Green method by National Environmental Methods Index and Eco-Scale Assessment for evaluation of gatifloxacin-based product by HPLC.

The literature reveals gaps in the availability of green analytical methods for assessing products containing gatifloxacin (GFX), a fluoroquinolone. Presently, method development is supported by tools such as the National Environmental Methods Index (NEMI) and Eco-Scale Assessment (ESA), which offer objective insights into the environmental friendliness of analytical procedures. The objective of this work was to develop and validate a green method by the NEMI and ESA to quantify GFX in eye drops using HPLC. The method utilized a C8 column (4.6 × 150 mm, 5 µm), with a mobile phase of purified water containing 2% acetic acid and ethanol (70:30, v/v). The injection volume was 10 µL and the flow rate was 0.7 mL/min in isocratic mode at 25°C, with detection performed at 292 nm. The method demonstrated linearity in the range of 2-20 µg/mL, and precision at intra-day (relative standard deviation [RSD] 1.44%), inter-day (RSD 3.45%), and inter-analyst (RSD 2.04%) levels. It was selective regarding the adjuvants of the final product (eye drops) and under forced degradation conditions. The method was accurate (recovery 101.07%) and robust. The retention time for GFX was approximately 3.5 min. The greenness of the method, as evaluated by the NEMI, showed four green quadrants, and by ESA, it achieved a score of 88.

Conjunctival sac flora and drug susceptibility analysis in normal children in East China.

PURPOSE: To investigate the distribution characteristics of conjunctival sac flora and assess the susceptibility of commonly used topical antimicrobial agents in normal children under the age of 18 in East China. METHODS: In 2019, a study was conducted at Qingdao Eye Hospital of Shandong First Medical University to analyze the microorganism cultures of conjunctival sac in 1258 normal children (2516 eyes; average age, 6.21 ± 3.78 years) in East China. Exclusion criteria included children with ocular surface diseases and those who had used any topical antimicrobial agents recently. The microorganism species in the conjunctival sac were analyzed using the M-38A protocol (microdilution method; investigators read the minimum inhibitory concentration [MIC] values) by the Clinical and Laboratory Standards Institute to determine drug susceptibility. RESULTS: The incidence of conjunctival sac microorganism in children was 32.87% (827/2516), a total of 541 cases (male 293, female 248). Children with conjunctival sac flora in a single eye were 255 and in both eyes were 286 (no statistical difference, P > 0.05). The concordance rate of children with binocular conjunctival sac flora was 32.16% (174/541; male 84, female 90). A total of 42 species of bacteria were detected. Children with Gram-positive cocci accounted for the highest proportion, 91.54% (757/827). The top three bacteria with the highest detection rates were Staphylococcus epidermidis (S. epidermidis; 52.12%), Streptococcus (12.09%), and Staphylococcus aureus (S. aureus; 10.76%). Streptococcus mitis (5.20%) accounted for the highest proportion of Streptococcus.S. epidermidis had the highest proportion in all age groups and was positively correlated with age (r = 0.89, P = 0.03). Before six years of age, the streptococcal proportion(mainly S. mitis) was greater than that of Staphylococcus aureus. The drug susceptibility analysis showed that S. epidermidis was most sensitive to gatifloxacin (98.61%), while it had the highest resistance rate to erythrocin (87.94%). S. aureus had the highest susceptibility to moxifloxacin (100%). Streptococcus was most sensitive to moxifloxacin (96.97%) and had the highest resistance rate to tobramycin (92.93%). CONCLUSIONS: Conjunctival sac flora in children was dominated by Gram-positive cocci, mainly S. epidermidis, S. aureus, and Streptococcus. S. epidermidis increased with age; the proportion of Streptococcus was higher than S. aureus among children aged 0-6 years. The typical conjunctiva sac flora was generally sensitive to quinolones, such as moxifloxacin and gatifloxacin; Streptococcus displayed high resistance to tobramycin antibiotics; and the female children had higher resistance to tobramycin than the male children.

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.

A molecularly imprinted electrochemical sensor with dual functional monomers for selective determination of gatifloxacin.

A molecularly imprinted electrochemical sensor was designed for the selective determination of gatifloxacin (GTX) based on dual functional monomers. Multi-walled carbon nanotube (MWCNT) enhanced the current intensity and zeolitic imidazolate framework 8 (ZIF8) provided a large surface area to produce more imprinted cavities. In the electropolymerization of molecularly imprinted polymer (MIP), p-aminobenzoic acid (p-ABA) and nicotinamide (NA) were used as dual functional monomers, and GTX was the template molecule. Taking [Fe(CN)6]3-/4- as an electrochemical probe, an oxidation peak on the glassy carbon electrode was located at about 0.16 V (vs. saturated calomel electrode). Due to the diverse interactions among p-ABA, NA, and GTX, the MIP-dual sensor exhibited higher specificity towards GTX than MIP-p-ABA and MIP-NA sensors. The sensor had a wide linear range from 1.00 × 10-14 to 1.00 × 10-7 M with a low detection limit of 2.61 × 10-15 M. Satisfactory recovery between 96.5 and 105% with relative standard deviation from 2.4 to 3.7% in real water samples evidenced the potential of the method in antibiotic contaminant determination.

Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1-b][1,3,4]thiadiazole moiety.

Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.

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.

Roles of CCL2 and CCL3 in intraocular inflammation during Bacillus endophthalmitis.

Bacillus cereus (B. cereus) endophthalmitis is a vision-threatening bacterial infection. Uncontrolled inflammatory responses are the hallmark of this disease which cause irreversible damage to the retina. We recently reported C-X-C chemokines as a vital modulators which impacted the pathogenesis of this disease. Here, we investigated the impact of two highly upregulated C-C chemokines, CCL2 and CCL3, on intraocular inflammation this disease. B. cereus was injected into the eyes of C57BL/6J (WT), CCL2-/-, and CCL3-/- mice to induce endophthalmitis. Infected eyes were examined for bacterial growth, retinal function, and inflammation. Bacterial growth in CCL2-/- and CCL3-/- mice were similar, but retained retinal function was greater in CCL2-/- and CCL3-/- eyes compared to that of C57BL/6J eyes. The retinal architecture of infected eyes of CCL2-/- mice were conserved for a longer period of time than in infected CCL3-/- eyes. Infected CCL2-/- and CCL3-/- eyes had less inflammation than did infected C57BL/6J eyes. Based on these results, we assessed the efficacies of intravitreal anti-CCL2 or anti-CCL3 with or without the antibiotic gatifloxacin. Compared to infected untreated eyes, there was significantly less inflammation and greater retention of retinal function in eyes treated with anti-CCL2 or anti-CCL3 with gatifloxacin. This study showed that B. cereus endophthalmitis in CCL2-/- mice had a better clinical outcome than in CCL3-/- mice. Intravitreal administration of anti-CCL2 and anti-CCL3 with gatifloxacin significantly reduced inflammation and provided protection of retinal function. These results suggest that CCL2 and CCL3 are prospective anti-inflammatory targets that should be tested along with other antibiotics for treating Bacillus and perhaps other forms of endophthalmitis.

Antibiotic resistance status of helicobacter pylori strains isolated from initial eradication patients in Ningbo, China, from 2017 to 2021.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. AIM: To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H. pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H. pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. RESULTS: The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. CONCLUSION: With the increasing resistance rate and multiple resistance of H. pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.

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.

New Potential Pharmacological Targets of Plant-Derived Hydroxyanthraquinones from Rubia spp.

The increased use of polyphenols nowadays poses the need for identification of their new pharmacological targets. Recently, structure similarity-based virtual screening of DrugBank outlined pseudopurpurin, a hydroxyanthraquinone from Rubia cordifolia spp., as similar to gatifloxacin, a synthetic antibacterial agent. This suggested the bacterial DNA gyrase and DNA topoisomerase IV as potential pharmacological targets of pseudopurpurin. In this study, estimation of structural similarity to referent antibacterial agents and molecular docking in the DNA gyrase and DNA topoisomerase IV complexes were performed for a homologous series of four hydroxyanthraquinones. Estimation of shape- and chemical feature-based similarity with (S)-gatifloxacin, a DNA gyrase inhibitor, and (S)-levofloxacin, a DNA topoisomerase IV inhibitor, outlined pseudopurpurin and munjistin as the most similar structures. The docking simulations supported the hypothesis for a plausible antibacterial activity of hydroxyanthraquinones. The predicted docking poses were grouped into 13 binding modes based on spatial similarities in the active site. The simultaneous presence of 1-OH and 3-COOH substituents in the anthraquinone scaffold were emphasized as relevant features for the binding modes' variability and ability of the compounds to strongly bind in the DNA-enzyme complexes. The results reveal new potential pharmacological targets of the studied polyphenols and help in their prioritization as drug candidates and dietary supplements.