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Setting: The shorter treatment regimen (STR) for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) has achieved successful outcomes in many countries. However, there are few studies on high-dose gatifloxacin-based STR with adverse drug reactions (ADRs) and management. Design: A prospective observational study was conducted with MDR/RR-TB patients who were treated with a standardized 9 or 12 - month regimen: including gatifloxacin (Gfx), clofazimine (Cfz), ethambutol (EMB), and pyrazinamide (PZA), and supplemented by amikacin (Am), isoniazid (INH), and prothionamide (Pto) during an intensive phase of 4 or 6 - month. Monitored ADRs monthly until treatment completion and then followed up every three months for one year. Results: Among the 42 eligible patients, 35 (83.3%) completed treatment successfully, 1 (2.4%) lost to follow-up (LTFU), and 6 (14.3%) failed due to ADRs, with no death. The most important ADR was drug-induced liver damage, which occurred in 24 out of 42 (57.1%) patients and resulted in 4 (9.5%) failed treatments and 4 (9.5%) adjusted treatments. QT interval prolongation occurred in 17 out of 42 (40.5%) patients, 9 (21.4%) of them with the corrected QT interval according to Fridericia (QTcF) > 500 ms resulting in 7 (16.7%) adjusted treatments. Conclusions: This study confirmed the effectiveness of the high-dose gatifloxacin-based STR but severe ADRs, especially hepatotoxicity and QT interval prolongation should never be ignored.

PURPOSE The objective of this study was to compare the clinical and microbiological profiles of culture-proven pure Corynebacterium keratitis with mixed infection and their antibiotic susceptibility patterns over a 2-year period. METHODS A retrospective analysis of culture-proven cases of Corynebacterium keratitis over a 2-year period was performed in 3 different tertiary eye care centers. All isolates were tested for antibiotic susceptibility in vitro using the disc-diffusion method for 7 antibiotics. RESULTS Altogether 108 cases were identified as culture-positive Corynebacterium keratitis in 3 tertiary eye care centers. Of these, 60.2% (n = 65) and 39.8% (n = 43) of cases were due to pure Corynebacterium and mixed infection, respectively. The mean duration of symptoms was 23.2 ± 29.6 days. In the mixed-infection group, fungus was identified as the coexistent pathogen in 22 cases (51.1%). Ocular surface disorder was the most common risk factor (33.9%) in Corynebacterium keratitis. The most frequently isolated species was Corynebacterium amycolatum (22.2%) in both groups. Therapeutic keratoplasty was performed in 8.3% of cases. There was no significant difference in the outcome between the 2 groups. Cefazolin resistance was seen in 13.9% of patients, and all isolates were susceptible to vancomycin. The resistance pattern showed emerging resistance toward fluoroquinolone because the isolates were resistant to gatifloxacin (58.3%), moxifloxacin (47.2%), ciprofloxacin (54.6%), and ofloxacin (45.4%). CONCLUSIONS Ocular surface disorder is the most common risk factor in Corynebacterium keratitis. Although fluoroquinolones are commonly used as first-line therapy in microbial keratitis, the in vitro resistance pattern indicates that these are less likely to be effective in infection with Corynebacterium species.

Objectives Gatifloxacin (GAT), as one of the representatives of the fourth-generation fluoroquinolones (FQs) has been used to treat drug-resistant tuberculosis. Although DNA gyrase mutations are the leading cause of FQs resistance, mutations conferring resistance to GAT remain inadequately characterized. Methods In the present study, GAT-resistant mutants were selected from 7H10 agar plates containing 0.5 mg/L GAT (the critical concentration). Mutations involved in GAT resistance were identified through whole-genome sequence. Results A total of 123 isolates were demonstrated to resistance to GAT. Among those isolates, 55.3% (68/123) mutants had gyrA gene mutations (G280A (D94N), A281G (D94G), G280T (D94Y) and G262T (G88C)). The remain (44.7%, 55/123) harbored gyrB gene mutations (A1495G (N499D), C1497A (N499K), C1497G (N499K) and A1503C (E501D)). Conclusions In summary, mutations in gyrA and gyrB are the primary mechanism of GAT resistance. The findings provides new insight of resistance to GAT and contribute to molecular diagnosis of GAT resistance in the clinical setting.

Ophthalmic infections can cause damage to the structure of the eye which can lead to vision loss and blindness if left untreated. Ophthalmic infection or eye infections are caused by exposure to bacterial, fungal viral and protozoan are common with frequently reported in Asian countries. In the present study, the external ocular infected samples collected from Thanjavur Medical College Hospital, Thanjavur. Seven strains were isolated from the external ocular infected samples and identified a standard manual of Determinative Bacteriology by Bergy’s manual 12th edition. The commercial antibiotics and eye drops tested against Bacillus cereus, B. subtilis, Escherichia coli, Klebsiella sp. Pseudomonas sp. Streptococcus sp. and Staphylococcus aureus. The majority of the isolates were sensitive to tobramycin followed by moxifloxacin, gatifloxacin and ofloxacin. The resistant antibiotics are ciprofloxin and sensitive antibiotic was ampicillin was recorded with respective bacteria.

Introduction The US Food and Drug Administration issued safety warnings about neuropathy in 2013 and dysglycemia in 2018 caused by fluoroquinolone use, mainly based on case reports and case series. We conducted this systematic review to evaluate the safety of fluoroquinolones in diabetic patients by investigating their dysglycemic and neuropathic effects. Methods PubMed, Scopus, and Google Scholar were searched for randomized controlled trials and observational studies published from inception till September 2019 evaluating the safety of fluoroquinolones. Efficacy studies of fluoroquinolones reporting these adverse effects were also included. Primary outcomes were hypoglycemia, hyperglycemia, and neuropathy among patients with or without diabetes and treated with fluoroquinolones compared with placebo or other antibiotics. The Cochrane Collaboration tool for randomized controlled trials and modified Newcastle-Ottawa quality-assessment scale were used for assessment of the included studies. Results and discussion A total of 725 studies were identified in the initial search. After screening of titles and abstracts and full-text review, 16 articles fulfilled the inclusion criteria. The sampled patients were aged 30-78 years. Hyperglycemia was reported in 1,588 patients that received fluoroquinolone among eight studies with 4,663 patients, and hypoglycemia was reported in 2,179 patients that received fluoroquinolones among eleven studies with 6,208 patients. Dysglycemia was not generally associated with diabetes mellitus per se. Nevertheless, patients with more comorbidities, especially those with chronic kidney disease, receiving antidiabetics and/or steroids had more glycemic events when treated with fluoroquinolones. Conclusion Moxifloxacin was found to be associated the most and ciprofloxacin the least with dysglycemia. fluoroquinolones must be used with great caution among diabetic patients who have comorbidities and are receiving antidiabetics and/or steroids. Further evidence is required from studies on neuropathy caused by fluoroquinolones.

Актуальность. Проблема гнойно-воспалительных осложнений при травмах вспомогательного аппарата глаза остается актуальной для клинической офтальмохирургии, поскольку данные состояния нередко обусловливают тяжелое протекание пред- и послеоперационного периода, которое проявляется нарушением общих и местных механизмов регулирования, генерализацией процесса и задержкой заживления ран. Цель исследования заключалась в изучении видового состава микрофлоры ран вспомогательного аппарата глаза, определении чувствительности выделенных микроорганизмов к наиболее часто используемым антибиотикам и их способность образовывать биопленки. Материалы и методы. В работе исследовали видовой состав микрофлоры ран 53 пациентов с травматическими повреждениями вспомогательного аппарата глаза за 2018–2019 годы. Осуществлено исследование мазков с ран с последующим определением видового состава и идентификацией микроорганизмов, которые проводили с использованием классических бактериологических методик. Результаты. Идентифицировали 67 штаммов микроорганизмов. Доминирующим оказался Staphylococcus aureus, второе место занял Acinetobacter spp., третье — Micrococcus spp. Частота выявления микроорганизмов в монокультуре с ран составила 33 (66 %), в 17 (34 %) случаях — в ассоциациях. Исследовали чувствительность выделенных штаммов к наиболее часто используемым антибиотикам, среди которых наиболее активным оказался гатифлоксацин. Провели оценку формирования биопленок штаммами S. aureus, поскольку он является комменсалом и превалирует в этиологии раневой инфекции (31 %). Выводы. Установлено, что у штаммов S. aureus (n = 21), которые выделили из ран пациентов, в 15 случаях (71 %) наблюдалась высокая способность к формированию биопленок, в 6 случаях (29 %) отмечалось умеренное биопленкообразование.

In an effort to produce ideal wound dressing, gellan gum/collagen hydrogel films containing different concentrations of gatifloxacin were prepared via evaporative casting method. The films were examined in terms of physical appearances, water uptake and water vapour transmission rate (WVTR). All the films showed good physical appearances. Swelling percentages of the films were decreased, whereas WVTR values were increased as the addition of gatifloxacin was increased. Swelling percentage of gellan gum/collagen film with the lowest percentage of gatifloxacin (GG/C-GAT01) has the highest swelling ratio (2057%). Meanwhile, the WVTR value of GG/C-GAT1 has the highest WVTR value among all films which is 1245 g m-2 day-1. The formulation of GG/C films with the addition of gatifloxacin with good water absorbance and acceptable WVTRs value offered promising materials to be applied as wound dressing materials.

A novel drug delivery system provides the delivery of drugs at a required rate into the body during the period of treatment as directed by the body. Formulation and evaluation of Noisome containing gatifloxacin using different concentrations of the polymer for controlled release. Pre-formulation study confirms the purity of the drug and compatibility of the drug with excipients using FT-IR. Tween 80 was found significant with the experimental results. An extensive investigation is needed concerning the depth of penetration into the skin, determination of zeta potential, and confirmation of configuration of phospholipids in the lipid bilayer. A significant loss of entrapped drug was found at the end of three month period when liposomal dispersions were stored at high temperature i.e. 25±20C. All gels were found under pH range 7.0 to 7.4, Spreadability under the range 6.6 to 7.6 cm, % drug content 98 to 100%, the viscosity of gels 98 to 115cp, and % permeation found in rage 75 to 91%. Excellent % Permeation Gel formulation GF-4 was found 91%. The drug release at raised temperatures may be associated with the lipid degradation in the bilayers results in membrane packing defects them leaky.

Gatifloxacin is the drug of choice in the treatment of community-acquired pneumonia in many studies. However, cytotoxicity was reported at its high doses. Therefore, gatifloxacin overdose monitoring is very important. In this sense, there is a need for developing fast and cheap analytical methods for gatifloxacin quantitation in biological fluids. In the present study, a novel detection strategy involving gatifloxacin quantification in urine samples was developed. The approach has been adapted for the use of solid inner contact and rapid disposal screen-printed graphitic carbon electrodes exhibiting high sensitivity toward gatifloxacin without interference from several ions found in urine samples. The developed electrodes showed linear responses in the concentration ranges from 1 × 10–5 to 0.01 and 1 × 10–6 to 0.01 M for a solid contact glassy carbon ion selective electrode (GSC) and a screen printed electrode (GSP), respectively. The analytical applicability of the approach was demonstrated through recovery experiments of gatifloxacin trace concentrations in urine. GSP ion selective electrode (ISE) was found to have superior stability, shorter response time, higher selectivity and sensitivity and longer shelf life compared to GSC ISE. GSP ISE showed the best Nernestian slope as well as the lowest detection limit. Moreover, the inherent advantages of screen-printed electrodes technology (low sample consumption, low cost and point of care testing) make this methodology very attractive in this field. As a result, the developed ISEs can be the best choice for in-line determination of gatifloxacin in urine samples to detect overdose intake and its associated symptoms as well as for quality-control laboratories without pre-treatment or separation steps.

The explants of two varities rosea and alba of Catharanthus roseus used for in vitro propagation and found to be more than 50% of the cultures became contaminated. The most common bacterial contaminants were Bacillus licheniformis, Micrococcus, Panibacillus and fungal contaminants were Fusarium, Alternaria, Cladosporium and Aspergillus. Combinations of different antibiotics (Penicillin, norfloxacin, tobramycin, gatifloxacin, ofloxacin) and fungicides (Bavastin, captan, fluconazole and trichoderma) were used to control the growth of the contaminants. Gatifloxacin and ofloxacin inhibited 100% growth of bacteria whereas, bavastin and captan appeared to be the most effective fungicides. Combination of gatifloxacin, ofloxacin with bavastin and captan inhibited the growth of contaminants at their minimum phytotoxic concentration (MIC). The observed minimum phytotoxic concentration (MPC) of ofloxacin, gatifloxacin, bavastin and captan was 15, 9, 6 and 5% at their respective MIC. More than 90% of the cultures responded for callus formation in the combination of gatifloxacin (4%) + bavastin (1%). While the combination of gatifloxacin and captan was highly toxic that reduces the growth of the culture. Plant Tissue Cult. & Biotech. 30(2): 297-305, 2020 (December)

Highlights • Shorter treatment regimen for multidrug-resistant tuberculosis. • Effect of companion drug resistance on adverse outcomes. • Gatifloxacin and isoniazid minimum inhibitory concentration. • Whole-genome sequencing. • Non-eligibility for the regimen not associated with adverse outcome. • Exclusions justified only in the case of fluoroquinolone or kanamycin resistance., Objectives We investigated whether companion drug resistance was associated with adverse outcomes of the shorter multidrug-resistant tuberculosis (MDR-TB) treatment regimen in Bangladesh after adjustment for fluoroquinolone resistance. Methods MDR-TB/rifampicin-resistant tuberculosis patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB treatment regimen were selected for the study. Drug resistance was determined by the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole-genome sequencing. Results Low-level fluoroquinolone resistance and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line-injectable-susceptible tuberculosis, non-eligibility for the shorter MDR-TB treatment regimen (initial resistance to pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (adjusted odds ratio 1.01; 95% confidence interval 0.4–2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant tuberculosis. Conclusions Our results suggest that resistance to companion drugs in the shorter MDR-TB treatment regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone resistance. and possibly kanamycin resistance.

Objective: To determine bacteria obtained from eye infections, both resistance and minimal inhibitory concentration (MIC) to gatifloxacin, moxifloxacin, tigecycline, linezolid and imipenem, in vitro. Methods: A cross-sectional descriptive study was undergone with 50 samples from 50 eyes of patients diagnosed with keratitis or endophthalmitis, who came to a consultation at the Fundacion Oftalmologica de Santander (Floridablanca, Colombia) from August to November 2014. The MICs of the isolated microorganisms were established through Etest® strips (BioMerieux SA, Marcy-l'Etoile - France). Results: Of the 50 samples in total, 17 different bacteria species or groups were isolated. The main isolate for gram-positives was Methicillin Resistant Coagulase-Negative Staphylococcus (17 samples), and for gram-negatives was Pseudomonas aeruginosa (6 samples). The susceptibility percentages sorted from highest to lowest for gram-positive isolates (n=38) were: imipenem 90.3%, linezolid 87.9%, tigecycline 78.1%, gatifloxacin 68.8% and moxifloxacin 68.8%. For gram-negative isolates (n=12), they were: imipenem 72.7%, gatifloxacin 70%, moxifloxacin 66.7% (no reference cut-off points were found for Pseudomonas aeruginosa), tigecycline 22.2%, and linezolid 0% (as expected according to its inhibition spectrum). Conclusions: Although fourth generation fluoroquinolones are currently the preferred initial empirical monotherapy in our practice, given the increasing bacterial resistance, in cases in which gram-positive bacteria were isolated in the initial staining imipenem, linezolid or tigecycline could be used as an alternative. On the other hand, for cases of gram-negative bacteria, no antimicrobial susceptibility exceeded 80%, so using two antimicrobials looking for a synergy between them could be a better option. Abbreviations: S = Susceptibility, IS = Intermediate susceptibility, R = Resistance.

The growing technology of stationary phase chemistry has a great impact on the chromatographic system performance and analysis economics. In this context, a simple rapid reversed phase high-performance liquid chromatography method development is presented for the analysis of gatifloxacin (GFN) and dexamethasone sodium phosphate (DSP) in their ophthalmic formulation. A two-step optimization approach has been conducted using optimum chromatographic conditions as well as proper selection of stationary phase. The chromatographic separation was carried out using sodium phosphate buffer pH 3.0 ± 0.1 and acetonitrile 72:28 v/v, respectively, with flow rate 1 mL min−1 and simultaneous detection at 243 nm. Three different column technologies were investigated at the optimum set of the chromatographic conditions: Xbridge® bridged ethylene hybrid silica, Kinetex™ Core-Shell and the Onyx™ Monolithic stationary phase. The monolithic column has shown better chromatographic separation, based on system suitability testing as well as shorter analysis time and sensitivity. The proposed method was validated according to International Conference on Harmonization guidelines. The linearity was achieved for GFN and DSP in the range 0.58–120 μg mL−1 and 0.50–120 μg mL−1, respectively, with acceptable accuracy, precision and selectivity.

Purpose. to evaluate the efficacy of perioperative antibacterial prophylaxis using eye drops with fluoroquinolones with the evaluation of conjunctival microflora structure with its antibiotic resistance.Patients and Methods. The study was carried out using the results of one preoperative and four times postoperative swabs taken from the conjunctival cavity in 50 patients (52 eyes) aged 49 to 91 undergoing phacoemulsification. All the strains were undergoing the 16 antibacterial drugs-panel susceptibility testing including the most common ophthalmic dosage form in the Russian Federation. The antibacterial drugs instillations were used during the postoperative period: levofloxacin in group 1 (30 eyes) and moxifloxacin in group 2 (22 eyes).Results. The structure of conjunctival microflora in the two groups was similar prior to phacoemulsification. In 32 cases (61.5 %) bacterial growth was obtained preoperatively. Among them S. epidermidis strains were detected in 68.8 %, S. aureus strains were detected in 31.2 %. During the use of postoperative antibiotic prophylaxis, the number of positive swabs was constantly decreasing. In 1 hour a qualitative change in the microflora structure was observed. The number of S. aureus strains reduced. The number of S. epidermidis strains increased to 80 %. And previously undetected Corynebacterium spp. strains were found. In 1 day the conjunctival microflora was represented only by S. epidermidis. In 1 week all the swabs were sterile. In 1 month after phacoemulsification, positive swabs were obtained in 7.7 % (mainly S. epidermidis) only in group 1, where levofloxacin instillations were used as the postoperative antibiotic prophylaxis (р < 0,05). Moxifloxacin, gatifloxacin and antiseptic drugs showed the highest in vitro activity against selected strains.Conclusion. The strains of coagulase-negative staphylococcus S. epidermidis prevailed in conjunctival microflora structure. During the use of postoperative antibiotic prophylaxis, the number of positive swabs is progressively reduced to zero by the 7th day in both groups. A more persistent permanent effect of moxifloxacin, maintaining for 1 month after the operation was found in comparing two patients’ groups received fluoroquinolone eye drops to prevent infection after phacoemulsification.

Three type III secretion system (T3SS) inhibitors (compounds 5, 19, and 32) were identified by virtual screening and biological evaluation. These three compounds were evaluated against a panel of Salmonella species strains including S. enteritidis, S. typhi, S. typhimurium, S. paratyphi, and S. abortus equi, and their minimum inhibitory concentrations ranged from 1 to 53 μg/ml. Especially, these compounds showed comparable activity as the of the positive control gatifloxacin towards S. abortus equi. The present results suggest that these new T3SS inhibitors could be used as a potential lead molecule for drug development of anti-Salmonella.

Purpose The purpose of this study was to explore the C-X-C chemokines CXCL2 and CXCL10 as potential anti-inflammatory targets for Bacillus endophthalmitis. Methods Bacillus endophthalmitis was induced in C57BL/6J, CXCL2-/-, and CXCL10-/- mice. At specific times postinfection, eyes were analyzed for Bacillus, retinal function, and inflammation. The efficacies of intravitreal anti-CXCL2 and anti-CXCL10 with or without gatifloxacin in B. cereus endophthalmitis were also assessed using the same techniques. Results Despite similar Bacillus growth in eyes of C57BL/6J, CXCL2-/-, and CXCL10-/- mice, retinal function retention was greater in eyes of CXCL2-/- and CXCL10-/- mice compared to that of C57BL/6J mice. Neutrophil migration into eyes of CXCL2-/- and CXCL10-/- mice was reduced to a greater degree compared to that of eyes of C57BL/6J mice. Infected CXCL2-/- and CXCL10-/- mouse eyes had significantly less inflammation compared to that of C57BL/6J eyes. Retinal structures in infected eyes of CXCL2-/- mice were preserved for a longer time than in CXCL10-/- eyes. Compared to untreated eyes, there was less inflammation and significant retention of retinal function in eyes treated with anti-CXCL2 and anti-CXCL10 with or without gatifloxacin. Conclusions For Bacillus endophthalmitis, the absence of CXCL2 or CXCL10 in mice resulted in retained retinal function and less inflammation. The absence of CXCL2 led to a better clinical outcome than the absence of CXCL10. The use of anti-CXCL2 and anti-CXCL10 limited inflammation during B. cereus endophthalmitis. These results highlight the utility of CXCL2 and CXCL10 as potential targets for anti-inflammatory therapy that can be tested in conjunction with antibiotics for improving treating Bacillus endophthalmitis.

Introduction: Fluoroquinolone eye drops are prescribing by Ophthalmologist in many ocular diseases as conjunctivitis, keratitis, bacterial corneal ulcers etc in more and more amount. There are many brands of fluoroquinolones drugs available in Indian market. Costly drugs can lead to economic burden on patients. Modifications in pharmaceutical policy are required, and prices of the drug should be controlled in effective way for all the drugs. Hence this study was done to assess the cost variation of fluoroquinolones ophthalmic solutions available in Indian market. Materials and Method: The maximum and minimum price of each brand of the drug in INR was noted by using CIMS January to April 2018 edition Drug Today April to June 2018 Vol-1. The cost ratio and the percentage cost variation for individual drug brands was calculated. The cost of each eye drop was calculated. At last the cost ratio and percentage cost variation of various brands was compared. Result:Percentage variation in cost for fluoroquinolones eye preparations marketed in India was found to be Eye drop Ciprofloxacin (0.3%) of 5ml:210.39, Eye drop Ciprofloxacin (0.3%) of 10 ml:162, Eye drop Gatifloxacin (0.3%) of 5ml:156, Eye drop Moxifloxacin (0.5%) of 5ml:196.95, Eye drop Ofloxacin (0.3%) of 5ml:245.16,Eye drop Ofloxacin(0.3%) of 10ml:62.5,Eye drop Norfloxacin(0.3%) of 5ml:120.68, Eye drop Sparfloxacin (0.3%):8.31,Eye drop Lomefloxacin (0.3%):16.17 Conclusion:There is a wide difference in the cost of different brands of fluoroquinolones eye preparations available in India. The clinicians prescribing these drugs should be aware of these variations in cost to reduce the cost of drug therapy. Keywords: Fluoroquinolones, Percentage cost variation, Keratitis, Bacterial corneal ulcer, Conjunctivitis

Fluoroquinolones are available only with a physician's prescription and are sold in tablet and injectable forms. Examples of these medicines are moxifloxacin ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, enoxacin, gatifloxacin, and sparfloxacin. In the wake of the anthrax terrorist attacks in the United States in 2001, ciprofloxacin received extensive media attention because it was the only drug labeled as approved by the Food and Drug Administration (FDA) for both prophylaxis and treatment of inhalation anthrax (the most serious form of the disease). However, in late October 2001, the FDA issued a notice clarifying that the antibiotic doxycycline is also approved for anthrax prophylaxis and that doxycycline and amoxicillin are also approved for treatment for all forms of anthrax. This study is intended to understand the side effects of using these drugs especially when it comes to the calf pain, tendonitis and rupture.

Purpose: To assess trends in antibiotic sensitivity of pseudomonas and compare multidrug resistance (MDR) between Pseudomonas endophthalmitis cases presenting in two consecutive 6-year time frames in a tertiary center in South India. Methods: This is a retrospective comparative series of all Pseudomonas endophthalmitis cases treated from June 2004 to May 2016. Microbiological culture results in all endophthalmitis patients were screened for pseudomonas. Positive cases in the initial 6 and final 6 years were compared for sensitivity to antibiotics and the proportion of MDR. MDR was defined as resistance to at least two different classes of antibiotics. Results: Pseudomonas accounted for 74 of 389 endophthalmitis cases (19%), 42 in initial 6 and 32 in final 6 years. Sensitivity to ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, and ceftazidime was 85.7%, 82.9%, 76.5%, 76.9%, 88.1% up to 2010 which reduced to 75%, 59.4%, 68.8%, 56.3%, 56.3%, respectively, after 2010, being significant for ofloxacin (P = 0.0349) and ceftazidime (P = 0.0028). Susceptibility to amikacin, gentamicin, and tobramycin changed non-significantly from 83.3%, 43.9%, 47.6% to 71.9%, 61.3%, 61.3%, respectively. Twenty of 74 cases (27%) were MDR with 16.7% in first 6 years versus 40.6% in final 6 years. Postoperative MDR cases rose from 10.3% to 50% (P = 0.0048). Conclusion: This study shows rising resistance of Pseudomonas to fluoroquinolones, amikacin, and ceftazidime in endophthalmitis. MDR also showed an upward trend, particularly in postsurgical cases.

In this context, a simple RP-HPLC method is presented for the concurrent determination of Ofloxacin (OFX), Gatifloxacin (GFN), Dexamethasone sodium phosphate (DSP), and Prednisolone acetate (PA). The method has the strengths of being green, rapid, accurate, reproducible and cost-effective. The chromatographic separation utilized sodium phosphate as buffer with pH 3.0 ± 0.1 and acetonitrile 70:30 v/v for 3 min then reversing the ratio for the rest of the run with flow rate 1 mL min−1, Xselect® C18 column and detection at 243 nm for DSP and PA, and 290 nm for OFX and GFN. Another chromatographic method was designed for the assay of the same drugs, namely TLC-Densitometric method. This method has the advance of being eco-friendly, simple and robust. The separation was obtained using mobile phase mixture of butanol/acetic acid/water (60:20:20 v/v/v) and normal phase silica gel plates as the stationary phase with simultaneous detection at 243 nm. The suggested methods can be adopted for the analysis of the four drugs in different binary combinations of eye drops saving money and solvents, and chemicals. They were validated with the guidance of ICH guidelines, with acceptable accuracy, precision, and selectivity.

AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections. METHODS: This study applied a retrospective analysis of 3690 bacterial isolates from ocular specimens, which were obtained from the conjunctiva, cornea, aqueous humor, vitreous body, and other ocular sites of the patients at Shandong Eye Institute in northern China from January 2013 to December 2017. The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics. In the analysis of antibiotic sensitivities, the bacteria were divided into four groups according to gram staining, and statistical methods were used to compare their antibiotic sensitivities. RESULTS: Among the 3690 isolated bacterial strains, Staphylococcus epidermidis (2007, 54.39%) accounted for the highest proportion. As for the total isolates, their sensitivity rate to gatifloxacin was up to 90.01%, with four types of gram-stained bacteria being all highly sensitive to it, but their sensitivity rate to levofloxacin was only 51.91%. The sensitivity rate of gram-negative bacilli (G-B) to levofloxacin was 83.66%, significantly higher than the other three types of gram-stained bacteria (P

Gatifloxacin (GAT) is a new generation fluoroquinolone antibiotic and its adsorption onto iron minerals influenced by coexisting trace elements [e.g., Cu(II)] has not been well investigated. To evaluate the adsorption behavior of GAT and Cu(II) onto goethite and hematite, the complexation constants of GAT with Cu(II) were determined using potentiometric titration, and the effects of Cu(II) concentration and solution pH on GAT adsorption were investigated using batch experiments. It was observed that GAT adsorption was negatively correlated with molar concentration ratio of Cu(II) to GAT. In our experimental pH range (i.e., 3.0-10.8), the calculated main species involved in GAT adsorption were Cu(GAT± )2+ and Cu(GAT± )22+ under acidic to neutral conditions, and formation of Cu(GAT- )2 (s) facilitated the removal of GAT from solution under alkaline condition. The adsorption data were well fitted by the Freundlich model and showed high nonlinearity. In adsorption onto goethite, the primary interactions shifted from electrostatic repulsion to formation of goethite-Cu(II)-GAT ternary surface complexes with increase of GAT concentration. For hematite, electrostatic repulsion was the main inhibiting mechanism and became stronger with increase of Cu(II) concentration. Our findings suggest that it is necessary to consider the complexation between GAT and coexisting metal cations in evaluating its transport in soils rich in different iron minerals.

A unique cucurbit[6]uril-based (CB[6]) supramolecular assembly [Na4CB[6](H2O)10DMF]·2BPDS·2H2O (1) was successfully synthesized by using an aromatic compound 4,4′-biphenyldisulphonic acid (H2BPDS) as a structure-directing agent. More impressively, 1 displayed high sensitivity and quick response toward two commonly used fluoroquinolone antibiotics, levofloxacin (LUX) and gatifloxacin (GAT), through luminescence quenching.

Gatifloxacin is end up being one of the potential medications against H. pylori infection. As conventional drug delivery systems do not remain in the stomach for delayed periods, they can't convey the Gatifloxacin to the site of infection in effective concentrations. Hence it planned to develop a new floating in situ gelling system of Gatifloxacin with increased residence time using sodium alginate as gelling polymer and HPMC as thickening agent with a potential of H. Pylori eradication. The formulations were evaluated on the basis of Pharmacopoeial specification. Clarity, visual appearance, pH, gelling capacity, viscosity, gelation, buoyancy, water uptake, density of gel, gel strength, drug content, assessment of drug release, release kinetics were carried out as per specifications and results were found to be complied with the Pharmacopoeial specification. The formulation F6 shows good result as compared to other formulation. The findings of prepared in situ gelling formulations of Gatifloxacin increased the gastric residence time and also float in the gastric condition.

Aim To evaluate the relative efficacy and safety of besifloxacin for treatment of acute bacterial conjunctivitis. Methods A comprehensive search in PubMed, EMBASE Web of Science, Cochrane Central Database and CNKI was undertaken for randomized controlled trials (RCTs) comparing besifloxacin with other treatments or placebo. The primary outcome measures were clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, and bacterial eradication rates of different kinds of pathogens. Safety outcomes were the number of adverse effects (AEs). The final search was performed on August 2018. Results Six RCTs were included. Four studies compared the efficacy and safety of besifloxacin with placebo, 1 study compared besifloxacin with moxifloxacin, and 1 study compared besifloxacin with gatifloxacin. A total of 2780 patients met the inclusion criteria. Besifloxacin presented higher efficacy and safety than did placebo in clinical resolution, rates of bacterial eradication, individual clinical outcomes, cure rates, bacterial eradication rates of different kinds of pathogens and the number of AEs. There was no significant difference between besifloxacin and moxifloxacin or gatifloxacin in the comparison items mentioned above. Conclusion Besifloxacin is highly effective and safe for treatment of acute bacterial conjunctivitis. Further comparative trials regarding the effect of besifloxacin for treatment of acute bacterial conjunctivitis will aid in treatment decisions.

The equilibrium solubility of gatifloxacin in four nonaqueous solvent mixtures of N,N-dimethylformamide (DMF,1) + methanol (2), DMF (1) + ethanol (2), DMF (1) + isopropanol (2), and DMF (1) + n-pro...

Numerous clinical studies have evaluated the performance of Sanjin tablets (SJTs) in the treatment of acute lower urinary tract infections (ALUTIs) in China. The present meta-analysis aimed to determine the efficacy and safety of SJT combined with antibiotics for the treatment of patients with ALUTIs and to evaluate the quality of evidence. The Cochrane Library, PubMed, EMBASE, Web of Science, Chinese BioMedical Database, China National Knowledge Infrastructure, WanFang and VIP databases were searched for entries added between inception and December 2018 to identify relevant randomized controlled trials (RCTs). The Cochrane risk-of-bias tool and Consolidated Standards of Reporting Trials for Traditional Chinese Medicine were used for assessing the methodological quality and reporting quality of eligible studies, respectively. Meta-analysis and quality of evidence assessment were performed with RevMan 5.3 and Grading of Recommendations, Assessment, Development and Evaluations (GRADE), respectively. A total of 8 RCTs comprising 790 patients with ALUTIs were included in the present meta-analysis. The cure rate of SJTs combined with gatifloxacin tablets (GTs) was higher than that of GTs alone [relative ratio (RR)=1.30, 95% CI=1.07-1.57, P=0.009]. The cure rate of SJTs combined with levofloxacin tablets (LTs) was higher than that of LTs alone (RR=1.13, 95% CI=1.04-1.24, P=0.006). SJTs combined with LTs was better in improving the total effective rate than LTs alone (RR=1.11, 95% CI=1.03-1.19, P=0.005). The recurrence rate for SJTs combined with antibiotics was lower than that associated with antibiotics alone (RR=0.35, 95% CI=0.13-0.97, P=0.04). The bacterial clearance rate achieved with SJTs combined with antibiotics was higher than that obtained with antibiotics alone (RR=1.41, 95% CI=1.09-1.84, P=0.009). The present meta-analysis demonstrated that, compared with the effects of antibiotics treatment, SJTs combined with antibiotics improved the cure rate, total effective rate and bacterial clearance rate, and decreased the recurrence rate. In addition, no serious adverse reactions were observed in patients with ALUTIs. However, the GRADE quality of evidence was low. Thus, further large-scale and rigorously designed clinical trials are required to improve the quality of evidence.

To evaluate the in vitro efficacy of three commercial ophthalmic solutions (gatifloxacin, levofloxacin and gentamicin) against cysts of Acanthamoeba species.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.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.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.

AIM: To evaluate the quantitatively changes in lipid layer thickness (LLT) when 3% diquafosol eye drop is used for dry eye patients using the tear film interferometer. METHODS: A total 124 participants (32 males, 92 females; mean age, 28.9y) diagnosed with dry eye disease (DED) received topical instillation of 4 ophthalmic solutions in one eye: diquafosol, normal saline, 0.1% sodium hyaluronate and 0.3% gatifloxacin, in a masked manner. LLT was measured using an interferometer at baseline and 20min after the instillation of each ophthalmic solutions. RESULTS: Changes of LLT after instillation (nm, mean± standard error) were as follows: 12.6±2.0 for diquafosol (P

Purpose We explored the potential synergistic effect of bedaquiline (BDQ) combined with moxifloxacin (MFX), gatifloxacin (GAT), clofazimine (CLO), and linezolid (LZD) for treatment of extensively drug-resistant tuberculosis (XDR-TB). Methods Of 191 XDR-TB isolates, 20 exhibiting minimal inhibitory concentration (MIC) values ≥0.063 μg/mL for BDQ were selected to study potential synergistic, additive, or antagonistic drug effects using a checkerboard assay. Results Antagonism occurred in 14 (70.0%), 0 (0.0%), 13 (65.0%), and 4 (20.0%) XDR-TB isolates for BDQ-MFX, BDQ-GAT, BDQ-LZD, and BDQ-CLO combinations, respectively. Conclusion Our in vitro data demonstrate no observed synergistic effects against XDR-TB for drug combinations that included BDQ in combination with MFX, GAT, LZD, or CLO.

Four novel zinc coordination compounds of gatifloxacin (Hgati), a third-generation quinolone, with a N,N′-donor heterocyclic ligand, such as 2,2′-bipyridylamine, 1,10-phenanthroline or 2,2′-bipyridine, were characterized with physicochemical techniques and various spectroscopies. The antimicrobial activity of the compounds against the microorganisms Xanthomonas campestris, Escherichia coli, Bacillus subtilis and Staphylococcus aureus was similar or better than that of free Hgati. The complexes may bind to calf-thymus DNA via intercalation as concluded via a series of studies employing DNA-viscosity measurements, UV–Vis spectroscopy and competition with ethidium bromide. The complexes may bind to albumins in order to get transferred through the bloodstream.

This study concerns the oxidative degradation and mineralization of gatifloxacin in aqueous solution at pH = 3 and in the presence of Fe2+ as catalyst  using electro-Fenton (EF) process, with carbon felt as a cathode and platinum as an anode. The mineralization is evaluated by the chemical oxygen demand by assessing the applied current value and concentration of catalyst Fe2+. Some stable by-products of gatifloxacin have been identified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. The second part of this paper concerns the study of the biodegradability in determining of BOD5/COD during the mineralization of gatifloxacin by EF in order to evaluate the possibility of coupling electro-Fenton process with the biological one. This leads to an efficient treatment of water contaminated by this antibiotic with lower cost.

Purpose: To compare equal concentrations (0.5%) of moxifloxacin and gatifloxacin ophthalmic solutions with regard to conjunctival bacterial reduction as well as anterior chamber penetratio...

Endophthalmitis, an intraocular infection, may lead to irreversible loss of vision. Antimicrobial chemotherapy is prescribed prior to ocular surgical procedures to avoid endophthalmitis. Fluoroquinolones are the most commonly prescribed and used antibiotics during such procedures. However, the selection of a single entity and proper regimen is not specified in medical guidelines. The objective of this study is to develop a rapid and selective simultaneous high-performance liquid chromatography-tandem mass spectroscopic method to explore the bioavailability of 4 fluoroquinolones, including 0.5% moxifloxacin hydrochloride, 0.3% gatifloxacin, 0.3% ciprofloxacin hydrochloride, and 0.3% ofloxacin, in human aqueous humor after antibiotic topical administration using gemifloxacin as Internal Standard according to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidelines. The newly validated method was capable of accurately and precisely quantifying each antibiotic at the lowest reported lower limit of quantification of 10 ng/mL and operating on a very low pipetting volume of 15 μL, indicating a reliable quantitation of all analytes simultaneously using a very small quantity of aqueous humor with total chromatographic run time of 2.5 min. Sixty-seven patients were divided into 4 groups for each antibiotic. Before the cataract surgery, each group received 4 drops of one of the antibiotics over 1 h, separated by 15 min time interval. After 15–20 min from the last drop, approximately 50–100 μL of aqueous humor was collected during surgery for analysis. The average concentrations of moxifloxacin, gatifloxacin, ofloxacin and ciprofloxacin in aqueous humor samples were 891.8, 271.7, 191.4 and 69.5 ng/mL, respectively. Only moxifloxacin average concentration was higher than the minimum inhibitory concentration for the common endophthalmitis pathogens.

Infectious diseases are caused by pathogens, such as viruses, bacteria, fungi, and parasites. Quinolones work by inhibition of bacterial topoisomerase IV and/or gyrase, a group of oxadiazole derivatives were incorporated into C7 piperazine ring of Gatifloxacin, a well-known antibacterial fluoroquinolone, in order to increase bulkiness at C7 leading to reduce bacterial resistance and improve anti-bacterial activity. In the current work , the synthesized compounds V(a-e) were screened for their antibacterial activity against gram negative bacteria: Klebsiella pneumonia and Escherichia coli and gram positive bacteria Streptococcus pyougenes and Staphylococcus aureus bacteria, the tested compounds showed an interesting activity against gram positive and gram negative bacteria, these tested compounds give significant antibacterial activity in comparison to Gatifloxacin as a starting compound and DMSO as a control, confirmations and characterization of the chemical structures related to these compounds were performed using 1H-NMR spectroscopy, FT-IR spectroscopy, and some physicochemical properties such as melting points. Docking study of the final synthesized compounds gave evidence about the affinity of these compounds toward topoisomerase IV enzyme, statistical results show the elevated inhibitory zones of the prepared compounds compared with Gatifloxacin, regarding S. aureus bacteria the inhibition zone elevated from 18mm in Gatifloxacin to 24 in (Vb and Ve) and 26mm in Vd, also for K. pneumonia bacteria the zone of inhibition raised from 18mm in Gatifloxacin to 20mm in Vb and 24mm in Ve.

The concerns regarding the occurrence of pharmaceuticals in wastewater treatment plants have increased in the last decades. Gatifloxacin (GAT), the fourth generation of fluoroquinolones, has been widely used to treat both Gram-positive and Gram-negative bacteria and has a limited metabolization. The present study aimed to evaluate ozonation as a technique to degrade GAT. An exchange A UHPLC-MS/MS by an UHPLC-MS/MS method was used to quantify the residual of GAT and to assess its degradation products. The removal efficiency was higher under alkaline conditions (pH = 10), reaching up to 99% of GAT after 4 min. It was also observed that the first ozone attack on the GAT molecule was through the carboxylic group. In contrast, under acid conditions (pH = 3), the ozone attack was first to the piperazinyl ring. The antimicrobial activity was evaluated using Escherichia coli and Bacillus subtilis as test organisms, and it was observed that the residual activity reduced most under alkaline conditions. In contrast, the best condition to remove the residual toxicity evaluated for the marine bacteria V. fischeri was the acidic one. Due to this, ozonation seemed to be an exciting process to remove GAT in aqueous media. Highlights Ozonation at pH 3 did not increase solution residual toxicity.; Antimicrobial activity decreased proportional to gatifloxacin conversion.; Ozonation at pH >7 increased solution residual toxicity.; Degradation products presented lower antimicrobial activity.; Proposed by-products presented lower toxicity.

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.

Despite the introduction of modern methods of treatment, the creation of new generations of antibacterial agents, and the constant improvement of aseptic and antiseptic methods, the treatment of purulent–inflammatory processes remains one of the most complex and urgent problems in veterinary practice. The article presents the results of the isolation of indigenous microbiota from various biotopes of healthy cats, as well as the study of their biological marker properties for the selection of the most optimal strains in probiotic medicines for the control of surgical infections. It was demonstrated that isolated cultures of bifidobacteria and lactobacilli, which we isolated, revealed high sensitivity to antibiotics of the β-lactam group (excepting L. acidophilus No. 24, L. plantarum “Victoria” No. 22, L. rhamnosus No. 5, L. rhamnosus No. 20, and L. rhamnosus No. 26, which showed a significant variability in sensitivity to antibacterial drugs of this group, indicating the great potential of these microorganisms) and resistance to aminoglycosides, lincosamides, and fluoroquinolones (with the exception of gatifloxacin, which showed high efficiency in relation to all lactic acid microorganisms). The adhesive properties of the isolated lactobacteria and bifidobacteria were variable, even within the same species. It was found that the B. adolescentis No. 23 strain of the Bifidobacterium genus, as well as the L. plantarum No. 8, L. plantarum “Victoria” No. 22, L. rhamnosus No. 6, L. rhamnosus No. 26, L. acidophilus No. 12, and L. acidophilus No. 24 strains of the Lactobacillus genus had the highest adhesive activity. Thus, when conducting a detailed analysis of the biological marker properties of candidate cultures (determining their sensitivity to antimicrobial agents, studying the adhesive properties, and antagonistic activity in relation to causative agents of surgical infection in cats), it was found that the most promising are L. plantarum “Victoria” No. 22, L. rhamnosus No. 26, and L. acidophilus No. 24.

The human-to-human transmitted respiratory illness in COVID-19 affected by the pathogenic Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), which appeared in the last of December 2019 in Wuhan, China, and rapidly spread in many countries. Thereon, based on the urgent need for therapeutic molecules, we conducted in silico based docking and simulation molecular interaction studies on repurposing drugs, targeting SARS-CoV-2 spike protein. Further, the best binding energy of doxorubicin interacting with virus spike protein (PDB: 6VYB) was observed to be −6.38 kcal/mol and it was followed by exemestane and gatifloxacin. The molecular simulation dynamics analysis of doxorubicin, Reference Mean Square Deviation (RMSD), Root Mean Square fluctuation (RMSF), Radius of Gyration (Rg), and formation of hydrogen bonds plot interpretation suggested, a significant deviation and fluctuation of Doxorubicin-Spike RBD complex during the whole simulation period. The Rg analysis has stated that the Doxorubicin-Spike RBD complex was stable during 15,000–35,000 ps MDS. The results have suggested that doxorubicin could inhibit the virus spike protein and prevent the access of the SARS-CoV-2 to the host cell. Thus, in-vitro/in-vivo research on these drugs could be advantageous to evaluate significant molecules that control the COVID-19 disease.

Most antibiotics, insecticides, and other chemicals used in agricultural and fishery production tend to persist in the environment. Fenvalerate, sulfide gatifloxacin, and ridomil are widely used in aquaculture as antibacterial, antifungal, and antiparasitic drugs; however, their toxicity mechanism remains unclear. Thus, we herein analyzed the effects of these three drugs on the hepatopancreas of Procambarus clarkii at the transcriptome level. Twelve normalized cDNA libraries were constructed using RNA extracted from P. clarkii after treatment with fenvalerate, sulfide gatifloxacin, or ridomil and from an untreated control group, followed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. In the control vs fenvalerate and control vs sulfide gatifloxacin groups, 14 and seven pathways were significantly enriched, respectively. Further, the effects of fenvalerate and sulfide gatifloxacin were similar on the hepatopancreas of P. clarkii. We also found that the expression level of genes encoding senescence marker protein-30 and arylsulfatase A was downregulated in the sulfide gatifloxacin group, indicating that sulfide gatifloxacin accelerated the apoptosis of hepatopancreatocytes. The expression level of major facilitator superfamily domain containing 10 was downregulated, implying that it interferes with the ability of the hepatopancreas to metabolize drugs. Interestingly, we found that Niemann pick type C1 and glucosylceramidase-β potentially interact with each other, consequently decreasing the antioxidant capacity of P. clarkii hepatopancreas. In the fenvalerate group, the downregulation of the expression level of xanthine dehydrogenase indicated that fenvalerate affected the immune system of P. clarkii; moreover, the upregulation of the expression level of pancreatitis-associated protein-2 and cathepsin C indicated that fenvalerate caused possible inflammatory pathological injury to P. clarkii hepatopancreas. In the ridomil group, no pathway was significantly enriched. In total, 21 genes showed significant differences in all three groups. To conclude, although there appears to be some overlap in the toxicity mechanisms of fenvalerate, sulfide gatifloxacin, and ridomil, further studies are warranted.

Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20 a-g, 21 a-g, and 22 a-g) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram-positive and -negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline (21 a) showed the highest activity against C. albicans (MIC50 =0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.

Importance Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this indication. Ophthalmia neonatorum was previously considered a different indication from bacterial conjunctivitis in older children and adults because of uncertain similarities in the cause of disease and the treatment course between the 2 populations. Prospective therapeutic clinical studies were required to demonstrate the effectiveness of treatment for ophthalmia neonatorum. Objective To review the therapeutic clinical trials for patients with bacterial conjunctivitis to evaluate the similarity in the cause of disease and the treatment response between neonates and older children and adults. Design, setting, and participants In this comparative effectiveness research review of pooled data from the most recent 30 bacterial conjunctivitis trials (N = 2018) submitted to the FDA to support the approval of topical ophthalmic solutions for older children and adults, 95% CIs were constructed from clinical cure rates. Cure rates in 3 neonatal randomized clinical trials (N = 392) of patients treated with ophthalmic anti-infective solutions of ciprofloxacin, gatifloxacin, and moxifloxacin were constructed and compared. The baseline ocular swab cultures were analyzed. Main outcomes and measures Cure rates of neonatal trials were compared with the 95% CIs among older children and adults. The bacterial organisms isolated from these 2 populations were compared. Results The 3 neonatal trials enrolled a total of 392 patients, and the 30 trials of older children and adults enrolled a total of 2018 patients. Neonatal clinical cure rates for moxifloxacin (day 4, 48%), ciprofloxacin (day 4, 49%; day 5, 61%), and gatifloxacin (day 7, 79%) were within the 95% CI for products approved to treat older children and adults with bacterial conjunctivitis. Bacterial organisms were consistent between these 2 populations. Conclusions and relevance Comparison of the pooled analysis of these historical trial data suggests similarity in the cause of disease and the treatment response between neonates and older children and adults with bacterial conjunctivitis. Therefore, it was appropriate to extrapolate the effectiveness from older children and adults to neonates to support the approval of therapies for ophthalmia neonatorum. Based on this analysis, ophthalmic solutions of ciprofloxacin, gatifloxacin, and moxifloxacin are now approved for all age groups. This analysis presents an approach of using pooled data from previously underpowered individual trials to establish the similarities in the cause of disease and in treatment response between children and adults, which are the fundamental elements used to evaluate whether extrapolation of effectiveness can be used to support drug approval.

SUMMARY This paper presents the thermodynamic analysis of solubility of gatifloxacin in the N,N-Dimethylformamide (DMF) + methanol (MeOH) cosolvent system at 10 temperatures. From the solubility data, the thermodynamic functions of solution, mixing, and transfers are calculated and analyzed using the Perlovich graphical method. On the other hand, an enthalpy-entropy compensation analysis is performed and the preferential solvation parameters are calculated using the inverse Kirkwood-Buff integral (IKBI) method. The result of the performed calculations indicates that the gatifloxacin solution process is endothermic with entropic favor, where the addition of DMF has a positive cosolvent effect in all cases. Regarding preferential solvation, the results are not entirely conclusive, since in all cases the values of the preferential solvation parameter are less than 0.01, so that, negligible preferential solvation takes place. RESUMEN Este artículo presenta el análisis termodinâmico de la solubilidad de gatifloxacina en el sistema cosolvente de A,A-Dimetilformamida (DMF) + metanol (MeOH) a 10 temperaturas. A partir de los datos de solubilidad se calculan las funciones termodinámicas de solución, mezcla y transferencia. Para el análisis además se utiliza el método gráfico Perlovich. Por otro lado, se realiza un análisis de compensación entalpía-entropía y se calculan los parámetros de solvatación preferencial utilizando el método de las integrales inversas de Kirkwood-BufF (IIKB). Los resultados del análisis termodinámico indican que el proceso de solución de gatifloxacina es endotérmica con favorecimiento entrópico, donde la adición de DMF tiene un efecto cosolvente positivo en todos los casos. En cuanto a la solvatación preferencial, los resultados no son del todo concluyentes, debido a que en todos los casos los valores del parámetro de solvatación preferencial son menores a 0,01 indicando una solvatación insignificante.