Practice of Perioperative Rational Use of Antibacterial Drugs Based on Drug Pathway

[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.

An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global population.From the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system.These diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual death.Despite the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency.This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

Recognition and quality mapping of traditional herbal drugs:way forward towards artificial intelligence

The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Antibacterial effect of Allium sativum cloves and Zingiber officinale rhizomes against multiple-drug resistant clinical pathogens

Objective:To evaluate the antibacterial properties ot Allium sativum(garlic) cloves and Zingiber officinale(ginger) rhizomes against multi-drug resistant clinical pathogens causing nosocomial infection.Methods:The cloves of garlic and rhizomes of ginger were extracted with 95%(v/v) ethanol.The ethanolic extracts were subjected to antibacterial sensitivity test against clinical pathogens.Results:Anti-bacterial potentials of the extracts of two crude garlic cloves and ginger rhizomes were tested against five gram negative and two gram positive multi-drug resistant bacteria isolates.All the bacterial isolates were susceptible to crude extracts of both plants extracts.Except Enterobacter sp.and Klebsiella sp.,all other isolates were susceptible when subjected to ethanolic extracts of garlic and ginger.The highest inhibition zone was observed with garlic(19.4S mm) against Pseudomonas aeruginosa(P.aeruginosa).The minimal inhibitory concentration was as low as 67.00 μg/mL against P.aeruginosa.Conclusions:Natural spices of garlic and ginger possess effective anti-bacterial activity against multi-drug clinical pathogens and can be used for prevention of drug resistant microbial diseases and further evaluation is necessary.

Potential antibacterial activity of berberine against multi drug resistant enterovirulent Escherichia coli isolated from yaks(Poephagus grunniens) with haemorrhagic diarrhoea

Objective:To evaluate the antimicrobial efficacy of berberine,a plant alkaloid.Methods:Five multi-drug resistant（MDR） STEC/EPEC and five MDR ETEC isolates from yaks with haemorrhagic diarrhoea were selected for the study.Antibacterial activity of berberine was evaluated by broth dilution and disc diffusion methods.The binding kinetics of berberine to DNA and protein was also enumerated.Results:For both categories of enterovirulent Escherichia coli（E.roli） isolates, berberine displayed the antibaclerial effect in a dose dependent manner.The MIC50 of berberine chloride for STEC/EPEC isolates varied from 2.07μM to 3.6μM with a mean of（2.95±0.33）μM where as for ETEC strains it varied from 1.75 to 1.96μM with a mean of（1.87±0.03）μM. Berberine bind more tightly with double helix DNA with Bmax and Kd of（24.68±2.62） and（357.8±57.8）,respectively.Berberine reacted with protein in comparatively loose manner with Bmax and Kd of（18.9±3.83） and 【286.2±113.6),respectively.Conclusions:The results indicate clearly that berberine may serve as a good antibacterial against multi drug resistant E.coli.

<i>In Vitro</i>Antibacterial Activity of Flavonoid Extracts of Two Selected Libyan Algae against Multi-Drug Resistant Bacteria Isolated from Food Products

This study aimed to evaluate the antibacterial activity of flavonoids extracted from two Libyan brown algae namely Cystoseira compressa and Padina pavonica using microwave-assisted extraction method against pathogenic bacteria isolated from meat, meat products, milk and dairy products (Staphylococcus aureus subsp. aureus (5 isolates), Bacillus cereus (3 isolates), Bacillus pumilus (1 isolate), Salmonella enterica subsp. enteric (4 isolates) and Enterohaemor-rhagic Escherichia coli O157 (EHEC O157) (4 isolates)). All of these isolates were muti-drug resistant with high MAR index. The results showed that C. compressa extract exhibited better and stronger antibacterial activities against the seventeen tested isolates with inhibition zones diameter ranged from 14 - 22 mm compared to P. pavonica extract which showed positive effect against 9 isolates with low inhibition zone ranged from 11 - 16.5 mm. Flavonoids extracted from C. compressa also displayed the best spectrum of bactericidal effect with a ratio MBC/MIC ≤ 4 obtained on all susceptible tested bacterial strains. Flavonoids and proanthocyanidins significantly contributed to the antibacterial properties. The mode of action of these active extracts is under investigation.

Effects of intervention measures on irrational antibiotics/antibacterial drug use in developing countries: A systematic review

Irrational antibiotics/antibacterial (AB) drug use is a global problem, especially in developing countries. This results in an increased emergence of resistance to most common bacteria, higher cost of treatment, prolonged hospitalization and adverse drug reactions. Interventions measures have been instituted to avert the problem but it still persists. A systematic review was conducted to determine the effect of different interventions (education, managerial, diagnostic tests, regulatory, economic and multifaceted) on misuse of AB drugs in developing countries. A total of 722 articles were retrieved and 55 were reviewed. About 10.9% of the studies were from Africa, 63.6% from Asia, 9.1% from Latin America, and 16.4% from Southeastern Europe. A total of 52.7% of the studies were from hospital settings, 5.5% from outpatient departments, 21.8% were from public health care facilities, 12.7% from private pharmacies/drug stores, and 7.3% from the communities. Education intervention had 27.3% studies, managerial had 20%, managerial/education had 3.6%, regulatory had 9.1%, education/regulation had 9.1% and diagnostic had 3.6% studies. Multifaceted intervention had 27.3% studies, with 63% improvement in appropriate AB doses prescribed, 2.6% mean number of AB encounter reduction, 23% AB prescription reduction, 18.3% generic AB prescription improvement, 32.1% reduction in AB use, 89% reduction in AB use in acute respiratory infection, 82% in surgery, 62.7% mean reduction in deliveries, 39% in STDs, 36.3% mean reduction in diarrhea, 14.6% mean reduction AB use in malaria, and 6%-11% in the cost of treating bacteria-resistant organisms. Also noted was 6.3% reductions in mean AB encounters after 1 month of intervention, and then increased to 7.7% after 3 months thus lacking sustainability. Multifaceted interventions were effective in reducing irrational AB drug use in the various health facilities and communities as well as reduction in the emergence of resistance to the commonest bacteria in the developing countries though there was lack of sustainability or continuity of rational drug use over the time.

Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their role in emergence of bacterial resistance

During the post-antibiotic golden age, it has seen a massive antibiotic/antibacterial production and an increase in irrational use of these few existing drugs in the medical and veterinary practice, food industries, tissue cultures, agriculture and commercial ethanol production globally. The irrational drug use has been further exacerbated by the increased marketing and promotion of these drugs by the pharmaceutical companies thus increasing their accessibility in the public and hence their improper use. The lack of production and introduction of the newer and effective antibiotic/antibacterial drugs in clinical practice in the post-antibiotic golden age has seen an increase in the emergence of the resistant pathogenic bacterial infections creating a significant problem in the global health of humankind. The massive productions of the antibiotic/antibacterial drugs have contributed to the poor disposal of these drugs and hence many of them are discharged in various water bodies contributing to the environmental antibiotic/antibacterial drug pollution. In the environment, these drugs exert pressure on the environmental bacteria by destroying useful bacteria that are responsible for the recycling of the organic matter and as well as promoting the selection of the resistant pathogenic bacteria that can spread in human and animal population thus causing an increase in the observed bacterial disease burden and hence a significant global public health problem. The resistant bacterial diseases lead to the high cost, increased occurrence of adverse drug reactions, prolonged hospitalization, the exposure to the second- and third-line drugs like in MDR-TB and XDR-TB that leads to toxicity and deaths as well as the increased poor production in agriculture and animal industry and commercial ethanol production.

Antibacterial Activity of Exogenous Glutathione and Its Synergism on Antibiotics in Methicillin-Associated Multidrug Resistant Clinical Isolates of Staphylococcus aureus

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most problematic human pathogens. Antibiotic treatment of MRSA often associated with resistance to multiple classes of antibiotics is extremely challenging and urgently demands action to treat MRSA. Glutathione (GSH) is a biogenic thiol-compound that maintains an optimal intracellular redox-potential required for various normal cellular processes. Antibacterial activity of exogenous GSH has been reported in some bacterial pathogens but is largely unknown in MRSA. Aim: This study aimed to understand antibacterial activity of GSH, its role in antibiotic susceptibility, and a potential antibacterial mechanism in clinical isolates of S. aureus. Materials and Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), checkerboard, time-killing, and bacterial killing assays were performed for 14 clinical isolates of S. aureus including 10 MRSA and two type strains (ATCC 700699 and 35556). Results: MIC and MBC levels for the clinical and type strains were 15 - 20 mM and 25 - 40 mM of GSH, respectively. Subinhibitory concentrations of GSH synergistically enhanced susceptibility of all tested-antibiotics, resulting in sensitizing all-tested S. aureus. Bacterial-killing produced by GSH-mediated acidity was significantly higher than that by hydrochloric acid-mediated acidity. Conclusion: Overall results concluded that GSH exhibited antibacterial activity on S. aureus regardless of antibiotic susceptibility and synergistically enhanced antibiotic susceptibility. Additionally, GSH-mediated acidity was one of the antibacterial mechanisms. These findings suggest that GSH may be a potential antimicrobial agent or adjuvant for the conventional anti-MRSA regimens.

An intravenous clarithromycin lipid emulsion with a high drug loading, H-bonding and a hydrogen-bonded ion pair complex exhibiting excellent antibacterial activity

The aim of this study was to develop an intravenous clarithromycin lipid emulsion(CLE)with good stability and excellent antibacterial activity. The CLE was prepared by the thinfilm dispersed homogenization method. The interaction between clarithromycin(CLA) and cholesteryl hemisuccinate(CHEMS) was confirmed by DSC, FT-IR and^1H NMR analysis. The interfacial drug loading, thermal sterilization, freeze–thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and^1H NMR spectra showed that CHEMS(CLA: CHEMS, M ratio 1:2) could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE.Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer.The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze–thaw cycles. The in vitro susceptibility test revealed that the CLA–CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED50 of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation.

A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Rational drug design,synthesis,and biological evaluation of novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamides as potential antimalarial,antifungal,and antibacterial agents

Objective Sulfanilamide,sulfadiazine,and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process,which is essential for parasite survival.Therefore,we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.Methods All compounds were synthesized by the conventional method,and the products were characterized by spectral analysis(1 H NMR and mass spectrometry).The progression of the reaction was monitored using thin-layer chromatography(TLC).All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2.Antibacterial and antifungal activities were determined using the broth dilution method.Results S6(N-(2-thiazol-4 yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S9(N-(1 H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds;S8(N-(2-1 H-imidazol-2 yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10(N-(1 H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed four hydrogen bonds with the allosteric site of the enzyme.Considering the docking scores and formation of hydrogen bonds with the target enzyme,the novel derivatives were processed for wet lab synthesis.All the newly synthesized derivatives were subjected to in vitro antimalarial,antifungal,and antibacterial activities.All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards.Moreover,compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities.They also exhibited powerful molecular interactions in molecular docking studies.Conclusion Based on the above results,it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial,antifungal,and antibacterial agents.

Strategies for translating proteomics discoveries into drug discovery for dementia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

Antibacterial Activity of Essential Oil from <i>Citrus aurantifolia</i>(Christm.) Swingle Peels against Multidrug-Resistant Bacterial Isolates

The study investigated the antibacterial activity of essential oil from the peel of Citrus aurantifolia against eleven multidrug-resistant (MDR) bacterial isolates of clinical origin. The Kirby-Bauer disc diffusion method was used to determine the antibiotic resistance profile of the isolates. Essential oil (EO) from the peels of lime purchased at a market in Ile-Ife was extracted by the hydro-distillation method, while the sensitivity of the isolates to EO was done via agar well diffusion method. The minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of the EO against the tested isolates were determined following standard methods. All the tested isolates exhibited multidrug resistance (MDR) characteristics. The multiple antibiotics resistant indexes (MARI%) for Gram-positive bacterial isolates ranged between 70% and 100% while that of Gram-negative was 100%. The yield of EO was 1% and the EO demonstrated activities at 25%, 50% and 100% v/v against the MDR bacterial isolates. The activity of EO was mostly not significantly different at the same concentration for all the isolates, and at different concentrations for each of the isolates. The MIC range for Gram-negative and Gram-positive isolates was between 0.195% to 3.125% v/v and 0.39% to 3.125% respectively while the range was between 1.563% to 3.125% and 0.781% to 6.250% v/v for MBC respectively. The study showed that EO from the peel of lime fruits demonstrated excellent in vitro antibacterial activity against MDR bacterial isolates. This potential can be further explored as an alternative for the treatment and management of infections caused by MDR bacterial isolates.

Peptide drugs: a new direction in cancer immunotherapy

Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.

Microglia in drug addiction:A perspective from neuroimmunopharmacology

Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.

Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.