Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration

OBJECTIVE: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. METHODS: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 microm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at -70 degrees C until assayed by high-performance liquid chromatography. RESULTS: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean +/- standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 +/- 10.99 microg/g (n = 18), 10.77 +/- 5.90 microg/g (n = 23), and 18.23 +/- 20.51 microg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 +/- 0.231 microg/mL (n = 15), 0.135 +/- 0.111 microg/mL (n = 20), and 0.372 +/- 0.546 microg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). CONCLUSION: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.     

Corneal deposits and topical ofloxacin--the effect of polypharmacy in the management of microbial keratitis

PURPOSE: To report six cases of corneal deposits after administration of topical ofloxacin in the treatment of bacterial keratitis. METHOD/RESULT: Six cases of microbial keratitis treated with multiple topical medications, including topical ofloxacin, resulted in corneal precipitates and poor wound healing. In five cases, the precipitates resolved with discontinuation of ofloxacin treatment. However, in one patient, some residual deposits persisted following discontinuation of ofloxacin. The cornea epithelialised, but deposits were identified subepithelially. DISCUSSION: Fluoroquinolone antibiotic drops have been extensively used in bacterial keratitis because of their ease of availability, broad spectrum of activity, and lack of toxicity. While corneal precipitates have been reported with cases of topical ciprofloxacin and norfloxacin, little has been documented on corneal deposits and topical ofloxacin in the treatment of bacterial keratitis. The predisposing factors resulting in corneal deposits and the role of polypharmacy are important features that may impair epithelialisation. Clinical management should be aimed at reducing the toxic environment and promoting ocular surface stability.     

Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans

The ocular penetration and pharmacokinetics of moxifloxacin in comparison to other fluoroquinolones (ofloxacin, ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin, and lomefloxacin) have been determined by in vitro and ex vivo techniques, as well as in animal and human studies. This article reviews the original pharmacokinetics work performed by Alcon and other studies reported in the ocular fluoroquinolone literature. The results consistently demonstrate higher maximum concentrations for moxifloxacin relative to the other fluoroquinolones in ocular tissues with levels well above its minimum inhibitory concentrations for relevant ocular pathogens. This superior performance is due to the unique structure of moxifloxacin that combines high lipophilicity for enhanced corneal penetration with high aqueous solubility at physiological pH. The latter property creates a high concentration gradient at the tear film/corneal epithelial interface providing a driving force for better ocular penetration for moxifloxacin. In addition, the higher concentration of moxifloxacin in VIGAMOX (i.e., 0.5% vs. 0.3%) allows more antibiotic to be available to ocular tissues. It is clear from the array of studies summarized in this report that moxifloxacin penetrates ocular tissues better (two- to three-fold) than gatifloxacin, ciprofloxacin, ofloxacin, or levofloxacin. This consistent, enhanced penetration of topical moxifloxacin offers powerful advantages for ophthalmic therapy.     

Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous

PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections. SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium. The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery. Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence. RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC. The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL. Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous. The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL. Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous. Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353). Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001). CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes. Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber. The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy.     

Corneal and scleral permeability of quinolones--a pharmacokinetics study.

PURPOSE: To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits. METHODS: The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes. RESULTS: Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.     

Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity

To assess the potential of fluoroquinolones as topical antimicrobial agents, we evaluated in vitro the antimicrobial activity of five fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, and temafloxacin), as well as gentamicin, tobramycin, and cefazolin against 96 isolates of common bacterial corneal pathogens. Ciprofloxacin and temafloxacin were the most active quinolones [minimal inhibitory concentration inhibiting 90% of stains (MIC90) of 1 microgram/ml], followed by ofloxacin (MIC90 2 micrograms/ml), and norfloxacin and pefloxacin (MIC90s 4 micrograms/ml). In contrast, gentamicin and tobramycin MIC90s were 32 and 64 micrograms/ml, respectively; cefazolin MIC90 was greater than 2048 micrograms/ml. The corneal epithelial cytotoxicity of the fluoroquinolones also was evaluated utilizing an in vitro assay of 3H-thymidine uptake of rabbit corneal epithelial cell cultures. The least to greatest toxicity of the fluoroquinolones were as follows: ciprofloxacin and temafloxacin less than norfloxacin less than ofloxacin less than pefloxacin. Our study suggests that the fluoroquinolones, especially ciprofloxacin and temafloxacin, possess excellent in vitro activity against common bacterial corneal pathogens and are less toxic to the corneal epithelium than the aminoglycosides.     

Effect of propolis in the treatment of experimental Staphylococcus aureus keratitis in rabbits

PURPOSE: The aim of this study was to investigate the antimicrobial and anti-inflammatory properties of an ethanolic extract of propolis, a natural resin produced by honeybees, and to determine synergistic activity between ciprofloxacin and propolis in the treatment of experimental Staphylococcus aureus keratitis. METHODS: Sixteen young New Zealand white rabbits were given intrastromal injections of S. aureus strains. Twenty-four hours later, the rabbits were randomly divided into 4 groups: group 1 was treated with topical 0.3% ciprofloxacin drops along with the ethanolic extract of propolis drops; group 2 received topical 0.3% ciprofloxacin drops; group 3 was administered the ethanolic extract of propolis drops, and group 4, the control group, was treated with phosphate-buffered saline (PBS) drops. Drugs were instilled 8 times/day for 72 h. Twenty-four and 96 h after inoculation of bacteria, the eyes were examined by slit lamp to assess corneal opacity. Corneas were removed to count bacteria. RESULTS: Slit lamp examination showed that the corneal opacity scores were significantly lower in eyes that received propolis plus ciprofloxacin than in those treated with ciprofloxacin (p = 0.041) or propolis (p = 0.006) or control eyes treated with PBS (p = 0.0001). There was no significant difference in eyes treated with ciprofloxacin and propolis (p = 1.00). There were significantly fewer bacteria in eyes that received propolis plus ciprofloxacin than in those treated with ciprofloxacin (p = 0.0001) or propolis (p = 0.0001) or control eyes treated with PBS (p = 0.0001). There was no significant difference in eyes treated with ciprofloxacin and propolis (p = 0.38). CONCLUSIONS: Taking these findings into consideration, we suggest that the ethanolic extract of propolis has antimicrobial and anti-inflammatory properties for S. aureus keratitis. The combination of ciprofloxacin and propolis had better therapeutic effects than either agent alone.     

人眼滴用氧氟沙星和环丙沙星及妥布霉素的前房穿透性研究

目的 比较人眼滴用氧氟沙星、环丙沙星及妥布霉素的前房穿透性差异。方法 2003年4～8月在我院门诊预行白内障超声乳化术的老年白内障患者125例(125只单侧眼),使用随机数字表分为3个大组：氧氟沙星组(42只眼),环丙沙星组(41只眼),妥布霉素组(42只眼),每个大组再使用随机排列表分为5个小组,每个小组8或9只眼。按不同大组,术前局部给予0．3％氧氟沙星、0．3％环丙沙星或0．3％妥布霉素,滴眼6次,每次间隔15min。手术时按不同小组,于最后1次给药后7．5、15．0、30．0、60．0、120．0min时抽取前房水约100μl。使用高效液相色谱仪分析前房水中药物浓度。结果 各时间点前房内氧氟沙星浓度均明显高于环丙沙星,氧氟沙星生物利用度是环丙沙星的6倍。高效液相色谱仪未能检测到妥布霉素,故其浓度低于最低检测限0．05μg／ml。结论 人眼滴用氧氟沙星、环丙沙星和妥布霉素的结果表明氧氟沙星前房穿透性最好,提示可作为预防和治疗眼内炎的首选局部用药。     

Penetration of amikacin into aqueous humor of rabbits

Amikacin is an aminoglycoside antibiotic that has poor corneal penetration due to its hydrophilic properties. The purpose of this study was to compare and evaluate the penetration of amikacin sulfate into aqueous humor of the rabbit eye when applied by different routes and concentrations, namely 100 or 250 mg/ml topical fortified amikacin eye drops, 100 or 250 mg/ml amikacin-embedded soft contact lenses and 25 mg subconjunctival amikacin injection. One hour after application, amikacin was not detectable in any of the 100 mg/ml concentration groups. High levels of amikacin above the minimum inhibitory concentration for susceptible bacteria were detected when applied subconjunctivally and by 250 mg/ml topical fortified routes. Topical fortified amikacin 250 mg/ml reached the highest value in the aqueous (p < 0.05). Our results point out the poor corneal penetration of amikacin in standard concentrations from the intact rabbit cornea and that subconjunctival injections might provide satisfactory penetration.     

In vivo effects of fluoroquinolones on rabbit corneas

Purpose: The use of topical fluoroquinolones to treat microbial keratitis is associated with an increased incidence of corneal perforation compared to other standard treatments. This study examined the effects of topical fluoro­quinolones on corneal collagen and keratocytes in intact rabbit corneas and corneas with an epithelial defect. Methods: Studies consisted of one group of intact corneas and one group of corneas where a 6‐mm epithelial defect was created with a surgical scrape. Within each group, eyes were randomly assigned to one of four topical medications (0.3% ciprofloxacin, 0.3% ofloxacin, fortified antibiotics (1.36% tobramycin, 5% cefrazolin) or Tears Naturale (Alcon Laboratories, Frenchs Forest, NSW, Australia). Two drops were instilled hourly for 48 h and then 2‐hourly for an additional 48 h. At 96 h the corneas were removed and processed for light microscopy, immunohistology for collagen IV, V and VI, and apoptosis staining. Results: In intact rabbit corneas there was no demonstrable difference between treatment groups. In corneas with an epithelial defect, both fluoroquinolones delayed epithelial healing when compared to fortified antibiotics or tears. Keratocyte loss was seen in all groups and was greatest in the ofloxacin group. Median stromal thickness with keratocyte loss were: ofloxacin 30%; ciprofloxacin 10%; fortified antibiotics 7.5%; and tears 15% (ofloxacin vs tears, Mann?Whitney = 16.0, P = 0.09). Keratocyte loss did not correlate with the amount of demonstrable apoptosis. Collagens IV, V and VI showed no differences between treatments. Conclusions: These results suggest that ofloxacin is potentially cytotoxic to corneal keratocytes. Such an effect could lead to the observed increased incidence of corneal per­foration in microbial keratitis.     

Ocular penetration of topical ciprofloxacin and norfloxacin drops and their effect upon eyelid flora.

A double blind, prospective study was undertaken to compare aqueous humour penetration of topical 0.3% norfloxacin and 0.3% ciprofloxacin and their effect upon normal eyelid flora in 39 patients undergoing cataract surgery. Lid swabs were taken before and after six 1 hourly applications of single drops of ciprofloxacin or norfloxacin given before surgery. Aqueous humour was aspirated at surgery and antibiotic concentration assayed using high performance liquid chromatography. The mean aqueous humour concentrations were: ciprofloxacin 220 ng ml-1, norfloxacin 140 ng ml-1. Although this difference was not statistically significant (p = 0.112) the trend demonstrated may be relevant clinically, especially considering the greater activity of ciprofloxacin. Both coagulase negative staphylococcal (p = 0.004) and total bacterial (p = 0.019) lid counts dropped sixfold after ciprofloxacin treatment but the smaller reductions noted after norfloxacin application did not achieve statistical significance (p > 0.1). The reduction of external eye flora experienced with ciprofloxacin suggests that this may be a useful presurgical prophylactic agent.     

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.     

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.     

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.     

Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes

 · Background: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. · Methods: Cataract patients (n=224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3×1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50–100 μl aqueous humor was aspirated and stored at –80 °C. The HPLC method was used for measuring the concentration. · Results: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8±327.8 μg/l (range 33–1388 μg/l), norfloxacin 182.1±118.1 μg/l (range 38–480 μg/l) and ofloxacin 563.9±372.1 μg/l (range 64–1455 μg/l). These mean concentration are all above the MIC₉₀ of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC₉₀ of Staphylococcus aureus and Staphylococcus epidermidis · Conclusions: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC₉₀ values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa. Received: 8 September 1997 Revised version received: 19 March 1998 Accepted: 8 April 1998     

Mycobacterium fortuitum keratitis. A comparison of topical ciprofloxacin and amikacin in an animal model.

The effect of topical amikacin or topical ciprofloxacin on Mycobacterium fortuitum keratitis was studied in a rabbit model. Two strains of M fortuitum were used: ATCC-6841 [for which mean inhibitory concentrations (MICs) indicated in vitro sensitivity to both drugs] and a cutaneous isolate from a human infection (for which MICs indicated relative in vitro resistance to amikacin but in vitro sensitivity to ciprofloxacin). Both drugs reduced the number of organisms in eyes infected with either strain (all p values < or = 0.01), but in no cases were organisms eliminated from eyes after 4 days of treatment. Amikacin was more effective in reducing the number of organisms in corneas infected with ATCC-6841 than in corneas infected with the patient isolate (p = 0.004), whereas ciprofloxacin was equally effective for treatment of both strains (p > 0.10). These results suggest that topical amikacin or ciprofloxacin may be useful in the treatment of M fortuitum keratitis. However, neither drug was shown to be more effective for treatment of either strain studied (all p values > 0.3).     

Serratia corneal ulcers: a retrospective clinical study

PURPOSE: To study the clinical and microbiological profile of Serratia corneal ulcers at the Cornea Service of the Wills Eye Hospital. METHODS: This was a retrospective, observational case series. The clinical records of patients with Serratia marcescens corneal ulcers seen at the Cornea Service of the Wills Eye Hospital between January 1, 1998 and December 31, 2002 were reviewed. RESULTS: Twenty-four cases of Serratia keratitis were identified in 21 patients. Two patients (9.5%) had recurrent keratitis, 1 of which recurred twice. Both had corneal graft edema and were on topical steroids and antiglaucoma drops. The Serratia infection in 15 patients (71%) was associated with an abnormal corneal surface. Twelve of these patients (57%) had the ulcer in a corneal graft, 4 (19%) of which were associated with suture infiltrates. Fifteen patients (71%) were on topical medications-15 used corticosteroids and 13 used antiglaucoma drops. Six patients (29%) were contact lens wearers-1 had a concomitant suture infiltrate associated with a corneal graft, and 5 had otherwise healthy corneas. One isolate lacked in vitro susceptibility to ciprofloxacin and ofloxacin but was susceptible to gentamicin and tobramycin. Nineteen patients had a favorable response to medical therapy. Two patients with poor outcome had large corneal ulcers with severe necrosis and thinning associated with delay in treatment. CONCLUSIONS: Serratia marcescens keratitis is associated with the presence of an abnormal corneal surface, use of topical medications, and contact lens wear. Prompt medical therapy results in a good clinical response in the majority of cases.     

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.     

Comparative efficacy of topical moxifloxacin versus ciprofloxacin and vancomycin in the treatment of P. aeruginosa and ciprofloxacin-resistant MRSA keratitis in rabbits

PURPOSE: To evaluate the in vivo efficacy of topical moxifloxacin 0.5% versus ciprofloxacin 0.3% in the treatment of Pseudomonas aeruginosa keratitis and topical moxifloxacin 0.5% versus vancomycin 50 mg/mL in the treatment of ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) keratitis in rabbits. METHODS: Experimental bacterial keratitis was induced in rabbits by corneal intrastromal injection. Infection proceeded for 12 hours, after which topical antibiotics were applied hourly for 12 hours. Corneal homogenates were plated with serial dilutions for quantitative bacteriology. RESULTS: Both moxifloxacin and ciprofloxacin performed significantly better than control in the treatment of Pseudomonas aeruginosa keratitis (P=0.0046 and 0.0069, respectively); there were no significant differences between these 2 drugs in bactericidal activity (P=0.1120). Moxifloxacin performed significantly better than control in the treatment of ciprofloxacin-resistant MRSA (P=0.0321) keratitis, and vancomycin showed a trend toward statistical significance in performing better than control (P=0.0576); there were no significant differences between these 2 drugs in bactericidal activity (P=0.5205). CONCLUSIONS: Topical moxifloxacin 0.5% and ciprofloxacin 0.3% have similar efficacy in the treatment of Pseudomonas aeruginosa keratitis in rabbits. Topical moxifloxacin 0.5% and vancomycin 50 mg/mL have similar efficacy in the treatment of ciprofloxacin-resistant MRSA keratitis in rabbits. These results suggest a potential value for topical moxifloxacin as a broad-spectrum agent in the treatment of bacterial keratitis.     

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.