Treatment Of Bacterial Infections Research Articles

Does Phage Therapy Need a Pan-Phage?

The emergence of multidrug-resistant bacteria is undoubtedly one of the most serious global health threats. One response to this threat that has been gaining momentum over the past decade is 'phage therapy'. According to this, lytic bacteriophages are used for the treatment of bacterial infections, either alone or in combination with antimicrobial agents. However, to ensure the efficacy and broad applicability of phage therapy, several challenges must be overcome. These challenges encompass the development of methods and strategies for the host range manipulation and bypass of the resistance mechanisms developed by pathogenic bacteria, as has been the case since the advent of antibiotics. As our knowledge and understanding of the interactions between phages and their hosts evolves, the key issue is to define the host range for each application. In this article, we discuss the factors that affect host range and how this determines the classification of phages into different categories of action. For each host range group, recent representative examples are provided, together with suggestions on how the different groups can be used to combat certain types of bacterial infections. The available methodologies for host range expansion, either through sequential adaptation to a new pathogen or through genetic engineering techniques, are also reviewed.

Pro-inflammatory cytokines and antioxidative enzymes as salivary biomarkers of dentofacial infections in children.

Dentofacial infection resulting from untreated dental caries or periodontal disease is a serious disease that can spread to deeper tissues of the face and neck. The present study aimed to analyze the salivary cytokine profile and oxidative stress parameters as potential biomarkers of acute odontogenic infections in children. The prospective study group (DI) consisted of 28 children aged 3-17 years with acute dentofacial infections, and the control group (CG) comprised 52 children aged 4-17 years with uncomplicated dental caries. The cytokine profile was analyzed using the Bio-Plex Pro™ Human Cytokine 27-plex kit. In addition, oxidative stress parameters, such as catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), manganese SOD (Mn-SOD), copper-zinc SOD (CuZn-SOD), total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA), in the saliva of children in both groups were compared. The levels of interleukin 6 (IL-6), macrophage inflammatory protein 1 alpha (MIP-1α) and tumor necrosis factor alpha (TNF-α) were significantly increased in children with dentofacial infections as compared to CG. In contrast, the levels of other pro-inflammatory cytokines, such as IL-1β, IL-1 receptor agonist (IL-Ra), IL-8, monocyte chemoattractant protein 1 (MCP-1), and MIP-1β, did not show statistically significant differences between the 2 groups. Among the measured oxidative stress and antioxidative parameters, only CAT and GR were elevated in children with dentofacial infections as compared to controls. IL-6, MIP-1α, TNF-α, CAT, and GR can serve as selective biomarkers of oral cavity inflammation in children. These biomarkers can be useful in identifying and monitoring the progress and treatment of bacterial infections resulting in dentofacial inflammation.

Aspartic acid-Cu(Ⅱ)-based nanozymes for combating bacterial infections

Nanozymes based on the coordination of amino acids and metal ions exhibit pronounced peroxidase (POD)-like activity, holding promising prospects in mitigating bacterial resistance caused by antibiotic misuse and harboring tremendous potential in the treatment of bacterial infections. In this study, L-/D-aspartic acid (L-/D-Asp) were individually coordinated with copper ions using a simple self-assembly approach, culminating in the creation of L-/D-hydrogel and nanofibers (L-/D-Gel and NFs) with POD-like actiity. These materials displayed excellent inhibitory effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Particularly, compared to L-/D-Gel, L-/D-NFs demonstrated excellent catalytic activity at extremely low concentrations. Moreover, our prepared nanozymes exhibited higher catalytic activity over a broader range of temperature and pH levels compared to the natural enzyme horseradish peroxidase (HRP). In summary, the prepared L-/D-Gel and NFs, as a novel type of nanozyme, hold great promise for widespread applications in the treatment of bacterial infections in wounds.

A 2D self-cascade catalytic system based on CoCuFe-LDH nanosheets for accelerated healing of infected wounds

The emergence of drug-resistant bacteria has rendered traditional antibiotics ineffective, posing a serious threat to human health. There is an urgent need to find alternative antimicrobial agents. Inspired by enzyme immobilization and multi-enzyme biocatalysis, we have designed a tri-metal layered double hydroxide (LDHs)-based cascade catalytic system (CoCuFe-LDH@Gox nanosheets) for treating drug-resistant bacterial infections and promoting wound healing. The synergistic effects of the Co, Cu, and Fe in the tri-metal LDHs structure endow CoCuFe-LDH nanosheets with excellent peroxidase (POD)-like activity. The large specific surface area of CoCuFe-LDH nanosheets render them ideal carriers for glucose oxidase (Gox). CoCuFe-LDH@Gox nanosheets can catalyze glucose to produce gluconic acid and H2O2. The generated gluconic acid decreases the local pH, further enhancing the POD-like activity of CoCuFe-LDH@Gox nanosheets at wound site. CoCuFe-LDH@Gox nanosheets can then catalyze H2O2 generating hydroxyl radicals (•OH) to effectively kill drug-resistant bacteria. This synergistic integration of the catalytic LDHs and the Gox components enables the cascade catalytic system to be highly effective against drug-resistant bacteria. In addition to its remarkable antibacterial properties, this LDHs-based system also exhibits excellent biocompatibility and considerable immunomodulatory capabilities. It can accelerate the healing of drug-resistant bacteria-infected wounds by inhibiting the inflammatory response and regulating macrophage polarization. These multifunctional attributes make the CoCuFe-LDH@Gox nanosheets a highly promising candidate for the treatment of drug-resistant bacterial infections in future clinical applications.

Potential therapeutic agents of Bombyx mori silk cocoon extracts from agricultural product for inhibition of skin pathogenic bacteria and free radicals.

Pathogenic bacteria are the cause of most skin diseases, but issues such as resistance and environmental degradation drive the need to research alternative treatments. It is reported that silk cocoon extract possesses antioxidant properties. During silk processing, the degumming of silk cocoons creates a byproduct that contains natural active substances. These substances were found to have inhibitory effects on bacterial growth, DNA synthesis, the pathogenesis of hemolysis, and biofilm formation. Thus, silk cocoon extracts can be used in therapeutic applications for the prevention and treatment of skin pathogenic bacterial infections. The extract of silk cocoons with pupae (SCP) and silk cocoons without pupae (SCWP) were obtained by boiling with distilled water for 9 h and 12 h, and were compared to silkworm pupae (SP) extract that was boiled for 1 h. The active compounds in the extracts, including gallic acid and quercetin, were determined using high-performance liquid chromatography (HPLC). Furthermore, the total phenolic and flavonoid content in the extracts were investigated using the Folin-Ciocalteu method and the aluminum chloride colorimetric method, respectively. To assess antioxidant activity, the extracts were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Additionally, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of silk extracts and phytochemical compounds were determined against skin pathogenic bacteria. This study assessed the effects of the extracts and phytochemical compounds on growth inhibition, biofilm formation, hemolysis protection, and DNA synthesis of bacteria. The HPLC characterization of the silk extracts showed gallic acid levels to be the highest, especially in SCP (8.638-31.605 mg/g extract) and SP (64.530 mg/g extract); whereas quercetin compound was only detected in SCWP (0.021-0.031 mg/g extract). The total phenolics and flavonoids in silk extracts exhibited antioxidant and antimicrobial activity. Additionally, SCP at 9 h and 12 h revealed the highest anti-bacterial activity, with the lowest MIC and MBC of 50-100 mg/mL against skin pathogenic bacteria including Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Cutibacterium acnes and Pseudomonas aeruginosa. Hence, SCP extract and non-sericin compounds containing gallic acid and quercetin exhibited the strongest inhibition of both growth and DNA synthesis on skin pathogenic bacteria. The suppression of bacterial pathogenesis, including preformed and matured biofilms, and hemolysis activity, were also revealed in SCP extract and non-sericin compounds. The results show that the byproduct of silk processing can serve as an alternative source of natural phenolic and flavonoid antioxidants that can be used in therapeutic applications for the prevention and treatment of pathogenic bacterial skin infections.

Antibody-Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections.

Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely. This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics. A literature review was conducted addressing the following topics about antibody-antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages. Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells. A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Screening of Short-Chain Antimicrobial Peptide LKARI with Broad-Spectrum Bactericidal Properties and Its Application in Promoting Wound Healing.

Due to the extensive use of antibiotics, many highly resistant bacteria and extensively resistant bacteria have been produced. In recent years, the increase of drug-resistant bacteria and the resulting proliferation of drug-resistant bacteria have increased the incidence of hospital-acquired infections and caused great harm to human health. Antimicrobial peptides (AMPs) are considered to be an innovative antibiotic and belong to the latest advances in this field. We designed a polypeptide and verified its low minimum inhibitory concentration and broad-spectrum activity against Gram-positive bacteria, Gram-negative bacteria, and fungi in microbiology and pharmacology. Several experiments have confirmed that the screened antimicrobial peptides have significant antidrug resistance and also show significant therapeutic properties in the treatment of systemic bacterial infections. In addition, through our experimental research, it was proved that the antibacterial hydrogel composed of poly(vinyl alcohol), sodium alginate, and antimicrobial peptides had excellent antibacterial properties and showed good wound healing ability.

In vitro antimicrobial activity of silver nanoparticles against selected Gram-negative and Gram-positive pathogens

Background and aim. Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for S aureus, E coli, MRSA, E faecalis, K pneumoniae and P aeruginosa indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections. This study focuses on comparing the antibacterial activity of antibiotics versus antibiotics combined with silver nanoparticles against various bacteria, by comparing inhibition zones obtained for both. We aim to prove that the size of the inhibition zone for antibiotics combined with silver nanoparticles is greater, thus confirming the improved antibacterial effect. Metods. In this study we tested the antibacterial activity of solutions of silver nanoparticles alone or in combination with different antibiotics. We used standard bacterial strains, ATCC, both Gram positive bacteria Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as Gram negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, but also on clinical isolates: a strain MRSA (Methicillin Resistant Staphylococcus aureus) and a PDR strain (pan drug resistant) of Klebsiella pneumoniae. Bacterial identification was performed using Vitek MS analyzer (bioMerieux). Antibiotic susceptibility determination was performed with VITEK2 COMPACT SYSTEM (bio Merieux, Inc Durham NC) with ready to use VITEK AST cards. The interpretation of the results was done in compliance with EUCAST 2023-2024 standards. Testing was performed for several classes of antibiotics, silver nanoparticle solutions in 2 concentrations (10 μg/mL and 100 μg/mL) and for combinations of antibiotics with silver nanoparticle solutions. The diameter of the inhibition zone (ZOI) for silver nanoparticles, antibiotics and silver nanoparticles combined with antibiotic against each bacterium was expressed in millimeters. The Kirby-Bauer disk-diffusion method, in accordance with current EUCAST standards, was used to analyze the antibacterial effect of antibiotics, silver nanoparticles, and antibiotics combined with silver nanoparticles at biocompatible doses of 10 and 100 μg/mL. The experiments were conducted in triplicate, and the results were almost identical. Results. The results of this study show that the silver nanoparticles displayed antibacterial activity, proven by the appearance of the inhibition zone, in various sizes, for all bacteria studied. The antibiotic classes tested were beta-lactamins, first, second, third and fourth generation cephalosporins, macrolides, fluoroquinolones, lincosamides, aminoglycosides, glycopeptides, tetracyclines, oxazolidinones, sulfonamides, rifamycins, amphenicols. Testing S aureus ATCC 29213, the highest zone of inhibition was demonstrated for cephalosporins (32.6667 ± 0.701 mm), macrolides (31.6667 ± 0.701 mm, and lincosamides (29.6667 ± 0.701 mm). Testing MRSA (internal code GR0333), the highest zone of inhibition for combination of silver nanoparticles and antibiotics was demonstrated for fluoroquinolones (36.3333 ± 0.701 mm), lincosamides (32.3333 ± 0.701 mm), Fusid acid (32.3333 ± 0.701 mm) and aminoglicosides (31.3333 ± 0.701 mm). Testing E coli ATCC 25922 the highest zone of inhibition was for Fosfomycine, 39 mm and for E faecalis ATCC 29212 for aminoglicosides was 19 mm. For K pneumoniae (internal code GQ8575) the inhibition zone for silver nanoparticles 100 μg/mL was 12.3333 ± 0.701 mm and for P aeruginosa ATCC 27253 was 16 ± 1.214 mm. Conclusions. The use of metallic nanoparticles, especially silver ones, as antimicrobial agents with definite bactericidal activity has led medical specialists to consider this new treatment which may change antibacterial therapy. Studies of in vitro combinations between silver nanoparticles and different classes of antibiotics represent a highly efficient and effective new antibacterial treatment against multidrug-resistant bacteria. To avoid the problem of antimicrobial resistance associated with conventional antibiotics, it is necessary to understand the adaptive mechanisms of bacteria under the action of metal nanoparticles, which could be exploited in future studies. Further in vitro and in vivo studies that would assess specify the biocompatibility and toxicity of silver nanoparticles will make these super nanomaterials the medicines of the future.

Antibacterial Activity of Polyalthia longifolia Leaf Extracts against Staphylococcus aureus and Escherichia coli

Study’s Novelty/ Excerpt Using the disc diffusion method, this study demonstrated the antibacterial properties of Polyalthia longifolia leaf extracts against Staphylococcus aureus and Escherichia coli. Phytochemical screening revealed the presence of alkaloids, anthraquinone, phenolic acids, and saponins, while flavonoids and steroids were absent. Both ethanolic and aqueous extracts showed significant antibacterial activity, with MIC and MBC values of 100 mg/mL, suggesting that Polyalthia longifolia leaves hold potential as alternative treatments for bacterial infections. Full Abstract Polyalthia longifolia, commonly known as the masquerade plant is a tropical evergreen plant with cultural and medicinal importance in Nigeria. This study used the disc diffusion method to analyze the antibacterial activity of Polyalthia longifolia leaves extracts against Staphylococcus aureus and Escherichia coli. The leaves were dried grounded, and ethanolic and aqueous extracts were used for antibacterial screening against the test isolates. The test isolates were confirmed based on cell morphology, gram reaction, and biochemical tests. The leaf extracts were subjected to phytochemical screening for alkaloids, saponins, flavonoids, steroids, phytosterols, and tannins. Phytochemical analysis of the leaf extracts of Polyalthia longifolia revealed that the leaves of this plant contain alkaloids, anthraquinone, phenols acid, and saponins, while flavonoids and Steroids were absent. The results of the antibacterial screening for aqueous and ethanolic extracts of the plant indicated that ethanol and aqueous extracts of the plant exhibited antibacterial activities with Minimum Inhibitory Concentration and Minimum Bactericidal Concentrations of 100mg/mL for both MIC and MBC.In conclusion, the leaves of the Polyalthia longifolia plant can be used as an alternative medicine for treating bacterial infections caused by Staphylococcus aureus and Escherichia coli

Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning.

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/or infectious diseases. Treatment options for infections caused by multidrug-resistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms.

One problem, multiple potential targets: Where are we now in the development of small molecule inhibitors against Shiga toxin?

Shiga toxin-producing Escherichia coli (STEC) are a group of enteric pathogens which carry phage-encoded Shiga toxins (Stx). STEC infections begin with severe abdominal pain and non-bloody diarrhoea, which can progress to bloody diarrhoea after approximately 4-days post-infection. In high-risk groups such as children and the elderly, patients may develop haemolytic uremic syndrome (HUS). HUS is characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and in severe disease acute renal failure. Traditional antibiotics have been linked with increased toxin production due to the activation of recA-mediated bacterial stress response, resulting in poorer patient outcomes. Therefore, treatment relies on supportive therapies. Antivirulence strategies have been explored as an alternative treatment for bacterial infections and blockers of virulence factors such as the Type III Secretion System. Recent improvements in the mechanistic understanding of the Stx pathway have led to the design of inhibitors to disrupt the pathway, leading to toxin-mediated ribosome damage. However, compounds have yet to progress beyond Phase III clinical trials successfully. This review explores the progress in developing small molecule inhibitors by collating lead compounds derived from in-silico and experimental approaches.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. Statement of significanceThe advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

Ta4C3 Nanosheets as a Novel Therapeutic Platform for Photothermal-Driven ROS Scavenging and Immune Activation against Antibiotic-Resistant Infections in Diabetic Wounds.

The accumulation of excessive reactive oxygen species (ROS) and recurrent infections with drug-resistant bacteria pose significant challenges in diabetic wound infections, often leading to impediments in wound healing. Addressing this, there is a critical demand for novel strategies dedicated to treating and preventing diabetic wounds infected with drug-resistant bacteria. Herein, 2D tantalum carbide nanosheets (Ta4C3 NSs) have been synthesized through an efficient and straightforward approach, leading to the development of a new, effective nanoplatform endowed with notable photothermal properties, biosafety, and diverse ROS scavenging capabilities, alongside immunogenic attributes for diabetic wound treatment and prevention of recurrent drug-resistant bacterial infections. The Ta4C3 NSs exhibit remarkable photothermal performance, effectively eliminating methicillin-resistant Staphylococcus aureus (MRSA) and excessive ROS, thus promoting diabetic wound healing. Furthermore, Ta4C3 NSs enhance dendritic cell activation, further triggering T helper 1 (TH1)/TH2 immune responses, leading to pathogen-specific immune memory against recurrent MRSA infections. This nanoplatform, with its significant photothermal and immunomodulatory effects, holds vast potential in the treatment and prevention of drug-resistant bacterial infections in diabetic wounds.

Phase III Study to Evaluate the Efficacy and Safety of Two Novel Fixed-Dose Vaginal Ovule Formulations in the Treatment of Various Vaginal Infections: One-Shot Study Running Title: Phase III study of two novel vaginal ovules

Objective: This study aimed to evaluate the efficacy and safety of two novel formulations: one containing fenticonazole nitrate 600 mg + tinidazole 1000 mg + lidocaine 100 mg (Formulation A) and the other with fenticonazole nitrate 600 mg + tinidazole 2000 mg + lidocaine 100 mg (Formulation B) in the treatment of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonas vaginitis (TV), and mixed vaginal infections (MVIs) in comparison to comparator medication (Gynomax® XL). Materials and methods: This phase III study enrolled 562 adult, pre-menopausal patients with BV, VVC, TV, or MVIs. Of these, 544 received the study medication (included in the safety analysis), and 440 completed the study (included in the efficacy analysis). Patients were randomized into Formulation A, Formulation B, or comparator medication arms. Follow-up visits were conducted two weeks post-treatment, with clinical and microbiological evaluations. Results: Initial clinical diagnoses indicated BV (62.0%), VVC (19.8%), MVIs (15.5%), and TV (2.7%). High clinical recovery rates were observed with Formulation A (96.7% of BV, 81.8% of VVC, and 96.3% of MVIs), Formulation B (97.7% of BV, 88.2% of VVC, 90.9% of MVIs), and comparator medication (98.9% of BV, 90.3% of VVC, 100.0% of MVIs). None of the patients discontinued medications due to an adverse event or intolerability. Conclusion: All formulations are considered as safe, well-tolerated, and highly effective for treating BV, VVC, and MVIs. Formulation A or B may be particularly advantageous due to anticipated greater patient compliance with their single-dose administration.

Clinically important pharmacokinetic drug-drug interactions with antibacterial agents.

Antimicrobial agents are widely used, and drug interactions are challenging due to increased risk of adverse effects or reduced efficacy. Among the interactions, the most important are those affecting metabolism, although those involving drug transporters are becoming increasingly known. To make clinical decisions, it is key to know the intensity of the interaction, as well as its duration and time-dependent recovery after discontinuation of the causative agents. It is not only important to be aware of all patient treatments, but also of supplements and natural medications that may also interact. Although they can have serious consequences, most interactions can be adequately managed with a good understanding of them. Especially in patients with polipharmacy it is compulsory to check them with an electronic clinical decision support database. This article aims to conduct a narrative review focusing on the major clinically significant pharmacokinetic drug-drug interactions that can be seen in patients receiving treatment for bacterial infections.

Effect of Essential oil and Extracts of Artemisia Herba – Alba Plant Against Some E Pathogenic Bacteria

Artemisia Herba – Alba is the one of the most important genus of Asteraceae family. It has numerous values because of medicine properties. Artemisia Herba – Alba has numerous application in traditional medicine from ancient times. In this research, antimicrobial effects of leaf aqueous, alcoholic extracts and essential oil of Artemisia Herba – Alba against Staphylococcus aureus PTCC 1431 and Escherichia coli PTCC 1399 were studied, using agar disc diffusion method. Methanol and ethanol extracts obtained from leaves of A. Herba – Alba exhibited antimicrobial activity against test microorganisms. In addition Artemisia herba-alba essential oil was inhibitory effects against all studied pathogenic bacteria. The results showed that essential oil of Artemisia herba-alba had the most inhibition diameter zone in Staphylococcus aureusthan E.coli (25-17mm successively). Therefore in this research we showed that the positive gram bacteria are more sensitive than negative gram bacteria. our results indicate the possibility of using essential oil in the treatment of bacterial infections, and the results of this study was encouraging, despite the need for clinical studies to determine of the real effectiveness and potential toxic effects in vivo

Bacteriophages

In this month's article, George Winter discusses how attention has been turning increasingly towards a natural antibacterial phenomenon that could influence the treatment of bacterial infections

Cefiderocol for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol. Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Given existing evidence, the estimates of the value of cefiderocol are highly uncertain. Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value. No registration of this study was undertaken. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.

Revolutionizing Nitrofurantoin Delivery: Unraveling Challenges and Pioneering Solutions for Enhanced Efficacy in UTI Treatment

Abstract: Nitrofurantoin is an antimicrobial drug, highly effective in the treatment of critical or chronic bacterial infections of the urinary tract, and hence, it is the first line choice of drug for the treatment of urinary tract infections (UTI). Although the molecule is legacy in nature, there are many challenges in terms of drug product formulation and efficacy thereof. The authors are main-ly focused in this literature review on, but not limited to, understanding the molecule in terms of physico-chemical properties of the drug, pharmacokinetics and pharmacodynamics, approved and withdrawn formulations, challenges concerning drug formulation, the cause of drug shortage in the market, improvement areas in terms of formulation and its therapeutic effectiveness. The au-thors found during their widespread review that the major challenge in the existing conventional drug delivery system of nitrofurantoin is the fluctuation of plasma concentration owing to its var-iability in drug absorption. Further, they understood that the variability in absorption is due to in-herent variability in particle size distribution. Based on the findings, authors also explored the possibilities to deliver the drug in novel drug delivery systems such as nano self-emulsifying emulsions, nanoemulsions and multiple emulsions where the drug can be presented in soluble form and hence the variability in absorption and fluctuation in plasma concentration of drug can be avoided and described briefly the salient features of each drug delivery in this review.