Ciprofloxacin-resistant Pseudomonas keratitis.

OBJECTIVE: To determine ciprofloxacin resistance of corneal isolates of Pseudomonas and to review the clinical response to topical therapy in cases of ciprofloxacin-resistant Pseudomonas keratitis, where medical therapy was begun with 0.3% ciprofloxacin. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Medical and microbiology records of 141 culture-proven cases of Pseudomonas keratitis, examined between January 1991 and June 1998, were reviewed retrospectively. METHODS: All isolates of the Pseudomonas species from corneal scrapings were tested for their susceptibility to routinely used antibiotics by the Kirby-Bauer disc-diffusion method. The minimum inhibitory concentration of ciprofloxacin was determined by the agar-dilution method for most of the isolates found resistant to ciprofloxacin. Clinical response to initial therapy with 0.3% ciprofloxacin was determined in cases of keratitis caused by ciprofloxacin-resistant Pseudomonas. MAIN OUTCOME MEASURES: Resistance of Pseudomonas isolates to ciprofloxacin and clinical response to initial therapy with 0.3% ciprofloxacin. RESULTS: By use of the in vitro antimicrobial susceptibility test, 22 cases of keratitis caused by ciprofloxacin-resistant Pseudomonas were identified. The minimum inhibitory concentration of ciprofloxacin for these isolates was > or =16 microg/ml (mean = 43 microg/ml). Gentamicin resistance occurred in 63.6% of isolates also, but 90.9% ciprofloxacin-resistant isolates were susceptible to amikacin. Fifteen (76.7%) of 19 patients who initially received ciprofloxacin did not show any clinical improvement even after 3 days of intensive medical therapy. The infiltrate resolved in all 8 cases where the antibiotic therapy was modified on the basis of susceptibility test. Four eyes were subjected to penetrating keratoplasty, and three were eviscerated following failure of treatment with ciprofloxacin. CONCLUSION: True resistance to ciprofloxacin is emerging in ophthalmology even among Pseudomonas isolates; therefore, the empiric treatment of infectious keratitis with ciprofloxacin monotherapy must be critically reviewed at this time.     

A comparison of topical chlorhexidine, ciprofloxacin, and fortified tobramycin/cefazolin in rabbit models of Staphylococcus and Pseudomonas keratitis.

AIMS: Chlorhexidine was evaluated as a potential topical therapy for experimental bacterial keratitis. METHODS: Chlorhexidine (0.01%) was compared to ciprofloxacin (0.3%) and tobramycin (1.36%)/cefazolin (5%) both in vitro and in vivo for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa infections. The minimum inhibitory concentration (MIC) was established for each organism for each antibiotic, using a standardized method. One thousand (1000) colony-forming units (CFU) of S. aureus or P. aeruginosa was intrastromally injected into rabbit cornea. A total of 92 corneas were infected and then treated topically with antibiotics. The control eyes were treated with artificial tears. The rabbits were later sacrificed, and the corneal buttons were harvested. RESULTS: The MIC for chlorhexidine was 相似文献   

A laboratory evaluation of antibiotic therapy for ciprofloxacin-resistant Pseudomonas aeruginosa

PURPOSE: The emergence of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) has created a new therapeutic challenge in ophthalmology. We evaluated ophthalmic antibiotics in vitro and in a rabbit keratitis model to determine effective therapy. DESIGN: Experimental laboratory investigation. METHODS: The susceptibilities of 12 CRPA isolates were determined in vitro for amikacin, ceftazidime, tobramycin, polymyxin B, gentamicin, ticarcillin, and the fluoroquinolones (that is, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) using E-tests and National Committee of Clinical Laboratory Standards. A rabbit keratitis model was used to determine the reduction in colony counts of CRPA and ciprofloxacin-susceptible P. aeruginosa (CSPA) isolates following topical treatment with polymyxin B/trimethoprim, tobramycin (14 mg/ml), ceftazidime (50 mg/ml), and ciprofloxacin (3 mg/ml). RESULTS: For 12 CRPA isolates, the susceptibilities and median minimum inhibitory concentrations ([MIC]microg/ml) were as follows: amikacin (92%, 14.0), ceftazidime (75%, 4.0), tobramycin (67%, 1.75), polymyxin B (42%, 7.0), gentamicin (17%, 7.0), ticarcillin (0%, >32.0), and all fluoroquinolones (0%, >32.0). While no antibiotic regimen reduced colony counts in the time frame of the animal model for CRPA, ciprofloxacin alone demonstrated a significant decrease in colony counts for CSPA. Comparing CRPA with CSPA, both tobramycin and ciprofloxacin demonstrated a significant decrease in colony counts for CSPA. CONCLUSION: Our laboratory studies suggest that current antibiotics may be suboptimal in treating CRPA keratitis. Until new antibiotics are available, combination therapy such as fortified tobramycin and ticarcillin, and others may prove effective in aggressive topical long-term therapy.     

Methicillin-resistant Staphylococcus aureus keratitis in the rabbit: therapy with ciprofloxacin, vancomycin and cefazolin.

To determine the efficacy of a fluoroquinolone antibiotic in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) keratitis, topical administration of 0.3% ciprofloxacin was compared with topical 5.0% vancomycin or 5.0% cefazolin in experimental infections in the rabbit eye. The infections were established by intrastromal injection of 100 colony forming units (CFU) of MRSA, which resulted in greater than 10(6) CFU per cornea by 12 hr postinfection. Chemotherapy (one drop every 15 min) was given from 4-9, 10-15, or 10-20 hr postinfection. Early therapy (4-9 hr postinfection) with ciprofloxacin rendered all eyes free of bacteria; ciprofloxacin was significantly more effective than vancomycin or cefazolin. When treatment was initiated 6 hr later (10-15 hr postinfection), no corneas became free of bacteria, but ciprofloxacin was again more effective than vancomycin or cefazolin. Bacterial killing by ciprofloxacin after treatment from 10-20 hr postinfection was also significantly greater than that of vancomycin. Overall, the results show that ciprofloxacin is effective in killing methicillin-resistant staphylococcus aureus, and is most effective when applied during the very early stages of infection.     

Topical 0.5% moxifloxacin prevents endophthalmitis in an intravitreal injection rabbit model.

INTRODUCTION: Intravitreal injections for the treatment of retinal disease have increased the risk of endophthalmitis. We developed a rabbit model to investigate whether topical 0.5% moxifloxacin could prevent endophthalmitis after an intravitreal injection. METHODS: A rabbit model of intravitreal injection to produce endophthalmitis was developed by injecting triamcinolone into the vitreous through a depot of subconjunctival Staphylococcus aureus (10(7) cfu). Endophthalmitis was evaluated clinically and confirmed by culture. The model was tested with a commercially available brand of topical 0.5% moxifloxacin (N = 10) and saline (N = 10). In brief, after bacterial subconjunctival challenge, a topical treatment was administered every 15 min for 1 h. Immediately thereafter, triamcinolone was injected into the vitreous through the treated bacterial depot. Topical 0.5% moxifloxacin and saline were administered QID over the next 72 h. All rabbits were examined daily, euthanized, and tested for viable bacteria when clinical signs of endophthalmitis were observed. RESULTS: Anti-infective treatment with topical 0.5% moxifloxacin prevented the development of endophthalmitis (0/9 rabbits), compared to topical saline (6/10 rabbits; P = 0.01; power = 0.99). CONCLUSIONS: Topical 0.5% moxifloxacin provided effective prophylaxis to prevent endophthalmitis after an intravitreal injection of triamcinolone. This unique model may prove valuable to demonstrate prophylaxis for other anti-infectives at an intravitreal injection site.     

Fourth-generation fluoroquinolone-resistant bacterial keratitis after refractive surgery

We report the first 2 cases of bacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). The first patient had Pseudomonas aeruginosa keratitis after PRK despite treatment with moxifloxacin. The second patient was on gatifloxacin post-LASIK when she had methicillin-resistant Staphylococcus aureus (MRSA) keratitis diagnosed. In both cases, culture susceptibilities showed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical aminoglycosides and surgical intervention was necessary to effect a cure. These cases show the potential limitations in the coverage of these antibiotics.     

Zymar (Gatifloxacin 0.3%) shows excellent Gram-negative activity against Serratia marcescens and Pseudomonas aeruginosa in a New Zealand White rabbit keratitis model

PURPOSE: Whereas gatifloxacin, a newer fluoroquinolone, was engineered to increase its Gram-positive potency, we assessed whether it still retained significant Gram-negative activity in vivo. Specifically, we compared the efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the New Zealand White (NZW) rabbit keratitis model. METHODS: A total of 30 NZW rabbits each were intrastromally inoculated in both eyes with approximately 1000 CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs; microg/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control. One drop was instilled in both eyes every 15 minutes for 5 doses and then every 30 minutes for 14 doses. One hour after the final treatment, the animals were euthanized, and bacterial colony counts from the corneas were determined. RESULTS: For SM, Zymar and Ciloxan significantly reduced (P < 0.001, ANOVA) the colony counts compared with tobramycin and saline control. Zymar was more effective than Ciloxan (P < 0.001, ANOVA). For PA, all antibiotics reduced equivalently the colony counts compared with the saline control (P = 0.005, ANOVA). CONCLUSIONS: The enhanced Gram-positive activity of gatifloxacin is not associated with any decreased Gram-negative activity in vivo. Zymar may prove useful for SM and PA keratitis.     

Activity of newer fluoroquinolones against gram-positive and gram-negative bacteria isolated from ocular infections: an in vitro comparison

BACKGROUND: To determine the antibacterial activity of newer fluoroquinolones and compare their activity between ciprofloxacin-susceptible and resistant bacterial isolates from patients with keratitis and endophthalmitis. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) of ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin was determined for 123 bacterial isolates, using E test. Among the 123 isolates, 68 were gram-positive (Staphylococcus spp, Streptococcus spp, Corynebacterium spp, Bacillus spp.) and 55 were gram-negative (Pseudomonas aeruginosa). The bacterial isolates were divided into three groups: susceptible/intermediate/resistant to ciprofloxacin. The MIC values for various fluoroquinolones were compared between the three groups and between gram-positive and gram-negative bacteria. RESULTS: For gram-positive isolates, median MICs of fourth generation fluoroquinolones were lower than second generation. The median MIC was lowest for gatifloxacin and moxifloxacin (0.094 mg/ml) in ciprofloxacin-susceptible isolates of gram-positive bacteria. For ciprofloxacin-susceptible gram-negative bacteria, the median MIC of ciprofloxacin (0.19 mg/ml) was significantly lower than ofloxacin, levofloxacin, gatifloxacin and moxifloxacin (1.5, 0.5, 0.5 and 2 mg/ml respectively). Ciprofloxacin-resistant isolates of gram-positive bacteria showed higher MIC of levofloxacin, moxifloxacin and gatifloxacin though they remained susceptible to them. None of the fluoroquinolones were effective against ciprofloxacin-resistant gram-negative bacteria. Overall, for gram-positive bacteria, median MICs of levofloxacin, moxifloxacin and gatifloxacin were below ciprofloxacin, the MIC of gatifloxacin and moxifloxacin was equal for gram-positive bacteria. CONCLUSIONS: Levofloxacin, gatifloxacin and moxifloxacin are statistically more effective against gram-positive bacteria, the latter two being equally effective. Ciprofloxacin remains the most effective fluoroquinolone against gram-negative bacteria.     

Quantitative comparison of fluoroquinolone therapies of experimental gram-negative bacterial keratitis

PURPOSE: To determine the effectiveness of topically applied fluoroquinolones for experimental Pseudomonas or Serratia keratitis. METHODS: Bacteria were injected intrastromally (10(3) colony forming units [CFU]). From 16 to 22 hours post-infection (PI), a single topical drop of moxifloxacin (Vigamox, 0.545%), levofloxacin (Quixin, 0.5%), ofloxacin (Ocuflox, 0.3%) or ciprofloxacin (Ciloxan, 0.3%) was applied every 30 minutes. At 23 hours PI, corneas were cultured quantitatively. RESULTS: For Pseudomonas keratitis, untreated eyes contained 7 log CFU/cornea and antibiotic-treated eyes demonstrated a > or = 5-log reduction in CFU/cornea (p < or = 0.0001). Moxifloxacin, levofloxacin, or ciprofloxacin therapies were not significantly different from each other (p > or = 0.67). For Serratia keratitis, untreated eyes contained 7 logCFU/cornea whereas treated eyes had a > or = 2-log reduction (p < or = 0.0001). Moxifloxacin therapy proved most effective (p < or = 0.001). CONCLUSIONS: Overall, moxifloxacin was the most effective of the four fluoroquinolones in reducing CFU/cornea in the rabbit model of gram-negative keratitis.     

Pseudomonas aeruginosa in vitro corneal isolate sensitivity to ofloxacin, ciprofloxacin, and trovafloxacin: a comparative study

PURPOSE: To compare sensitivity of Pseudomonas aeruginosa corneal isolates to ofloxacin, ciprofloxacin, and trovafloxacin. METHODS: Sensitivities of P. aeruginosa corneal isolates to each antibiotic from the periods 1985 to 1987 (n = 32) and 1995 to 1999 (n = 85) were evaluated in vitro with E tests (AB Biodisk; Remel, Lenexa, Kansas). RESULTS: Overall, the percent of P. aeruginosa corneal isolates sensitive in vitro to ofloxacin (106/117, 90.6%) was significantly less than to ciprofloxacin (113/117, 96.6%, P =.016) and trovafloxacin (113/117, 96.6%, P =.016). We observed trends of decreasing sensitivity to ciprofloxacin and trovafloxacin, which were not statistically significant. Sensitivity to ofloxacin remained unchanged; however, sensitivity to ofloxacin was always less than sensitivity to ciprofloxacin and trovafloxacin. CONCLUSION: Although in vitro susceptibilities may not correlate with in vivo efficacy, our data suggest that ciprofloxacin and trovafloxacin are superior to ofloxacin in the treatment of P. aeruginosa keratitis.     

Caspase-1 inhibitor reduces severity of pseudomonas aeruginosa keratitis in mice

PURPOSE: To test an inhibitor of IL-1beta converting enzyme (ICE), with or without ciprofloxacin, in a C57BL/6 mouse model of keratitis induced by Pseudomonas aeruginosa in which corneal perforation is expected. METHODS: Clinical score, histopathology, myeloperoxidase (MPO) activity, bacterial counts, and ELISA analysis were used to assess the efficacy of treatment initiated at 18 hours postinfection (p.i.) with ICE inhibitor versus placebo; and with ICE inhibitor plus ciprofloxacin versus placebo plus ciprofloxacin. Efficacy of the ICE inhibitor was also tested and evaluated for clinical score in experimental corneal infection induced by a clinical isolate and a ciprofloxacin-resistant bacterial strain. RESULTS: Clinical scores were reduced at 3, 5, and 7 days p.i. in ICE inhibitor versus placebo-treated mice; reduced scores also were observed with a combined treatment (ICE inhibitor and ciprofloxacin). Further testing (MPO assay) revealed reduced PMN number, particularly striking in ICE inhibitor and ciprofloxacin versus placebo and ciprofloxacin-treated mice. Corneal protein levels for IL-1beta and MIP-2 also were reduced in mice treated with the ICE inhibitor versus placebo and in ICE inhibitor and ciprofloxacin versus ciprofloxacin and placebo-treated mice. Treatment with ICE inhibitor also reduced clinical scores after corneal infection with a clinical isolate, KEI-1025, and with a ciprofloxacin-resistant P. aeruginosa strain. CONCLUSIONS: Downregulation of IL-1beta by ICE together with ciprofloxacin to kill bacteria may provide alternate therapy to current treatment.     

The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental Pseudomonas keratitis

An aminoglycoside-resistant strain of Pseudomonas aeruginosa was injected intrastromally into the corneas of rabbits, and keratitis was allowed to develop over a 22-h period. Rabbits were treated with either 0.75% ciprofloxacin, 1% norfloxacin, or 1.36% tobramycin administered topically every 15 min for 1 h and then every 30 min for the following 3 h. All therapy ceased 26 h postinoculation. Rabbits were killed 1 h after the treatment, and the number of bacteria per cornea were quantified in terms of bacterial colony-forming units. Aqueous humor specimens were obtained from rabbits receiving norfloxacin and ciprofloxacin, and bioassays were performed to determine drug concentration. Ciprofloxacin caused a 5 log reduction in the number of bacterial colony-forming units, as compared with untreated controls (p less than 0.0001); it also produced a significantly greater reduction in bacterial colony-forming units than either norfloxacin or fortified tobramycin drops (p less than 0.0001). Norfloxacin produced a 2 log reduction in bacterial colony-forming units, as compared with untreated controls (p less than 0.0001). The mean aqueous concentration of norfloxacin (7.5 micrograms/ml) was substantially less than that achieved by ciprofloxacin (30.5 micrograms/ml). We conclude that ciprofloxacin may be a useful broad spectrum, topical chemotherapeutic agent in the therapy of aminoglycoside-resistant P. aeruginosa keratitis.     

Fourth-generation fluoroquinolone-resistant bacterial keratitis

Corneal scrapings were collected from a case of keratitis and microbiological investigations done. Coagulase-negative Staphylococcus (Staphylococcus epidermidis) was identified on culture, and antibiotic susceptibility tests were performed. Treatment was started with topical cefazolin sulfate 5% and gatifloxacin 0.3%; this was subsequently changed to vancomycin 5% and tobramycin sulfate 1.3% based on the sensitivity pattern. The isolates of this bacterium were susceptible to vancomycin, tobramycin, and gentamicin, and resistance was present against moxifloxacin, gatifloxacin, ciprofloxacin, and cefazolin. The case highlights the occurrence of keratitis caused by coagulase-negative Staphylococcus that is resistant to treatment with moxifloxacin.     

Comparative bioavailability and efficacy of fortified topical tobramycin

Topical treatment of severe ocular infections may require the use of antibiotics fortified in concentration beyond commercially available preparations. The authors studied tear pharmacokinetics, tissue bioavailability, epithelial toxicity, and comparative antibacterial efficacy of topical tobramycin concentrations ranging from 0.3-5.0%. Tear pharmacodynamics demonstrate bioassay-measurable levels with each preparation up to 6 hr after a single 50-microliter drop challenge. Comparing various fortified concentration levels yields progressive parallel-biphasic decay curves in antibiotic tear-film concentrations. Both tear and corneal data demonstrate increases in measured antibiotic levels largely proportional to the increases in drug concentration instilled. Tobramycin was undetectable in corneas treated with 0.3% tobramycin, yet measurable with higher drug levels. A rabbit epithelial wound-healing model demonstrated progressive toxicity ranging from no effect of 0.3% tobramycin on healing rates compared with paired controls, to a significant decrease in re-epithelialization rates with 1.1% (P = 0.03) and 4.0% (P = 0.02) tobramycin. Finally, a Pseudomonas aeruginosa keratitis model in the rat demonstrates the antibiotic efficacy of topical tobramycin treatment over untreated controls (P less than 0.00001), and a progressively enhanced efficacy with increasing tobramycin concentrations is suggested. Concentration enhancement of topical ocular medication is useful in the treatment of severe ocular infection.     

Intracameral Vigamox (moxifloxacin 0.5%) is non-toxic and effective in preventing endophthalmitis in a rabbit model

PURPOSE: To determine whether Vigamox (moxifloxacin 0.5% ophthalmic solution) can be safely injected intracamerally to prevent Staphylococcus aureus endophthalmitis in a rabbit model. DESIGN: Animal study. METHODS: The safety and bactericidal-effectiveness of Vigamox were evaluated in three stages using 189 New Zealand White rabbits. (Stage 1) The toxicity of two intravitreal doses of Vigamox (moxifloxacin 500, 250 microg) was compared with vancomycin (1 mg) and saline. (Stage 2) A reproducible rabbit model of Staphylococcus aureus endophthalmitis was established. (Stage 3) The bactericidal effect of intracameral Vigamox (moxifloxacin 500, 250, 125, 50 microg) was compared with vancomycin (1 mg) and saline. Intracameral antibiotic therapy commenced immediately after Staphylococcus aureus intravitreal challenge (5000 cfu). Toxicity was evaluated by masked clinical examination using a slit-lamp, an indirect ophthalmoscope, and corneal-ultrasound pachymetry. The clinical examination included the exterior eye, cornea, anterior chamber, vitreous, and retina. The presentations were graded on a severity scale of 0, 0.5, 1, 2, and 3. The bactericidal efficacy was determined using intracameral colony counts. RESULTS: In the toxicity studies without bacterial challenge, the clinical scores of rabbits injected intracamerally with Vigamox were statistically equivalent to rabbits given intracameral vancomycin or saline. In the efficacy studies, eyes treated intravitreally with Vigamox, at all doses, or vancomycin were negative for Staphylococcus aureus and nontreated controls remained culture-positive. CONCLUSIONS: Vigamox appears to be nontoxic for intracameral injection and effective in preventing experimental endophthalmitis in the rabbit model. Further studies will determine the clinical role of intracameral Vigamox for surgical prophylaxis and postoperative therapy.     

Lomefloxacin is an effective treatment of experimental bacterial keratitis

PURPOSE: Lomefloxacin was evaluated as a potential topical therapy for bacterial keratitis. METHODS: Lomefloxacin was compared with ciprofloxacin in different rabbit keratitis models. A total of 216 corneas were infected with Staphylococcus aureus (ciprofloxacin-susceptible and -resistant), Streptococcus viridans, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens and were treated with lomefloxacin (0.3%), ciprofloxacin (0.3% Ciloxan), and the control phosphate-buffered saline (PBS), respectively. The data were analyzed statistically comparing the decrease in the number of recovered viable bacteria. RESULTS: Compared with PBS-treated control corneas, the colony counts for all bacterial isolates were significantly reduced (p < 0.05) after topical treatment with either lomefloxacin or ciprofloxacin. For gram-positive bacteria, lomefloxacin and ciprofloxacin were equally effective. For gram-negative bacteria, lomefloxacin, while effective, was less so than ciprofloxacin under experimental conditions (p < 0.05). CONCLUSION: Our data, using multiple bacterial keratitis models, suggest that lomefloxacin is promising for therapy of bacterial keratitis. Further clinical studies are needed to expand its use for keratitis therapy.     

A Case Report of Severe Corneal Toxicity following 0.5% Topical Moxifloxacin Use

Moxifloxacin is a widely used topical antibiotic in various bacterial infections of the eye. Its safety and efficacy have been proved by many studies. We report a case of a rare adverse effect following its use. A 10-year-old female who had presented with acute bacterial conjunctivitis in both eyes with no corneal involvement was started on preservative-free 0.5% topical moxifloxacin four times a day. The child developed a severe form of corneal toxicity in both eyes with circumcorneal congestion and corneal edema following its use. The child''s visual acuity had dropped from 20/20 to 20/400 in both the eyes. Topical moxifloxacin was discontinued, following which the cornea cleared dramatically and the visual acuity became normal. This case indicates that though rare, topical moxifloxacin can cause severe keratitis and that more studies need to be conducted to evaluate its safety.Key Words: Topical moxifloxacin, Fluoroquinolones, Keratitis     

In vitro activity of fluoroquinolones, vancomycin, and gentamicin against methicillin-resistant Staphylococcus aureus ocular isolates

PURPOSE: To determine the antibacterial activity of fluoroquinolones, vancomycin, and gentamicin against methicillin-resistant Staphylococcus aureus (MRSA) ocular surface isolates. DESIGN: Retrospective review. METHODS: MRSA isolates were obtained from 21 patients. The MIC(50) (mean inhibitory concentration)(microg/ml) values of 31 MRSA ocular surface isolates were determined for gatifloxacin, moxifloxacin, ciprofloxacin, ofloxacin, vancomycin, and gentamicin using the Etest (AB Biodisk, Solna, Sweden) or the VITEK system (bioMérieux, Inc, Durham, North Carolina, USA). Susceptibility data were interpreted based on criteria specified by the Clinical and Laboratory Standards Institute (CLSI). MAIN OUTCOME MEASURES: MIC(50) values in microg/ml and interpretation of susceptibility or resistance. RESULTS: In vitro resistance rates and median MIC(50) in microg/ml for the MRSA isolates were: gatifloxacin (71%, 8.0), moxifloxacin (68%, 8.0), ciprofloxacin (94%, 8.0), ofloxacin (94%, 8.0), vancomycin (0%, 1.0), and gentamicin (3%, 0.5). CONCLUSIONS: MRSA ocular isolates exhibited a relatively high rate of in vitro resistance to all fluoroquinolones tested, including the fourth generation. In contrast, MRSA isolates were found to be highly sensitive to vancomycin and gentamicin.     

A comparison of moxifloxacin and levofloxacin topical prophylaxis in a fluoroquinolone-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> rabbit model

PURPOSE: Moxifloxacin, a fourth-generation fluoroquinolone (FQ), was compared to levofloxacin, a thirdgeneration FQ, for preventing FQ-resistant, methicillin-resistant Staphylococcus aureus (FQrMRSA) endophthalmitis in a rabbit model. METHODS: Three regimens of topical treatments (moxifloxacin 0.5%, levofloxacin 0.5%, and saline) were tested to prevent endophthalmitis. For each regimen, drops were instilled every 15 min for 1 h into the left eyes of 15 rabbits. After anesthesia, 2 x 10(4) cfu of FQrMRSA was injected into the aqueous. One drop of treatment was given immediately, and another four drops were applied over 24 h. At 24 h, the eyes were clinically graded for endophthalmitis. After the rabbits were sacrificed, the aqueous and vitreous were tapped for bacterial colony counts. RESULTS: Topical moxifloxacin (12/15, 80%) significantly (P = 0.0001) prevented clinical endophthalmitis in more rabbits than levofloxacin (2/15, 13%) or saline (2/15, 13%). The total median clinical score for moxifloxacin treatment (1.0) was significantly (P = 0.0004) lower than that for levofloxacin (20.0) or saline (23.0). Culture-negative eyes were less frequent for levofloxacin (8/15, 53%) and saline (1/15, 7%) treatments than for moxifloxacin treatment (12/15, 80%). CONCLUSION: This in vivo study indicates that moxifloxacin, a fourth-generation FQ, may be more effective than levofloxacin, a third-generation FQ, in preventing experimental FQrMRSA. endophthalmitis.     

Comparison of ophthalmic gatifloxacin 0.3% and ciprofloxacin 0.3% in healing of corneal ulcers associated with Pseudomonas aeruginosa-induced ulcerative keratitis in rabbits.

OBJECTIVE: Evaluation of gatifloxacin 0.3% ophthalmic solution efficacy in a corneal ulcer model of Pseudomonas keratitis. METHODS: Heptanol-induced corneal ulcers in New Zealand White rabbits (n = 41; 8 females/group) were inoculated with 10(6) CFU of Pseudomonas aeruginosa. Gatifloxacin 0.3% dosing varied among 4 groups with frequencies of 16-48 doses/day (days 1-2), 3-16 doses/day (days 3-7), and maintenance dosing of 3-4 doses/day (days 8-22). Ciprofloxacin 0.3% was administered as labeled for corneal ulcers, with 44 doses on day 1, 16 doses on day 2, and 4 doses/day on days 3-21. RESULTS: All eyes showed evidence of infection by 48 hours postinoculation with 36 of 41 eyes (87.8%) exhibiting moderate-to-severe keratitis. All eyes exhibited corneal healing by day 15, with no significant differences among groups. Three of 4 groups receiving gatifloxacin tended to have smaller fluorescein retention area scores than did the ciprofloxacin group. No eyes tested positive for Pseudomonas at the end of the study. No corneal precipitates were found following as many as 48 doses/day of gatifloxacin. CONCLUSION: Ophthalmic gatifloxacin 0.3% is at least as effective as ciprofloxacin at healing corneal ulcers infected with Pseudomonas aeruginosa when gatifloxacin is administered less frequently than ciprofloxacin. Trends favored gatifloxacin in fluorescein retention scores.