Moxifloxacin HCl -loaded Cellulose Acetate Butylate In Situ Forming Gel for Periodontitis Treatment.

Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an in situ forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10-45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, in vitro degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25-45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower in vitro degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, and Porphyromonas gingivalis. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB. HIGHLIGHTS: Moxifloxacin HCl-loaded 10-45% cellulose acetate butyrate (CAB)-based in situ forming gels (ISG) were developed. They were evaluated for physicochemical properties, drug release, in vitro degradation, and antimicrobial activities. ISGs with 25-45% CAB showed swift matrix formation and plastic deformation Adequate CAB content sustained Mx release with Fickian diffusion mechanism They promise for periodontitis treatment because of effective inhibition of related pathogens.

BPaLM Regimen Against Drug-Resistant Tuberculosis in India: A Need of the Hour.

India has a high burden of drug-resistant tuberculosis (DR-TB) cases. The management of this severe form of TB is associated with a number of issues like long treatment durations, high pill burden, and multiple adverse drug reactions. Efforts are on through various research studies and trials for finding solutions to the issues linked to the current drug regimens against drug-resistant tuberculosis. One such remarkable development is the introduction of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM)-based regimens to fight against two of the most severe forms of tuberculosis, i.e., multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB). This editorial throws light on this newer regimen and discusses the same in the Indian context.

Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

BACKGROUND: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. METHODS: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. RESULTS: Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46 vs. 0.38 episodes/1000 transplant-days; p =  .8) and multidrug-resistant gram-negative bacilli infection (0 vs. 0.7 episodes per 1000 transplant-days; p =  .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. CONCLUSION: A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.

Enhancement of sensitivity for moxifloxacin spectrofluorimetric analysis through photoinduced electron transfer inhibition. Green assessment with application to pharmaceutical eye drops.

A green, simple, rapid, selective, and highly sensitive fluorimetric protocol has been established for quantitative analysis of the antibacterial drug moxifloxacin in its pure form and pharmaceutical dosage form. Owing to photoinduced electron transfer, moxifloxacin exhibits low native fluorescence in neutral media. Based on that, the developed fluorimetric protocol depends on inhibiting the photoinduced electron transfer effect of the nitrogen atom presented on the pyrrolidine ring in moxifloxacin by suitable adjusting of pH of the medium surrounding it, leading to its protonation. It is simply achieved by using 0.5 M acetic acid. This protonation enhances the native fluorescence of moxifloxacin, turning it into a stronger one. This fluorescence was measured at 498 nm after excitation at 295 nm with a linearity range from 10 to 60 ng mL-1 and a high correlation coefficient value of 0.9998. The fluorimetric approach could be applied for moxifloxacin detection with a limit of 0.89 ng mL-1 and a quantification limit of 2.69 ng mL-1. The developed method has been validated according to ICH guidelines, indicating high accuracy and excellent precision. Furthermore, the developed fluorimetric protocol was applied successfully for moxifloxacin analysis in pharmaceutical eye drops. As a result, the proposed protocol could be easily applied for quality control of moxifloxacin in different laboratories all over the world.

Surface tracking integrated extended depth-of-field microscopy for rapid non-contact examination of conjunctival goblet cells in humans.

Conjunctival goblet cells (CGCs) are specialized epithelial cells playing key roles for ocular surface homeostasis, and their examination is important for diagnosing ocular surface diseases. Despite recent advancements in high-contrast CGC imaging for non-invasive examination, significant challenges remain for human applications. High-speed large-area imaging over the curved ocular surface is needed to assess statistically meaningful CGCs in the extensive human conjunctiva. To address this challenge, we developed a novel surface detection method and an integrated microscopy system for human use. With both a long detection range of 2 mm and a high update rate of 50 Hz, the surface detection method enabled real-time surface tracking during large-area imaging. The integrated microscopy could complete 5 × 2 patch imaging in approximately 10 s. CGC density analysis showed significantly reduced uncertainties with large-area imaging. This is the first demonstration of non-contact large-area cellular examination in humans, and this new development holds promise for non-invasive CGC examination and accurate diagnosis of ocular surface diseases.

Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment.

Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance. Studies have already shown the beneficial role of the oral antidiabetic metformin as an anti-tuberculosis adjuvant drug. This work aimed to develop an inhalatory dry powder co-formulation of metformin and moxifloxacin to figure out a future option for P-TB treatment. Pre-formulation evaluations indicated the physicochemical compatibility of constituents, demonstrating powder crystallinity and acceptable drug content. Eight moxifloxacin-metformin dry powder formulations were produced by spray drying, and solid-state characterizations showed partial amorphization, ascribed to moxifloxacin. Four formulations containing L-leucine exhibited micromeritic and in vitro deposition profiles indicating pulmonary delivery suitability, like spherical and corrugated particle surface, geometric diameters < 5 µm, high emitted doses (>85 %), and mass median aerodynamic diameters between 1-5 µm. The use of a second spray dryer model further optimized the aerodynamic properties and yield of the best formulation, demonstrating the influence of the equipment used on the product obtained. Moreover, the final formulation showed high in vitro cell tolerability and characteristics in permeability studies indicative of good drug retention in the lungs.

Comparative Efficacy and Safety of Moxifloxacin and Levofloxacin in a Short Standardised Rifampicin Resistant TB Regimen: A STREAM 2 Secondary Analysis.

(1) Background: The World Health Organisation (WHO) categorises moxifloxacin and levofloxacin as Group A drugs, which should be prioritised in the treatment of rifampicin-resistant tuberculosis. We compare their relative efficacy and safety using data from the STREAM trial; (2) Methods: Marginal structural models were used to balance differences in the baseline characteristics of participants receiving the STREAM control regimen containing either moxifloxacin or levofloxacin as this was not a randomised comparison. The difference in proportions between regimens was estimated for favourable outcome, any grade 3/4 adverse event, QTcF increase to ≥500 ms, QTcF increase from baseline by at least 60 ms, and any grade 3/4 adverse event excluding QT events, using weighted analyses; (3) Results: In efficacy analyses (n = 123), the weighted risk difference (moxifloxacin-levofloxacin, wRD) for a favourable outcome was -0.045 (-0.213, 0.123), p = 0.60. Similarly, estimates from the safety analyses (n = 127) showed no evidence of a difference between the fluoroquinolones, other than a suggestion of fewer QTcF increases from baseline on levofloxacin (wRD 0.160 (-0.026, 0.346), p = 0.091); (4) Conclusions: In this small dataset, we found no statistically significant difference in key efficacy or safety outcomes between the moxifloxacin- and levofloxacin-containing regimens; there was a suggestion that QTcF increases from baseline were fewer on levofloxacin.

Toxicity of Moxifloxacin on the Growth, Photosynthesis, Antioxidant System, and Metabolism of Microcystis aeruginosa at Different Phosphorus Levels.

Moxifloxacin (MOX), a widely used novel antibiotic, may pose ecological risks at its actual environmental concentrations, as has been detected in aquatic systems. However, its ecotoxicity to aquatic organisms and regulatory mechanisms of phosphorus in eutrophic aqueous environments are still limited. This study aimed to analyze its physiological and biochemical parameters, including cellular growth, chlorophyll fluorescence, photosynthetic pigments, oxidative stress biomarkers, and metabolomics to elucidate the toxicity induced by environmental concentrations of MOX in Microcystis aeruginosa at different phosphorus levels. The results revealed that the EC50 values of MOX on M. aeruginosa at different phosphorus concentrations were 8.03, 7.84, and 6.91 µg/L, respectively, indicating MOX toxicity was exacerbated with increasing phosphorus levels. High phosphorus intensified the suppression of chlorophyll fluorescence and photosynthetic pigments, while activating the antioxidant enzyme, indicating severe peroxidation damage. Metabolomic analysis showed MOX induced different discriminating metabolites under different phosphorus levels, and perturbed more biological pathways at higher phosphorus concentrations, such as starch and sucrose metabolism, pyrimidine metabolism, and glycerolipid metabolism. This indicates that phosphorus plays an important role in regulating metabolism in M. aeruginosa exposed to MOX. The findings provide valuable information on the mechanisms involved in cyanobacteria responses to antibiotic stress, and offer a theoretical basis for accurately assessing antibiotic toxicity in eutrophic aqueous environments.

Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.

Mycobacterium tuberculosis (TB) remains the leading cause of infection-related mortality worldwide. Drug resistance, need for multiple antimycobacterial agents, prolonged treatment courses, and medication-related side effects are complicating factors to TB cure. The introduction of treatment regimens containing the novel agents bedaquiline, pretomanid, and linezolid, with or without moxifloxacin (BPaL-M or BPaL, respectively) have substantially reduced TB-related morbidity and mortality and are associated with favorable rates of treatment completion and cure. This review summarizes key information on the pharmacology and treatment principles for moxifloxacin, bedaquiline, delamanid, pretomanid, linezolid, and tedizolid in the treatment of multi-drug resistant TB, with recommendations provided to address and attenuate common adverse effects during treatment.

Anti-Infection of Nasopharyngeal Carcinoma Combined with Non-Tuberculous Mycobacteria: A Case Report and Literature Review.

Background: Patients with nasopharyngeal carcinoma (NPC) combined with non-tuberculous Mycobacteria-pulmonary disease (NTM-PD) are very rare in the clinic, and our case is the first patient with NPC combined with NTM-PD. For oncologists, rapid control of the symptoms of infection is essential to the treatment of the primary disease. Case Presentation: A 58-year-old man who developed a NTM-PD after chemotherapy for nasopharyngeal carcinoma. Granulocytosis after chemotherapy is a major factor in the development of various infectious diseases. Nasopharyngeal tumor was found on MRI of the patient's head, and nasopharyngeal malignant tumor was considered after pathological examination after endoscopic resection of intranasal lesion, and then nasopharyngeal non-keratonic carcinoma (T4N1M0, stage IV) was confirmed in the department of oncology. The patient developed bone marrow suppression after chemotherapy and was admitted to hospital due to septic shock. Chest CT examination indicated pulmonary infection, and empirical antibiotic treatment was not effective. The NGS results showed that the patient was infected with Mycobacterium abscess. We treated with cefoxitin followed by moxifloxacin to reduce the lung lesions significantly. Conclusion: NPC with NTM-PD is very rare, and the treatment of NTM-PD is very important for the prognosis of the patient's primary disease. Our study provides experience for anti-infection treatment of patients with immunosuppression.

Immunomodulatory Effects and Protection in Sepsis by the Antibiotic Moxifloxacin.

Sepsis is a leading cause of death in Intensive Care Units. Despite its prevalence, sepsis remains insufficiently understood, with no substantial qualitative improvements in its treatment in the past decades. Immunomodulatory agents may hold promise, given the significance of TNF-α and IL-1ß as sepsis mediators. This study examines the immunomodulatory effects of moxifloxacin, a fluoroquinolone utilized in clinical practice. THP1 cells were treated in vitro with either PBS or moxifloxacin and subsequently challenged with lipopolysaccharide (LPS) or E. coli. C57BL/6 mice received intraperitoneal injections of LPS or underwent cecal ligation and puncture (CLP), followed by treatment with PBS, moxifloxacin, meropenem or epirubicin. Atm-/- mice underwent CLP and were treated with either PBS or moxifloxacin. Cytokine and organ lesion markers were quantified via ELISA, colony-forming units were assessed from mouse blood samples, and DNA damage was evaluated using a comet assay. Moxifloxacin inhibits the secretion of TNF-α and IL-1ß in THP1 cells stimulated with LPS or E. coli. Intraperitoneal administration of moxifloxacin significantly increased the survival rate of mice with severe sepsis by 80% (p < 0.001), significantly reducing the plasma levels of cytokines and organ lesion markers. Notably, moxifloxacin exhibited no DNA damage in the comet assay, and Atm-/- mice were similarly protected following CLP, boasting an overall survival rate of 60% compared to their PBS-treated counterparts (p = 0.003). Moxifloxacin is an immunomodulatory agent, reducing TNF-α and IL-1ß levels in immune cells stimulated with LPS and E. coli. Furthermore, moxifloxacin is also protective in an animal model of sepsis, leading to a significant reduction in cytokines and organ lesion markers. These effects appear unrelated to its antimicrobial activity or induction of DNA damage.

Clinical Characteristics of Moxifloxacin-Related Arrhythmias and Development of a Predictive Nomogram: A Case Control Study.

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

A clinical metagenomic study of biopsies from Mexican endophthalmitis patients reveals the presence of complex bacterial communities and a diversity of resistance genes.

Infectious endophthalmitis is a severe ophthalmic emergency. This infection can be caused by bacteria and fungi. For efficient treatment, the administration of antimicrobial drugs to which the microbes are susceptible is essential. The aim of this study was to identify micro-organisms in biopsies of Mexican endophthalmitis patients using metagenomic next-generation sequencing and determine which antibiotic resistance genes were present in the biopsy samples. In this prospective case study, 19 endophthalmitis patients were recruited. Samples of vitreous or aqueous humour were extracted for DNA extraction for metagenomic next-generation sequencing. Analysis of the sequencing results revealed the presence of a wide variety of bacteria in the biopsies. Resistome analysis showed that homologues of antibiotic resistance genes were present in several biopsy samples. Genes possibly conferring resistance to ceftazidime and vancomycin were detected in addition to various genes encoding efflux pumps. Our findings contrast with the widespread opinion that only one or a few bacterial strains are present in the infected tissues of endophthalmitis patients. These diverse communities might host many of the resistance genes that were detected, which can further complicate the infections.

Impact of Airborne Exposure to PM10 Increases Susceptibility to P. aeruginosa Infection.

The effects of exposure to airborne particulate matter with a size of 10 µm or less (PM10) on C57BL/6 mouse corneas, their response to Pseudomonas aeruginosa (PA) infection, and the protective effects of SKQ1 were determined. C57BL/6 mouse corneas receiving PBS or SKQ1 were exposed to control (air) or PM10 for 2 weeks, infected, and the disease was documented by clinical score, PMN quantitation, bacterial plate count, RT-PCR and Western blot. PBS-treated, PM10-exposed corneas did not differ at 1 day postinfection (dpi), but exhibited earlier (3 dpi) corneal thinning compared to controls. By 3 dpi, PM10 significantly increased corneal mRNA levels of several pro-inflammatory cytokines, but decreased IL-10, NQO1, GR1, GPX4, and Nrf2 over control. SKQ1 reversed these effects and Western blot selectively confirmed the RT-PCR results. PM10 resulted in higher viable bacterial plate counts at 1 and 3 dpi, but SKQ1 reduced them at 3 dpi. PM10 significantly increased MPO in the cornea at 3 dpi and was reduced by SKQ1. SKQ1, used as an adjunctive treatment to moxifloxacin, was not significantly different from moxifloxacin alone. Exposure to PM10 increased the susceptibility of C57BL/6 to PA infection; SKQ1 significantly reversed these effects, but was not effective as an adjunctive treatment.

Determination of levofloxacin, norfloxacin, and moxifloxacin in pharmaceutical dosage form or individually using derivative UV spectrophotometry.

PURPOSE: In this study, first, second, third, and fourth-order derivative spectrophotometric methods utilizing the peak-zero (P-O) and peak-peak (P-P) techniques of measurement were developed for the determination of levofloxacin, norfloxacin, and moxifloxacin. These methods were applied to their combined pharmaceutical dosage form or individually for levofloxacin, norfloxacin, and moxifloxacin. METHODS: Linearity was established in the concentration range of 2-20 µg/mL. The procedures are simple, quick, and precise. The developed methods are sensitive, accurate, and cost-effective, demonstrating excellent correlation coefficients (R2 = 0.9998) and mean recovery values ranging from 99.20% to 100.08%, indicating a high level of precision. RESULTS: The developed approach was effectively employed to determine the levofloxacin, norfloxacin, and moxifloxacin content in commercially available pharmaceutical dosages. CONCLUSIONS: Statistical analysis and recovery tests confirmed the method's linearity and accuracy. The results suggest that this method can be utilized for routine analysis in both bulk and commercial formulations. The simplicity, accuracy, and cost-effectiveness of the developed methods make them valuable for pharmaceutical analysis.

Optimization of graphene polypyrrole for enhanced adsorption of moxifloxacin antibiotic: an experimental design approach and isotherm investigation.

The presence of antibiotics in water systems had raised a concern about their potential harm to the aquatic environment and human health as well as the possible development of antibiotic resistance. Herein, this study investigates the power of adsorption using graphene-polypyrrole (GRP-PPY) nanoparticles as a promising approach for the removal of Moxifloxacin HCl (MXF) as a model antibiotic drug. GRP-PPY nanoparticles synthesis was performed with a simple and profitable method, leading to the formation of high surface area particles with excellent adsorption properties. Characterization was assessed with various techniques, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET). Box-Behnken experimental design was developed to optimize the adsorption process. Critical parameters such as initial antibiotic concentration, nanoparticle concentration, and pH were investigated. The Freundlich isotherm model provided a good fit to the experimental data, indicating multilayer adsorption of MXF onto the GRP-PPY-NP. As a result, a high adsorption capacity of MXF (92%) was obtained in an optimum condition of preparing 30 µg/mL of the drug to be adsorbed by 1 mg/mL of GRP-PPY-NP in pH 9 within 1 h in a room temperature. Moreover, the regeneration and reusability of GRP-PPY-NP were investigated. They could be effectively regenerated for 3 cycles using appropriate desorption agents without significant loss in adsorption capacity. Overall, this study highlights the power of GRP-PPY-NP as a highly efficient adsorbent for the removal of MXF from wastewater as it is the first time to use this NP for a pharmaceutical product which shows the study's novelty, and the findings provide valuable insights into the development of sustainable and effective wastewater treatment technologies for combating antibiotic contamination in aquatic environments.

Dual Drug-Loaded Coaxial Nanofiber Dressings for the Treatment of Diabetic Foot Ulcer.

Introduction: Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization. Rationale: To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds. Results: The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups. Conclusion: These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.