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.     

In vitro activity of fluoroquinolones against ocular bacterial isolates in São Paulo, Brazil

PURPOSE: To compare the in vitro susceptibility profiles of bacterial ocular isolates and to determine minimum inhibitory concentrations (MICs) of gatifloxacin and moxifloxacin (fourth-generation fluoroquinolones) versus ciprofloxacin and ofloxacin (second-generation fluoroquinolones). METHODS: Gram-positive and gram-negative isolates were recovered from cases of keratitis, conjunctivitis, and endophthalmitis between 2002 and 2004 and were identified and extracted from the Microbiology Data Bank of the Federal University of S?o Paulo, S?o Paulo, Brazil. The comparison of in vitro MIC and susceptibility profiles for ofloxacin, ciprofloxacin, gatifloxacin, and moxifloxacin in gram-positive and gram-negative (n = 219) isolates was performed using the E test method. RESULTS: The fourth-generation fluoroquinolones were statistically more potent than the second generations for gram-positive bacteria. The MIC90 level was lower for moxifloxacin than that for gatifloxacin against Staphylococcus aureus, methicillin-susceptible coagulase-negative Staphylococcus (CoNS), and S. pneumoniae, whereas the levels were equal against S. viridans and the gatifloxacin MIC90 was lower in methicillin-resistant CoNS. There was no statistically significant difference between moxifloxacin and gatifloxacin when the permutation method from the MULTTEST procedure (SAS proc multtest) was used to obtain the adjusted P value. MIC90 for ciprofloxacin was lower in gram-negative bacteria. MIC90 for ofloxacin was higher against Haemophilus spp. and Moraxella spp. Ciprofloxacin was the most statistically potent fluoroquinolone for Pseudomonas spp. Ciprofloxacin was statistically just as potent as gatifloxacin for the other gram-negative isolates. CONCLUSION: From susceptibility profiles achieved with in vitro testing, the fourth-generation fluoroquinolones may offer some advantages over the currently available fluoroquinolones; however, a combination of the pharmacodynamics and pharmacokinetics of the drug, infection site, and the MIC is needed to predict the in vivo efficacy and best clinical applicability.     

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.     

Penetration of second-, third-, and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model

AIMS: This study was designed to investigate the penetration of second-, third- and fourth-generation topical fluoroquinolone into aqueous and vitreous humour in a rabbit endophthalmitis model. METHODS: Thirty New Zealand white rabbits were divided into six groups. Left eye was infected with an intravitreal inoculum of Staphylococcus aureus. Groups 1, 2, 3, 4, and 5 received topical ofloxacin, ciprofloxacin, lomefloxacin, levofloxacin, or moxifloxacin treatment 24 h after the inoculation, respectively. No treatment was given to group 6 as the control group (n=5). Aqueous and vitreous samples were obtained 30 min after the last drop. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the normal and inflamed eyes, mean aqueous concentrations of ofloxacin were 1.90 and 2.69 mug/ml, ciprofloxacin were 2.16 and 3.65 mug/ml, lomefloxacin were 3.54 and 1.19 mug/ml, levofloxacin were 2.89 and 9.41 mug/ml, and moxifloxacin were 4.92 and 43.33 mug/ml, respectively. Mean vitreous concentrations of ofloxacin were 0.25 and 0.07 mug/ml, ciprofloxacin were 0.08 and 0.32 mug/ml, lomefloxacin were 0.001 and 0.03 mug/ml, levofloxacin were 0.03 and 0.09 mug/ml, and moxifloxacin were 0.28 and 2.68 mug/ml, in normal and inflamed eyes, respectively. Moxifloxacin achieved a significantly higher concentration in aqueous and vitreous humour of infected eyes compared with ofloxacin (P<0.01), ciprofloxacin (P<0.05), lomefloxacin (P<0.01), and levofloxacin (P<0.05). CONCLUSION: This study demonstrated that fourth-generation fluoroquinolone, moxifloxacin, seems to have better penetration to inflamed ocular tissues in rabbit.     

Overview of the potency of moxifloxacin ophthalmic solution 0.5% (VIGAMOX)

Antibiotics have been the mainstay of therapy for infectious diseases since their origins in the 1940s. As microorganisms changed and resistance developed, more advanced antibiotics were ultimately needed to provide adequate coverage and spectrum. By selecting optimal antibiotics and dosing regimens, clinicians can avoid treatment failures and adverse events and can help prevent the emergence of further antibiotic resistance. The fourth-generation ophthalmic fluoroquinolones include moxifloxacin (VIGAMOX, Alcon Laboratories, Inc., Fort Worth, TX) and gatifloxacin (Zymar, Allergan, Irvine, CA), and they are now approved for the treatment of bacterial conjunctivitis. This review highlights four scientific methods that compare and rank antibiotic potencies and predict their clinical efficacy and their propensity to develop resistance: 1) in vitro assay for minimum inhibitory concentrations, 2) in vivo models for pharmacokinetic and pharamacodynamic properties, 3) therapeutic index or inhibitory quotient, and 4) in vitro assay for mutant prevention concentration. The fourth-generation ophthalmic fluoroquinolones perform well in these assays. Both antibiotics have better in vitro activity against gram-positive bacteria than ciprofloxacin or ofloxacin. Moxifloxacin penetrates better into ocular tissues than gatifloxacin and older fluoroquinolones; in vitro activity of moxifloxacin and gatifloxacin against gram-negative bacteria is similar to that of older fluoroquinolones. Moxifloxacin also has better mutant prevention characteristics than other fluoroquinolones. These findings support the use of the newer fluoroquinolones for the prevention and treatment of serious ophthalmic infections (e.g., keratitis, endophthalmitis) caused by susceptible bacteria.     

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates

PURPOSE: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN: Laboratory investigation. METHODS: Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS: MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS: The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.     

Safety of moxifloxacin as shown in animal and in vitro studies

Topical treatment of ocular bacterial infection is practiced widely, and the choice of the antibacterial agent depends on the nature of the infection, including the susceptibility of the organism, the tissue affected, and the safety profile of the agent. Moxifloxacin is a fourth-generation fluoroquinolone approved for ophthalmic use as moxifloxacin ophthalmic solution 0.5% (VIGAMOX, Alcon, Fort Worth, TX). Moxifloxacin ophthalmic solution 0.5% is self-preserved at a near-neutral pH of 6.8. In treating ocular infection, the three important aspects of therapeutic control are potency, penetration of the drug to the target site, and safety of the drug and the drug product. Moxifloxacin ophthalmic solution 0.5% provides antibacterial potency and high penetration of target ocular tissues. The ocular and systemic safety profile of moxifloxacin compares favorably with those of other fluoroquinolone antimicrobial agents, with a low risk of recognized quinolone-related toxicity. In vitro studies of fluoroquinolones with human or rabbit corneal epithelial cells or keratocytes suggest that moxifloxacin is similar in cytotoxicity potential to other drugs of this family. Specialized in vivo corneal wound-healing studies draw little distinction between moxifloxacin-treated eyes and those treated with other fluoroquinolones. Repeated-dose topical ocular studies in rabbits and monkeys, with high concentrations (up to 3%) of moxifloxacin and at treatment durations and regimens well in excess of label-prescribed use, demonstrated a high safety margin for ocular and extraocular tissues. Cornea, the tissue with highest exposure, was found to be unaffected by these high exposures, with slit-lamp biomicroscopy, corneal thickness measurement, intraocular pressure, and specular microscopy of the corneal endothelium (monkeys only), and histologic evaluation showing no effects, as compared with controls. Moxifloxacin ophthalmic solution 0.5% affords superior efficacy and ocular tissue penetration, with a favorable safety profile.     

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS--This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS--Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS--Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS--Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.     

眼部细菌对氟喹诺酮类药物的体外敏感试验研究

目的 探讨眼部细菌对4种氟喹诺酮类抗菌药物体外药物敏感性的异同.方法 非随机对照、回顾性研究.对2005年1月至2006年12月问首都医科大学附属北京同仁医院、北京市眼科研究所微生物室培养阳性的619株细菌,采用纸片扩散法测量抑菌环直径,观察其对加替沙星、左氧氟沙星、氧氟沙星及环丙沙星的药物敏感性.结果 619株细菌中革兰阳性球菌372株(60.1%),革兰阴性球菌7株(1.1%),革兰阳性杆菌60株(9.7%),革兰阴性杆菌177株(28.6%),其他待鉴定3株(0.5%).加替沙星、左氧氟沙星、氧氟沙星及环丙沙星的总敏感性分别为88.4%、72.1%、64.8%及54.4%.常见葡萄球菌对加替沙星的敏感性(89.9%)高于左氧氟沙星(61.6%)、氧氟沙星(48.2%)及环丙沙星(38.8%);链球菌属对加替沙星(93.2%)、左氧氟沙星(89.2%)及氧氟沙星(87.8%)敏感性显著高于环丙沙星(62.2%);革兰阳性杆菌对加替沙星(86.7%)敏感性高于环丙沙星(58.3%),以上差异均有统计学意义(P＜0.0083);革兰阴性球菌、假单胞菌属及肠杆菌科对4种抗菌药物的敏感性比较,差异均无统计学意义(P＞0.0083).结论 眼部多数细菌对加替沙星敏感性的高于其他氟喹诺酮类抗菌药物,尤其是革兰阳性菌.(中华眼科杂志,2008,44:233-236)     

氟喹诺酮药物的眼部表皮葡萄球菌防耐药突变浓度的测定

目的探讨氟喹诺酮药物对眼部分离的表皮葡萄球菌的防耐药突变浓度(MPC),并比较MPC与最低抑菌浓度(MIC)的关系。方法采用标准琼脂二倍稀释法测定表皮葡萄球菌对环丙沙星(CIP)、氧氟沙星(OFL)、左氧氟沙星(LVF)及加替沙星(GTF)的MIC值。挑选血液琼脂培养基上表皮葡萄球菌菌落,置于MullerHinton肉汤(MH)中增菌,菌液浓度至1×108cfu/ml,1∶10稀释,每种药每个浓度MullerHinton琼脂培养基(MHA)上接种1μl菌液,菌接种量104cfu。采用混菌法测定MPC值。以上述各种药物对该菌群的MIC50为参考,选择测定MPC时的药物浓度。每平皿中加入1ml药液和19ml细菌与MHA的混悬液,最终菌接种量约1010cfu。结果GTF的MIC90最低,为0.25mg/L;LVF次之,为0.50mg/L;CIP和OFLMIC90相等,为1.00mg/L。GTF对表皮葡萄球菌的MPC50和MPC90最低,分别是1.00mg/L和2.00mg/L;其次是LVF和CIP,均分别为2.00mg/L和4.00mg/L;OFL的MPC50和MPC90分别是2.00mg/L和8.00mg/L。结论LVF和GTF不仅抗菌作用强,而且在预防表皮葡萄球菌耐药突变方面有着明显的优势。(中华眼科杂志,2006,42989-991)     

A novel in vivo rabbit model that mimics human dosing to determine the distribution of antibiotics in ocular tissues.

PURPOSE: The aim of this study was to establish a novel method to predict the human ocular penetration and distribution of topical antibiotics by using a controlled rabbit model that mimics the human eye with manual blinking and tear flow. METHODS: After anesthetizing the rabbits, a single dose of commercial antibiotic formulations was given with precision directly onto the cornea. This was followed by a 30-min controlled period applying manual blinking (4 blinks/min) and a supplementary tear flow (2 microL/min) that mimics the human eye. Tear samples were collected every 5 min and after euthanasia, conjunctival, aqueous humor, iris-ciliary body, and scleral samples were collected. The corneas were mounted in perfusion chambers to determine the level and continuing rate of release of the antibiotics, the levels of which were all determined using high-performance liquid chromatography analysis. RESULTS: U.S. formulations achieved conjunctival and corneal levels (mug/g) as follows: moxifloxacin, 6.6 +/- 0.3 and 50 +/- 5; tobramycin, 3.1 +/- 1.4 and 20 +/- 5; gentamicin, <2 and <2; levofloxacin, 1.5 +/- 0.3 and 19 +/- 2; gatifloxacin, 0.9 +/- 0.1 and 11 +/- 1; and trimethoprim, <0.1 and 2 +/- 1. Japan formulations achieved conjunctival and corneal levels as follows: levofloxacin 2.1 +/- 0.8 and 12 +/- 2; gatifloxacin, 2.2 +/- 0.9 and 7 +/- 1; ofloxacin, 1.6 +/- 0.5 and 7 +/- 1; and tosufloxacin, 0.7 +/- 0.1 and 1.5 +/- 0.3 (mean +/- standard error, n = 4). CONCLUSIONS: Moxifloxacin achieved the highest levels of antibiotic in ocular tissues. In the conjunctiva and cornea, the moxifloxacin level was 3-30 times the level of other fluoroquinolones, at least twice the level of the aminoglycosides, and 25 times the level of the antibacterial trimethoprim.     

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.     

四种氟喹诺酮类药物对眼部分离细菌的体外敏感试验

目的研究眼部分离细菌对4种氟喹诺酮类药物的敏感性。方法对525份眼部标本行体外细菌培养,K-B法观察培养阳性细菌对环丙沙星、氧氟沙星、左氧氟沙星和加替沙星的敏感性。结果体外培养阳性细菌321株,革兰阳性球菌最多,为245株(76.3%),其次,革兰阴性杆菌48株(15.0%),革兰阳性杆菌20株(6.2%),革兰阴性球菌8株(2.5%),环丙沙星、氧氟沙星、左氧氟沙星和加替沙星的总敏感性分别为59.2%、66.4%、80.7%和96.6%。环丙沙星、氧氟沙星对表皮葡萄球菌的敏感性(47.6%,55.3%)明显低于左氧氟沙星和加替沙星(76.0%和97.1%)(P<0.05)。结论眼部分离细菌以表皮葡萄球菌最多,其次为金黄色葡萄球菌。加替沙星的敏感性最好,其次是左氧氟沙星。     

In vitro and in vivo potency of moxifloxacin and moxifloxacin ophthalmic solution 0.5%, a new topical fluoroquinolone

Fluoroquinolones are a class of synthetic antibacterial agents that were approved for ocular therapy in 1991 and have become popular therapy for the treatment and prevention of various ocular infections. These agents are synthetic, broad-spectrum, rapidly bactericidal, and have good penetration into ocular tissues. Their main mechanism of action is the inhibition of bacterial enzymes needed for bacterial DNA synthesis. However, antibiotic resistance occurred swiftly to the earlier fluoroquinolones and better fluoroquinolones were needed. The fourth-generation fluoroquinolones, such as moxifloxacin and gatifloxacin, have enhanced activity against gram-positive bacteria while retaining potent activity against most gram-negative bacteria. These fourth-generation fluoroquinolones have improved penetration into the anterior chamber and have also demonstrated increased in vivo efficacy in several animal models of ocular infections. In addition, topical ophthalmic antibiotic products can deliver antibiotic concentrations directly to the eye that are thousands of times higher than their MICs. This article reviews published data describing the in vitro potency of moxifloxacin and its in vivo activity for treating and preventing experimental ocular infections.     

Ocular toxicity of fluoroquinolones

The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 microg. Intravitreal injections of ciprofloxacin 100 microg, ofloxacin 50 microg/mL, trovafloxacin 25 microg or less, moxifloxacin 160 microg/0.1 mL or less and pefloxacin 200 microg/0.1 mL are considered safe.     

Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones

The three topical ophthalmic fluoroquinolones recently introduced into the U.S. market--levofloxacin, gatifloxacin, and moxifloxacin--offer several advantages over the previously available fluoroquinolones (norfloxacin 0.3%, ciprofloxacin 0.3%, and ofloxacin 0.3%). These include enhanced spectrum and potency for Gram-positive cocci and possibly atypical mycobacterial species, improved penetration into the anterior segment, and reduced propensity to promote the development of resistance. Although published data and clinical experience with these agents is quite limited given their relatively recent entry into the U.S. market, this perspective will attempt to provide an understanding of the potential role of these newer fluorquinolones in addressing the problem of increasing fluoroquinolone resistance amongst bacterial ocular isolates.     

Fourth-generation fluoroquinolones: new topical agents in the war on ocular bacterial infections

PURPOSE OF REVIEW: The fourth-generation fluoroquinolones, moxifloxacin and gatifloxacin, were introduced in 2003 promising improved spectrum of activity and delayed development of resistance. Although these topical agents have recently been introduced in commercial form, there is already a growing body of evidence showing excellent potency in the war on ocular infections. The purpose of this review is to discuss the literature to date regarding these two agents. RECENT FINDINGS: Since their introduction in 1990 in the United States, fluoroquinolones have rapidly become the standard of care in the topical antibiotic arena. Unfortunately, recent evidence has shown the widespread use of fluoroquinolones, not only in eye care, but also in agriculture, and general medical and surgical use, has lead to decreasing susceptibilities of important ocular bacterial pathogens. Moxifloxacin and gatifloxacin have improved potency and are able to overcome resistant isolates. These agents also provide improved penetration into ocular tissues. SUMMARY: Moxifloxacin and gatifloxacin offer improved spectrum of activity, increased penetration into ocular tissues, and delayed propensity to the development of bacterial antibiotic resistance.     

2007-2013年角膜铜绿假单胞菌感染的细菌耐药性分析

目的 分析2007-2013年北京同仁医院角膜铜绿假单胞菌的药物敏感性和耐药性,以期为临床药物治疗提供指导。设计 实验研究。 研究对象 2007年1月～2013年12月北京同仁医院眼科临床微生物检查送检标本中分离的角膜来源铜绿假单胞菌100株。方法 将角膜分离培养并分纯出的铜绿假单胞菌调制菌液,涂布于Mueller-Hinton（M-H）琼脂平皿并贴上药敏纸片,以进行Kirby-Bauer纸片扩散法的体外药物敏感性试验;根据抑菌圈直径和临床实验室标准化协会（CLSI）标准进行敏感性的判读。基于细菌生化试验的原理,应用ATB半自动细菌鉴定仪行细菌鉴定;采用WHONET 5.6和SPSS 16.0进行数据处理。主要指标 药物敏感性和耐药性。结果 9种试验抗菌药物的敏感率与耐药率依次为：阿米卡星93.8%和3.1%,妥布霉素86.9%和12.1%,庆大霉素67.3%和17.3%,环丙沙星89.1%和8.7%,左旋氧氟沙星88.7%和10.3%,氧氟沙星86.9%和11.1%,加替沙星87.4%和11.5%,莫西沙星41.7%和36.5%,头孢他啶84.8%和8.1%。3%的菌株对所有试验药物均耐药。结论  铜绿假单胞菌对阿米卡星敏感率最高,耐药率最低;环丙沙星、左旋氧氟沙星、氧氟沙星、加替沙星及妥布霉素敏感率均在85%以上,临床应用中应考虑联合用药;角膜分离的铜绿假单胞菌对莫西沙星的耐药率较高,临床应用中应加以注意。     

Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and moxifloxacin

PURPOSE: To study the use of prophylactic fourth-generation fluoroquinolone antibiotics, gatifloxacin and moxifloxacin, and bacterial sensitivity in cases of acute postoperative endophthalmitis following cataract surgery. DESIGN: Retrospective, consecutive, observational case series. METHODS: Forty-two eyes of 42 patients with acute endophthalmitis occurring within six weeks after cataract surgery were identified. All patients were seen in a referral vitreoretinal practice over a two-year time interval. The number of patients using prophylactic gatifloxacin or moxifloxacin and results of bacterial culture and sensitivity to all fluoroquinolone antibiotics were recorded. RESULTS: Thirty-one of 42 eyes (74%) were treated with perioperative gatifloxacin or moxifloxacin and 24 eyes (57%) were continuously taking one of these antibiotics at the time of diagnosis. Nineteen eyes (45%) had a positive bacterial culture. The most frequent organism isolated was coagulase-negative Staphylococcus. Sensitivities were performed for 14 gram-positive organisms, and sensitivities to ciprofloxacin (50%), ofloxacin (44%), levofloxacin (46%), gatifloxacin (38%), and moxifloxacin (38%) were noted. Five organisms were resistant to gatifloxacin and moxifloxacin with a minimum inhibitory concentration of 8 microg/ml. All gram-positive organisms were sensitive to vancomycin. Median visual acuity improved from hand motions to 20/40 at last follow-up. CONCLUSION: Acute endophthalmitis can develop after cataract surgery despite the prophylactic use of fourth-generation fluoroquinolone antibiotics. Gram-positive organisms causing acute endophthalmitis are frequently resistant to all fluoroquinolones, including a significant number of cases resistant to gatifloxacin and moxifloxacin.