Enoxacin Up-Regulates MicroRNA Biogenesis and Down-Regulates Cytotoxic CD8 T-Cell Function in Autoimmune Cholangitis.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is a prototypical organ-specific autoimmune disease that is mediated by autoreactive T-cell attack and destruction of cholangiocytes. Despite the clear role of autoimmunity in PBC, immune-directed therapies have failed to halt PBC, including biologic therapies effective in other autoimmune diseases. MicroRNA (miRNA) dysregulation is implicated in the pathogenesis (PBC). In the dominant-negative TGF-ß receptor type II (dnTGFßRII) mouse model of PBC, autoreactive CD8 T cells play a major pathogenic role and demonstrate a striking pattern of miRNA down-regulation. Enoxacin is a small molecule fluoroquinolone that enhances miRNA biogenesis, partly by stabilizing the interaction of transactivation response RNA-binding protein with Argonaute (Ago) 2. APPROACH AND RESULTS: We hypothesized that correcting aberrant T-cell miRNA expression with enoxacin in dnTGFßRII mice could modulate autoreactive T-cell function and prevent PBC. Here, we show that liver-infiltrating dnTGFßRII CD8 T cells have significantly decreased levels of the miRNA biogenesis molecules prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and Ago2 along with significantly increased levels of granzyme B and perforin. Enoxacin treatment significantly up-regulated miRNAs in dnTGFßRII CD8 T cells and effectively treated autoimmune cholangitis in dnTGFßRII mice. Enoxacin treatment directly altered T cells both ex vivo and in vitro, resulting in altered memory subset numbers, decreased proliferation, and decreased interferon-γ production. Enoxacin significantly decreased CD8 T-cell expression of the transcription factor, Runx3, and significantly decreased perforin expression at both the mRNA and protein levels. CONCLUSIONS: Enoxacin increases miRNA expression in dnTGFßRII CD8 T cells, reduces CD8 T-cell pathogenicity, and effectively halted progression of autoimmune biliary disease. Targeting the miRNA pathway is a therapeutic approach to autoimmunity that corrects pathological miRNA abnormalities in autoreactive T cells.

Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma.

Imbalance miRNAs contribute to tumor formation; therefore, the development of small-molecule compounds that regulate miRNA biogenesis is an important strategy in oncotherapy. Here, (-)-Gomisin M1 (GM) was found to modulate miRNA biogenesis to inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. GM modulated expression profiles of miRNA and protein in HCC cells and suppressed tumor growth in a mouse model. Mechanistically, GM affected miRNA maturation by targeting TAR RNA-binding protein 2 (TRBP), with an efficacy higher than that of enoxacin, and promoted the binding of TRBP with Dicer. Structural simplification and a preliminary structure-activity relationship study via the synthesis of 20 GM derivatives showed that compound 9 exhibited more potent inhibitory activity in HCC cell proliferation and affinity for TRBP than did GM. These results suggest that TRBP may be a novel potential therapeutic target in HCC and compound 9 may be a potential drug candidate for the treatment of HCC.

Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model.

The prevalence of extensively drug-resistant tuberculosis (XDR-TB), defined as TB that is resistant to isoniazid, rifampin, fluoroquinolones, and aminoglycosides, is rising worldwide. The extent of Mycobacterium tuberculosis resistance to fluoroquinolones depends on the mutation in the DNA gyrase, the only target of fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone against M. tuberculosis, may be lower than its peak serum level for some ofloxacin-resistant strains of Mycobacterium tuberculosis. Therefore, if the MIC of moxifloxacin is lower than its peak serum level, it may be effective against XDR-TB. Our objective was to determine the efficacy of moxifloxacin in treating ofloxacin-resistant TB. We selected isogenic fluoroquinolone-resistant mutants of M. tuberculosis H37Rv in vivo. We infected Swiss mice with either wild-type H37Rv or one of three mutant strains with different MICs that are commonly seen in clinical practice. The MICs of the mutant strains ranged from below to above the peak moxifloxacin level seen in humans (3 µg/ml). Each mouse was treated with one of four moxifloxacin doses for 1 month. Moxifloxacin was effective against mutant strain GyrB D500N, with the lowest MIC (0.5 µg/ml), when the standard dose was doubled. Moxifloxacin reduced mortality in mice infected with mutant strain GyrA A90V with an intermediate MIC (2 µg/ml). However, it had no impact on the mutant strain GyrA D94G with the highest MIC (4 µg/ml). Our study underscores current WHO recommendations to use moxifloxacin when there is resistance to early-generation fluoroquinolones such as ofloxacin, restricting this recommendation to strains with moxifloxacin MICs of less than or equal to 2 µg/ml.

[Enoxacin for type III A prostatitis: a clinical observation].

OBJECTIVE: Chronic prostatitis, especially type III A, is a common disease in adult males, for which there are quite a few therapeutic methods. This study aimed to investigate the clinical efficacy of enoxacin in the treatment of III A prostatitis. METHODS: We selected 198 cases of III A prostatitis with complete treatment and follow-up data from the outpatients, all treated by enoxacin injection for 1 week, followed by oral medication of enoxacin for 2 weeks. Then we evaluated the therapeutic effect based on the NIH-CPSI scores and changes in the indexes of expressed prostatic secretions (EPS). RESULTS: The rate of total effectiveness was 86.4%, cure 8.6% (17/198), remarkable effectiveness 58.1% (115/198), improvement 19.7% (39/198), and ineffectiveness 13.6% (27/198). Only 16 cases (8.1%) complained of transitory gastrointestinal tract discomfort and/or skin itching. CONCLUSION: Enoxacin has desirable efficacy and few adverse effects on type III A prostatitis.

Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs.

The RNA interference (RNAi) process encompasses the cellular mechanisms by which short-noncoding RNAs posttranscriptionally modulate gene expression. First discovered in 1998, today RNAi represents the foundation underlying complex biological mechanisms that are dysregulated in many diseases. MicroRNAs are effector molecules of gene silencing in RNAi, and their modulation can lead to a wide response in cells. Enoxacin was reported as the first and unique small-molecule enhancer of microRNA (SMER) maturation. Herein, the biological activity of enoxacin as SMER is discussed to shed light on its innovative mode of action, its potential in treating different diseases, and the feasibility of using enoxacin as a chemical template for inspiring medicinal chemists. We debate its mechanism of action at the molecular level and the possible impact on future ligand and/or structure-guided chemical optimizations, as well as opportunities and drawbacks associated with the development of quinolones such as SMERs.

Bis­enoxacin blocks alveolar bone resorption in rats with ovariectomy­induced osteoporosis.

Postmenopausal osteoporosis is a common systemic skeletal disease that is associated with estrogen­deficiency. Bone loss associated with bisphosphonates therapy can increase the risk of developing oral osteonecrosis. Recent studies have indicated that enoxacin may inhibit osteoclast formation and bone resorption via a different mechanism from that of bisphosphonates. Therefore, the authors hypothesized that the use of an enoxacin such as bis­enoxacin (BE) in association with bisphosphonates may be effective in the treatment of postmenopausal osteoporosis­associated alveolar bone resorption and reduce the risk of oral osteonecrosis by allowing the dose of bisphosphonates to be reduced. A total of 30 6­month­old female Sprague­Dawley rats were randomly assigned to five groups: The Sham, Vehicle, zoledronic acid (ZOL), low concentrations of BE (BE­L) and high concentrations of BE (BE­H) groups. The results demonstrated that the ZOL, BE­L and BE­H groups had an increased bone volume/tissue volume, trabecular thickness, mineral apposition rate, mineralizing surface/bone surface and a decreased trabecular separation when compared with the Vehicle group. The microscopic evaluation of histological sections clearly supported the results of the micro­computed tomography. The number of tartrate­resistant acid phosphatase­positive osteoclasts was markedly decreased in the ZOL, BE­L and BE­H groups, indicating that BE may inhibit osteoclast formation. The anti­resorptive effect in the BE­H group was close to or better than that exhibited by the ZOL group; however, this effect was poorer in the BE­L group. In conclusion, BE has the potential to block alveolar bone resorption resulting from ovariectomy­induced osteoporosis in rats in a dose­dependent manner.

Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives.

BACKGROUND: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease-induced oxidative stress during oral infection. METHODS: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis-enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham-infected rats. RESULTS: Rats infected with the periodontal pathogens displayed a five-fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone-targeted antiresorptives bis-enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis-enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. CONCLUSION: To the best of the authors' knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone-targeted antiresorptives.

The expanding role of fluoroquinolones.

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose. Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.

Clinical overview of enoxacin.

Enoxacin is a new fluoroquinolone that will be available as oral and intravenous preparations. This drug is bactericidal for a wide range of organisms, including Staphylococcus aureus, S. epidermidis, Enterobacteriaceae and Pseudomonas aeruginosa. In addition, Neisseria gonorrhoeae is exquisitely susceptible, as is Branhamella catarrhalis. The evaluation of the clinical activity of enoxacin is still relatively new, but published studies reveal a good deal of potential in the treatment of infections caused by susceptible bacteria in the urinary tract, upper and lower respiratory tracts, bones and joints, and the gastrointestinal tract. The general use of this drug has been associated with few adverse reactions. Further published data, as well as the results of comparative trials now in progress, will permit a thorough clinical evaluation of this useful drug.

Tissue penetration and clinical efficacy of enoxacin in urinary tract infections.

The fluoroquinolones in general, and particularly enoxacin, show great promise in the treatment of urinary tract infection. Orally administered enoxacin achieves high concentrations in the serum and urine as well as in prostate tissue, kidney and perirenal fat and muscle. These concentrations are generally in excess of the minimum inhibitory concentrations (MIC) for 95% of the common uropathogens, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella spp., Proteus spp., Enterobacter spp., Serratia marcescens and Staphylococcus saprophyticus. In comparative clinical trials, treatment with oral enoxacin has achieved satisfactory clinical results (symptoms improved or absent) in 67 to 96% of patients and satisfactory bacteriological results (less than 10(4) colony count of the original bacteria) in 77 to 98% of patients. Clinical cure or improvement occurred in 94 to 100% of patients in uncontrolled trials, with corresponding satisfactory bacteriological results of 82 to 100%. In a number of studies of patients with difficult-to-treat infections, satisfactory clinical results were achieved in 92 to 100% of patients and satisfactory bacteriological results in 89 to 100% of patients.

Tissue penetration and clinical efficacy of enoxacin in respiratory tract infections.

Enoxacin, in common with other new oral 4-quinolones, has a broad spectrum of antimicrobial activity which includes most pulmonary pathogens (with the exception of Streptococcus pneumoniae, against which its activity is poor); this spectrum has provided the impetus for investigation of its potential in the treatment of respiratory infections. Initial pharmacokinetic studies have demonstrated that the drug has a large volume of distribution and achieves concentrations in the secretions of the respiratory tract that are at least as high as those attained in the serum. These concentrations are sufficient to suggest that enoxacin would be effective treatment for most respiratory infections. Furthermore, the concentration of enoxacin that is achieved within the bronchopulmonary tissues is considerably higher than peak serum concentrations and suggests not only that there is an active transport mechanism, but also that the drug could be expected to eradicate organisms in the lungs such as streptococci that are considered moderately sensitive to the drug in vitro. There are relatively few clinical studies of, and thus limited data on, the efficacy of enoxacin in the treatment of respiratory tract infections. A review of the evidence suggests that enoxacin is as successful as other therapies used in the treatment of acute exacerbations of chronic bronchitis. There have sometimes been failures of eradication of, and occasional superinfections with, pneumococci. Enoxacin is also likely to interact with the metabolism of theophylline and so lead to elevated theophylline plasma concentrations. Hence when these 2 agents are given concurrently, careful monitoring of theophylline concentrations and/or dosage adjustments are recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Review of tissue penetration and clinical efficacy of enoxacin in skin and skin structure infections and in osteomyelitis.

Enoxacin achieves a high penetration into skin tissue and blister fluid, reaching a maximum serum concentration (Cmax) of 3.7 mg/L at a time to reach maximum concentration (tmax) of 1.9 hours and a blister-fluid Cmax of 2.9 mg/L at a tmax of 3.7 hours after an oral dose of 600 mg. The half-life of enoxacin is 6.2 hours in serum and 7.2 hours in blister fluid. In a multicentre, open, non-comparative trial, clinical cure or improvement in skin or skin structure infections was achieved after oral administration of enoxacin 200 to 600 mg twice daily in 88% of 196 evaluable patients. Overall satisfactory bacteriological response was obtained in 76% of patients. In a multicentre, randomised, double-blind trial comparing oral enoxacin 400 mg twice daily with cephalexin 500 mg twice daily, satisfactory clinical outcome was achieved in 92% of 73 evaluable patients receiving enoxacin and in 99% of 72 evaluable patients receiving cephalexin. Furthermore, there was no statistically significant difference between the bacteriological efficacy of the 2 agents. In 3 single-centre trials, satisfactory clinical results were achieved in 75 to 100% of patients, and satisfactory bacteriological results occurred in 47 to 76% of patients after administration of oral enoxacin 400 mg twice daily for 7 to 14 days. In vitro uptake of enoxacin in bone leads to a concentration of 300 micrograms/g, with 83% being retained by bone after 3 washings with saline at pH 7.2. Clinical trials involving oral enoxacin in osteomyelitis are currently under way.

Enoxacin: a reappraisal of its clinical efficacy in the treatment of genitourinary tract infections.

Enoxacin is a 6-fluoronaphthyridinone antibacterial agent with good in vitro activity against Neisseria gonorrhoeae and most Gram-negative urinary tract pathogens. It is less active in vitro against Acinetobacter spp., Pseudomonas aeruginosa, and most Gram-positive bacteria, than against Gram-negative organisms. Enoxacin is rapidly absorbed, with a high oral bioavailability (87 to 91%). Of the absorbed dose, 44 to 56% is excreted unchanged in the urine, with peak urinary concentrations (>500 mg/L within 4 hours) remaining high (>100 mg/L) for up to 24 hours, sufficient to inhibit most urinary tract pathogens. Single (400 mg) and multiple oral dose regimens (100 to 600 mg twice or 3 times daily for 5 to 14 days) of enoxacin are as effective for the treatment of patients with complicated or uncomplicated urinary tract infections as other antibacterial agents such as amoxicillin, cefuroxime axetil, cotrimoxazole (trimethoprim-sulfamethoxazole) or trimethoprim. Noncomparative data suggest that enoxacin is also an effective agent for the treatment of prostatitis. Single 400 mgoral doses of enoxacin produce >/- 95% bacteriological cure rates in gonococcal infections, comparable to those produced by single intramuscular doses of ceftriaxone 250 mg. Perioperative doses of oral enoxacin 200 mg provide effective prophylaxis against postoperative bacteriuria after transurethral resection of the prostate. Concomitant administration of enoxacin with a number of commonly used therapeutic agents (e.g. antacids, methylxanthines, warfarin) affects the pharmacokinetic properties of either enoxacin or the coadministered agents. Enoxacin is reasonably well tolerated, with the incidence of adverse experiences ranging from 0 to 24%. Adverse events are mainly gastrointestinal, neurological or dermatological and resolve with minimal intervention. Overall, although enoxacin exhibits a number of clinical characteristics that are similar to those of other agents for the treatment of genitourinary tract infections, the advantages offered by this agent generally do not outweigh those of alternative fluoroquinolone agents. Thus, it is likely to prove to be yet another addition to the list of agents available for the management of these infections.

Enoxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Enoxacin is a new addition to the class of 4-quinolone antibacterial drugs. It has a broad spectrum of in vitro antibacterial activity, and is particularly potent against Gram-negative organisms and staphylococci. The pharmacokinetic profile of enoxacin is similar to that of ofloxacin, achieving higher plasma and tissue concentrations and possessing a longer half-life than norfloxacin or ciprofloxacin. In comparative studies, clinical and/or bacteriological efficacy was comparable or (in studies which statistically analysed the results) not significantly different between enoxacin and amoxycillin in acute cystitis, acute Gram-negative exacerbations of chronic bronchitis and acute or chronic otitis media, between enoxacin and cephalexin in skin, skin structure and soft tissue infections, between enoxacin and trimethoprim in acute cystitis, between enoxacin and co-trimoxazole in complicated urinary tract infection and between enoxacin and pipemidic acid in suppurative otitis media. Significantly (p less than 0.01) more clinical and/or bacteriological cures were effected by enoxacin than pipemidic acid in acute cystitis and complicated urinary tract infection. In uncomplicated gonococcal infections single oral doses of enoxacin were effective in over 90% of patients. Enoxacin is a well-tolerated, orally active broad spectrum antibacterial drug which should prove a worthwhile alternative to currently available antibacterial therapy.

Enoxacin: in vitro efficacy and its future therapeutic role in the Pakistani health-care system.

Because laboratory microbiological diagnosis is not readily available for 80% of the total population of Pakistan (120 million people), clinicians in large rural areas have been compelled to use several antibiotics in any individual case of resistant and severe infection. This practice has resulted in an increasing number of resistant strains, particularly those of Salmonella, Pseudomonas, Escherichia coli, Klebsiella, Enterobacter, Staphylococcus, and Shigella. Also, multiple resistance to penicillin, ampicillin, carbenicillin, cotrimoxazole, chloramphenicol, fosfomycin, gentamicin, nalidixic acid, vancomycin, amoxicillin, cefotaxime, and cloxacillin has been recognized. In view of this limitation in antimicrobial therapy, enoxacin, a second-generation quinolone, has been assessed in vitro against resistant and other organisms, and its breakpoint sensitivity has been compared with another quinolone, ofloxacin. The findings indicate that new quinolones such as enoxacin may prove to be helpful in the treatment of individuals suffering from severe and resistant bacterial infections for which no microbiologic diagnosis is available.

Enoxacin in the treatment of typhoid fever.

Enoxacin 400 mg twice daily was given orally to 40 patients who had Salmonella typhi- or Salmonella paratyphi-positive blood or bone marrow cultures. One patient was switched to parenteral therapy within 48 hours of study enrollment, but the remaining 39 patients were given enoxacin for 10 to 14 days. All 39 patients were cured by enoxacin, even though 23 (58.9%) strains were resistant to cotrimoxazole and 16 (41%) strains were multiply resistant to ampicillin, chloramphenicol, and cotrimoxazole. No adverse events necessitated the interruption of therapy. In this study, enoxacin was well tolerated and efficacious in the treatment of typhoid fever.

Comparison of enoxacin versus trimethoprim-sulfamethoxazole in the treatment of patients with complicated urinary tract infection.

Given the prevalence of complicated urinary tract infection (UTI) and the resistance patterns of common uropathogens, antimicrobial therapy for complicated UTI must be carefully selected. For patients with complicated UTI who can be treated with oral medication, the quinolones or trimethoprim-sulfamethoxazole (TMP-SMX) are reasonable treatment choices. Enoxacin and TMP-SMX were compared for efficacy, safety, and bacteriologic response in this study. A total of 260 patients with complicated UTI were enrolled in a multicenter, open-label, randomized study and received enoxacin or TMP-SMX. Short-term assessments 5 to 9 days posttherapy and long-term assessments 4 to 6 weeks posttherapy included physical and clinical evaluations, laboratory testing, urine cultures, and susceptibility testing. Although enoxacin and TMP-SMX demonstrated comparable short-term efficacy rates, enoxacin exerted a potent, long-term bacteriologic response, particularly against Escherichia coli. Enoxacin therapy achieved a 94.7% long-term eradication rate against E coli compared with a 76.0% eradication rate against this pathogen with TMP-SMX. Most adverse events were mild, and a comparable incidence (approximately 17%) occurred in both treatment groups. These data indicate that enoxacin is an excellent addition to the armamentarium of agents commonly used in the treatment of patients with complicated UTI.

The role of quinolones in staphylococcal infection.

Quinolones are highly active against gram-negative aerobic bacteria, especially enterobacteriaceae. The minimum inhibitory concentrations against, e.g. Escherichia coli are between 0.008-0.03 mg/l for ciprofloxacin, 0.06-0.25 mg/l for norfloxacin, 0.031-1.0 mg/l for ofloxacin, and 0.063-2.0 mg/l for pefloxacin. Against Staphylococcus aureus, higher concentrations are required in vitro: 0.12-0.5 mg/l for ciprofloxacin and ofloxacin, 0.25-4 mg/l for norfloxacin, and 0.06-0.5 mg/l for pefloxacin. These compounds have been shown to be active at similar concentrations also against Staphylococcus epidermidis and both oxacillin-sensitive and resistant Staphylococcus aureus and Staphylococcus epidermidis. Clinical experience (in the order of number of patients treated) has been gathered most extensively with ciprofloxacin, followed by pefloxacin, ofloxacin, norfloxacin, and enoxacin.

Enoxacin therapy for experimental pseudomonas keratitis.

Pseudomonas keratitis is difficult to treat and aminoglycosides, the drugs now used for this purpose, are not always effective. New drugs are thus needed to cure gentamicin resistant pseudomonas ocular infections. Enoxacin, a new quinolone, active in vitro against Pseudomonas aeruginosa, was evaluated in experimental ulcerative keratitis produced by a gentamicin resistant isolate of Pseudomonas aeruginosa in rabbits. Our study shows that enoxacin eye drops eliminated pseudomonas infection of the cornea and achieved therapeutic levels in the aqueous humor. Supplementation with parenterally given enoxacin augmented this effect. Enoxacin did not penetrate the vitreous. Enoxacin eye drops may be evaluated for their clinical usefulness in case of keratitis caused by Gram-negative bacilli.