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Gatifloxacin (GAT), an antibiotic belonging to the fluoroquinolone (FQ) class, is a toxicant that may contaminate food products. In this study, a method of ultrasensitive immunochromatographic detection of GAT was developed for the first time. An indirect format of the lateral flow immunoassay (LFIA) was performed. GAT-specific monoclonal antibodies and labeled anti-species antibodies were used in the LFIA. Bimetallic core@shell Au@Ag nanoparticles (Au@Ag NPs) were synthesized as a new label. Peroxidase-mimic properties of Au@Ag NPs allowed for the catalytic enhancement of the signal on test strips, increasing the assay sensitivity. A mechanism of Au@Ag NPs-mediated catalysis was deduced. Signal amplification was achieved through the oxidative etching of Au@Ag NPs by hydrogen peroxide. This resulted in the formation of gold nanoparticles and Ag+ ions, which catalyzed the oxidation of the peroxidase substrate. Such "chemical enhancement" allowed for reaching the instrumental limit of detection (LOD, calculated by Three Sigma approach) and cutoff of 0.8 and 20 pg/mL, respectively. The enhanced assay procedure can be completed in 21 min. The enhanced LFIA was tested for GAT detection in raw meat samples, and the recoveries from meat were 78.1–114.8%. This method can be recommended as a promising instrument for the sensitive detection of various toxicants. [ABSTRACT FROM AUTHOR]

In this paper, the adsorption of gatifloxacin (GAT) by three types of polystyrene nano-plastics (PSNPs), including 400 nm polystyrene (PS), amino-modified PS (PS-NH2), and carboxyl-modified PS (PS-COOH) was studied and the adsorption mechanism were assessed. Experimental findings revealed that the equilibrium adsorption capacity of PSNPs to GAT followed the order PS-NH2 > PS-COOH > PS. The adsorption was regulated by both physical and chemical mechanisms, with intra-particle and external diffusion jointly controlling the adsorption rate. The adsorption process was heterogeneous, spontaneous, and entropy-driven. Sodium chloride (NaCl), alginic acid, copper ions (Cu2+), and zinc ions (Zn2+) inhibited adsorption, with Cu2+ and Zn2+ having the strongest effect on PS-NH2. Theoretical computations indicated that π-π and electrostatic interactions dominated PS adsorption of GAT, while PS-COOH and PS-NH2 adsorbed GAT through electrostatic interactions, hydrogen bonds, and van der Waals (vdW) forces. The surface electrostatic potential of PS-COOH and PS-NH2 was considerably higher than that of PS, with the maximum vdW penetration distance of GAT-PS-NH2 being 1.20 Å. This study's findings provide a theoretical foundation for the migration and synergistic removal of antibiotics, micro-plastics (MPs), and nano-plastics (NPs). [ABSTRACT FROM AUTHOR]

This study aims to develop contact lenses with improved drug-release duration time by layer-by-layer (LBL) coating with natural polymers on contact lenses containing the drug gatifloxacin. LBL coating was performed in single and double layers on contact lenses containing gatifloxaxin using natural polymers carrageenan and polylysine. The performance of contact lenses was evaluated based on various physical properties and antibacterial properties. As a result, contact lenses containing gatifloxacin have reduced physical properties compared to lenses without gatifloxacin. As the concentration of gatifloxacin increased, oxygen permeability and wettability decreased, and antibacterial properties increased. LBL coating improved the wettability and antibacterial properties of contact lenses and increased the drug-release duration. Double-layers coated lenses increased the duration of drug release more than single-coated lenses. Double layer-coating with poly-L-lysine and carrageenan on contact lenses [ABSTRACT FROM AUTHOR]

Drug delivery to ocular tissues is challenging due to the rapid removal of instilled drugs due to the low resident time in ocular tissues. The study aimed to formulate an ophthalmic in situ gel that delivers two drugs (betamethasone sodium phosphate [BSP] and gatifloxacin [GTN]). The new combination will allow the simultaneous administration and extended release of the two drugs, which could potentially improve resident time in ocular tissues, patient compliance, and treatment adherence. Formulations containing different gelling agents at different concentrations were prepared to choose the optimum combination regarding physical properties and release. Formulations containing 17% poloxamer 407 and 0.5% gellan gum with different percentages of methylcellulose were prepared and compared regarding gelation temperature, gelling capacity, gelation time, and release and mucoadhesive, permeation study. Increasing the concentration of MC enhanced all the physical properties of the poloxamer-gellan gum gel. The optimum formula (F3) which contains 0.3% MC had a gelation time of 5 sec. at 31oC and remained in gel form for 24 hr. Both drugs had extended-release time and increased the viscosity and mucoadhesion force of the preparation. The results indicated an outsized increase in viscosity at 37°C with the addition of MC which provided sustained release of the drug over 10 hours. and the formulation is isotonic to the eye as well no irritation on the rabbit eye was observed when tested on animals. Conclusion: F3 in situ gel was used to produce a simultaneous and prolonged release of the two drugs. The capacity to administer hydrophilic and hydrophobic medications using a single formulation, eliminating the need for two drops, will increase patient compliance and, consequently, treatment compliance.

As a widely-used fluoroquinolone antibiotics, 1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (gatifloxacin, GAT) has aroused much concern recently and it is of great importance to realize the accurate and efficient detection. Herein, the silver sulfide/reduced graphene oxide composite (Ag2S/RGO) was synthesized with one-pot method and was coated on the glassy carbon electrode to develop an effective electrochemical sensor for GAT. After the optimization of the size of Ag2S, the pH of buffer solution, and the scanning rate, the Ag2S/RGO modified electrode exhibits good linear relationship to GAT within wide ranges of 0.2 µM − 20 µM and 20 µM − 250 µM with a detection limit of 0.0667 µM. Besides, the proposed sensor shows good selectivity to GAT versus multiple interferences, including organic compounds, ions, and other antibiotics. At last, the proposed sensor was successfully applied in the GAT analysis in various real samples (including shrimp, fish, and chicken) with satisfying recoveries of 91.8 % − 102.4 %. In general, the proposed Ag2S/RGO-based electrochemical sensor provides a novel strategy for the GAT analysis, which is of significance for the development of efficient analytical techniques for antibiotics.

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. [ABSTRACT FROM AUTHOR]

Gatifloxacin, a fluoroquinolone-class antibacterial agent, is effective but has been associated with dysglycemic side effects, leading to the withdrawal of its oral formulation. Patients treated with gatifloxacin have shown notable decrease blood glucose level and after four days of treatment there will be increases in blood glucose levels. To mitigate this issue, novel gatifloxacin derivatives were designed and assessed for their efficacy and safety through in silico molecular docking studies. The derivatives aim to prevent dysglycemia by blocking human pancreatic alpha-amylase (PDB ID: 5TD4). These modifications are hypothesized to retain antibacterial effectiveness while minimizing blood glucose fluctuations. Using AutoDock, molecular docking of gatifloxacin and its derivatives with α -amylase (PDB ID: 5TD4) revealed binding energies, with gatifloxacin exhibiting a binding interaction of -7.1 Kcal/mol; meanwhile derivatives i) Gati I = -9.0 Kcal/mol, ii) Gati-II showed -8.2 Kcal/mol; iii) Gati III -8.5 Kcal/mol; iv) Gati IV = -9.3 Kcal/mol; v) Gati V = -8.9 Kcal/mol; vi) Gati VI = -7.6 Kcal/mol; Acarbose = -13.8 Kcal/mol. Unlike gatifloxacin, these derivatives demonstrated stronger binding interactions with 5TD4, potentially reducing dysglycemic risks. This study contributes to design the targeted antibacterial agents that minimize dysglycemia-related complications, thus enhancing clinical outcomes. [ABSTRACT FROM AUTHOR]

The increase in bacterial antibiotic resistance poses a significant threat to the effectiveness of antibiotics, and there is growing evidence suggesting that global warming may speed up this process. However, the direct influence of temperature on the development of antibiotic resistance and the underlying mechanisms is not yet fully understood. Here we show that antibiotic resistance exhibits a nonlinear response to elevated temperatures under the combined stress of temperatures and antibiotics. We find that the effectiveness of gatifloxacin against Escherichia coli significantly diminishes at 42 °C, while resistance increases 256-fold at 27 °C. Additionally, the increased transcription levels of genes such as marA, ygfA, and ibpB with rising temperatures, along with gene mutations at different sites, explain the observed variability in resistance patterns. These findings highlight the complexity of antibiotic resistance evolution and the urgent need for comprehensive studies to understand and mitigate the effects of global warming on antibiotic resistance.

In this work, the reaction between the drug gatifloxacin (as a ligand) with Ru(III) ions was investigated and the resulting complex was structurally and morphologically characterized. The structural properties of the complex were assessed using elemental analyses, molar conductance, thermogravimetry, UV-Vis, and IR spectroscopies, where the morphological characteristics were evaluated using SEM-EDX and XRD methods. The analyses suggested that two ligand molecules were coordinated to the Ru(III) ion via the nitrogen atoms of piperazine rings. The complex was formulated as [Ru(L)2(Cl)2]Cl, where the Ru(III) ion has a six-coordinate mode, and the coordination sphere is complemented by chlorine atoms. The interaction of the ligand with the Ru(III) ions leads to the product having an organized smooth plate-like structure with a main diameter of 39.42 nm. The RuO2 oxide in the nanoscale range was generated by the thermal decomposition of the [Ru(L)2(Cl)2]Cl complex at 600 oC for 3 hours. SEM micrographs indicated that the RuO2 material possesses uniform and organized microstructures with many internal cavities enabling it to be used as a catalyst for the heterogeneous degradation of dyes and organic pollutants.

Gatifloxacin (GAT), an antibiotic belonging to the fluoroquinolone (FQ) class, is a toxicant that may contaminate food products. In this study, a method of ultrasensitive immunochromatographic detection of GAT was developed for the first time. An indirect format of the lateral flow immunoassay (LFIA) was performed. GAT-specific monoclonal antibodies and labeled anti-species antibodies were used in the LFIA. Bimetallic core@shell Au@Ag nanoparticles (Au@Ag NPs) were synthesized as a new label. Peroxidase-mimic properties of Au@Ag NPs allowed for the catalytic enhancement of the signal on test strips, increasing the assay sensitivity. A mechanism of Au@Ag NPs-mediated catalysis was deduced. Signal amplification was achieved through the oxidative etching of Au@Ag NPs by hydrogen peroxide. This resulted in the formation of gold nanoparticles and Ag+ ions, which catalyzed the oxidation of the peroxidase substrate. Such “chemical enhancement” allowed for reaching the instrumental limit of detection (LOD, calculated by Three Sigma approach) and cutoff of 0.8 and 20 pg/mL, respectively. The enhanced assay procedure can be completed in 21 min. The enhanced LFIA was tested for GAT detection in raw meat samples, and the recoveries from meat were 78.1–114.8%. This method can be recommended as a promising instrument for the sensitive detection of various toxicants.

We have synthesized and characterized N-substituted-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives and were evaluated for their antibacterial activity against Staphylococcus Aureus, Micrococcus Luteus, Bacillus subtilis and Gram-negative Escherichia Coli, Pseudomonas aeruginosa and Flavobacterium Devorans pathogens and found that any modification is done at C-3 position then the activity of quinolone scaffold is decreased. This shows that presence of carboxylic acid group at C-3 position is very important for antibacterial activities. To gain more molecular insight into the binding interaction of the synthesized compounds, docking studies with to S. aureus DNA gyrase (PDB: 2XCT) were conducted. Based on its potential anti-bacterial properties, the most active molecule, 5a, was submitted to molecular docking simulations using Schrödinger Glide software. The fluoroquinolones mechanism of action is entirely compatible with the binding interaction of the compound 5a. Further, all the synthesized compounds tested for In Silico ADME prediction and observed that all the compounds followed the criteria for orally active drug and therefore, these compounds can be further developed an oral drug candidate. [ABSTRACT FROM AUTHOR]

In this work, the reaction between the drug gatifloxacin (as a ligand) with Ru(III) ions was investigated and the resulting complex was structurally and morphologically characterized. The structural properties of the complex were assessed using elemental analyses, molar conductance, thermogravimetry, UV-Vis, and IR spectroscopies, where the morphological characteristics were evaluated using SEM-EDX and XRD methods. The analyses suggested that two ligand molecules were coordinated to the Ru(III) ion via the nitrogen atoms of piperazine rings. The complex was formulated as [Ru(L)2(Cl)2]Cl, where the Ru(III) ion has a six-coordinate mode, and the coordination sphere is complemented by chlorine atoms. The interaction of the ligand with the Ru(III) ions leads to the product having an organized smooth plate-like structure with a main diameter of 39.42 nm. The RuO2 oxide in the nanoscale range was generated by the thermal decomposition of the [Ru(L)2(Cl)2]Cl complex at 600 oC for 3 hours. SEM micrographs indicated that the RuO2 material possesses uniform and organized microstructures with many internal cavities enabling it to be used as a catalyst for the heterogeneous degradation of dyes and organic pollutants. [ABSTRACT FROM AUTHOR]

Based on density functional theory (DFT), the initial structure of gatifloxacin was optimized at the M06 - 2X/ 6 - 311G(d, p) basis set level The vibration frequency is calculated According to the analysis of potential energy distribution (PED), the characteristic vibration modes in the frequency range are completely assigned by VEDA4 software package and compared with the experimental spectrum The molecular surface electrostatic potential was plotted, which can be predicted where the molecule may undergo electrophilic and nucleophilic reactions The excited state of the gatifloxacin molecule was calculated by time - dependent density functional theory (TDDFT), and the intramolecular electronic transition of gatifloxacin was discussed This study provides a theoretical basis for the analysis of the spectrum and electronic structure of gatifloxacin. [ABSTRACT FROM AUTHOR]

Gatifloxacin (GAT), a fluoroquinolone, does not present a monograph described in official compendia and the literature presents some analytical methods for its evaluation, but with space for eco-efficient methods. The objective was to develop and validate a green and indicative of stability method by UV for quantitative evaluation of GAT in eye drops. Purified water, as a diluent, quartz cubette and 286 nm were used. The method was linear in the range of 4 – 12 µg mL-1 (0.9997), precise (RSD < 5 %), selective in the comparison of standard and sample and by the forced degradation, exact with average recovery of 100.21 %, robust against changes in wavelength, source of purified water and use of ultrasound. The method was able to quantify and evaluate the stability of GAT in eye drops in green form according to the Eco-Scale Assessment.

Two mixed-ligand complexes of Ru(III) ions were synthesized and used to generate nanostructured RuO2 oxide. Complex A contains gatifloxacin (L1), the amino acid glycine (L2), and Ru(III) ions in a 1:1:1 ratio. Complex B contains gatifloxacin (L1), the amino acid alanine (L3), and Ru(III) ions in a 1:1:1 ratio. The synthesized complexes were characterized using UV-Visible and IR spectroscopies, molar conductance, elemental analyses, thermogravimetry, XRD, and SEM-EDX techniques. In both complexes, the L1 ligand acts as a bidentate and uses the nitrogen atoms of the piperazine ring to capture the Ru(III) ions, while the L2 and L3 ligands capture the Ru(III) ions using their oxygen atom of the carboxylate group and the nitrogen atom of the amino group. The atmosphere around the Ru(III) ion is octahedral, and the complexes were formulated as [RuL1L2(H2O)2]Cl2 and [RuL1L3(H2O)2]Cl2 for Complex A and Complex B, respectively. Complex A was directly decomposed in air at 600 °C for 3 h to produce RuO2 oxide (Oxide A), and complex B was decomposed under the same conditions to produce RuO2 oxide (Oxide B). Morphologically, oxide A and oxide B have a coral reef-like texture with large holes and cavities. [ABSTRACT FROM AUTHOR]

Postoperative endophthalmitis (POE) has been the most threatening complication after cataract surgery, which perhaps can be solved by the antibiotic-loaded intraocular lens (IOL). However, most drug-loaded IOLs demonstrate insufficient drug quantity, short release time, increased implantation-related difficulties or other noticeable drawbacks. To prevent POE and to address these deficiencies, a drug-loaded copolymer IOL, prepared from poly (urethane acrylate) prepolymer, isobornyl methacrylate (IBOMA), N-vinyl-2-pyrrolidone (NVP), Irgacure 819, RUVA-93, and gatifloxacin (GAT), was rapidly fabricated via photocuring and by using a 3D-printed mold. This composite displayed an outstanding and controllable GAT release behavior in vitro, a high light transmittance, and a moderate refractive index. Also, it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material. In vivo tests demonstrated satisfying released drug concentration at the early treatment stage. In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL, which also displayed good biocompatibility. These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE, also the proposed methods could inspire more designs for various medical applications.

Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization–probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug release, antimicrobial efficacy (against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa), and ex vivo permeation. The lead formulation exhibited desired physicochemical characteristics, an extended release of GTX over a 12 h period, and was stable over three months at the three storage conditions (refrigerated, room temperature, and accelerated). The transcorneal flux and permeability of GTX from the GTX-NLC formulation were 5.5- and 6.0-fold higher in comparison to the commercial eyedrops and exhibited a similar in vitro antibacterial activity. Therefore, GTX-NLCs could serve as an alternative drug delivery platform to improve treatment outcomes in BC. [ABSTRACT FROM AUTHOR]

In this work, we extracted, purified, and characterized two active pharmaceutical ingredients, levocetirizine and levosalbutamol (from commercial tablet formulations), and used them as chiral selectors for enantioresolution of gatifloxacin through thin-layer chromatographic (TLC) method. The silica gel was impregnated with a chiral selector for the enantioresolution of gatifloxacin. The mobile phase used was a combination of acetonitrile, methanol, and triethylamine (4:4:2, V/V, pH 9) and (2:6:2, pH 9), respectively, with levocetirizine and levosalbutamol (as chiral selector in stationary phase at pH 5). The detection limit for enantiomers of gatifloxacin was observed to be 4.2 and 4.9 μg spot‒1, respectively, with levocetirizine and levosalbutamol as chiral selectors. This is the first report on levocetirizine and levosalbutamol as chiral selectors for TLC resolution of gatifloxacin enantiomers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Using polystyrene two‐dimensional photonic crystal as template, gatifloxacin (GTFX) as imprinting molecule, methanol as solvent, acrylic acid as functional monomer, ethylene glycol dimethyl acrylate as crosslinking agent and 2,2‐diethyloxyacetophenone as initiator, after UV initiation polymerization the GTFX molecularly imprinted two‐dimensional photonic crystal hydrogel (GTFX‐MIPCH) sensor was prepared. The response performance of the hydrogel was investigated by measuring the diameter change of the Debye ring. The experimental results showed that the prepared GTFX‐MIPCH has a sensitive response to GTFX. When the concentration of GTFX increases from 0 to 1 × 10−4 mol L−1, the diameter of the Debye ring decreases by 8.50 mm, the corresponding particle spacing increases by 29.1 nm, and the color of the sensor changes from purple to orange. Also there was a linear relationship between the change of particle spacing (Δd) and the logarithm of GTFX concentration (lg c) in the range 10−12–10−6 mol L−1. It is noteworthy that the limit of detection of GTFX‐MIPCH is as low as 10−14 mol L−1. In addition, in a solution of GTFX analogues enrofloxacin, levofloxacin, ciprofloxacin and norfloxacin, the change of particle spacing of the GTFX‐MIPCH sensor is 13.3, 11.6, 11.1 and 10.3 nm respectively, indicating that GTFX‐MIPCH has good specific recognition ability for GTFX. Moreover, GTFX‐MIPCH shows good reusability and can also be used for the detection of GTFX in water samples. This GTFX‐MIPCH can achieve a visual detection effect on GTFX through the Debye ring and color change. © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye can cause an increased risk of ocular infection due to loss of corneal epithelial integrity and changes to tear film homeostasis. Polymeric nanofibers with unique physicochemical and biological properties have attracted a lot of attention due to the improved in vivo performance of their conventional ocular formulations. The purpose of this present exposition was to assess the in vitro and in vivo efficacy of gatifloxacin (GAF)-loaded polyacrylonitrile (PAN) nanofiber in dry eye conditions. Methods: The nanofibers were characterized for morphology, drug entrapment, swelling behavior, drug release, oxygen permeability, biodegradability, antimicrobial potential, and sterility. Draize test, in vivo antibacterial activity, corneal healing characteristics, and tear quality profiles were also used to determine in vivo safety and efficacy. Results: Experimental findings suggested that electrospinning at defined conditions (applied voltage of 18 kV, flow rate of 0.5 mL/h, and tip to collector distance of 10 cm) produced smooth and continuous nanofibers with an average diameter of 480 nm. High drug entrapment of 95% combined with swelling indices of around 180% increased the controlled drug delivery capability of the prepared formulation. A slow degradation rate of 3±0.75% ensured a long-term cumulative drug release of 90% within 16 days. The inhibition diameter of the optimized formulation was found to be 15 ± 0.31 mm for E. coli and 13 ± 0.26 mm for S. aureus. Furthermore, after 3 days in an experimental dry eye animal model, the drug-loaded nanofiber showed better antibacterial activity, corneal healing, and tear film stability than the commercial eye drop. Conclusion: Overall, the study concluded that the GAF-loaded PAN nanofiber has good application prospects in the treatment of dry eye due to its safety and controlled drug release profile. [ABSTRACT FROM AUTHOR]

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.

Intraocular infections are prevalent after traumatic injuries or after common ocular surgeries. Infections cause inflammation that can damage the retina and architecture of the eye, often resulting in poor visual outcomes. Severe cases may result in blindness or require enucleation of the eye. Treatments for intraocular infections include intravitreal antibiotics and corticosteroids or surgical vitrectomy in serious cases. The increase in multidrug-resistant infections calls for novel treatment options. In the present study, a biomimetic erythrocyte-derived nanosponge was tested for the ability to neutralize pore-forming toxins from the most frequent Gram-positive bacterial causes of intraocular infections (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus). Nanosponge pretreatment of supernatants reduced hemolytic activity in vitro. In a murine sterile endophthalmitis model, nanosponge pretreatment of injected supernatants resulted in greater retinal function and less ocular pathology compared to that in eyes injected with untreated supernatants from all pathogens except methicillin-resistant S. aureus In a murine bacterial endophthalmitis model, treatment with gatifloxacin and gatifloxacin-nanosponges reduced intraocular bacterial burdens, except in the case of methicillin-sensitive S. aureus For all pathogens, eyes in both treatment groups showed decreased ocular pathology and inflammation. Overall, reductions in retinal function loss afforded by gatifloxacin-nanosponge treatment were significant for E. faecalis, S. pneumoniae, and methicillin-resistant S. aureus but not for B. cereus and methicillin-sensitive S. aureus These results suggest that clinical improvements in intraocular infections following nanosponge treatment were dependent on the complexity and types of toxins produced. Nanosponges might serve as an adjunctive therapy for the treatment of ocular infections.IMPORTANCE Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.

Design of experiment (DOE) assisted simple, rapid, precise and accurate stability indicating HPLC method has been developed for simultaneous estimation of Gatifloxacin (GTF) and Loteprednol (LOT) along with their forced degradation products. The developed method has been optimized and developed by using central composite design (CCD) in response surface methodology (RSM). Trails have been undertaken and ratio of phosphate buffer in mobile phase, pH of buffer and flow rate are selected as factors. Resolution, tailing factor (GTF) and tailing factor (LOTE) are selected for determining the system response in the process of method optimization. The responses have been optimized using the Derringer's desirability function. The effective separation is achieved on Phenomenex EVO-C18 column (250 mm x 4.6 mm i.d, 5 μm particle size) with mobile composed of 10 mM phosphate buffer, pH 3.5 and organic phase composed of mixture of acetonitrile and methanol 60:40 % v/v, the flow rate was 1.0 mL/min, the signals were detected at 267 nm. The developed method was validated for linearity, accuracy, precision, and robustness. The method was applied successfully for stability samples. [ABSTRACT FROM AUTHOR]

• This article is the successful synthesis of a novel crystalline molecular salt formed between gatifloxacin (GAT) and sulfanilamide derivative sulfamerazine (SMZ), designated as GAT-SMZ. • This innovative complex aims to enhance the physicochemical properties of GAT while improving its antibacterial efficacy. • Single-crystal X-ray diffraction studies revealed that the incorporation of SMZ into the GAT lattice significantly alters the zwitterionic structure of GAT, leading to the formation of a stable tetrameric arrangement between GAT and SMZ molecules. • Pharmaceutical evaluations demonstrated that the resulting molecular salt exhibits notable improvements in solubility and permeability compared to the parent drug, gatifloxacin. • Remarkably, these enhanced physicochemical properties translate into superior in vitro antibacterial activity, characterized by larger inhibition zones and reduced minimum inhibitory concentration (MIC) values. A molecular salt combined with the fluoroquinolone antibacterial gatifloxacin (GAT) and the sulfonamides antibacterial sulfamerazine (SMZ) is designed and synthesized successfully, which is the first report of the dual-drug cocrystallization of gatifloxacin. The precise structure of the acquired molecule salt GAT-SMZ has been characterized via single crystal X-ray diffraction and other techniques. Single crystal diffraction analysis displays that due to the transfer of protons from SMZ to GAT, the molecular salt of GAT-SMZ is formed, and the supramolecular network is dominated by charge-assisted one-dimensional hydrogen bond chain and two-dimensional accumulation layer in the crystal. Such structural feature endows molecular salt with superior physicochemical properties, including enhanced solubility and permeability. More importantly, the superior pharmaceutical performances of the dual-drug salt resulted in enhanced antibacterial activity against the tested strains. These observations are strongly supported by theoretical studies based on Hirshfeld surface and molecular docking analyses. Thus, this contribution not only highlights the validity of combining theory with experiment to drive the problem of physicochemical properties of drugs through co-crystallization methods, but also fills in the previous studies gatifloxacin dual-drug salt synergistic antibacterial research blank. [ABSTRACT FROM AUTHOR]

• A novel molecular salt of gatifloxacin conjugated to salicylic acid was synthesized. • The physicochemical properties and antibacterial efficacy of it were improved. • These findings are supported by theoretical calculations. To improve the physicochemical characteristics of gatifloxacin (GAT) and refine its antibacterial efficacy, a novel crystalline molecular complex combining GAT with salicylic acid (SAL), namely GAT-SAL has been successfully synthesized. Precise salt structure revealed by single crystal X-ray diffraction displayed that the entry of SAL into the GAT lattice destroyed the zwitterionic structure of GAT itself, resulting in the formation of a tetramer structure between GAT and SLA molecules, thus laying a foundation for improving the physicochemical properties of GAT. The pharmaceutical research indicated that the molecular salt exhibited concurrent enhancements in both solubility and permeability surpassing the parent drug gatifloxacin. Notably, the refined physicochemical attributes bestow GAT-SAL with heightened in vitro antibacterial potency, showing larger inhibition rings and smaller MIC values. These observations can be supported by theoretical studies involving theoretical research based on density functional theory (DFT) , Hirshfeld surfaces and molecular docking. The present contribution emphasizes the effectiveness of combining theory and experiment to solve the GAT problem by means of the cocrystallization approach, thus providing the new idea for the rapid screening of novel antimicrobial agents. [ABSTRACT FROM AUTHOR]

Quinolone antibiotics are widely used to prevent and treat diseases caused by bacterial infection. However, overuse of antibiotics may lead to their residue in the environment and food, posing potential threats to human health. In this study, a ratiometric fluorescent probe based on nitrogen and sulfur co-doped carbon quantum dots (N, S-CQDs) was synthesized, which can realize the detection of moxifloxacin (MXF), gatifloxacin (GAT) and ofloxacin (OFX) in milk. After addition of these antibiotics, the fluorescence at 440 nm originating from N, S-CQDs was significantly quenched due to the fluorescence resonance energy transfer (FRET), while the fluorescence at 525 nm (MXF), 500 nm (GAT) and 515 nm (OFX) were enhanced due to aggregation induced emission (AIE). The fluorescence changes were completed within 30 s and stabilized for at least 14 days. Good linear relationships between the fluorescence intensity ratios (F 525 /F 440 for MXF, F 500 /F 440 for GAT and F 515 /F 440 for OFX) and the antibiotic concentrations ranging from 0.1 to 100 mg L−1 were obtained, with R2 above 0.99. The limits of quantitation were in the range of 1.67–6.20 μg L−1, and MXF, GAT and OFX can be well identified by linear discriminant analysis. The probe enabled quantitative analysis of MXF, GAT and OFX in milk samples, with recoveries ranging from 82% to 107%. A test strip based on the ratiometric fluorescence probe was successfully applied for the detection of MXF and GAT in milk in combination with a smartphone. This method exerted high specificity and sensitivity, which has the potential to achieve in-site detection of MXF, GAT and OFX in milk. [Display omitted] • N, S-CQDs can serve as a ratiometric fluorescent probe for detecting MXF, GAT and OFX. • FRET and AIE mechanisms contribute to the fluorescence quenching and enhancement of the probe. • The fluorescence changes occur within 30 s and remain stable for up to 14 days. • The N, S-CQD probe can distinguish MXF, GAT and OFX in combination with LDA. • On-site detection of NFX and OFX in milk can be realized using probe test strips in combination with a smartphone. [ABSTRACT FROM AUTHOR]

As a widely-used fluoroquinolone antibiotics, 1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (gatifloxacin, GAT) has aroused much concern recently and it is of great importance to realize the accurate and efficient detection. Herein, the silver sulfide/reduced graphene oxide composite (Ag 2 S/RGO) was synthesized with one-pot method and was coated on the glassy carbon electrode to develop an effective electrochemical sensor for GAT. After the optimization of the size of Ag 2 S, the pH of buffer solution, and the scanning rate, the Ag 2 S/RGO modified electrode exhibits good linear relationship to GAT within wide ranges of 0.2 µM − 20 µM and 20 µM − 250 µM with a detection limit of 0.0667 µM. Besides, the proposed sensor shows good selectivity to GAT versus multiple interferences, including organic compounds, ions, and other antibiotics. At last, the proposed sensor was successfully applied in the GAT analysis in various real samples (including shrimp, fish, and chicken) with satisfying recoveries of 91.8 % − 102.4 %. In general, the proposed Ag 2 S/RGO-based electrochemical sensor provides a novel strategy for the GAT analysis, which is of significance for the development of efficient analytical techniques for antibiotics. [ABSTRACT FROM AUTHOR]

In the present study, chitosan (C), walnut (W), and almond shell (A) powder adsorbent (in different combinations as almond shells:walnut:chitosan 2:1:1 (AWC), chitosan:almond shell:walnut 2:1:1 (CAW), and walnut:almond shells:chitosan 2:1:1 (WAC)) powder were combined in different ratios to produce low-cost composite adsorbent beads for the removal of antibiotics gatifloxacin (GAT) from synthetic wastewater. The beads were characterized by a scanning electron microscope, Fourier transform infrared spectrum spectrophotometer, and energy-dispersive X-ray spectroscopy. The batch adsorption approach was employed to remove the antibiotic from the water. Moreover, isotherm and kinetics were conducted to illustrate the adsorption mechanism. Parameters like the effect of the adsorbent's dosage, pH, initial concentration, and contact time on antibiotic adsorption were evaluated. Adsorption percentage increased slightly with the increase in adsorbent dosage. The optimum pH for GAT adsorption on beads was 5–7. In addition, adsorption increased with initial antibiotic concentration and time rise. The adsorption isotherm data were successfully fitted to Langmuir isotherm for AWC and CAW beads, while WAC beads followed the Freundlich isotherm. The highest adsorption was attained at pH 5 on CAW beads and pH 7 on AWC and WAC beads. The optimal contact time for equilibrium studies was 120 min for all types of beads. The adsorption isotherm data in AWC beads fit well with the Langmuir model and Freundlich adsorption for CAW and WAC beads. The rate of adsorption on beads follows Lagergren pseudo-second-order kinetics. The results indicate that prepared combination beads can be used to remove antibiotics from wastewater. [ABSTRACT FROM AUTHOR]

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.

Abdulrhman Althaqafi,1,&ast; Majid Ali,2 Yusuf Alzahrani,3 Long Chiau Ming,4,&ast; Zahid Hussain5 1Department of Pharmacy, Al-Noor Hospital, Makkah, Saudi Arabia; 2College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 3College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 4PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Gadong, Brunei Darussalam; 5Faculty of Health, University of Canberra, Canberra, ACT, Australia&ast;These authors contributed equally to this workCorrespondence: Majid Ali; Zahid Hussain Email maaali@uqu.edu.sa; zahid.hussain@canberra.edu.auIntroduction: 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.Keywords: gatifloxacin, moxifloxacin, ciprofloxacin, levofloxacin, hyperglycemia, hypoglycemia, safety, adverse drug reaction