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.     

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.     

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.     

Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin,ciprofloxacin, and ofloxacin using bacterial keratitis isolates

PURPOSE: We compared the in vitro susceptibility patterns and the minimum inhibitory concentrations (MICs) of gatifloxacin (GAT) and moxifloxacin (MOX) (fourth-generation fluoroquinolones) to ciprofloxacin (CIP) and ofloxacin (OFX) (second-generation fluoroquinolones) and levofloxacin (LEV; third-generation fluoroquinolone) using bacterial keratitis isolates. The goal was to determine whether the fourth-generation fluoroquinolones offer any advantages over the second- and third-generation fluoroquinolones. DESIGN: Experimental laboratory investigation. In contrast to an epidemiologic prevalence study, this study was designed to compare the relative susceptibility of each bacterial group to different fluoroquinolones by deliberate selection of representative isolates that were both susceptible and resistant to second-generation fluoroquinolones. METHODS: In retrospect, the MICs of 177 bacterial keratitis isolates were determined to CIP, OFX, LEV, GAT, and MOX using E tests. A relative susceptibility analysis was performed for each bacterial group that included separate bacterial groups that were resistant to second-generation fluoroquinolones. The NCCLS susceptibility patterns and the MICs were compared statistically. Comparing MICs, the antibiotic with the lower MICs has greater antibacterial activity. RESULTS: For most keratitis isolates, there were no susceptibility differences among the five fluoroquinolones. The fourth-generation fluoroquinolones did, however, demonstrate increased susceptibility for Staphylococcus aureus isolates that were resistant to CIP, LEV and OFX. In general, CIP demonstrated the lowest MICs for gram-negative bacteria. The MICs for fourth-generation fluoroquinolones were statistically lower than the second-generation fluoroquinolones for all gram-positive bacteria tested. Comparing the two fourth-generation fluoroquinolones, MOX demonstrated lower MICs for most gram-positive bacteria, whereas GAT demonstrated lower MICs for most gram-negative bacteria. CONCLUSIONS: Based on in vitro testing, the fourth-generation fluoroquinolones may offer some advantages over those currently available for the treatment of bacterial keratitis. Clinical studies will be required to confirm these results.     

Ophthalmic infections and their anti-infective challenges

This introduction provides an overview of the succeeding articles contained within this supplement on the new fourth-generation fluoroquinolone antibiotic product, moxifloxacin ophthalmic solution 0.5% (VIGAMOX, Alcon Laboratories, Inc., Fort Worth, TX). Moxifloxacin was developed specifically to address the increasing incidence of resistance to earlier-generation antibiotic molecules. Structural modifications to the moxifloxacin molecule have decreased the likelihood of the development of resistant organisms. This antibiotic has been shown to possess greater activity than previous-generation molecules against gram-positive bacteria while maintaining excellent potency against gram-negative organisms and nontuberculous (atypical) mycobacteria. Moxifloxacin ophthalmic solution 0.5% exhibits enhanced bioavailability due to a unique molecular structure that combines high lipophilicity for enhanced corneal penetration with high aqueous solubility at physiological pH. Numerous studies have shown that moxifloxacin ophthalmic solution 0.5% has high potency against a broad range of microbial species and a favorable profile in terms of safety and tolerability. The results presented in this supplement provide additional evidence for the potential benefits of moxifloxacin ophthalmic solution 0.5% in surgical prophylaxis and treatment of sight-threatening infections, such as bacterial conjunctivitis, endophthalmitis and keratitis.     

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given by different methods before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of 2 new fourth-generation fluoroquinolone antibiotics, gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops, was affected by different methods of administration before cataract surgery. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized study comprised 193 patients. The patients were divided into 2 main groups. One group received gatifloxacin eyedrops and the other, moxifloxacin eyedrops. Each group was subdivided into 4 subgroups. All patients received the drops 4 times a day starting 2 days preoperatively. The first subgroup did not receive any more antibiotics. The second subgroup received the antibiotic drops 3 times, starting approximately 2 hours preoperatively. The third subgroup received a wick soaked in a dilating mixture containing the antibiotic. The fourth subgroup received the wick and the antibiotic drops at the time of preparation for surgery. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and sent under ice by courier to the Provincial Laboratory for analysis by high-performance liquid chromatography. RESULTS: The study included 124 women and 69 men. The mean concentrations in the aqueous humor were 0.19, 0.82, 0.22, and 0.30 microg/mL in the 4 gatifloxacin subgroups, respectively, and 0.38, 2.16, 0.88, and 0.97 microg/mL in the 4 moxifloxacin subgroups, respectively. Analysis of variance showed the differences between the 2 antibiotics to be statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin regardless of the method of administration. Both antibiotics penetrated the aqueous humor well when given in drop form. They reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis. Only moxifloxacin reached these levels when the wick was used.     

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.     

Wirksamkeit neuer Fluorchinolone gegenüber der bakteriellen Normalflora der Bindehaut

BACKGROUND: Our aim was to determine the antibiotic susceptibility of the preoperative conjunctival bacterial flora against 25 commonly used antibiotics, especially the new fluoroquinolones levofloxacin, gatifloxacin, and moxifloxacin. PATIENTS AND METHODS: The Kirby-Bauer disk-diffusion technique was used to test for the in vitro antibiotic susceptibility of conjunctival bacterial strains isolated from 160 patients (median=74 years, mean=71 years) undergoing cataract surgery at the Department of Ophthalmology, Stanford University, CA, USA. RESULTS: Among the 256 bacteria isolated, 201 (79%) were coagulase-negative staphylococci (CNS), 26 Staphylococcus aureus, 15 Streptococcus group D and 14 gram-negative rods. A total of 100 of these 256 strains (39%) were classified as multiresitant (resistant to>or=five antibiotics). The resistance rate (RR) of commonly used antibiotics for all CNS was: gatifloxacin=moxifloxacin相似文献   

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.     

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.     

Future of ophthalmic anti-infective therapy and the role of moxifloxacin ophthalmic solution 0.5% (VIGAMOX)

The vintage antibiotics that were available in the 1950s-1980s were sometimes toxic, had limited spectra, and were bacteriostatic agents, and they have been replaced by significantly broader-spectrum therapies. We ask more of our future antibiotic products for ophthalmology: they must be 1) broad spectrum, 2) convenient to use, 3) useful prophylactically, 4) effective therapeutically, 5) benzalkonium chloride-free, 6) comfortable, and 7) nontoxic. The emergence of antibiotic resistance has focused us on more potent agents effective against resistant strains of bacteria. Fluoroquinolones have become a dominant family of ophthalmic antibiotics. But even the older fluoroquinolones (e.g., ofloxacin, ciprofloxacin) have lost much of their effectiveness against some important ocular isolates. Considering all of the characteristics for an ideal ophthalmic antibiotic product available today, moxifloxacin ophthalmic solution 0.5% represents a primary antibiotic product of choice for treating and preventing ophthalmic infections.     

Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis

We report a case of mycobacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) with fourth-generation fluoroquinolone prophylaxis. While receiving moxifloxacin post LASIK, the patient was diagnosed with moxifloxacin-resistant Mycobacterium chelonae keratitis. Culture susceptibilities revealed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical amikacin and clarithromycin with oral doxycycline and clarithromycin along with flap amputation was necessary to control the infection. This case demonstrates the potential limitations in the coverage of these antibiotic agents.     

Antibiotic susceptibility of preoperative normal conjunctival bacteria

PURPOSE: To determine the antibiotic susceptibility of preoperative conjunctival bacterial flora. DESIGN: In vitro study. METHODS: Antibiotic susceptibility of conjunctival bacterial strains isolated from 164 patients undergoing intraocular surgery was determined using the Kirby-Bauer disk-diffusion technique. RESULTS: Among the 162 bacteria isolated, 124 (76%) were coagulase-negative staphylococci (CNS), with 2% resistant to gatifloxacin and moxifloxacin, and none were resistant to vancomycin or minocycline. Other bacteria isolated were 19 Staphylococcus aureus (S. aureus), 8 Streptococcus Group D, and 11 gram-negative rods. Most S. aureus (>85%) were susceptible to all antibiotics except for the penicillin and macrolide groups. No streptococci were resistant to gatifloxacin, levofloxacin, moxifloxacin, mezlocillin, imipenem, or vancomycin. None of the gram-negative rods were resistant to the fluoroquinolones. Approximately one half of all bacteria were resistant to erythromycin. One in three patients harbored multi-resistant bacteria (resistant to > or = five antibiotics). CONCLUSIONS: Newer-generation fluoroquinolones provide excellent broad-spectrum coverage against conjunctival bacterial flora.     

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.     

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.     

Hydrophilic acrylic intraocular lens as a drug-delivery system for fourth-generation fluoroquinolones

PURPOSE: To evaluate the ability and safety of a hydrophilic acrylic intraocular lens (IOL) as a drug-delivery system for commercially available gatifloxacin and moxifloxacin. SETTING: David J. Apple, MD, Laboratories for Ophthalmic Research, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah, USA. METHODS: Thirty rabbits were divided into 2 similar groups. In Group A (15 rabbits, 30 eyes), hydrophilic acrylic IOLs (C-flex, Rayner Intraocular Lenses, Ltd.) presoaked for 24 hours in commercially available solutions of gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL were implanted after evacuation of the crystalline lens. Group B (15 rabbits, 30 eyes) had topical preoperative and postoperative cataract prophylaxis with gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL; IOLs that were not presoaked were also implanted after evacuation of the crystalline lenses. In both groups, aqueous humor samples were taken 4, 8, or 12 hours after IOL implantation (5 eyes at each time point) to determine the antibiotic concentrations. Clinical examinations were performed 24 hours postoperatively. RESULTS: The antibiotic concentrations in Group A (presoaked IOLs) were statistically significantly higher than those in Group B (topical) for both antibiotics in all postoperative samples except moxifloxacin at 12 hours. In both groups, there was no statistically significant difference between the concentrations of the 2 antibiotics. No eye showed signs of clinical toxicity. CONCLUSION: Results show the C-flex IOL is a safe and effective drug-delivery system for fourth-generation fluoroquinolones.     

Comparative penetration of moxifloxacin and gatifloxacin in rabbit aqueous humor after topical dosing

PURPOSE: To evaluate the aqueous penetration of the fourth-generation fluoroquinolones moxifloxacin and gatifloxacin. SETTING: University of Arizona, Tucson, Arizona, USA. METHODS: Forty eyes of 20 New Zealand white rabbits were divided into 2 experimental groups. In Experiment I rabbits (20 eyes), a commercial preparation of topical gatifloxacin 0.3% was administered to 9 eyes and moxifloxacin 0.5% to 9 eyes; 2 eyes served as a control. Eyes were dosed according to a keratitis protocol; ie, every 15 minutes for 4 hours. The aqueous humor was sampled 10 minutes after the last dose. Experiment II rabbits (20 eyes) were dosed according to a cataract prophylaxis protocol; ie, 4 times a day for 10 days. The aqueous humor was sampled 1 hour after the last dose of antibiotic in 12 eyes and 24 hours after the last dose in 8 eyes. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the keratitis dosing protocol, the mean concentration of moxifloxacin in the aqueous (n=9) was 11.057 microg/mL (range 7.66 to 18.87 microg/mL), which was significantly higher than the mean concentration of gatifloxacin (n=8) (7.570 microg/mL [range 4.75 to 10.86 microg/mL]) (P=.030). In the cataract prophylaxis dosing protocol, the mean aqueous concentration of moxifloxacin (n=6) was 1.745 microg/mL (range 0.92 to 3.87 mg/mL). The mean concentration of gatifloxacin (n=6) was 1.207 microg/mL (range 0.44 to 2.44 microg/mL). The difference was not statistically significant (P=.359). CONCLUSIONS: Higher mean levels (x1.46) of aqueous penetration were achieved with moxifloxacin than with gatifloxacin in the keratitis-dosing model. There was no statistically significant difference between the 2 drugs in the cataract prophylaxis dosing model. Both antibiotics had aqueous levels in excess of the minimum inhibitory concentration for most pathogenic organisms in both models.     

Vitreous penetration of topical moxifloxacin and gatifloxacin in humans

PURPOSE: To determine the vitreous penetration of the new fourth-generation topical fluoroquinolones moxifloxacin 0.5% and gatifloxacin 0.3%. METHODS: A prospective randomized clinical trial comprising 12 eyes of 12 patients scheduled for pars plana vitrectomy between August 2003 and September 2003 was performed in a clinical practice. The patients were randomly assigned to receive topical moxifloxacin 0.5% (n = 6) or gatifloxacin 0.3% (n = 6). One half the patients in each antibiotic group received 1 drop every 15 minutes for a total of 3 doses starting 1 hour before surgery, and the other one half self-administered the antibiotic drop 4 times daily for 3 days before surgery and at 7 am on the day of surgery. Undiluted vitreous samples were obtained and analyzed using high-performance liquid chromatography. RESULTS: Either moxifloxacin 0.5% or gatifloxacin 0.3% was detected in the vitreous in all 12 patients in the study. There was no significant difference between the mean vitreous concentration of moxifloxacin 0.5% given over 1 hour preoperatively (0.012 +/- 0.011 microg/mL) and that given in the 3-day regimen (0.011 +/- 0.008 microg/mL) (P = 0.93). There was also no significant difference between the mean vitreous concentration of gatifloxacin 0.3% given over 1 hour preoperatively (0.001 +/- 0.0003 microg/mL) and that given over 3 days (0.008 +/- 0.006 microg/mL) (P = 0.11). Vitreous concentrations of moxifloxacin 0.5% and gatifloxacin 0.3% in each eye were all lower than the 90% minimum inhibitory concentration for the commonest bacterial isolates causing endophthalmitis. With both dosing regimens, the mean vitreous concentration of moxifloxacin 0.5% was higher than that of gatifloxacin 0.3% administered at the same regimen, but this was not statistically significant. CONCLUSION: Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis.     

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.     

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given in different concentrations in a wick before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops was affected by altering their concentrations in the dilating mixture in which the wick used to dilate the pupil before cataract surgery was soaked. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized open-label study comprised 65 women and 35 men who were divided into 2 main groups. One group received 1 mL of the antibiotic in the dilating mixture and the other, 2 mL. Each group was divided into 2 subgroups, 1 for gatifloxacin and 1 for moxifloxacin. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and couriered to the provincial laboratory for analysis by high-performance liquid chromatography. RESULTS: In the first group, the mean concentration of gatifloxacin in the aqueous humor was 0.30 microg/mL +/- 0.21 (SD) and of moxifloxacin, 0.97 +/- 0.63 microg/mL. When the volume of the antibiotic in the dilating mixture was doubled, the mean concentration increased to 0.34 +/- 0.25 microg/mL and 1.37 +/- 0.79 microg/mL, respectively. Only the increased penetration of moxifloxacin was statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin when given in a wick soaked in the dilating mixture before cataract surgery. Only the penetration of moxifloxacin increased significantly when the volume of the antibiotic in the dilating mixture was doubled. In both groups, only moxifloxacin reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis.