Effective Antibacterial Drugs Research Articles

High-frequency ultrasound modulation of Zn2+ release from nanoclay supported ZnO antibacterial composites

Bacterial infections pose considerable health risks, emphasising the critical need for effective and biocompatible antibacterial drugs. Considerably, we developed an efficient antimicrobial system incorporating the combined potential of high-frequency ultrasound and antimicrobial drugs against bacterial infections. A ZnO–kaolinite (Kaol) composite with antibacterial properties was synthesised by growing ZnO on the Kaol nano-clay surface using the co-precipitation method. High-frequency ultrasound efficiently promotes the release of Zn2+, which enhances the antibacterial properties. Furthermore, in-depth in vitro antibacterial studies and bacterial live/dead staining experiments validate the exceptionally high antibacterial performance of the composite. Therefore, owing to the synergistic effects of high-frequency ultrasound and antibacterial properties, the as-prepared novel antibacterial composite is a promising potential substitute for conventional antibacterial agents.

Identification of coumarin – benzimidazole hybrids as potential antibacterial agents: Synthesis, in vitro and in vivo biological assessment, and ADMET prediction

The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 μg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs.

Synthesis and In-silico Docking Analysis of 2-Phenylindolizine Acetamide Scaffolds: Potent Anticancer and Antibacterial Ta

Background: Although several specialized methods for treating various cancers have been developed, clinical outcomes for patients with colon cancer have shown unfavorable effects in addition to chemotherapeutic drug resistance. Therefore, finding medicinal substances with minimal to no side effects is crucial in the fight against cancer. Further, this study underscores the significance of 2-phenylindolizine acetamide due to the diverse biological features and the extensive application of this moiety as an effective anticancer and antibacterial drug. Objective: The goal of the study was to investigate novel, prospective 2-phenylindolizines as anticancer and antibacterial drugs. Methods: The synthesized compounds were characterized by different spectral analyses like 1 H NMR, 13C NMR, IR, and mass spectrometry. Pharmacokinetics in-silico studies were performed to predict the drug performance in the body using the SwissADME kit. The molecular docking was performed to check the catalytic binding site between the Topoisomerase-IV from S. pneumoniae and synthesized compounds. The antibacterial activity was assessed using the agar well diffusion method, and the compounds were screened for in vitro anticancer activity using an MTT assay with doxorubicin as a reference. Results: Interestingly, 2-phenylindolizine scaffolds 7c, 7f, and 7g revealed a remarkable antibacterial activity against relevant organisms S. aureus, E. coli, S. pneumoniae, and P. aeruginosa. The target compounds 7e and 7h showed excellent anticancer activity against Colo-205 and MDA-MB-231 cell lines with IC50 values of 68.62, 62.91, 54.23, and 46.34 µM, respectively. Compounds 7a, 7f, and 7c exhibited the highest hydrogen bonding amino acid interactions Asp83 (2.23 Å), Asp83 (2.08 Å), His74 (2.05 Å), His76 (1.71 Å), and Ser80 (1.05 Å) with active site of Topoisomerase-IV from S. pneumoniae (4KPE). Conclusion: This research focused on recent advances in drug design and development, as well as Phenylindolizine derivatives and how they work on anticancer and antibacterial sites of action.

Analysis of Distribution and Drug Susceptibility Test Results of Pathogenic Bacteria in Diabetic Foot Ulcers.

This study aimed to determine the pathogen distribution and drug susceptibility of diabetic foot wound secretions in a tertiary hospital in a coastal area of southeastern China to guide clinical antibiotic selection. A retrospective analysis was conducted on 212 patients with diabetic foot hospitalized at Xiamen Third Hospital from 2018 to 2023, and foot wound secretions were collected for microbial culture and drug susceptibility testing. Among 212 cases of patients with diabetic foot wound secretions, 163 cases (76.9%) were cultured with pathogenic bacteria, and a total of 207 strains of pathogenic bacteria were cultured, including 75 strains (36.23%) of Gram-positive (G+) bacteria, 118 strains of Gram-negative (G-) bacteria (57.00%), 14 strains of fungi (6.76%), 120 cases of single microorganism infection (73.62%), 43 cases of mixed infection (26.38%), and 15 strains of multidrug-resistant bacteria (7.25%). The top three pathogenic bacteria were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. G+ bacteria were dominated by S.aureus. Drug susceptibility results showed that G+ bacteria were highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. Among G- bacterial infections, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Proteus were the major species. Drug susceptibility testing indicated that carbapenems such as imipenem and ertapenem were the most effective antibacterial drugs against G- strains, followed by amikacin, piperacillin, and tazabactams to which these bacteria were also relatively sensitive, while resistance to penicillins and first-generation cephalosporins increased significantly. We isolated one strain of pathogenic bacteria from a Wagner grade1 ulcer, which was G+ bacteria. In Wagner grade2 ulcers, the distribution of pathogenic bacteria was mainly G+ bacteria. In Wagner grade3 and 4 ulcers, the distribution of pathogenic bacteria was mainly G- bacteria, and the increased rate of mixed infection was mainly due to mixed infection of G+ and G-. Two strains of pathogenic bacteria were isolated at Wagner grade5, which were mixed infections of G+ and G-. Pathogenic bacteria in diabetic foot wounds are predominantly G- bacteria, followed by G+ bacteria. As the Wagner ulcer grade increases, the distribution of pathogenic bacteria changes from G+ bacteria to G- bacteria, and the mixed infection rate increases. G+ bacteria are highly susceptible to vancomycin, linezolid, tigecycline, quinupristin/dalfopristin, rifampicin, and furotoxin, and somewhat resistant to penicillin, erythromycin, clindamycin, and cefoxitin. G- bacteria are more sensitive to the antimicrobial drugs ertapenem, imipenem, amikacin, piperacillin tazobactam, and have high resistance to penicillin and first-generation cephalosporins.

Tuning the Physical Properties of Ag and ZnO Nanoparticles to be Applied in Various Applications

Silver nanoparticles (Ag-NPs) accompanied by zincite (ZnO) and hematite (Fe2O3) (Ag-Z-H) at different annealing temperatures (as dried, 400°C) were prepared using the Flash auto-combustion method. X-ray diffraction pattern assured the cubic structure of Ag-NPs for both samples. The morphology using atomic force microscopy assured the formation of nanoparticles with small agglomeration. By increasing the annealing temperature, the crystallite and particle sizes increased. Moreover, Fourier transforms infrared analysis assured the bond formation of the nanoparticles. The magnetic measurement indicated the increase of the coercivity (Hc) of (Ag-Z-H) nanoparticles at 400°C by nine-fold compared with the as-dried sample. Contrarily, the as-dried (Ag-Z-H) nanoparticles showed 1.8-fold larger saturation magnetization (Ms) than at 400°C. The high-frequency application was studied from the magnetic measurement and showed that both samples could be applied in the ultra-high frequency microwave region in the P band. As a result of the antimicrobial study, (Ag-Z-H) nanoparticles at 400°C showed stronger antimicrobial activities than the as-dried sample. Thus, the strong recommendation of as-dried (Ag-Z-H) nanoparticles at 400°C could be used as an effective alternative antibacterial drug, especially (Ag-Z-H) nanoparticles at 400°C.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be “charge-on-backbone” that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

Mucous cell histopathology and label-free quantitative proteomic analysis of skin mucus in fat greenling (Hexagrammos otakii) infected with Vibrio harveyi

Hexagrammos otakii is favored by consumers and aquaculture practitioners because of its strong adaptability and fast growth. However, recently, frequent outbreaks of diseases in the breeding of H. otakii have led to significant economic losses, especially due to bacterial diseases, which limit the healthy breeding of H. otakii. As a luminescent Gram-negative bacterium, Vibrio harveyi is the main pathogenic bacteria of H. otakii. In this study, the histopathology and label-free quantitative proteomics analysis were performed to reveal the changes of skin mucus proteins in H. otakii after infection with V. harveyi. The histopathological changes in the skin of H. otakii showed that when the bacteria were injected into the epithelial cells, it caused an increase in the number of mucous cells and a certain degree of damage and deformation in skin. Moreover, the quantitative proteomics analysis revealed a total of 364 differentially expressed proteins (DEPs), and these DEPs were found to be involved in environmental information processing, metabolism, infectious diseases: bacteria, replication and repair. More importantly, the enrichment analysis of the DEPs revealed that these different proteins were mainly targeted immune-related pathways. After infection of bacteria, the host's immune ability will be weakened, causing V. harveyi to enter the organism more easily, resulting in increased mucus in H. otakii, which will eventually lead to a decline in its physical function. These results provided an insight into a series of physiological changes after the bacterial infection of fish at the proteomic level and basic data for further exploration of the potential mechanism of skin mucus. Taken together, the results indicated more opportunities for the future designs and discoveries of effective antibacterial vaccines and antibacterial drugs for H. otakii.

Bacterial contamination on clinical surfaces and oxygen device accessories in the emergency unit of a tertiary health facility in Ghana

BackgroundNosocomial infections have gradually become an emerging threat to the healthcare system over the past decades and have been attributed to poor decontamination of hospital articles and weak antibacterial stewardship policies. This study sought to investigate the effect of disinfection on the prevalence and resistance profile of bacterial contaminants on oxygen device accessories, and clinical surfaces at the emergency unit of a tertiary health facility in Ghana.MethodsThe study employed a cross-sectional study design to evaluate the occurrence of bacteria on surfaces in a tertiary hospital. Luminal swabs of the oxygen device accessories and swabs from clinical surfaces used by healthcare providers were collected for isolation and identification of bacteria. The identified bacteria isolates were then tested for their susceptibility to antibacterial agents. Data from this study were analyzed using Excel (Microsoft Office Suite), and GraphPad Prism 8 software programs.ResultsA quarter of the total 44 bacterial isolates obtained from both post-disinfected and pre-disinfected surfaces were Gram-positive, with the remaining isolates being Gram-negative. Pseudomonas aeruginosa was the most frequent bacteria species isolated (41%) followed by Citrobacter sp. (21%). P. aeruginosa, S. aureus, and S. pneumoniae were found to be highly resistant to Chloramphenicol (36%), and Sulfamethoxazole (100%); whereas Ciprofloxacin (91%) was the most effective antibacterial drug used.ConclusionThe almost equal prevalence of multidrug-resistant bacteria from both post-disinfected and pre-disinfected surfaces of inanimate objects, and oxygen device accessories connote an ineffective disinfection process which may influence resistance in bacterial contaminants. This requires the overhaul of disinfection protocol and training of hospital staff, and rational use of antibacterial agents at the hospital to mitigating the burden of nosocomial infections.

Lactobacilli and Klebsiella: Two Opposites in the Fight for Human Health.

The problem of antibiotic resistance is currently very acute. Numerous research and development of new antibacterial drugs are being carried out that could help cope with various infectious agents. One of the promising directions for the search for new antibacterial drugs is the search among the probiotic strains present in the human gastrointestinal tract. This review is devoted to characteristics of one of these probiotic strains that have been studied to date: Limosilactobacillus reuteri. The review discusses its properties, synthesis of various compounds, as well as role of this strain in modulating various systems of the human body. The review also examines key characteristics of one of the most harmful among the currently known pathogenic organisms, Klebsiella, which is significantly resistant to antibiotics existing in medical practice, and also poses a great threat of nosocomial infections. Discussion of characteristics of the two strains, which have opposite effects on human health, may help in creation of new effective antibacterial drugs without significant side effects.

Isolation, identification, and antibacterial activity of endophytic fungus from Acanthus ilicifolius

Abstract Antimicrobial-resistant bacteria pose serious public health risks, necessitating bioprospecting for novel antimicrobial drugs. The endophytic fungi of the mangrove ecosystem are hotspots for discovering new bioactive chemical compounds. In this context, an investigation was designed to determine the isolation of the major endophytic fungi inhabiting the leaves of Acanthus ilicifolius, a mangrove plant with a long history of traditional use in the Chinese and Indian medical systems. Based on the morphological characterizations and molecular analysis of internal transcribed spacer rDNA sequence data, the study identified three unique endophytic fungal species, namely, Periconia macrospinosa, Coprinopsis cinerea, and Alternaria sp. Of these, P. macrospinosa was identified as the most dominant one, with the highest relative frequency (35.22%). The antibacterial activity of P. macrospinosa isolate (CMFRI/fPM-01) was evaluated by the well and diffusion method against six human pathogens, viz., Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus. The results demonstrated a high and wide spectrum of antimicrobial action of the isolate against all the tested human pathogens, with no significant difference (P > 0.05) in the activity between the pathogens. The antibacterial activity was further confirmed by determining the fungal culture supernatant's minimum inhibitory concentration and minimum bactericidal concentration. Although the studied fungi are known from other sources, this is the first report of P. macrospinosa and C. cinerea as endophytes in A. ilicifolius leaves. The outcomes also showed that the P. macrospinosa isolate could be used to discover effective antibacterial drugs against various human diseases.

Green synthesis of silver nanoparticles using curcumin: A comparative study of antimicrobial and antibiofilm effects on Acinetobacter baumannii against chemical conventional methods

Acinetobacter baumannii (A. baumannii) is an important pathogen that causes hospital-acquired illnesses worldwide. The biofilm-forming activity of the organism enhances its capacity to acquire significant levels of antibiotic resistance, hence necessitating the development of novel and effective antibacterial drugs. Nevertheless, nanoparticles have been documented as highly effective agents against bacterial growth and biofilm formation. So, the purpose of this work was to study the antibacterial and antibiofilm capabilities of silver nanoparticles synthesized by facile green method using curcumin (GS-AgNPs) on A. baumannii compared to the chemical method (CS-AgNPs) in vitro. Moreover, twenty-four clinical isolates of A. baumannii were collected and characterized by standard microbiological techniques. The results showed that all isolates of A. baumanii exhibited a significant degree of resistance to a wide range of antimicrobials. On the other hand, the minimum inhibitory concentration (MIC) for GS-AgNPs sample fell between 250 and 7.8 μg/ml. While the CS-AgNPs sample had MIC values that fell between 500 and 1000 µg/ml. Twenty out of 24 strains were biofilm producers. The lowest MIC of the tested AgNPs was mainly observed in the strains that produce weak biofilm. GS-AgNPs significantly inhibited the biofilm production by the tested isolates than AgNPs synthesized chemically and biofilm inhibition reached to 57.43 ± 9.50 %, and 50.57 ± 3.91 % of controls for strong producers, respectively. The results of the research suggest that GS-AgNPs demonstrate notable effectiveness as a secure and powerful antibacterial and antibiofilm agent against multidrug-resistant A. baumannii strains.

Green Synthesis of Silver Nanoparticles Using Extracts of Ehretia cymosa and Evaluation of Its Antibacterial Activity in Cream and Ointment Drug Delivery Systems

Objectives. The use of antibacterial drugs for the treatment of infections has been on for several decades but not without some challenges such as resistance. Research on natural products is on-going to mitigate this challenge. The aim of this study was to synthesize silver nanoparticles (SNPs) with aqueous and methanol extract of Ehretia cymosa leaf and to explore its antibacterial potentials in semisolid dosage delivery system as topical antibacterial cream and ointment. Methods. E. cymosa leaf was extracted by macerating in distilled water and methanol. The extracts were used to synthesize SNPs. SNPs were characterized and confirmed by visual observation, UV-visible spectroscopy, FTIR, atomic absorption spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. SNPs were used to formulate cream and ointment, and the antibacterial activity of the formulations was evaluated against Staphylococcus aureus and Escherichia coli. Results. Absorption band was observed at 450 nm for aqueous extract SNPs and 420 nm for methanol extract SNPs due to surface plasmon resonance. SNPs were agglomerated with the irregular size of 55 nm and 90 nm. The formulations had acceptable physicochemical properties with good drug-excipient compatibility. The antibacterial activity of cream formulations had a significantly ( p < 0.0001 ) higher antibacterial activity compared to ointment formulations. Both formulations with SNPs had higher antibacterial activity than ciprofloxacin. Conclusion. Cream and ointment formulations loaded with green synthesized E. cymosa leaf extract SNPs present a potential for a more efficient and effective antibacterial drug delivery to ameliorate the impact of antibacterial drug resistance.

Intermolecular Interactions as a Measure of Dapsone Solubility in Neat Solvents and Binary Solvent Mixtures.

Dapsone is an effective antibacterial drug used to treat a variety of conditions. However, the aqueous solubility of this drug is limited, as is its permeability. This study expands the available solubility data pool for dapsone by measuring its solubility in several pure organic solvents: N-methyl-2-pyrrolidone (CAS: 872-50-4), dimethyl sulfoxide (CAS: 67-68-5), 4-formylmorpholine (CAS: 4394-85-8), tetraethylene pentamine (CAS: 112-57-2), and diethylene glycol bis(3-aminopropyl) ether (CAS: 4246-51-9). Furthermore, the study proposes the use of intermolecular interactions as molecular descriptors to predict the solubility of dapsone in neat solvents and binary mixtures using machine learning models. An ensemble of regressors was used, including support vector machines, random forests, gradient boosting, and neural networks. Affinities of dapsone to solvent molecules were calculated using COSMO-RS and used as input for model training. Due to the polymorphic nature of dapsone, fusion data are not available, which prohibits the direct use of COSMO-RS for solubility calculations. Therefore, a consonance solvent approach was tested, which allows an indirect estimation of the fusion properties. Unfortunately, the resulting accuracy is unsatisfactory. In contrast, the developed regressors showed high predictive potential. This work documents that intermolecular interactions characterized by solute-solvent contacts can be considered valuable molecular descriptors for solubility modeling and that the wealth of encoded information is sufficient for solubility predictions for new systems, including those for which experimental measurements of thermodynamic properties are unavailable.

Back to Nature: Medicinal Plants as Promising Sources for Antibacterial Drugs in the Post-Antibiotic Era.

Undoubtedly, the advent of antibiotics in the 19th century had a substantial impact, increasing human life expectancy. However, a multitude of scientific investigations now indicate that we are currently experiencing a phase known as the post-antibiotic era. There is a genuine concern that we might regress to a time before antibiotics and confront widespread outbreaks of severe epidemic diseases, particularly those caused by bacterial infections. These investigations have demonstrated that epidemics thrive under environmental stressors such as climate change, the depletion of natural resources, and detrimental human activities such as wars, conflicts, antibiotic overuse, and pollution. Moreover, bacteria possess a remarkable ability to adapt and mutate. Unfortunately, the current development of antibiotics is insufficient, and the future appears grim unless we abandon our current approach of generating synthetic antibiotics that rapidly lose their effectiveness against multidrug-resistant bacteria. Despite their vital role in modern medicine, medicinal plants have served as the primary source of curative drugs since ancient times. Numerous scientific reports published over the past three decades suggest that medicinal plants could serve as a promising alternative to ineffective antibiotics in combating infectious diseases. Over the past few years, phenolic compounds, alkaloids, saponins, and terpenoids have exhibited noteworthy antibacterial potential, primarily through membrane-disruption mechanisms, protein binding, interference with intermediary metabolism, anti-quorum sensing, and anti-biofilm activity. However, to optimize their utilization as effective antibacterial drugs, further advancements in omics technologies and network pharmacology will be required in order to identify optimal combinations among these compounds or in conjunction with antibiotics.

Efficacy of a Novel Antibacterial Agent Exeporfinium Chloride, (XF-73), Against Antibiotic-Resistant Bacteria in Mouse Superficial Skin Infection Models.

The number of incidences of antimicrobial resistance is rising continually, necessitating new and effective antibacterial drugs. The present study aimed to assess the in vitro and in vivo activity of XF-73 against antibiotic-resistant Staphylococcus aureus (S. aureus) isolates and to investigate the potential mechanism of action of XF-73. The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. Two different superficial Staphylococcal skin infection murine models were established to study the in vivo efficacy of XF-73 against antibiotic-resistant strains. The effect of XF-73 on the ultrastructure and cellular morphology of S. aureus was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The MICs (minimum inhibitory concentration) determined by the broth microdilution method for XF-73 demonstrated that the compound had a high potency against S. aureus isolates with varying susceptibility to the study drugs. Also, the antibacterial activity of XF-73 was superior or similar to most of the tested antibacterial drugs. We also found that the XF-73 dermal formulation significantly inhibited S. aureus survival in both the murine skin tape-stripping and suture superficial skin infection models, maintained a consistently high inhibitory capacity against the antibiotic-resistant strains tested and was significantly more effective than mupirocin ointment, a commonly used antibiotic for the treatment of skin infections. The morphological studies using TEM suggest that XF-73 had a rapid (2 minute) bacterial cell wall disruption activity, with longer incubation (10 minute) subsequently causing membrane damage. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis. Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting.

Key issues in selecting an antibacterial drug for the treatment of acute respiratory infections in children: A review

Аcute respiratory diseases in children remain an urgent problem in pediatric practice. Most respiratory infections are due to viruses, but some may be due to bacterial pathogens or associations. During the pandemic of a coronavirus infection the number of unjustified prescriptions of antibiotics increased, which significantly complicated the situation with drug resistance of microorganisms and changed the strategy for choosing a starting antibacterial drug in children. Under the current circumstances, timely diagnosis of bacterial inflammation and the adequate choice of drug are the key issues in the practice of a pediatrician. On an outpatient basis it is important for a pediatrician to determine the indications timely and empirically prescribe an effective antibacterial drug. In Russia, in recent years, Federal Clinical Guidelines for various nosologies have been approved, defining indications for systemic antibiotic therapy. According to clinical guidelines, amoxicillin is the first-line antibiotic for most bacterial acute respiratory infections. In addition, there are cohorts of children who are expected to have risk factor as drug-resistant organisms and these children are eligible for protected amoxicillin as a first-line medication. The indications for prescribing macrolides and third-generation oral cephalosporins have fundamentally changed. The article presents the defining indications for systemic antibiotic therapy and the features of the choice of the starting antibacterial drug in children with acute respiratory infections.

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.

Due to the continued emergence of resistance and a lack of new and promising antibiotics, bacterial infection has become a major public threat. High-throughput screening (HTS) allows rapid screening of a large collection of molecules for bioactivity testing and holds promise in antibacterial drug discovery. More than 50% of the antibiotics that are currently available on the market are derived from natural products. However, with the easily discoverable antibiotics being found, finding new antibiotics from natural sources has seen limited success. Finding new natural sources for antibacterial activity testing has also proven to be challenging. In addition to exploring new sources of natural products and synthetic biology, omics technology helped to study the biosynthetic machinery of existing natural sources enabling the construction of unnatural synthesizers of bioactive molecules and the identification of molecular targets of antibacterial agents. On the other hand, newer and smarter strategies have been continuously pursued to screen synthetic molecule libraries for new antibiotics and new druggable targets. Biomimetic conditions are explored to mimic the real infection model to better study the ligand-target interaction to enable the designing of more effective antibacterial drugs. This narrative review describes various traditional and contemporaneous approaches of high-throughput screening of natural products and synthetic molecule libraries for antibacterial drug discovery. It further discusses critical factors for HTS assay design, makes a general recommendation, and discusses possible alternatives to traditional HTS of natural products and synthetic molecule libraries for antibacterial drug discovery.

Mechanistic Insight of Polymer Effects on the Kinetic of Solution-Mediated Phase Transformation of Nitrofurantoin Anhydrate to Monohydrate.

Nitrofurantoin is an effective antibacterial drug for the treatment of lower urinary tract infection. However, the anhydrate form can easily transform to the less soluble hydrate form (monohydrate) during dissolution, resulting in a reduction of dissolution rate and oral bioavailability. Therefore, inhibition of phase transformation is vital to stabilize the quality of drugs. In this work, the potential of polyethylene glycol (PEG 8000), polyvinyl pyrrolidone (PVP K30), poloxamer 188 and hydroxypropyl methylcellulose (HPMC) to inhibit the hydration of nitrofurantoin during dissolution was investigated by experimental and simulation approaches. The rates of phase transformation were decreased in the presence of PEG 8000 and poloxamer 188, and PVP K30 and HPMC completely inhibited the phase transformation of anhydrate. The abundant hydrogen bond donor and acceptor groups of PVP and HPMC may easily establish intermolecular interactions with nitrofurantoin molecules, accounting for stronger inhibition of nucleation. Besides, the molecular dynamic simulation further indicated the formation of more extensive interactions between PVP K30 (or HPMC) and the (111) face of monohydrate, suggesting that the strong absorption of polymers on the surface and thus block the sites for incorporation of new growth. This study provides a mechanistic insight into the inhibition of nitrofurantoin hydration by polymeric additives, which helps design formulations and improve the physical stability of anhydrate.

Synthesis, DFT study, theoretical and experimental spectroscopy of fatty amides based on extra-virgin olive oil and their antibacterial activity

Medication products from natural materials are preferred due to their minimal side effects. Extra-virgin olive oil (EVOO) is a highly acclaimed Mediterranean diet and a common source of lipids that lowers morbidity and disease severity. This study synthesised two fatty amides from EVOO: hydroxamic fatty acids (FHA) and fatty hydrazide hydrate (FHH). The Density Functional Theory (DFT) was applied to quantum mechanics computation. Nuclear magnetic resonance (NMR), Fourier transforms infrared (FTIR), and element analysis were used to characterise fatty amides. Likewise, the minimum inhibitory concentration (MIC) and timing kill assay were determined. The results revealed that 82 % for FHA and 80 % for FHH conversion were achieved. The amidation reagent/EVOO ratio (mmol: mmol) was 7:1, using the reaction time of 12 h and hexane as an organic solvent. The results further revealed that fatty amides have high antibacterial activity with low concentration at 0.04 μg/mL during eight h of FHA and 0.3 μg/mL during ten h of FHH. This research inferred that FHA and FHH could provide an alternative and effective therapeutic strategy for bacterial diseases. Current findings could provide the basis for the modernisation/introduction of novel and more effective antibacterial drugs derived from natural products.

Synthesis, Characterization, and Biological Evaluation Of [1,2,4 ]-Triazole-3yl]Sulfanyl Acetamide Derivative

A significant portion of recent papers is in the field of Mercapto substituted Triazole moiety received considerable attention in the literature.Characterization and Antibacterial activity against important medically Gram positive Bacteria likely Actinomyces, Clostridium, Mycobacterium, Strptococci, Staphylococci and Nocardia.Triazole is a class of N-Bridged Heterocyclic compounds especially in Chemotherapy. Triazole moiety seems to be very small but 1,2,4-Triazole derivatives have wide range of potential antibacterial activities against drug-resistant pathogens.Hybridization shows a high potential to develop novel drugs,reduce toxicity,and improve Pharmacokinetic profiles.More effective antibacterial studies might be obtained by the hybridization of 1,2,4-Triazole mercapto moiety. A number of clinically effective antibacterial drugs become more effective. Therefore, we shed, herein, more light on novel synthetic drug and its antibacterial activity.