested in mice against S. aureus LS-1). These findings substantiate that RIP is not strain specific in its inhibitory activity and that RIP is an effective inhibitor of bacterial pathology at multiple body sites following diverse routes and doses of administration. These findings strongly evidence the potential value of RIP as a chemotherapeutic agent.

Immunization with alpha-toxin toxoid protects the cornea against tissue damage during experimental Staphylococcus aureus keratitis.

Alpha-toxin is a major virulence factor in Staphylococcus aureus keratitis. Active or passive immunization with alpha-toxin toxoid could protect against corneal damage. Results show that either form of immunization did not kill bacteria but did significantly protect against corneal pathology, especially epithelial erosion.

Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit.

PURPOSE: To determine the efficacy of lysostaphin treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) keratitis in a rabbit model. METHODS: The sensitivity to lysostaphin and vancomycin were compared for 34 MRSA and 12 methicillin-sensitive strains. Methicillin-resistant S. aureus strain 301 (MRSA 301) or a methicillin-sensitive strain of low virulence, ISP546, was intrastromally injected into rabbit corneas. Rabbit eyes were treated topically every 30 minutes from 4 to 9 or 10 to 15 hours postinfection with 0.28% lysostaphin or 5.0% vancomycin. Rabbits were killed and corneas were excised and cultured to determine the number of colony forming units (CFU) per cornea. RESULTS: Ninety percent minimal inhibitory concentrations were at least 19-fold lower for lysostaphin than for vancomycin. With early therapy (4 -9 hours postinfection) lysostaphin sterilized all MRSA 301-infected corneas, whereas untreated corneas contained 6.52 log CFU/cornea (P < or = 0.0001). Corneas infected with MRSA 301 and treated similarly with vancomycin retained 2.3 +/-0.85 log CFU/cornea, and none were sterile. When therapy was begun later (10-15 hours postinfection) the residual bacteria in lysostaphin-treated eyes were significantly less numerous than in vancomycin-treated eyes (0.58 +/- 0.34 vs. 5.83 +/- 0.16 log CFU/cornea, respectively; P < or = 0.0001). Three experiments were performed to demonstrate that lysostaphin penetrated the cornea to kill bacteria in vivo; lysostaphin-treated eyes were found to recover from infection, bacteria that did not cause epithelial defects (ISP546) were susceptible to lysostaphin, and inhibition of lysostaphin when harvesting corneas did not alter the observed therapeutic values of lysostaphin. CONCLUSIONS: Lysostaphin is very effective in treating keratitis mediated by methicillin-sensitive or methicillin-resistant S. aureus.

Serratia marcescens keratitis: strain-specific corneal pathogenesis in rabbits.

PURPOSE: The purpose of this study was to develop an animal model of Serratia keratitis that is suitable to demonstrate the pathology of specific strains. METHODS: Serratia marcescens ocular strains 93-1399-1 and 94-EI-185-2, and an environmental strain (ATCC 14041) were characterized in vitro in terms of their motility, metabolic profiles, ribotypes, and protease production. The strains were then analyzed in the rabbit intrastromal injection model. Slit lamp examination (SLE) and enumeration of bacteria in the cornea was conducted every 6 hours for 30 hours post-infection. In vivo motilities were analyzed by quantification of bacteria in the peripheral and central areas of infected rabbit corneas. RESULTS: All strains were similar in their metabolic activity and production of extracellular proteases. The ocular isolates were distinct from the environmental strain in their ribotyping patterns and in their motility. Each strain grew logarithmically in the cornea up to 6 hours post-infection. SLE scores increased from 0 to 30 hours post-infection for strains ATCC 14041 and 93-1399-1, while the SLE score of strain 94-EI-185-2 reached its maximum at 18 hours post-infection. Strain-specific differences in pathology were noted from 18 to 30 hours post-infection. Strain 94-EI-185-2 produced iritis but only mild corneal changes. Strain 93-1399-1 produced a severe corneal infiltrate encompassing the entire corneal surface as well as severe conjunctival inflammation and iritis. Strain ATCC 14041 produced a localized, severe, exudative corneal abscess that contained infecting bacteria. CONCLUSIONS: A rabbit model of Serratia keratitis was developed in which bacterial growth kinetics and strain-specific ocular pathologic changes were reproducible.

HSV-1 migration in latently infected and naive rabbits after penetrating keratoplasty.

PURPOSE: To investigate the migration of herpes simplex virus type 1 (HSV-1) between latently infected and naive corneal tissues and trigeminal ganglion (TG) in rabbits after penetrating keratoplasty (PKP) and transcorneal epinephrine iontophoresis. METHODS: Two mutants, genetically constructed from HSV-1 strain 17syn+, were used to inoculate rabbit corneas: 17deltaPst, a latency associated transcript (LAT) negative, low-reactivating virus and 17Pr, a high-reactivating, LAT-positive rescuant of 17deltaPst. Latently infected rabbits were given corneal allografts from naive rabbits, and naive rabbits received grafts from latently infected rabbits. Ninety days after PKP, groups of the transplanted rabbits were induced to reactivate by transcorneal epinephrine iontophoresis, but others were not induced. Viral shedding was monitored by tear film cultures. Rabbits were killed 5 days after iontophoresis. Transplanted grafts, recipient corneal rims, and corresponding TG were obtained. Nucleic acids were extracted and amplified for detection of HSV-1 DNA and viral gene transcription. RESULTS: In naive rabbits receiving grafts transplanted from rabbits latently infected with 17Pr (LAT+), 3 of 6 corneal rims contained HSV DNA after induction. In contrast, none of the 5 corneal rims from naive rabbits receiving grafts from rabbits latent with 17deltaPst (LAT-) contained viral DNA. Viral DNA and gene transcripts were detected in 2 of 6 TG from naive rabbits that received grafts from 17Pr (LAT+) latently infected rabbits. In recipient corneal rims and TG of latently infected rabbits receiving grafts from naive rabbits, viral DNA concentration was significantly greater with induced reactivation, compared with the results in noninduced rabbits. The amount of viral DNA in naive grafts transplanted into 17Pr (LAT+) latently infected rabbits was significantly higher with induction than without induction (P = 0.018). More viral DNA and viral gene transcripts were found in tissues from rabbits latently infected with 17Pr (LAT+) than in rabbits latently infected with 17deltaPst (LAT-). CONCLUSIONS: Corneas from latently infected rabbits contain HSV-1 DNA that can replicate after induced reactivation. Viral migration can occur in both anterograde and retrograde directions between the transplanted graft and the recipient corneal rim and TG. The LAT negative HSV-1 construct 17deltaPst has a significantly reduced ability to replicate and migrate.

Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model.

OBJECTIVE: The relative analgesic potency of single doses of oral controlled-release oxycodone and oral controlled-release morphine were compared in a randomized, double-blind trial using a postoperative pain model. METHODS: Women (n = 169) with moderate to severe pain following abdominal hysterectomy received single oral doses of controlled-release oxycodone, 20 mg or 40 mg, or controlled-release morphine, 45 mg or 90 mg. Assessments were made at 30 min, 60 min, then hourly after dosing for 12 h or until remedication. RESULTS: The most precise estimates of relative potency showed that controlled-release oxycodone was 1.8 times more potent than controlled-release morphine for total effect (95% confidence limits 1.09-2.42; lambda 0.44) and 2.2 times more potent for peak effect (95% confidence limits 0.96-4.59; lambda 0.71). Controlled-release oxycodone at doses of 20 mg or 40 mg was comparable with controlled-release morphine at doses of 45 mg or 90 mg, respectively, for total and peak analgesic effects. For the two higher doses, time to peak relief was approximately 1 h shorter with controlled-release oxycodone than with controlled-release morphine. Most patients reported onset of analgesia within 1 h with all doses. Side effects were similar with the two opioids. CONCLUSION: Oral controlled-release oxycodone was twice as potent as oral controlled-release morphine in this single-dose, relative potency assay. When converting patients from oral morphine to oral oxycodone, an initial oral oxycodone dose of one-half the oral morphine dose is recommended.

Clarithromycin for experimental Staphylococcus aureus keratitis.

PURPOSE: Clarithromycin, a macrolide antibiotic not previously tested against the common causes of bacterial keratitis, was analyzed for its effectiveness in reducing the number of viable bacteria in a Staphylococcus keratitis model. An in vivo comparison of the effectiveness of clarithromycin to erythromycin, minocycline, and tetracycline for three strains of Staphylococcus aureus was done. METHODS: Rabbit eyes were intrastromally injected with 100 colony forming units of one of three strains of S. aureus. Two strains were methicillin-sensitive (ATCC 25923 and MSSA 309) and one strain methicillin-resistant (COL). Eyes were treated every 30 minutes with 0.3% clarithromycin, erythromycin, tetracycline, or minocycline from 4 to 9 hours postinfection. The number of colony forming units (CFU) per cornea in all eyes was determined at 10 hours postinfection. RESULTS: Vehicle-treated and untreated eyes (controls) contained over 6 logs of CFU per cornea, a value significantly higher than any of the antibiotic-treated eyes (P < or = 0.0001). Clarithromycin or erythromycin therapy significantly decreased the number of CFU per cornea by approximately 5 logs in the eyes infected with the methicillin-sensitive strains and by approximately 4 logs in the eyes infected with the methicillin-resistant strain. Tetracycline and minocycline were also successful in treating these strains, but overall showed less effectiveness than clarithromycin and erythromycin. CONCLUSIONS: Clarithromycin proved to be an effective ocular medication for the therapy of experimental S. aureus keratitis. The effectiveness of clarithromycin in this model and its known effectiveness for a variety of bacterial pathogens suggests a role for this drug as a useful ocular antibiotic.