Safety and Efficacy of Black Tea Extract in the Treatment of Acute Bacterial Conjunctivitis: A Rabbit Model.

PURPOSE: To determine the safety and efficacy of black tea extract in the treatment of bacterial conjunctivitis in a rabbit model and compare it with that of gatifloxacin drops. METHODS: Black tea extract was tested in vitro on bacterial cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Forty-two rabbit eyes were cultured with either MRSA (n=21) or P. aeruginosa (n=21) and further divided into a control group (n=5), a tea group (n=8) treated with black tea extract, and a gatifloxacin group (n=8) treated with 0.3% gatifloxacin eye drops. Conjunctival swabs were collected on the third and fifth days. RESULTS: The tea extract successfully inhibited the growth of both organisms at a concentration of 400 mg/mL. Rabbits in the treatment groups showed a reduction in the clinical index on day 2 (P<0.01), unlike the control group (P=0.1), for both organisms. Resolution of conjunctivitis was achieved on days 4 and 5 in the tea and gatifloxacin groups, respectively. On days 3 and 5, while the control group still showed considerable bacterial growth, the tea and gatifloxacin groups showed its inhibition. CONCLUSION: Tea extract has antimicrobial effects similar to those of gatifloxacin in a rabbit model of conjunctivitis.

Globally Vibrio cholera antibiotics resistance to RNA and DNA effective antibiotics: A systematic review and meta-analysis.

BACKGROUND: Vibrio cholera (V. cholera) is a facultative pathogen that colonizes the small intestine and produces cholerae toxin as the primary virulence factor that causes cholera and fatal diarrhea in humans. In recent decades, V. cholera has emerged as a notorious multidrug-resistant enteric pathogen. This meta-analysis estimated the pooled proportion of V. cholera antimicrobial resistance against RNA and DNA effective antibiotics. METHOD: A systematic search was performed for relevant literature until 05 June 2021 in PubMed, Scopus, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate weighted pooled resistance (WPR). RESULTS: The meta-analysis were included 164 articles. The WPR of V. cholera were as follows 76% [67,84] to furazolidone, 65% [29,94] to nitrofurantoin, 55% [44,66] to nalidixic acid, 10% [2,23] to rifampicin, 4%(0, 12) to novobiocin, 4% [2,6] to norfloxacin, 3% [1,4] to ciprofloxacin, 1%(0, 3) to sparofloxacin, 0%(0, 3) to levofloxacin, 0%(0, 2) to ofloxacin, 0%(0, 0) to gatifloxacin. CONCLUSION: V. cholera is a severe problem in Asia and Africa, especially in South Asian countries. The resistance patterns are various in geographical regions. novobiocin 0% (0, 0), and ofloxacin 0% (0, 1) in Africa, gatifloxacin 0% (0, 0), and levofloxacin 0% (0, 6) in Asia and ciprofloxacin 0% (0, 2) in North America are most effective antibiotis. The resistance rate to furazolidone, nalidixic acid, nitrofurantoin, and cephalothin has increased over the years. Monitoring antibiotic resistance and prescribing an appropriate antibiotic is vital to control resistance.

Toxicity, biodegradation of moxifloxacin and gatifloxacin on Chlamydomonas reinhardtii and their metabolic fate.

The novel fourth-generation fluoroquinolones (FQs) were developed to improve the antimicrobial activity and their utilization has rapidly increased in recent years. However, knowledge of the ecotoxicity and microalgae-mediated biodegradation of these novel FQs is limited. In this research, the toxic effects of moxifloxacin (MOX) and gatifloxacin (GAT) on Chlamydomonas reinhardtii as well as their biodegradation and metabolic fate were investigated. The results showed that the toxicity of MOX to C. reinhardtii was higher than that of GAT, and increased with culture time. Chlorophyll fluorescence and pigment content analyses suggested that the decrease in photosynthetic efficiency was primarily caused by the inhibition of electron transport after QA in PSII complex. These FQs induced oxidative damage in cells, and the antioxidation mechanisms of C. reinhardtii were analyzed. The maximum MOX removal of 77.67% by C. reinhardtii was achieved at 1 mg/L MOX, whereas the maximum GAT removal of 34.04% was attained at 20 mg/L GAT. The different hydrophilicity and lipophilicity of these FQs resulted in distinct findings in biodegradation experiments. Identification of the transformation products suggested that the likely biodegradation pathways of FQs by C. reinhardtii were hydroxylation, demethylation, and ring cleavage.

Evaluating the in vitro efficacy of gatifloxacin, levofloxacin and gentamicin against Acanthamoeba cysts.

PURPOSE: To evaluate the in vitro efficacy of three commercial ophthalmic solutions (gatifloxacin, levofloxacin and gentamicin) against cysts of Acanthamoeba species. DESIGN: Experimental study METHODS: Acanthamoeba cysts belonging to genotypes T3, T4 and T5 were incubated with three ophthalmic solutions for different periods of time; 1, 24, 48 and 72 h at 37 °C. After incubation, treated cysts were stained with trypan blue and counted to express the percent of growth inhibition. Additionally, the viability of treated cysts was assessed by culturing them in PYG medium at 30 °C for 72 h as well as on non-nutrient agar plates at 30 °C for 1 month. RESULTS: Acanthamoeba cysts of all genotypes were susceptible to gentamicin and gatifloxacin after exposure for 1 h and 24 h, respectively, and for levofloxacin, cysts of all genotypes were resistant to levofloxacin even after 72 h of incubation. Gentamicin and gatifloxacin showed statistically highly significant difference (P < 0.001), and levofloxacin showed statistically significant difference (P < 0.05) in comparison to non-treated control. CONCLUSIONS: Gentamicin and gatifloxacin were highly effective against Acanthamoeba cysts. Although our results should be confirmed in animal models, this result will guide the choice of the appropriate ophthalmic drugs for early treatment of eye infection caused by Acanthamoeba spp.

Using Mycobacterium tuberculosis Single-Nucleotide Polymorphisms To Predict Fluoroquinolone Treatment Response.

Clinical phenotypic fluoroquinolone susceptibility testing of Mycobacterium tuberculosis is currently based on M. tuberculosis growth at a single critical concentration, which provides limited information for a nuanced clinical response. We propose using specific resistance-conferring M. tuberculosis mutations in gyrA together with population pharmacokinetic and pharmacodynamic modeling as a novel tool to better inform fluoroquinolone treatment decisions. We sequenced the gyrA resistance-determining region of 138 clinical M. tuberculosis isolates collected from India, Moldova, Philippines, and South Africa and then determined each strain's MIC against ofloxacin, moxifloxacin, levofloxacin, and gatifloxacin. Strains with specific gyrA single-nucleotide polymorphisms (SNPs) were grouped into high or low drug-specific resistance categories based on their empirically measured MICs. Published population pharmacokinetic models were then used to explore the pharmacokinetics and pharmacodynamics of each fluoroquinolone relative to the empirical MIC distribution for each resistance category to make predictions about the likelihood of patients achieving defined therapeutic targets. In patients infected with M. tuberculosis isolates containing SNPs associated with a fluoroquinolone-specific low-level increase in MIC, models suggest increased fluoroquinolone dosing improved the probability of achieving therapeutic targets for gatifloxacin and moxifloxacin but not for levofloxacin and ofloxacin. In contrast, among patients with isolates harboring SNPs associated with a high-level increase in MIC, increased dosing of levofloxacin, moxifloxacin, gatifloxacin, or ofloxacin did not meaningfully improve the probability of therapeutic target attainment. We demonstrated that quantifiable fluoroquinolone drug resistance phenotypes could be predicted from rapidly detectable gyrA SNPs and used to support dosing decisions based on the likelihood of patients reaching therapeutic targets. Our findings provide further supporting evidence for the moxifloxacin clinical breakpoint recently established by the World Health Organization.

Design and characterization of multifaceted lyophilized liposomal wafers with promising wound healing potential.

Various dressings are available to heal chronic wounds which many times fail to achieve the expected results. To overcome some of their drawbacks, formulation of a novel dressing; lyophilized liposomal wafers having better wound healing potential has been proposed in the present study. The drug incorporated in the formulation is gatifloxacin (GTX) which is a fourth-generation fluoroquinolone antibiotic having in vitro activity against both Gram-negative and Gram-positive bacteria. The formulation was designed in three stages where at first liposomes were prepared, the liposomes were converted to gel using chitosan and lastly this gel was lyophilized to form liposomal wafers. Liposomes were prepared by varying the concentration of lipid and cholesterol and evaluated for particle size, entrapment efficiency, in vitro cumulative release, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Liposomes were converted to liposomal gel using chitosan and evaluated for texture, clarity, viscosity, spreadibility and in vitro drug release. Finally, this liposomal batch was subjected to lyophilization to convert it to liposomal wafers and subjected to SEM, differential scanning calorimetric, X-ray diffraction and drug release studies. The in vivo studies were carried out on Wistar rats where wound healing potential of the wafers was confirmed by histopathological evaluation.

Comparison of Mutant Prevention Concentrations of Fluoroquinolones Against ESBL-Positive and ESBL-Negative Klebsiella pneumoniae Isolates from Orthopedic Patients.

The majority of Klebsiella pneumonia isolates possess the extended-spectrum beta-lactamase (ESBL) enzymes. Therefore, K. pneumoniae can easily develop drug resistance. How to effectively overcome the problem of drug resistance in K. pneumoniae is still a research hotspot. This study aimed to compare the mutant prevention concentration (MPC) of ESBL-positive and ESBL-negative K. pneumoniae isolated from orthopedic patients, which may provide a basis for the effective use of drugs to control the enrichment of resistance mutants of K. pneumoniae. The MPC90 values of 55 isolates of ESBL-positive K. pneumoniae against 4 fluoroquinolones were 32 µg/mL for levofloxacin and gatifloxacin, 16 µg/mL for ciprofloxacin, and 4 µg/mL for gemifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin and 2 for gemifloxacin and gatifloxacin, respectively. For ESBL-negative K. pneumoniae isolates, the MPC90 values were 16 µg/mL for levofloxacin and ciprofloxacin, 4 µg/mL for gemifloxacin, and 32 µg/mL for gatifloxacin. The selection index value was 8 for levofloxacin and ciprofloxacin, 2 for gemifloxacin, and 4 for gatifloxacin. For the ESBL-positive K. pneumoniae, the %T>MIC90 order was gemifloxacin > levofloxacin > ciprofloxacin > gatifloxacin. For the ESBL-negative K. pneumoniae, the %T>MIC90 order was levofloxacin > gemifloxacin > ciprofloxacin > gatifloxacin. The mutant-preventing ability of gatifloxacin and gemifloxacin was the strongest among the 4 fluoroquinolones. So gemifloxacin may be the first choice of drug to treat K. pneumoniae infection.

Different responses of representative denitrifying bacterial strains to gatifloxacin exposure in simulated groundwater denitrification environment.

The impact of antibiotics on denitrification in the ecological environment has attracted widespread attention. However, the concentration threshold and inhibitory effect of the same antibiotic on denitrification mediated by mixed denitrifying microbes were conflicting in some studies. In this study, Paracoccus denitrificans, Acidovorax sp., and Pseudomonas aeruginosa were selected as representative denitrifying bacterial strains to explore the response of a single strain to gatifloxacin (GAT) exposure in groundwater denitrification. The results showed that the nitrate and nitrite removal efficiencies of Pseudomonas aeruginosa decreased by 34.87-36.25 % and 18.27-23.31 %, respectively, with exposure to 10 µg/L GAT, accompanied by a significant decline in denitrifying enzyme activity and gene expression. In contrast, the elevated denitrifying enzyme activity and gene expression of Paracoccus denitrificans promoted its nitrate and nitrite reduction by 2.09-10.00 % and 0-8.44 %, respectively. Additionally, there were no obvious effects on the removal of nitrate and nitrite by Acidovorax sp. in the presence of 10 µg/L GAT, which was consistent with the variation in denitrifying enzyme activity and total gene expression levels. The fit results of the Monod equation and its modification further elucidated the nitrate degradation characteristics from the perspective of denitrification kinetics. Furthermore, antibiotic resistance gene (ARG) analysis showed that the addition of 10 µg/L GAT (approximately 30 days) did not observably increase the relative abundance of ARGs. This study provides some preliminary understanding of the response differences of representative denitrifying bacterial strains to antibiotic exposure in groundwater denitrification.

Characterizing the gene mutations associated with resistance to gatifloxacin in Mycobacterium tuberculosis through whole-genome sequencing.

OBJECTIVES: Gatifloxacin (GAT), a fourth-generation fluoroquinolone (FQ), is used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQ resistance, mutations conferring resistance to GAT remain inadequately characterized. METHODS: GAT-resistant mutants were selected from 7H10 agar plates containing 0.5 mg/L GAT (critical concentration). Mutations involved in GAT resistance were identified through whole-genome sequencing. RESULTS: In total, 123 isolates demonstrated resistance to GAT. Among these isolates, 55.3% (68/123) had gyrA gene mutations [G280A (D94N), A281G (D94G), G280T (D94Y) and G262T (G88C)]. The remainder (44.7%, 55/123) harboured gyrB gene mutations [A1495G (N499D), C1497A (N499K), C1497G (N499K) and A1503C (E501D)]. CONCLUSIONS: Mutations in the gyrA and gyrB genes are the main mechanisms of GAT resistance. These findings provide new insight into GAT resistance, and contribute to molecular diagnosis of GAT resistance in the clinical setting.

Effects of moxifloxacin and gatifloxacin stress on growth, photosynthesis, antioxidant responses, and microcystin release in Microcystis aeruginosa.

Moxifloxacin (MOX) and gatifloxacin (GAT) are fourth-generation fluoroquinolone antibiotics that are frequently detected in surface water environments and pose a threat to aquatic organisms. However, research into their toxicity to Microcystis aeruginosa, a cyanobacterium, has thus far been limited. In the present study, we investigated the effects of these antibiotics on M. aeruginosa growth, photosynthesis, oxidative stress, and microcystin (MC) release. The results of the 96 h EC50 values of MOX and GAT were 60.34 and 25.30 µg/L, respectively, and the risk quotients calculated indicated that these antibiotics could pose considerable ecological risks at actual environmental concentrations. Photosynthetic fluorescence intensity was shown to decline markedly, and Fv/Fm significantly decreased without any evidence of recovery, suggesting that the organism's photosystems were irreversibly damaged. Chlorophyll a and carotenoid content decreased, whereas the ratio of carotenoids to chlorophyll a increased, indicating that carotenoids were less susceptible to damage than chlorophyll a. The reactive oxygen species and malondialdehyde content significantly increased, as well as the superoxide dismutase and catalase activities, indicating that exposure caused serious oxidative stress. Additionally, MC release increased. These results demonstrate that the environmental risks posed by MOX and GAT should be given serious consideration, particularly as their use is increasing.

In Vitro Antimicrobial Activity of Quinolones Against Major Bacterial Isolates from the Ocular Surface Bacterial Flora of Tertiary Hospital Patients in Japan.

Purpose: To determine the in vitro antimicrobial activity of quinolones against major bacterial isolates from the ocular surface bacterial flora of patients in a tertiary hospital for selection of optimal antibiotic eye drop during the perioperative stage. Methods: The conjunctival sac scraping of 933 patients who underwent ophthalmic surgery was cultivated and bacterial species of the isolates were identified. The minimum inhibitory concentrations (MICs) of gatifloxacin (GFLX), moxifloxacin (MFLX), levofloxacin (LVFX), and tosufloxacin (TFLX) were measured by microdilution methods. The cumulative percentages of MICs of 4 quinolones against major bacteria were calculated. The concentrations of quinolones inhibiting 50% (MIC50) and 90% (MIC90) of the major bacteria were compared. Results: The study mainly included 784 patients scheduled for cataract surgery, 73 for vitrectomy, 30 for corneal transplantation, 30 for conjunctival surgery, 11 for eyelid surgery. The most frequently isolated bacterium was coagulase-negative Staphylococci (CNS) (184 strains), followed by Corynebacterium (107 strains), Staphylococcus aureus (33 strains), Streptococcus (18 strains), and Enterococcus (13 strains). The percentages of methicillin-sensitive CNS isolates for which MIC of GFLX, MFLX, LVFX, and TFLX was 0.06 µg/mL or less were 8.0%, 13.4%, 5.4%, and 63.4%, respectively. Similarly, the percentage for Corynebacterium was 23.0%, 23.0%, 0%, and 35.6%, respectively. MIC50 of TFLX for Streptococcus and Enterococcus showed the lowest values, 0.12 and 0.25 µg/mL, respectively. Conclusions: Among 4 quinolones, TFLX has the highest in vitro antimicrobial activity against major bacterial isolates from the ocular surface bacterial flora of patients in a tertiary hospital.

Fluoroquinolones suppress gluconeogenesis by inhibiting fructose 1,6-bisphosphatase in primary monkey hepatocytes.

Dysglycemia is one of the most serious adverse events associated with the clinical use of certain fluoroquinolones. The purpose of this study was to investigate the effects of the representative fluoroquinolones moxifloxacin and gatifloxacin on hepatic gluconeogenesis using primary monkey hepatocytes. Glucose production was induced after the cells were incubated for 4 h with 10 mM sodium lactate and 1 mM sodium pyruvate as gluconeogenic substrates. Under these conditions, moxifloxacin and gatifloxacin dose-dependently suppressed gluconeogenesis at concentrations of 100 µM or higher. Transcriptome analysis of rate-limiting enzymes involved in hepatic gluconeogenesis revealed that moxifloxacin and gatifloxacin at a concentration of 1000 µM did not affect the expression of key gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase, glucose 6-phosphatase, and fructose 1,6-bisphosphatase. Furthermore, metabolome analysis, in vitro glucose production assay using additional gluconeogenic substrates, and fructose 1,6-bisphosphatase assay using the cell extracts showed that fluoroquinolones enzymatically suppressed hepatic gluconeogenesis by inhibiting fructose 1,6-bisphosphatase. These inhibitory effects may involve in the clinically relevant dysglycemia associated with fluoroquinolones in human.

The Search for Antifungal Prophylaxis After Artificial Corneal Surgery-An In Vitro Study.

PURPOSE: To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) and some promising antiseptics for antifungal prophylaxis in the setting of artificial corneal implantation. METHODS: Several commonly used antibiotics for antimicrobial prophylaxis after artificial corneal implantation, in addition to antiseptics [benzalkonium chloride (BAK), povidone-iodine (PI), and some ionic liquids (ILs)], were tested in vitro against Candida albicans, Fusarium solani, and Aspergillus fumigatus. The time-kill activity was determined. Toxicity was assayed in vitro on human corneal epithelial cultures using trypan blue. Adhesion and tissue invasion experiments were also carried out on porcine corneas and commonly used contact lenses, with or without gamma irradiation, and by analysis with fluorescence microscopy. RESULTS: Polymyxin B (PMB)/trimethoprim/BAK (Polytrim), PMB alone, gatifloxacin with BAK (Zymaxid), and same-concentration BAK alone exhibited antifungal activity in vitro. Moxifloxacin (MOX) or gatifloxacin without BAK-as well as trimethoprim, vancomycin, and chloramphenicol-had no effect. 1% PI and ILs had the highest efficacy/toxicity ratios (>1), and Polytrim was species dependent. Subfungicidal concentrations of Polytrim reduced adhesion of C. albicans to Kontur contact lenses. Gamma-irradiated corneas showed enhanced resistance to fungal invasion. CONCLUSIONS: Of antibiotic preparations already in use for bacterial prophylaxis after KPro surgery, Polytrim is a commonly used antibiotic with antifungal effects mediated by both PMB and BAK and may be sufficient for prophylaxis. PI as a 1% solution seems to be promising as a long-term antifungal agent. Choline-undecanoate IL is effective and virtually nontoxic and warrants further development.

Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo.

Gatifloxacin is a 4th generation fluoroquinolone antibiotic used in the clinic to treat ocular infection. One limitation of gatifloxacin is its relatively poor corneal penetration, and the increase of its trans-corneal delivery would be beneficial to reduce the amount or frequency of daily dose. In this study, ultrasound treatment was applied to enhance the trans-corneal delivery of gatifloxacin without damage. Experiments were conducted on mouse eyes in ex vivo and in vivo conditions. Ultrasound waves with 1 MHz in frequency, 1.3 W/cm2 in intensity were applied onto the mouse cornea for 5 minutes, and then gatifloxacin ophthalmic solution was instilled and left there for 10 minutes. 3D gatifloxacin distribution in the cornea was measured by two-photon microscopy (TPM) imaging based on its intrinsic fluorescence. Longitudinal TPM imaging of ultrasound treated mouse corneas showed the increase of initial gatifloxacin intensities on the corneal surface compared to untreated mouse corneas by 67%, and then the increased gatifloxacin delivery into the cornea from the surface at later time. The delivered gatifloxacin in the corneal epithelium stayed longer in the ultrasound treated corneas than in the untreated corneas. The enhanced trans-corneal delivery and extended stay of gatifloxacin in the mouse cornea by ultrasound treatment could be beneficial for therapeutic effects. This study demonstrated the detail process of enhanced trans-corneal gatifloxacin delivery by ultrasound treatment.

First derivative synchronous fluorescence spectroscopy for the determination of Gatifloxacin in presence of its oxidative degradation product: Application to pharmaceutical preparation.

A highly accurate and precise spectrofluorimetric method was established for quantitation of Gatifloxacin in pure material, pharmaceutical formulations and in the existence of its oxidative degradation product. The emission was recorded at 487 nm after the excitation at 290 nm. Using micelle, sodium dodecyl sulphate (SDS), enhanced fluorescence intensity of Gatifloxacin-SDS complex. The optimization of numerous experimental conditions was carried out. The improved emission showed a suitable linear correlation between derivative synchronous fluorescence power and concentration of Gatifloxacin over the range of 10 to 100 ng/mL with a determination coefficient equals 0.9996. Studying cytotoxicity and antimicrobial susceptibility for oxidative degradation product of Gatifloxacin was carried out using Gatifloxacin as a control. In comparison, the proposed method presented a superior sensitivity and enhanced stability over the reported method.

Different molecular characteristics and antimicrobial resistance profiles of Clostridium difficile in the Asia-Pacific region.

Molecular epidemiology of Clostridium difficile infection (CDI) has been extensively studied in North America and Europe; however, limited data on CDI are available in the Asia-Pacific region. A multicentre retrospective study was conducted in this region. C. difficile isolates were subjected to multilocus sequence typing (ST) and antimicrobial susceptibility testing. Totally, 394 isolates were collected from Hangzhou, Hong Kong, China; Busan, South Korea; Fukuoka, Japan; Singapore; Perth, Sydney, Australia; New York, the United States. C. difficile isolates included 337 toxin A-positive/B-positive/binary toxin-negative (A+B+CDT-), 48 A-B+CDT-, and nine A+B+CDT+. Distribution of dominant STs varied geographically with ST17 in Fukuoka (18.6%), Busan (56.0%), ST2 in Sydney (20.4%), Perth (25.8%). The antimicrobial resistance patterns were significantly different among the eight sites (χ2 = 325.64, p < 0.001). Five major clonal complexes correlated with unique antimicrobial resistances. Healthcare-associated (HA) CDI was mainly from older patients with more frequent antimicrobial use and higher A-B+ positive rates. Higher resistance to gatifloxacin, tetracycline, and erythromycin were observed in HA-CDI patients (χ2 = 4.76-7.89, p = 0.005-0.029). In conclusion, multiple C. difficile genotypes with varied antimicrobial resistance patterns have been circulating in the Asia-Pacific region. A-B+ isolates from older patients with prior antimicrobial use were correlated with HA-CDI.

Comparative Study Between Topical Gatifloxacin 0.5% and Moxifloxacin 0.5% as a Prophylactic Measure Before Intraocular Surgery.

Purpose: To compare equal concentrations (0.5%) of moxifloxacin and gatifloxacin ophthalmic solutions with regard to conjunctival bacterial reduction as well as anterior chamber penetration. Methods: One hundred patients were divided into 2 groups. Group A received moxifloxacin 0.5% ophthalmic solution and group B received gatifloxacin 0.5% ophthalmic solution 4 times a day for 3 days before surgery and 5 times with 30 min intervals on the day of surgery. Two conjunctival swabs were obtained: one before instillation of antibiotic and the second 30 min after instillation of the last antibiotic drop. Specimens were sent for culture and susceptibility testing. At the time of surgery, 0.1 mL of aqueous fluid was aspired, and aqueous concentration of fluoroquinolones was identified using reverse-phase high-pressure liquid chromatography assay technique. Results: The most common flora isolated was coagulase-negative Staphylococcus (32.9%), followed by Staphylococcus aureus (24.8%) and Corynebacterium diphtheria (19.1%). Moxifloxacin aqueous concentration was higher compared with gatifloxacin [1.75 ± 0.98 standard deviation (SD) and 0.75 ± 0.22 SD, respectively]. This 2.3-fold difference in aqueous humor antibiotic concentrations was statistically significant (P ≤ 0.001). There was significant difference between the means of conjunctival colony-forming unit after antibiotic administration in both the study groups (2.17 ± 1.54 SD in group A and 1.56 ± 1.09 SD in group B). Conclusions: Moxifloxacin 0.5% was found to penetrate anterior chamber more than gatifloxacin 0.5%, enforcing its use for prophylaxis before intraocular surgeries. However, gatifloxacin 0.5% eye drops were able to reduce conjunctival bacterial load, more supporting its use before extraocular and refractive surgeries.

Efficacy and Safety of 0.6% Pazufloxacin Ophthalmic Solution Versus Moxifloxacin 0.5% and Gatifloxacin 0.5% in Subjects with Bacterial Conjunctivitis: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of a novel ophthalmic solution of pazufloxacin on the ocular surface of patients with bacterial conjunctivitis after 7 days of intervention. METHODS: This is a phase 2, double-blind, controlled, multicenter, clinical trial of 300 subjects, randomized to either a 3 dosing regimen of pazufloxacin 0.6% ophthalmic solution (twice a day [BID], n = 90; 3 times a day [TID], n = 76; 4 times a day [QID], n = 68), moxifloxacin 0.3% TID (n = 82), or gatifloxacin 0.5% TID (n = 72). Follow-up was set on days 0, 3, and 7. Assessments of ocular signs were performed, both anterior and posterior segments. The primary outcome measures included conjunctival culture and clinical signs. Safety variables included adverse events (AEs), lisamine green, fluorescein ocular surface stains, and clinical signs of tolerability. RESULTS: After intervention, bacterial eradication was reported in all groups: pazufloxacin BID 79%, pazufloxacin TID 84%, pazufloxacin QID 84%, moxifloxacin 80%, and gatifloxacin 82%. There were no significant differences between treatments. Similar results were reported in clinical remission: pazufloxacin BID 89%, pazufloxacin TID 98%, pazufloxacin QID 92%, moxifloxacin 91%, and gatifloxacin 92% (P = 0.03 comparing pazufloxacin BID vs. TID). There were no differences between female and male responses. The AEs were not related to the interventions. CONCLUSIONS: A simplified dosing regimen was selected to follow the development of ophthalmic pazufloxacin based on its efficacy and safety profile. Pazufloxacin, 1 drop 3 times daily, showed similar rates of bacterial eradication and clinical remission compared with other fluoroquinolones.