Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

Versatile polymer-based strategies for antibacterial drug delivery systems and antibacterial coatings

Human health damage and economic losses due to bacterial infections are very serious worldwide. Excessive use of antibiotics has caused an increase in bacterial resistance. Fortunately, various non-antibiotic antibacterial materials...

Albumin grafted coaxial electrosparyed polycaprolactone-zinc oxide nanoparticle for sustained release and activity enhanced antibacterial drug delivery

Zinc oxide-cloxacillin incorporated nanoparticles coated with concentric layers of polycaprolactone and albumin via a coaxial electrospraying technique as an enhanced and sustained antimicrobial delivery system for respiratory infections.

The Antibacterial Activity of Catunaregam tomentosa Against Selected Gram-Positive and Gram-Negative Bacteria

Catunaregam tomentosa is a plant from Rubiaceae family that is used in traditional medicine for the treatment of stomatitis and ulcers due to bacterial infections. Besides, it also helps in the treatment of oliguria and dysuria. Indiscriminate use of commercial antibacterial medicines had led to the search for novel antibacterial drugs. Since for ages medicinal plants have been used to treat bacterial infection, so they can be excellent sources of the novel antibacterial drug. To evaluate the scientific basis of the use of plant, antibacterial activity leaves extract of C.tomentosa was investigated against selected Gram-positive and Gram-negative bacteria. The study also investigated the effect of pH on its antibacterial activity. Antibacterial activity of the plant extracts was evaluated against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa by using the disc diffusion method at 100mg/mL concentration. Extracts of C. tomentosa inhibit the activity of S. aureus but do not inhibit the activity of Gram-negative bacteria. Minimum inhibitory concentration (MIC) was also determined against S. aureus at concentration 100, 50, 25, 12.5, 6, 3, 1.5, 0.75 and 0.395mg/mL and 3mg/mL were the MIC value. Evaluation on the effect of different pH on antibacterial activity of plant extracts shows that the activity of the plant extracts does not affect when treated with acidic pH but increased at alkaline pH. Based on the present finding, C. tomentosa leaves extract have the potential to be a viable candidate in the discovery of a natural antibacterial agent against S. aureus infections. This study provides scientific knowledge to further determine the antibacterial values of C. tomentosa extracts.

New Possibilities of Antibiotic Therapy for Blepharoconjunctivitis in Children

The problem of drug therapy for bacterial eye infections in children has remained relevant for many years. The greatest interest of ophthalmologists in recent years is associated with the use of fluoroquinolones in the treatment of inflammatory eye diseases of the bacterial etiology. At the same time, new ophthalmic dosage forms of fluoroquinolones that have appeared in recent years naturally require additional research on their effectiveness.Objective: to study the clinical efficacy of the antibacterial drug Oftocypro (0.3 % cyprofloxacin in ophthalmic ointment) in the treatment of chronic blepharoconjunctivitis in children.Materials. The study involved 38 children aged 3 to 18 years (mean age 10.3 ± 2.7 years) with clinical manifestations of blepharoconjunctivitis. All patients were divided into 2 groups of equal size: 18 children (36 eyes) — with bacterial blepharoconjunctivitis and 20 (40) — with chlamydial blepharoconjunctivitis. The diagnosis was verified based on the clinical picture of blepharoconjunctivitis and laboratory data: detection of pathogenic microflora in the conjunctival cavity of patients of the first group and chlamydia antigen — in epithelial cells in scraping material from the conjunctiva by immunohistochemical analysis.Results. The analysis of the data obtained during the examination and treatment of children with blepharoconjunctivitis of bacterial etiology (group I), a reliable dynamics of controlled clinical and laboratory parameters was established. There was a significant positive dynamics of all controlled parameters of the clinical course of chronic bacterial blepharoconjunctivitis against the background of the drug Oftocipro ophthalmic ointment 0.3 % use. All children with chronic chlamydial blepharoconjunctivitis with the background of treatment with Oftocypro, ophthalmic ointment 0.3 %, showed a steady tendency towards relief of the estimated clinical signs of the disease. According to the results of laboratory studies, it was found that on the 28th day of treatment with Oftocypro chlamydia in the cells of the epithelium of the conjunctiva was re-detected in 4 out of 20 patients (20 %).Conclusion. The high efficacy of the drug Oftocypro ophthalmic ointment 0.3 %, in combination with the absence of pronounced side effects, makes it possible to recommend this drug for wider practical use.

A Double-Edged Sword: Thioxanthenes Act on Both the Mind and the Microbiome

The rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these ‘non-antibiotics’, as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines. Another chemically and pharmacologically related class is the thioxanthenes, differing in that the aromatic N of the central phenothiazine ring has been replaced by a C atom. Such “carbon-analogues” were primarily synthesized with the hope that these would be devoid of some of the toxic effects of phenothiazines. Intensive studies on syntheses, as well as chemical and pharmacological properties of thioxanthenes, were initiated in the late 1950s. Although a rather close parallelism with respect to structure activity relationships could be observed between phenothiazines and thioxanthenes; several thioxanthenes were synthesized in pharmaceutical industries and applied for human use as neuroleptics. Antibacterial activities of thioxanthenes came to be recognized in the early 1980s in Europe. During the following years, many of these drugs were found not only to be antibacterial agents but also to possess anti-mycobacterial, antiviral (including anti-HIV and anti-SARS-CoV-2) and anti-parasitic properties. Thus, this group of drugs, which has an inhibitory effect on the growth of a wide variety of microorganisms, needs to be explored for syntheses of novel antimicrobial agents. The purpose of this review is to summarize the neuroleptic and antimicrobial properties of this exciting group of bioactive molecules with a goal of identifying potential structures worthy of future exploration.

Toxicity Evaluation of Choline Ionic Liquid-Based Nanocarriers of Pharmaceutical Agent For Lung Treatment With Extra Antitumor Activity

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, i.e. p-aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS-2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non-small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 hours, was measured at concentrations range of 3.125‑100 μg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS-2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, i.e. Annexin-V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro-inflammatory activity of tested compounds towards cancer cells, while it was not observed against normal cell line. In summary, the anticancer property of linear copolymers with antibacterial drugs was shown.

Trends, Variation, and Factors Influencing Antibiotic Prescribing: A Longitudinal Study in Primary Care Using a Multilevel Modelling Approach

Antimicrobial resistance has become one of the greatest threats to global health. Over 80% of antibiotics are prescribed in primary care, with many prescriptions considered to be issued inappropriately. The aim of this study was to examine the association between prescribing rates and demographic, practice, geographic, and socioeconomic characteristics using a multilevel modelling approach. Antibiotic prescribing data by 320 GP surgeries in Northern Ireland were obtained from Business Services Organisation for the years 2014–2020. A linear mixed-effects model was used to identify factors influencing antibiotic prescribing rates. Overall, the number of antibacterial prescriptions decreased by 26.2%, from 1,564,707 items in 2014 to 1,155,323 items in 2020. Lower levels of antibiotic prescribing were associated with urban practices (p < 0.001) and practices in less deprived areas (p = 0.005). The overall decrease in antibacterial drug prescriptions over time was larger in less deprived areas (p = 0.03). Higher prescribing rates were linked to GP practices located in areas with a higher percentage of the population aged ≥65 (p < 0.001) and <15 years (p < 0.001). There were also significant regional differences in antibiotic prescribing. We advocate that any future antibiotic prescribing targets should account for local factors.

Discovery and Development of Antibacterial Agents: Fortuitous and Designed

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

Evaluation of effectiveness of combined use of COC and topical preparation containing azelaic acid for acne

The article presents the results of evaluating the effectiveness of the combined use of combined oral contraceptives (COC) and Skinoren cream in severe papular-pustular and moderate nodular-cystic acne.Material and methods. Patients of the first group (n = 11) used COC and an external antibacterial drug two times a day for the treatment of acne. Patients of the second group (n = 12) used COC and an external drug containing azelaic acid (Skinoren) for the treatment of acne two times a day. The duration of follow-up was 6 months. The efficiency assessment was carried out taking into account the dynamics of the indicators of the IGA (Investors Global Assessment) scale. The Manchester Scar Scale (MSS) was used to assess the effectiveness of post-acne correction. In addition, the effectiveness was evaluated based on the results of the mexametry.Results. When evaluating IGA in the comparison groups in patients with severe papulopustular acne and moderate nodular cystic acne, comparable efficacy was noted, but the best results were recorded in the COC + Skinoren group (p < 0.05). No effect and deterioration of the condition were observed in any group. When assessing MSS, the most pronounced changes were observed in patients of group 2, where the combination of COC + Skinoren was used. So, in group 1, the severity of scars decreased by 42.3 %, in group 2 by 48.2 % (p < 0.05). The evaluation of the results of the mexametry showed a more pronounced decrease in the amount of pigment in patients from group 2. When studying the results of the severity of erythema, the dynamics similar to the severity of the pigment was obtained. The best result was registered in group 2 (COC + Skinoren) (p < 0.05).Conclusions. The combined use of COC and Skinoren cream for severe papular-pustular and moderate nodular-cystic acne has proven to be an effective method both in relation to the number of inflammatory and retention elements, and in relation to hyperpigmentation.