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ObjectiveTo analyze the host factors affecting the drug resistance of Helicobacter pylori (Hp).MethodsPatients with Hp infection were consecutively recruited in the Affiliated Suzhou Hospital of Nanjing Medical University from November 2021 to October 2023. Endoscopic biopsy specimens were collected for pathological diagnosis, Hp strain culture and antimicrobial susceptibility test. Nineteen factors involving the basic information, lifestyle, dietary habits, and health status of the patients were collected through electronic medical records and questionnaires. Logistic regression was used to evaluate the association between the patients' factors and drug resistance to clarithromycin, levofloxacin, amoxicillin, furazolidone, tetracycline and metronidazole.ResultsA total of 115 patients (Hp strain 115) with Hp infection who met the inclusion and exclusion criteria were enrolled. There were 53 males (46.09%) and 62 females (53.91%), with an average age of (45.16±13.39) years. Gastroscopic pathology showed 86 cases (74.78%) of superficial gastritis, 6 cases (5.22%) of atrophic gastritis, 14 cases (12.17%) of intestinal metaplasia, 6 cases (5.22%) of low-grade intraepithelial neoplasia, and 3 cases (2.61%) of high-grade intraepithelial neoplasia/gastric cancer. The drug resistance rates of Hp strains to metronidazole, levofloxacin and clarithromycin were 91.30% (105/115), 53.04% (61/115) and 51.30% (59/115), respectively. Resistance to amoxicillin, furazolidone and tetracycline was not found. Dual drug resistance: levofloxacin + metronidazole dual resistance rate was 50.43% (58/115), clarithromycin + metronidazole dual resistance rate was 47.83% (55/115), clarithromycin + levofloxacin dual resistance rate was 36.52% (42/115). Multidrug resistance: clarithromycin + levofloxacin + metronidazole triple resistance rate was 34.78% (40/115). Multivariate Logistic regression analysis showed that (metronidazole was not included in the multivariate analysis due to the absence of sensitive strains), previous Hp eradication history (OR=74.782, 95% CI: 10.377-538.886, P < 0.001) and tap water (OR=4.919, 95% CI: 1.160-20.859, P=0.031) increased the risk of clarithromycin resistance, and age ≥50 years increased the risk of levofloxacin resistance (OR=4.261, 95% CI: 1.420-12.785, P=0.010), previous Hp eradication history (OR=5.855, 95% CI: 2.209-15.517, P < 0.001), 40-59 years old (OR= 3.269, 95% CI: 1.254-8.520, P=0.015) increased the risk of dual resistance to clarithromycin and levofloxacin.ConclusionsThe drug resistance rate of Hp strains isolated from patients in the Affiliated Suzhou Hospital of Nanjing Medical University to metronidazole, levofloxacin and clarithromycin were high, and dual drug resistance and multidrug resistance were prominent. Age, previous Hp eradication history and drinking water source may be associated with single or dual drug resistance to clarithromycin and levofloxacin. Comprehensive consideration, reasonable selection of antibiotics and individualized treatment should be taken into account during Hp eradication.

Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital for bacterial cells and an emerging drug target for various bacterial infections. Understanding the enzymatic mechanisms and structural intricacies of bacterial Pth is pivotal in designing novel therapeutics to combat antibiotic resistance. This review provides a comprehensive analysis of the multifaceted roles of Pth in bacterial physiology, shedding light on its significance as a potential drug target. This article delves into the diverse functions of Pth, encompassing its involvement in ribosome rescue, the maintenance of a free tRNA pool in bacterial systems, the regulation of translation fidelity, and stress response pathways within bacterial systems. Moreover, it also explores the druggability of bacterial Pth, emphasizing its promise as a target for antibacterial agents and highlighting the challenges associated with developing specific inhibitors against this enzyme. Structural elucidation represents a cornerstone in unraveling the catalytic mechanisms and substrate recognition of Pth. This review encapsulates the current structural insights of Pth garnered through various biophysical techniques, such as X-ray crystallography and NMR spectroscopy, providing a detailed understanding of the enzyme's architecture and conformational dynamics. Additionally, biophysical aspects, including its interaction with ligands, inhibitors, and substrates, are discussed, elucidating the molecular basis of bacterial Pth's function and its potential use in drug design strategies. Through this review article, we aim to put together all the available information on bacterial Pth and emphasize its potential in advancing innovative therapeutic interventions and combating bacterial infections. [ABSTRACT FROM AUTHOR]

COVID-19 emerged as a widespread worldwide ailment in 2019, with a continued breakdown of novel gamma and lambda variants. Given the high incidence of COVID-19 even in the vaccinated people, research is in progress to develop convenient used drugs to control coronavirus disease. Herein, to review the effectiveness and safety of the recent antiviral, antibacterial, and herbal medication utilized to treat COVID-19, electronic databases including Scopus, PubMed, and Cochrane Library were compiled from papers registered in clinical trials on COVID-19 from January 2021 to February 2022. Oseltamivir, remdesivir, ivermectin, casirivimab, imdevimab, sotrovimab, Tocilizumab, sarilumab, dexamethasone, methylprednisolon, paxlovid, fluvoxamine, molnupiravir, ruxolitinib, tofacitinib, baricitinib, favipiravir, molnupiravir, azithromycin, niclosamide, nitazoxanide, and tetracyclines are the most commonly used antiviral and antibiotics to control mild to severe COVID-19 illnesses in the clinic. Despite the efficacy of drugs solely and in combination, medicinal herbs and natural products were considered in some clinical trials due to the high cost and unwanted side effects. However, no substantial evidence has been reported to confirm the significant anti-COVID-19 impact of synthetic and herbal medicines. This scenario opens an exciting new perspective for the elucidation of convenient therapeutic pipelines.

ABSTRACT The urgent need for new antibacterial drugs arises from the emergence of bacterial multidrug resistance due to antibiotic overuse. Antimicrobial peptides, crucial components of innate immunity in animals and plants, exhibit effectiveness against multidrug-resistant bacteria while minimizing the development of drug resistance. In this study, the antibacterial peptide BsR1, comprising 21 amino acids, was finalized by predicting the active site of an antifungal gene and sequence optimization. BsR1 displayed broad-spectrum antibacterial activities against diverse Gram-positive and Gram-negative bacteria, with a low minimum inhibitory concentration of 4.25–17 μM. Stability experiments demonstrated that BsR1 has high resistance to thermal, ultraviolet, and acid-base conditions, while revealing increased sensitivity to divalent ions Ca2+ and Mg2+. The mode of action of BsR1 involved cell membrane damage, leading to bacterial cell structure disruption and subsequent death. Secondary structure prediction indicated a linear helical conformation with a positive charge of +7.5, facilitating its interaction with the target cell membrane. BsR1 exhibited excellent biological safety, as it did not induce necrosis in tobacco leaves, and the low observed hemolytic effect on mammalian cells with a value of 3.26%. Additionally, BsR1 demonstrated the ability to enhance disease resistance in rice and effectively curbed the spread of rice bacterial blight. This research presents BsR1 as a novel approach and potential medication in the development of antibacterial drugs, offering a valuable tool in combating pathogenic microorganisms, particularly in plants. IMPORTANCE This study addresses the critical need for new antibacterial drugs in the face of bacterial multidrug resistance resulting from antibiotic overuse. It highlights the significance of antimicrobial peptides as essential components of innate immunity in animals and plants, which have been proven effective against multidrug-resistant bacteria and are difficult to develop resistance against. This study successfully synthesizes a broad-spectrum antibacterial peptide, BsR1, with strong inhibitory activities against various Gram-positive and Gram-negative bacteria. BsR1 demonstrates favorable stability and a mode of action that damages bacterial cell membranes, leading to cell death. It also exhibits biological safety and shows potential in enhancing disease resistance in rice. This research offers a novel approach and potential medication for antibacterial drug development, presenting a valuable tool in combating pathogenic microorganisms, particularly in plants.

Objective: Antimicrobial drugs are frequently used in the intensive care unit (ICU) and may cause drug-drug interactions (DDIs) which change treatment outcomes. This study aims to determine the frequency of potential DDIs (pDDIs) caused by antimicrobial drugs in the ICU, according to two databases, address the differences between these two databases, discuss the clinical significance of pDDIs and investigate their relationship with clinical outcomes. Materials and Methods: This study was designed as a 1-year retrospective cross-sectional study. Patients over the age of 18 who used antimicrobials for at least 72 hours were included. pDDIs between other drugs and antimicrobials were checked using the "drug interactions" modules of the Lexicomp and Micromedex databases. Data were collected from the hospital's records by a clinical pharmacist. Results: A total of 393 drug profiles were evaluated for 100 patients, of which 84.2% were antibacterial drugs. According to at least one database, 88% of patients had pDDIs. Of these, 62.4% were classified as major according to at least one database. Only 27.3% of pDDIs had the same level of interaction in both databases. Common pDDIs posed risks such as additive nephrotoxicity, excessive sedation, respiratory depression and QT interval prolongation. Conclusion: pDDIs should be checked not only by one database but by multiple databases, coupled with the input of an experienced clinical pharmacist. [ABSTRACT FROM AUTHOR]

The 2:1 co-crystal of nadifloxacin [systematic name: 9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid] with oxalic acid, C19H21FN2O4·0.5C2H2O4, was prepared by slow evaporation from a chloroform:acetone solvent system. Nadifloxacin belongs to the group of antibacterial drugs. The co-crystal is stabilized through an intramolecular O—H...O bond and intermolecular hydrogen bonds. It was studied by FT–IR spectroscopy, differential scanning calorimetry and X-ray diffraction. Hirshfeld surface analysis indicated that the major contribution to the packing is from O...H/H...O interactions.

The title compound, C30H33N4O2F, can be obtained via a two-step synthetic scheme involving 1-benzyl-6-fluoro-4-oxo-7-(piperidin-1-yl)-1,4-dihydroquinoline-3-carbonitrile as a starting compound that undergoes substitution with hydroxylamine and subsequent cyclization with 4-methylcyclohexane-1-carboxylic acid. It crystallizes from 2-propanol in the triclinic space group P\overline{1} with a molecule of the title compound and one of 2-propanol in the asymmetric unit. After the molecular structure was clarified using NMR and LC/MS, the molecular and crystalline arrangements were defined with SC-XRD. A Hirshfeld surface analysis was performed for a better understanding of the intermolecular interactions. One strong (O—H...O) and three weak [C—H...F (intramolecular) and two C—H...O] hydrogen bonds were found. The contributions of short contacts to the Hirshfeld surface were estimated using two-dimensional fingerprint plots showing that O...H/H...O, C...H/H...C and C...C contacts are the most significant for the title compound and O...H for the 2-propanol. The crystal structure appears to have isotropically packed tetramers containing two molecules of the title compound and two molecules of 2-propanol as the building unit according to analysis of the distribution of pairwise interaction energies. A molecular docking study was carried out to evaluate the interactions of the title compound with the active centers of macromolecules corresponding to viral targets, namely, anti-hepatitis B activity [HBV, capsid Y132A mutant (VCID 8772) PDB ID: 5E0I] and anti-COVID-19 main protease activity (PDB ID: 6LU7). The data obtained revealed a noticeable affinity towards them that exceeded that of the reference ligands.

COVID-19 emerged as a widespread worldwide ailment in 2019, with a continued breakdown of novel gamma and lambda variants. Given the high incidence of COVID-19 even in the vaccinated people, research is in progress to develop convenient used drugs to control coronavirus disease. Herein, to review the effectiveness and safety of the recent antiviral, antibacterial, and herbal medication utilized to treat COVID-19, electronic databases including Scopus, PubMed, and Cochrane Library were compiled from papers registered in clinical trials on COVID-19 from January 2021 to February 2022. Oseltamivir, remdesivir, ivermectin, casirivimab, imdevimab, sotrovimab, Tocilizumab, sarilumab, dexamethasone, methylprednisolon, paxlovid, fluvoxamine, molnupiravir, ruxolitinib, tofacitinib, baricitinib, favipiravir, molnupiravir, azithromycin, niclosamide, nitazoxanide, and tetracyclines are the most commonly used antiviral and antibiotics to control mild to severe COVID-19 illnesses in the clinic. Despite the efficacy of drugs solely and in combination, medicinal herbs and natural products were considered in some clinical trials due to the high cost and unwanted side effects. However, no substantial evidence has been reported to confirm the significant anti-COVID-19 impact of synthetic and herbal medicines. This scenario opens an exciting new perspective for the elucidation of convenient therapeutic pipelines. [ABSTRACT FROM AUTHOR]

Antibacterial drug exposure (ADE) is a well-known potential risk factor for Clostridium difficile infection (CDI), but it remains controversial which certain antibacterial drugs are associated with the highest risk of CDI occurrence. To summarize CDI risk associated with ADE, we reviewed the CDI reports related to ADE in the FDA Adverse Event Reporting System database and conducted disproportionality analysis to detect adverse reaction (ADR) signals of CDI for antibacterial drugs. A total of 8063 CDI reports associated with ADE were identified, which involved 73 antibacterial drugs. Metronidazole was the drug with the greatest number of reports, followed by vancomycin, ciprofloxacin, clindamycin and amoxicillin. In disproportionality analysis, metronidazole had the highest positive ADR signal strength, followed by vancomycin, cefpodoxime, ertapenem and clindamycin. Among the 73 antibacterial drugs, 58 showed at least one positive ADR signal, and ceftriaxone was the drug with the highest total number of positive signals. Our study provided a real-world overview of CDI risk for AED from a pharmacovigilance perspective and showed risk characteristics for different antibacterial drugs by integrating its positive–negative signal distribution. Meanwhile, our study showed that the CDI risk of metronidazole and vancomycin may be underestimated, and it deserves further attention and investigation. [ABSTRACT FROM AUTHOR]

Nanotechnology has provided numerous cutting-edge applications in drug delivery, biosensors, nanorobots, biomedical devices and nanocarriers. Polyelectrolyte mediated nanocapsules contributes a significant development as drug carriers for more than a decade. Majority of the nanocapsules employed in the drug delivery system are fabricated using synthetic materials leading to many health complications. In this research, natural polyelectrolyte capsules are prepared using carboxy methyl cellulose (CMC) and chitosan by dip coating technique. The capsules are used for the delivery of antibacterial drug by encapsulating ciprofloxacin hydrochloride into the capsule interiors. The drug release study has been carried out by altering the permeability of the capsule shell. The optimal pH for the drug encapsulation has been established at 2.3 pH and 381 µg of drug is loaded in 60 min. The drug release study is performed at three different pH conditions of 2.0 pH, 6.0 pH, and 7.2 pH respectively and the release media chosen is water and PBS. Maximum amount of drug release (367 µg) is achieved at pH 2.0 within 48 hours. The study demonstrates an easy and effective delivery of antibacterial drug from natural polyelectrolyte capsules. [ABSTRACT FROM AUTHOR]

The 2:1 co-crystal of nadifloxacin [systematic name: 9-fluoro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid] with oxalic acid, C19H21FN2O4·0.5C2H2O4, was prepared by slow evaporation from a chloroform:acetone solvent system. Nadifloxacin belongs to the group of antibacterial drugs. The co-crystal is stabilized through an intramolecular O--H· · ·O bond and intermolecular hydrogen bonds. It was studied by FT-IR spectroscopy, differential scanning calorimetry and X-ray diffraction. Hirshfeld surface analysis indicated that the major contribution to the packing is from O· · ·H/H· · ·O interactions. [ABSTRACT FROM AUTHOR]

Isoprenoids, a diverse class of natural products, are present in all living organisms. Their two universal building blocks are synthesized via two independent pathways: the mevalonate pathway and the 2-C-methyl-ᴅ-erythritol 4-phosphate (MEP) pathway. The presence of the latter in pathogenic bacteria and its absence in humans make all its enzymes suitable targets for the development of novel antibacterial drugs. (E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), the last intermediate of this pathway, is a natural ligand for the human Vγ9Vδ2 T cells and the most potent natural phosphoantigen known to date. Moreover, 5-hydroxypentane-2,3-dione, a metabolite produced by Escherichia coli 1-deoxy-ᴅ-xylulose 5-phosphate synthase (DXS), the first enzyme of the MEP pathway, structurally resembles (S)-4,5-dihydroxy-2,3-pentanedione, a signal molecule implied in bacterial cell communication. In this review, we shed light on the diversity of potential uses of the MEP pathway in antibacterial therapies, starting with an overview of the antibacterials developed for each of its enzymes. Then, we provide insight into HMBPP, its synthetic analogs, and their prodrugs. Finally, we discuss the potential contribution of the MEP pathway to quorum sensing mechanisms. The MEP pathway, providing simultaneously antibacterial drug targets and potent immunostimulants, coupled with its potential role in bacterial cell–cell communication, opens new therapeutic perspectives. [ABSTRACT FROM AUTHOR]

The title compound, C30H33N4O2F, can be obtained via a two-step synthetic scheme involving 1-benzyl-6-fluoro-4-oxo-7-(piperidin-1-yl)-1,4-dihydroquinoline-3-carbonitrile as a starting compound that undergoes substitution with hydroxylamine and subsequent cyclization with 4-methylcyclohexane-1-carboxylic acid. It crystallizes from 2-propanol in the triclinic space group P[\overline{1}] with a molecule of the title compound and one of 2-propanol in the asymmetric unit. After the molecular structure was clarified using NMR and LC/MS, the molecular and crystalline arrangements were defined with SC-XRD. A Hirshfeld surface analysis was performed for a better understanding of the intermolecular interactions. One strong (O--H⋯O) and three weak [C--H⋯F (intramolecular) and two C--H⋯O] hydrogen bonds were found. The contributions of short contacts to the Hirshfeld surface were estimated using two-dimensional fingerprint plots showing that O⋯H/H⋯O, C⋯H/H⋯C and C⋯C contacts are the most significant for the title compound and O⋯H for the 2-propanol. The crystal structure appears to have isotropically packed tetramers containing two molecules of the title compound and two molecules of 2-propanol as the building unit according to analysis of the distribution of pairwise interaction energies. A molecular docking study was carried out to evaluate the interactions of the title compound with the active centers of macromolecules corresponding to viral targets, namely, anti-hepatitis B activity [HBV, capsid Y132A mutant (VCID 8772) PDB ID: 5E0I] and anti-COVID-19 main protease activity (PDB ID: 6LU7). The data obtained revealed a noticeable affinity towards them that exceeded that of the reference ligands. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant Acinetobacter baumannii (XDRAB) can acquire drug resistance genes, which are rapidly cloned and transmitted, leading to worldwide spread and posing significant treatment challenges. This study aimed to clarify effective treatment methods during XDRAB infection and factors affecting patient prognosis. Methods: Clinical features, treatment, and prognosis of 65 patients with hospital-acquired XDRAB pneumonia clinically diagnosed at Guangzhou First People's Hospital between January 2019 and December 2020 were retrospectively analyzed. Results: Of 65 subjects, only 37 survived. There was no significant difference in anti-A. baumannii activity according to type or combination of antibiotics administered between patients that survived and those that died (p > 0.05). The use of antibacterial drugs during infection did not effectively improve clinical outcomes. Advanced age, multiple organ failure, and disease severity were significantly negatively correlated while effective airway management was positively associated with bacterial clearance (p < 0.05). In multivariate analysis, age and APACHE score were independent risk factors affecting prognosis. Tracheotomy during infection was a protective factor contributing to survival (p < 0.05). Advanced age and disease severity independently affected patient prognosis, while use and type of antibacterial treatment did not substantially affect the prognosis. Conclusions: Advanced age and severe disease are independent risk factors that affect patient prognosis. Timely and effective airway management is key to improving the prognosis of patients with hospital-acquired XDRAB infection. [ABSTRACT FROM AUTHOR]

Objective To analyze the sensitivity of common pathogens and common antibiotics in burn and wound repair surgery patients, aiming to provide reference for the prevention and treatment of burn and various wounds. Methods From March 2019 to March 2021, 310 bacterial culture specimens of wound secretion from burn and wound repair surgery patients with suspected wound infection were collected. VITEK 2 Compact automatic bacterial identification instrument and VITEK MS automatic rapid microbial mass spectrometry detection system were used for pathogen identification. Disk diffusion method and instrumental method were employed to detect the antimicrobial susceptibility. The drug resistance of pathogens was analyzed by WHONET 5.6 software. Results Among 310 samples, 179 positive samples were detected, with a positive rate of 57.74%, 84 cases of Gram-positive bacteria, accounting for 46.93%, 91 cases of Gram-negative bacteria, accounting for 50.84% and 4 cases of fungi, accounting for 2.23%. Among them, Gram-negative bacteria were Pseudomonas aeruginosa （PAE）, Acinetobacter baumannii （ABA）, Klebsiella pneumoniae （KPN） and Escherichia coli （ECO）. Staphylococcus aureus （SAU） was the main Gram-positive bacteria. Among the detected Gram-negative bacteria, the sensitivity rate of PAE to polymyxin B, myxin and amikacin was more than 80.40%. The sensitivity rate of ABA to myxin, polymyxin B and tegacyclin exceeded 96.70%. The sensitivity rate of KPN to tegacyclin and polymyxin B antibiotics was higher than 88.90%. The sensitivity rate of ECO to cefotetan, amikacin, piperacillin/tazobactam and carbapenem antibiotics was >92.90%. Among the detected Gram-positive bacteria, the sensitivity of SAU to linezolid, vancomycin and tetracycline was up to 100.00%, and that of Enterococcus to tetracycline, vancomycin and linezolid was also 100.00%. Conclusions Gram-negative bacteria are the main pathogens in patients with wound infection from Department of Burn and Wound Repair Surgery. Antibiotic susceptibility rate of these bacteria were different. Necessary attention should be paid to these pathogens. During the treatment of infection, clinicians should cultivate and prepare bacterial specimens for accurate examination before selecting antibiotics. According to the results of drug sensitivity, they should choose proper antibiotics, and adopt definite treatment instead of empirical medication as early as possible, aiming to inhibit the generation of drug-resistant strains and improve the effectiveness of antibiotic treatment.

The objective of this study was to describe the prevalence of outpatient use and costs for systemic antibacterials by age and sex among adults in Finland from 2008–2019. Data from the Finnish statistical database Kelasto, containing information concerning all reimbursed medicines for 18+-year-olds during 2008–2019, were analyzed. In addition to the decreased (26%) use of systemic antibiotics, decreased use was observed in all antibiotic categories, notably including several wide-spectrum antibiotics. The use of quinolones decreased by 49% and of tetracyclines by 39%. The 10 most frequently used antibiotics covered 89% of all adult antibiotic prescriptions. Antibiotic use also decreased in every age group during the study period. Although the overall yearly costs of outpatient antibiotics during the 10-year study period decreased from EUR 36.4 million to EUR 30.7 million, the cost per prescription increased slightly. In conclusion, according to the findings of this study, concerning adults and the results of our previous study concerning children and adolescents (2008–2016), there has been a decreasing trend of outpatient antibacterial use among the whole Finnish outpatient population over the duration of nearly one decade. However, during the same time period, there has been a specific increasing trend for the Gram-negative AMR threat regarding E. coli resistance. Therefore, based on our important findings in Finland, methods other than the restriction of antibiotic use, such as new anti-infective innovations, including antibacterials, are needed as soon as possible to tackle this major global health threat—a silent pandemic. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles, with and without the inclusion of a magnetic core, were hydrothermally synthesized and employed as carrier of the antibiotic norfloxacin (NFX). The antibiotic-loaded materials were prepared by wet impregnation. Differences in drug content (and in further release profile) were directly related to changes in surface area, particle aggregation and hydrophobicity of the solids. The kinetics of NFX release has been studied in batch experiments. In all cases, more than 55% of the antibiotic was quickly desorbed during the first 5 min due to the localization of NFX on the external surface of the nanoparticles. The rest of the drug (situated inside the mesopores) was released through a diffusion-controlled transport and the rate was strongly dependent of the pH, reaching its minimum value at neutral pH. The calculated activation energy confirmed that the release was controlled by a diffusion process. Breaking of H-bonds and electrostatic and hydrophobic interactions appear to be responsible for NFX desorption from the solid surface. Such interactions increase, however, the thermal stability of the drug when the NFX and the carriers are combined. The antimicrobial activities of the drug loaded nanoparticles and the free antibiotic were compared and discussed. [ABSTRACT FROM AUTHOR]

Introduction. In the treatment of patients with pararectal fistula, relapses of the disease are quite common, as well as postoperative complications in the form of suppression of a postoperative wound, anal incontinence, etc. The aim of the work is to improve the results of treatment of patients with pararectal fistula by reducing the number of purulent-septic complications in the postoperative period. Materials and methods. Analysis of 105 cases of treatment of patients was carried out. All patients were divided into 2 groups by random sampling: in group I, patients, in addition to standard preoperative training, underwent fistula sanitization with 1% dioxidin solution. In the postoperative period, patients underwent dressings with 5% dioxidin ointment, and also administered per rectum ointment from 1 postoperative day for 7 days. In the second group, standard preoperative training was carried out. All patients of the comparison groups were intraoperatively seeded on the flora from the fistula. Postoperative healing of postoperative wounds, subsidence of local and systemic inflammatory response were evaluated. Results. The results show a statistically significant improvement in treatment outcomes of patients in the major group. Conclusions. Application of two-stage prevention of postoperative complications makes it possible to improve results of treatment of patients with pararectal fistulas due to reduction of amount of pathogenic microflora in area of postoperative wound, faster stopping of local and systemic inflammatory reaction, and also due to increase of number of patients with primary healing postoperative wound.

Antibacterial drug exposure (ADE) is a well-known potential risk factor for Clostridium difficile infection (CDI), but it remains controversial which certain antibacterial drugs are associated with the highest risk of CDI occurrence. To summarize CDI risk associated with ADE, we reviewed the CDI reports related to ADE in the FDA Adverse Event Reporting System database and conducted disproportionality analysis to detect adverse reaction (ADR) signals of CDI for antibacterial drugs. A total of 8063 CDI reports associated with ADE were identified, which involved 73 antibacterial drugs. Metronidazole was the drug with the greatest number of reports, followed by vancomycin, ciprofloxacin, clindamycin and amoxicillin. In disproportionality analysis, metronidazole had the highest positive ADR signal strength, followed by vancomycin, cefpodoxime, ertapenem and clindamycin. Among the 73 antibacterial drugs, 58 showed at least one positive ADR signal, and ceftriaxone was the drug with the highest total number of positive signals. Our study provided a real-world overview of CDI risk for AED from a pharmacovigilance perspective and showed risk characteristics for different antibacterial drugs by integrating its positive–negative signal distribution. Meanwhile, our study showed that the CDI risk of metronidazole and vancomycin may be underestimated, and it deserves further attention and investigation.

The global threat of antimicrobial resistance demands alternative tackling approaches with a unique mechanism of action. Antimicrobial peptides are currently explored widely as the potential next generation antimicrobials and anti‐infectives. They provide multiple advantages in terms of wide spectrum activity ranging from antimicrobial, anti‐infective to immunomodulatory agents. The most striking feature is the delayed resistance development. Owing to their reduced stability and easy degradation, the current research is focused on the development of small peptidomimetic molecules (SPMs) provides longer half‐life and improved stability. In addition, they are widely explored as quorum sensing inhibitors. These are proven to be effective quorum quenchers against both Gram ‐ positive and Gram – negative bacteria. Specifically these molecules are shown to have potent anti‐biofilm activity. In this regard, this review provides the structural aspects in the development of SPMs as both antibacterial and anti‐quorum drugs for the last five years. [ABSTRACT FROM AUTHOR]

Isoprenoids, a diverse class of natural products, are present in all living organisms. Their two universal building blocks are synthesized via two independent pathways: the mevalonate pathway and the 2-C-methyl-ᴅ-erythritol 4-phosphate (MEP) pathway. The presence of the latter in pathogenic bacteria and its absence in humans make all its enzymes suitable targets for the development of novel antibacterial drugs. (E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), the last intermediate of this pathway, is a natural ligand for the human Vγ9Vδ2 T cells and the most potent natural phosphoantigen known to date. Moreover, 5-hydroxypentane-2,3-dione, a metabolite produced by Escherichia coli 1-deoxy-ᴅ-xylulose 5-phosphate synthase (DXS), the first enzyme of the MEP pathway, structurally resembles (S)-4,5-dihydroxy-2,3-pentanedione, a signal molecule implied in bacterial cell communication. In this review, we shed light on the diversity of potential uses of the MEP pathway in antibacterial therapies, starting with an overview of the antibacterials developed for each of its enzymes. Then, we provide insight into HMBPP, its synthetic analogs, and their prodrugs. Finally, we discuss the potential contribution of the MEP pathway to quorum sensing mechanisms. The MEP pathway, providing simultaneously antibacterial drug targets and potent immunostimulants, coupled with its potential role in bacterial cell–cell communication, opens new therapeutic perspectives.

Drugs targeting the cell division cycle kinase 7 (Cdc7) are actively searched for the treatment of different pathologies such as amyotrophic lateral sclerosis and cancer. Cdc7 interacts with multiple protein partners, including protein Dbf4 to form the Dbf4-dependent kinase (DDK) complex which regulates DNA replication initiation. Cdc7 and its activator Dbf4 are over-expressed in some cancers. The antibacterial drug clofoctol (CFT), used to treat respiratory tract infections, has been shown to block Cdc7 kinase activity, acting as a non-ATP-competitive inhibitor, capable of arresting DNA synthesis in cancer cells. We have modeled the interaction of CFT with the DDK complex and identified four potential binding sites at the interface of the Cdc7/Dbf4 heterodimer: at T109 and D128 (Cdc7), V220 and I330 (Dbf4). CFT behaves as an interfacial protein-protein inhibitor of the Cdc7/Dbf4 complex, limiting drug access to the proximal kinase site. Six CFT analogues have been tested for binding to the kinase complex. Two potent binders were analyzed in detail. The CFT structure was modulated to replace the two chlorine atoms with hydroxyl groups. The empirical potential energy of interaction (ΔE) calculated with hydroxylated compounds points to a more favorable interaction with the DDK complex, in particular at D128 site with the compound bearing two ortho-OH groups. Our work contributes to the identification of novel DDK inhibitors. [ABSTRACT FROM AUTHOR]

Environmental sustainability is threatened by the widespread exploitation and unfettered release of chemical pollutants that require immediate detection and eradication. An instantaneous quantification technique is essential to understand the physiological roles of the antibacterial drug sulfaguanidine (SGN) in biological systems. The present work features the green and environmentally benign synthesis of rare earth metal sulfide nanorods incorporated carbon nitrides sheets (Ce2S3@CNS) by deep eutectic solvent-based fabrication with remarkable electrochemical properties. The morphological and structural analyses of the prepared electrocatalyst were characterized using various techniques including SEM, XRD, XPS, and EIS. The heterojunction of regimented structures bids synergistic quantum confinement effects and refines charge carriers endorsing enormous active sites. Furthermore, the obtained Ce2S3@CNS/GCE possess an exceedingly lower limit of detection (0.0053 μM) and high sensitivity of 8.685 μA·μM−1·cm−2 with superior electrocatalytic action and virtuous stability for the detection of SGN. This modified electrode could afford linearity in the range 0.01–1131.5 μM measured at 0.95 V (vs. Ag/AgCl) correlated to the concentration of SGN. Examining the real samples with this advanced electrocatalyst would support its hands-on applications in everyday life. Development of such innovative architectures with fewer energy necessities and nominal by-products scripts the superiority in characteristic synthetic methodology following the guidelines of green chemistry. [ABSTRACT FROM AUTHOR]

Drugs targeting the cell division cycle kinase 7 (Cdc7) are actively searched for the treatment of different pathologies such as amyotrophic lateral sclerosis and cancer. Cdc7 interacts with multiple protein partners, including protein Dbf4 to form the Dbf4-dependent kinase (DDK) complex which regulates DNA replication initiation. Cdc7 and its activator Dbf4 are over-expressed in some cancers. The antibacterial drug clofoctol (CFT), used to treat respiratory tract infections, has been shown to block Cdc7 kinase activity, acting as a non-ATP-competitive inhibitor, capable of arresting DNA synthesis in cancer cells. We have modeled the interaction of CFT with the DDK complex and identified four potential binding sites at the interface of the Cdc7/Dbf4 heterodimer: at T109 and D128 (Cdc7), V220 and I330 (Dbf4). CFT behaves as an interfacial protein-protein inhibitor of the Cdc7/Dbf4 complex, limiting drug access to the proximal kinase site. Six CFT analogues have been tested for binding to the kinase complex. Two potent binders were analyzed in detail. The CFT structure was modulated to replace the two chlorine atoms with hydroxyl groups. The empirical potential energy of interaction (ΔE) calculated with hydroxylated compounds points to a more favorable interaction with the DDK complex, in particular at D128 site with the compound bearing two ortho-OH groups. Our work contributes to the identification of novel DDK inhibitors. DOI: http://dx.doi.org/10.5281/zenodo.5527211

The objective of this study was to describe the prevalence of outpatient use and costs for systemic antibacterials by age and sex among adults in Finland from 2008–2019. Data from the Finnish statistical database Kelasto, containing information concerning all reimbursed medicines for 18+-year-olds during 2008–2019, were analyzed. In addition to the decreased (26%) use of systemic antibiotics, decreased use was observed in all antibiotic categories, notably including several wide-spectrum antibiotics. The use of quinolones decreased by 49% and of tetracyclines by 39%. The 10 most frequently used antibiotics covered 89% of all adult antibiotic prescriptions. Antibiotic use also decreased in every age group during the study period. Although the overall yearly costs of outpatient antibiotics during the 10-year study period decreased from EUR 36.4 million to EUR 30.7 million, the cost per prescription increased slightly. In conclusion, according to the findings of this study, concerning adults and the results of our previous study concerning children and adolescents (2008–2016), there has been a decreasing trend of outpatient antibacterial use among the whole Finnish outpatient population over the duration of nearly one decade. However, during the same time period, there has been a specific increasing trend for the Gram-negative AMR threat regarding E. coli resistance. Therefore, based on our important findings in Finland, methods other than the restriction of antibiotic use, such as new anti-infective innovations, including antibacterials, are needed as soon as possible to tackle this major global health threat—a silent pandemic.

The interaction of cefoxitin, being a compound of interest for antibiotic research, with Cu2+ resulted in the formation of a 1 : 1 complex. The electrochemical reduction at a hanging mercury drop electrode and oxidation at a renewable pencil graphite electrode of the formed cefoxitin‐Cu2+ complex was investigated using cyclic voltammetry and differential pulse voltammetry in Britton‐Robinson buffers (pH 2–9). For the electrochemical reduction or oxidation of the examined complex, a new well‐defined voltammetric peak was obtained and the features of the surface redox and oxidation peaks were studied. Calculations of the values of stability constant and the change on Gibbs free energy for cefoxitin‐Cu2+ complex suggest that the complexation is a spontaneous process. The sharp peak of the electroreduction and oxidation of the investigated complex associated with an effective interfacial accumulation of this complex facilitates the determination of the antibacterial drug cefoxitin in the bulk and blood serum samples. Cefoxitin was determined by electrochemical reduction and oxidation of the cefoxitin‐Cu2+ complex, with detection limits of 6.94×10−9M and 9.07×10−8M respectively. [ABSTRACT FROM AUTHOR]

Background & Aim: The use of bone scaffolds is one of the new and efficient techniques for repairing bone defects that provide a suitable platform for cell proliferation and growth to repair the target tissue. One of the most important causes of failure of transplants and surgical procedures is the invasion of bacteria at the site of the complication and the development of severe infection. The purpose of this study, which was carried out at the Faculty of New Sciences and Technologies, University of Tehran at 2017-2019, Antibacterial Properties of Porous Scaffolds Made of Gelatin, Calcium Phosphate Zeolite with Loading of Clindamycin. Material and methods: In this study, freeze-drying was made from a combination of gelatin, calcium phosphate, and natural zeolite of bone tissue scaffolds and then the drug was loaded with different amounts of clindamycin. The surface of the scaffold was examined by scanning electron microscopy and antibacterial test and drug release test were performed on the scaffold. Results: The results showed that the aforementioned composite scaffold did not induce growth inhibition in the antibacterial test, However, after loading the drug on the scaffold with a concentration of 0.01 drug, the growth zone was 2 and 4 mm in diameter for Escherichia coli and Staphylococcus aureus, respectively. Conclusions: Addition of the antibacterial agent clindamycin to the bone scaffold made a suitable substrate for drug delivery to bone tissue at the site of removal has been removed to prevent the growth of infection at the scaffold implant during the first period of repair. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. Methods The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J‐ACNES) trial was designed as a prospective, multicenter, randomized, open‐label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine‐18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. Results The results of this study are currently under investigation. Conclusion The J‐ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

The existing methods of disinfection of containers for fermented milk products proved to be ineffective. The present research featured an antimicrobial preparation based on silver, copper, and zinc nanoparticles as a disinfectant solution. The authors studied the properties of the antimicrobial in order to prove its effectiveness in processing containers to increase the shelf-life of fermented milk products. The size of the silver nanoparticles ranged from 1 to 10 nm. The nanoscale particles of copper were obtained by the method of electric explosion. It was established that the mass fraction of the active substance (active metals) in the antimicrobial was 50.1%; the mass fraction of water was 11.2%; the mass fraction of hydrogen peroxide was 1.0%. To assess the ability of the antimicrobial to increase shelf-life of fermented milk products, the authors analyzed the microbiological properties of cottage cheese. The 50-gram samples were packed in pre-treated polyethylene containers that had been cleaned with the antimicrobial. After that the samples were left for storage at minus 4 ± 1°C. The quality and the microbiological state of the cottage cheese was evaluated on days 3, 5, 7, 9, 11, and 13, which was justified by the experimental conditions and regulatory documentation. Eventually, it was established that the product contained no pathogenic bacteria, such as L. monocytogenes, Salmonella, E. coli, staphylococci, yeast, molds or any viable microbial cells. It was proved that the test sample retained its consumer properties for 13 days, while the control sample was found unusable by day 7. Thus, by using the antimicrobial, it was possible to increase the shelf life of the dairy product by more than 5 days.

Keywords: paralog; antibacterial drug; AcrAB-TolC; SkQ1; multidrug pump EN paralog antibacterial drug AcrAB-TolC SkQ1 multidrug pump N.PAG N.PAG 5 11/13/20 20201111 NES 201111 Introduction In recent years, bacterial resistance has become increasingly important for health care. It should be noted that, according to modern concepts, the AcrAB-TolC pump contains not only the AcrA, AcrB, and TolC proteins, but also the small accessory protein AcrZ (Hobbs et al., [7]; Du et al., [5]). Since AcrAB-TolC deletion mutants do not contain all proteins of the AcrAB-TolC pump and therefore the pump cannot be assembled in their cells, these bacteria are designated as (-). AcrAB-TolC Pump Does Not Ensure SkQ1 Resistance We might assume that the presence of the AcrAB-TolC pump means that cells will be resistant to SkQ1, but this is not the case. [Extracted from the article]

Acinetobacter infection is one of the main causes of mortality in the patients admitted to the intensive care units (ICUs). Activation of the MazF toxin in the Acinetobacter can be considered an effective antibacterial strategy against the pathogen. Like some antibiotics, the released MazF toxin from the MazF–MazE TA system is able to do a ribonucleolytic activity and dissociate of the bacterial DNA leading to the cell disruption. In this study, it was attempt to design the peptidomimetics that can target the Acinetobacter MazF–MazE interactions. The peptide sequence that was used to peptidomimetics designing was NWN and named the short peptide. The short peptide sequence was obtained from an original peptide sequence (NNWNN). By using both pharmacophore and shape similarity strategies, 200 peptidomimics were obtained. 58 of 200 mimetics agreed with the Lipinski's rule of five (RO5). All drug-like peptidomimetics were docked against MazF using AutoDock Vina in PyRx 0.8. Free energy of interaction and the number of hydrogen bonds were used to obtain binding affinity of the receptor (MazF) and each mimetic. Docking of the MazF-original peptide (NNWNN) and MazF-short peptide (NWN) were performed as controls. Peptidomimtics that had more hydrogen bonds and lower free energies can have higher binding affinity to the receptor and be suitable drug candidates against Acinetobacter for the future evaluations. Among all designed mimetics, nine best-ranked mimetics were selected based on the ligand–receptor binding energy. The best-ranked mimetics showed higher binding energies to the receptor compared to the binding energies of the original peptide-receptor and short peptide-receptor. The mimetics 2, 3, 5, 6, 7 and 9 formed more hydrogen bonds with the receptor compared to the short peptide. None of the mimetics formed more hydrogen bonds with the receptor compared to the original peptide. Based on the binding mode to the receptor (hydrogen bonds), mimetics 2, 3, 5, 6, 7 and 9 may be the best lead compounds among the novel designed mimetics. The potential compounds can be evaluated in vitro and in vivo for their activity as well as the cytotoxicity. [ABSTRACT FROM AUTHOR]

Nosocomial infections have increasingly been implicated in transferring fatal septic complications in burn patients. Also multidrug resistant profiles of microorganisms are being increasingly found in burn wounds which are very much alarming due to the limited number effective antibacterial drugs. Retrospective data were collected from burn patients at Sulaimani Burn and Plastic Surgery Hospital between January 2013 and December 2015. Culture& sensitivity tests were performed using wound surface swabs and tissue culture over the three year period. Their results were collected in a predesigned digital form. Statistical analysis was done and results plotted. Out of 500 burn positive swabs samples were previously taken from hospitalized patients, the commonest bacterial isolate were gram-positive bacterial infection; Methicillin-Resistant Staphylococcus Aureus (MRSA) 215(43%) followed by gram-negative bacterial infection; Acinetobacter baumannii and Pseudomonas aeruginosa 95(19%) and 85 (17%). Vancomycin has no any resistant rate for all gram-positive bacteria followed, but Teicoplanin is the second best drug especially, for MRSA 8.4%. Imipenem and Meropenem are antibiotics with no or less resistant rates for most of gram negative bacteria. Resistance to antibiotics is rapidly increasing in our community and burn wounds are frequently infected by these multidrug resistant organisms. Careful antibiotic selection and effective control of these strains can be translated into lower morbidity and mortality for these patients.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii , carbapenem-resistant Pseudomonas aeruginosa , carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae , vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus . Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae , the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium , while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus . In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles., Competing Interests: The authors declare no conflict of interest.

Importance: This study addresses the critical need for new antibacterial drugs in the face of bacterial multidrug resistance resulting from antibiotic overuse. It highlights the significance of antimicrobial peptides as essential components of innate immunity in animals and plants, which have been proven effective against multidrug-resistant bacteria and are difficult to develop resistance against. This study successfully synthesizes a broad-spectrum antibacterial peptide, BsR1, with strong inhibitory activities against various Gram-positive and Gram-negative bacteria. BsR1 demonstrates favorable stability and a mode of action that damages bacterial cell membranes, leading to cell death. It also exhibits biological safety and shows potential in enhancing disease resistance in rice. This research offers a novel approach and potential medication for antibacterial drug development, presenting a valuable tool in combating pathogenic microorganisms, particularly in plants., Competing Interests: The authors declare no conflict of interest.

The emergence of bacterial resistance to traditional small-molecule antibiotics is fueling the search for innovative strategies to treat infections. Inhibiting the expression of essential bacterial genes using antisense oligonucleotides (ASOs), particularly composed of nucleic acid mimics (NAMs), has emerged as a promising strategy. However, their efficiency depends on their association with vectors that can translocate the bacterial envelope. Vitamin B12 is among the largest molecules known to be taken up by bacteria and has very recently started to gain interest as a trojan-horse vector. Gapmers and steric blockers were evaluated as ASOs against Escherichia coli (E. coli). Both ASOs were successfully conjugated to B12 by copper-free azide-alkyne click-chemistry. The biological effect of the two conjugates was evaluated together with their intracellular localization in E. coli. Although not only B12 but also both B12-ASO conjugates interacted strongly with E. coli, they were mostly colocalized with the outer membrane. Only 6–9% were detected in the cytosol, which showed to be insufficient for bacterial growth inhibition. These results suggest that the internalization of B12-ASO conjugates is strongly affected by the low uptake rate of the B12 in E. coli and that further studies are needed before considering this strategy against biofilms in vivo.

The core purpose of the current study was to investigate the interactions of widely used broad-spectrum antibacterial drugs developed in response to the increasing rate of antibioticresistant various bacteria and to contribute to the field of drug design. Also, it is to broaden the current knowledge of paraoxonase 1 enzyme (EC: 3.1.8.1; PON1) which is a crucial drug-target enzyme. For this aim, first, we purified PON1 from human serum using rapid chromatographic techniques including, enzyme precipitation, IEX (ion-exchange) chromatography, and SEC (size exclusion chromatography), quickly. Following this, we researched the inhibitory effects of some antibacterial drugs. Finally, molecular docking tests were performed and analyzed in silico data. PON1 was found to be effectively inhibited by tigecycline, linezolid, ciprofloxacin lactate, and ertapenem sodium (Kis in the ranging from 0.018 to 125.540 mM). Drugs showed two different inhibition mechanisms: Linezolid was competitive; others were non-competitive. While Glide GScore of the linezolid for 1 V04 and 3SRE receptors were detected to be -4.442 and -4.915 kcal/mol in the SP mode, monitored as -3.548 and -3.791 kcal/mol in the XP mode, respectively [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia is not only a common pathology, but one of the main causes of death of the population. The aim of study is to conduct a comparative analysis of the causes of death from CAP in a highly affected region on HIV-infection due in 2017 compared to the year when HIV-infection began to be recorded in 2002. The cases of death of patients with CAP are analyzed in case histories in 2002 and 2017 in the pulmonology department of a large industrial center. In total, in the hospital in 2002, there were 1072 patients diagnosed with CAP, in 2017 there were 2327 patients. Mortality rate in 2002 was 2.6%, in 2017 - 1.1%. Analysis of mortality of patients with CAP for 2017 compared to 2002 showed that significant changes occurred: deaths from CAP in HIV-patients (in 2002 - 0%), increased detection of tuberculosis in 2017, died with tuberculosis 1.5% (2002 - 0%). The number of late visits and first aid calls has increased, more often men die, the age of the dead has decreased by almost 10 years. [ABSTRACT FROM AUTHOR]