Investigation of bioactive phytochemical compounds of the Ethiopian medicinal plant using GC-MS and FTIR.

Medicinal plants Highly aromatic crude materials are utilized for treating warts as an alternative medicine to surgical treatment because they can be permanently removed from the body. Thus, this investigation aimed to extract plant material from Calotropis procera leaves, describe the phytochemical screening, analyze anti-microbial activities, determine the functional groups in FTIR, and identify the chemical compounds in GC-MS. The PH, specific gravity, and viscosity of the crude extracts of Calotropis procera were determined at 4.5, 0.79, and 0.49, respectively. Analyze the solubility of crude extracts; ethanol can dissolve while water does not. Flavonoids, alkaloids, phenols, tannins, and saponins were also present in the phytochemical screening tests of the Calotropis procera extracts, triterpenoids, terpenoids, and steroids were not present in the crude extract. Flavonoids, alkaloids, phenols, tannins, and saponins are the primary phytochemical components found in therapeutic plant material. The Calotropis procera crude extracts analyzed for functional groups by FT-IR contained a hydroxyl group, alkane, carbonyl, aldehyde, ketone, phenols, ester, alcohol, and methylene. The chemical compounds analyzed by GC-MS of Calotropis procera crude material were found to have 22 main compounds. Of 22 compounds, 5 compounds are active ingredients for the applications of medical purposes. The bioactive compounds found in the Calotropis procera plant extract are neophytadiene, hexahydrofarnesyl, lanosterol, 2,4-dimethylbenzo [H]quinolone, and squalene. Those bioactive compounds have anti-bacterial, analgesic, antipyretic, anti-inflammatory, antimicrobial, antioxidant, antiviral, and anti-cancer properties. In an in vitro antimicrobial activity test, the crude extract effectively inhibited more gram-positive bacteria than gram-negative bacteria. This collective reason is why the traditional therapist uses this Calotropis procera plant for the treatment of warts.

Reduction of biofilm and pathogenic microorganisms using curcumin-mediated photodynamic inactivation to prolong food shelf-life.

Pathogenic microbial contamination (bacteria and fungi) in food products during production poses a significant global health risk, leading to food waste, greenhouse gas emissions, and aesthetic and financial losses. Bacteria and fungi, by forming solid biofilms, enhance their resistance to antimicrobial agents, thereby increasing the potential for cross-contamination of food products. Curcumin molecule-mediated photodynamic inactivation (Cur-m-PDI) technology has shown promising results in sterilizing microbial contaminants and their biofilms, significantly contributing to food preservation without compromising quality. Photosensitizers (curcumin) absorb light, leading to a chemical reaction with oxygen and producing reactive oxygen species (ROS) that effectively reduce bacteria, fungi, and biofilms. The mechanism of microorganism inhibition is caused by exposure to ROS generated via the type 1 pathway involving electron transfer (such as O2•-, H2O2, -OH•, and other radicals), the type 2 pathway involving energy transfer (such as 1O2), secondary ROS, and weakening of antioxidant enzymes. The effectiveness of the inactivation of microorganisms is influenced by the concentration of curcumin, light (source type and energy density), oxygen availability, and duration of exposure. This article reviews the mechanism of reducing microbial food contamination and inhibiting their biofilms through Cur-m-PDI. It also highlights future directions, challenges, and considerations related to the effects of ROS in oxidizing food, the toxicity of PDI to living cells and tissues, conditions/types of food products, and the stability and degradation of curcumin.

Anti-Microbial, Thermal, Mechanical, and Gas Barrier Properties of Linear Low-Density Polyethylene Extrusion Blow-Molded Bottles.

Microbial contamination can occur on the surfaces of blow-molded bottles, necessitating the development and application of effective anti-microbial treatments to mitigate the hazards associated with microbial growth. In this study, new methods of incorporating anti-microbial particles into linear low-density polyethylene (LLDPE) extrusion blow-molded bottles were developed. The anti-microbial particles were thermally embossed on the external surface of the bottle through two particle deposition approaches (spray and powder) over the mold cavity. The produced bottles were studied for their thermal, mechanical, gas barrier, and anti-microbial properties. Both deposition approaches indicated a significant enhancement in anti-microbial activity, as well as barrier properties, while maintaining thermal and mechanical performance. Considering both the effect of anti-microbial agents and variations in tensile bar weight and thickness, the statistical analysis of the mechanical properties showed that applying the anti-microbial agents had no significant influence on the tensile properties of the blow-molded bottles. The external fixation of the particles over the surface of the bottles would result in optimum anti-microbial activity, making it a cost-effective solution compared to conventional compounding processing.

Topical Chloramphenicol in Ophthalmology: Old is Gold.

PURPOSE: Topical chloramphenicol is one of the most ubiquitous antibiotics used in ophthalmology and oculoplastic surgery globally. It shows broad-spectrum activity against a variety of different pathogenic organisms, is well tolerated on the ocular surface and displays excellent topical pharmacokinetics. Chloramphenicol has been available for purchase over the counter in the United Kingdom since 2005. Despite this, the largest health economy in the world, The United States has had a de-facto moratorium on its use for the past 30 years. In this review, we aim to evaluate topical chloramphenicol in ophthalmology and oculoplastic surgery and to determine whether its reputation within the US is warranted and justified. METHODS: We conducted a comprehensive literature review to evaluate the different facets of chloramphenicol, providing a detailed understanding of the drug, its historical context, the benefits and perceived risks, including safety concerns, and clinical perspectives of its use in clinical practice. RESULTS: The mechanism of chloramphenicol, the context around which the drug's use in the US declined, and the drug's evidence base and safety data, including published case reports of serious adverse events, were analysed. The perceived benefits of the drug, particularly in light of antimicrobial resistance and its economic impact, were reviewed. Finally, perspectives on its use in clinical practice in ophthalmology and associated allied specialities were presented. CONCLUSION: Chloramphenicol and its topical application have been misunderstood for many decades, particularly in the United States. Its demise across the Atlantic was due to an overzealous response to a dubious association with a weak evidence base. Numerous authors have since validated the safety profile of the and its safety has been borne out. The benefits of chloramphenicol, an effective broad-spectrum agent with a positive cost differential in the era of anti-microbial resistance and fiscal tightening, cannot be understated. Its likely effectiveness as a therapeutic topical agent in ophthalmic surgery makes it a valuable tool in the ophthalmic anti-microbial armoury. We would encourage the reinstatement of this valuable yet misunderstood drug as a first-line agent for simple ophthalmic infections.

Recurrent Fungemia Due to Candida auris.

We present a case of recurrent multidrug-resistant Candida auris (C. auris) in a patient who required multiple hospitalizations. The patient's case was complicated by interval admissions to the intensive care unit for septic and hypovolemic shock for 12 months to manage C. auris fungemia. Despite adequate isolation precautions and appropriate antifungal treatment, this case demonstrates the profound implications of this emerging pathogen, specifically regarding invasive infections. Moreover, C. auris is rapidly becoming known as a multidrug-resistant organism, which limits treatment options and thus contributes to high mortality.

Synthesis, Characterization, DNA Binding, Biological Significance, and Molecular Docking Approaches of a Palladium(II) Complex with Ciprofloxacin for More Efficient Therapy.

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH2)2]2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic.

Anti-Microbial Drug Metronidazole Promotes Fracture Healing: Enhancement in the Bone Regenerative Efficacy of the Drug by a Biodegradable Sustained-Release In Situ Gel Formulation.

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures.

Bioactivity of synthetic peptides from Ecuadorian frog skin secretions against Leishmania mexicana, Plasmodium falciparum, and Trypanosoma cruzi.

Chagas disease, leishmaniasis, and malaria are major parasitic diseases disproportionately affecting the underprivileged population in developing nations. Finding new, alternative anti-parasitic compounds to treat these diseases is crucial because of the limited number of options currently available, the side effects they cause, the need for long treatment courses, and the emergence of drug-resistant parasites. Anti-microbial peptides (AMPs) derived from amphibian skin secretions are small bioactive molecules capable of lysing the cell membrane of pathogens while having low toxicity against human cells. Here, we report the anti-parasitic activity of five AMPs derived from skin secretions of three Ecuadorian frogs: cruzioseptin-1, cruzioseptin-4 (CZS-4), and cruzioseptin-16 from Cruziohyla calcarifer; dermaseptin-SP2 from Agalychnis spurrelli; and pictuseptin-1 from Boana picturata. These five AMPs were chemically synthesized. Initially, the hemolytic activity of CZS-4 and its minimal inhibitory concentration against Escherichia coli, Staphylococcus aureus, and Candida albicans were determined. Subsequently, the cytotoxicity of the synthetic AMPs against mammalian cells and their anti-parasitic activity against Leishmania mexicana promastigotes, erythrocytic stages of Plasmodium falciparum and mammalian stages of Trypanosoma cruzi were evaluated in vitro. The five AMPs displayed activity against the pathogens studied, with different levels of cytotoxicity against mammalian cells. In silico molecular docking analysis suggests this bioactivity may occur via pore formation in the plasma membrane, resulting in microbial lysis. CZS-4 displayed anti-bacterial, anti-fungal, and anti-parasitic activities with low cytotoxicity against mammalian cells. Further studies about this promising AMP are required to gain a better understanding of its activity.IMPORTANCEChagas disease, malaria, and leishmaniasis are major tropical diseases that cause extensive morbidity and mortality, for which available treatment options are unsatisfactory because of limited efficacy and side effects. Frog skin secretions contain molecules with anti-microbial properties known as anti-microbial peptides. We synthesized five peptides derived from the skin secretions of different species of tropical frogs and tested them against cultures of the causative agents of these three diseases, parasites known as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania mexicana. All the different synthetic peptides studied showed activity against one of more of the parasites. Peptide cruzioseptin-4 is of special interest since it displayed intense activity against parasites while being innocuous against cultured mammalian cells, which indicates it does not simply hold general toxic properties; rather, its activity is specific against the parasites.

Antimicrobial Potential of Pomegranate and Lemon Extracts Alone or in Combination with Antibiotics against Pathogens.

Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.

Engineering Whole-Cell Biosensors for Enhanced Detection of Environmental Antibiotics Using a Synthetic Biology Approach.

Bacterial Two component systems have evolved with many intricate sensory apparatuses for external stimuli like light, temperature, oxygen, pH and chemical compounds. Recent studies have shown the potential of two-component regulatory systems (TCSs) of bacteria in creating synthetic regulatory circuits for several applications. Antimicrobial resistance is increasing globally in both developing and developed countries and it is one of the foremost global threats to public health. The resistance level to a broad spectrum of antibiotics is rising every year by 5-10%. In this context, TCSs controlling microbial physiology at the transcriptional level could be an appropriate candidate for monitoring the antibiotics present in the environment. This review provided a wide opportunity to gain knowledge about the TCSs available in diverse species to sense the antibiotics. Further, this review explored the EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) based biosensors to repurpose the sensing modules from the microbial TCSs using the synthetic biology approach.

Biosynthesized MgONPs using Syzygium cumini seed extract: Characterization, In vitro anti-oxidant and anti-microbial activity.

The present study investigates S. cumini seed extracts which are considered as a promising and valuable source of bioactive compounds were prepared using different solvents such as methanol, ethanol, petroleum ether, acetone, chloroform, and diethyl ether. Among these solvents, methanol exhibited the highest extraction with a yield of 42 %. HPLC analysis revealed the highest concentration of quercetin flavonoids (49.62 mg/gm) in the methanolic S. cumini seed extract. Thus, the current work deals with the MgONPs synthesis through a biological approach using different S. cumini seed extracts. In vitro anti-oxidant properties were evaluated, which showed an IC50 value of 22.46 µg/mL for MgONPs synthesized from methanolic extract, surpassing the anti-oxidant potency of ascorbic acid by threefold. By leveraging the rich repository of bioactive compounds found within S. cumini seed extract, this study presents a novel approach to MgONPs synthesis. Exploring the symbiotic relationship between S. cumini seed extract and MgONPs, this research elucidates the pivotal role of bioactive compounds in guiding the formation and properties of nanostructures. Further anti-microbial studies on MgONPs from methanolic S. cumini seed extract were conducted against four different bacterial strains (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and S. typhimurium), revealing potent anti-microbial activity with 5.3 mm of inhibition for 100 µl against S. typhimurium. These findings suggest that S. cumini is a source of bioactive compounds responsible for the successful synthesis of MgONPs. Characterization studies of MgONPs were also carried out using UV-vis spectroscopy, FTIR, SEM, XRD, DSC and HPLC.

Exploring quinoxaline derivatives: An overview of a new approach to combat antimicrobial resistance.

Antimicrobial resistance (AMR) has emerged as a long-standing global issue ever since the introduction of penicillin, the first antibiotic. Scientists are constantly working to develop innovative antibiotics that are more effective and superior. Unfortunately, the misuse of antibiotics has resulted in their declining effectiveness over the years. By 2050, it is projected that approximately 10 million lives could be lost annually due to antibiotic resistance. Gaining insight into the mechanisms behind the development and transmission of AMR in well-known bacteria including Escherichia coli, Bacillus pumilus, Enterobacter aerogenes, Salmonella typhimurium, and the gut microbiota is crucial for researchers. Environmental contamination in third world and developing countries also plays a significant role in the increase of AMR. Despite the availability of numerous recognized antibiotics to combat bacterial infections, their effectiveness is diminishing due to the growing problem of AMR. The overuse of antibiotics has led to an increase in resistance rates and negative impacts on global health. This highlights the importance of implementing strong antimicrobial stewardship and improving global monitoring, as emphasized by the World Health Organization (WHO) and other organizations. In the face of these obstacles, quinoxaline derivatives have emerged as promising candidates. They are characterized by their remarkable efficacy against a broad spectrum of harmful bacteria, including strains that are resistant to multiple drugs. These compounds are known for their strong structural stability and adaptability, making them a promising and creative solution to the AMR crisis. This review aims to assess the effectiveness of quinoxaline derivatives in treating drug-resistant infections, with the goal of making a meaningful contribution to the global fight against AMR.

Comparative Evaluation of Anti-microbial Activity of Herbal, Homeopathic, and Conventional Dentifrices Against Oral Microflora Using the Disc Diffusion Method: An In Vitro Study.

Aim To assess the antimicrobial activity of herbal, homeopathic, and conventional dentifrices against oral microorganisms. Methodology Mueller Hilton agar was used to cultivate distinct strains of Streptococcus mutans and Enterococcus faecalis, whereas Candida albicans was cultured on a potato dextrose agar medium. Diffusion ratios of 1:5, 1:10, and 1:15 were obtained by diluting 1 gram of each dentifrice (KP Namboodiri, Homeodent, and Colgate Strong Teeth) in 4 ml, 9 ml, and 14 ml of distilled water, respectively. The culture medium was filled with sterile discs. Twenty µl of each dilution of prepared dentifrice formulations were incorporated using a micropipette. The agar plates were incubated for 24 hours at 37ºC. Result The findings indicate that there was a higher zone of inhibition against Streptococcus mutans with herbal dentifrice at 10 mm, 8 mm, and 6.5 mm, followed by conventional dentifrice at 10 mm, 7.5 mm, and 7 mm, and the lowest with homeopathic dentifrice at 8 mm, 7 mm, and 7 mm at 1:5, 1:10 and 1:15 dilutions, respectively. Conventional dentifrice was found to inhibit Enterococcus faecalis at 9 mm, 8 mm, and 7 mm with 1:5, 1:10, and 1:15 dilutions followed by herbal dentifrice at 9 mm, 7 mm with 1:5, 1:10 dilutions, and no inhibition at 1:15 dilution. In contrast, homeopathic dentifrice displayed no inhibition at 1:5, 1:10, and 1:15 dilutions. Neither homeopathic nor conventional dentifrices inhibited Candida albicans, but herbal dentifrices showed a 10 mm zone of inhibition at 1:10 dilution. Conclusion Conventional and herbal dentifrices were found to be more effective against Streptococcus mutans than the homeopathic dentifrice used in the study, whereas herbal dentifrice was more effective against Candida albicans when compared to conventional and homeopathic dentifrices.

Modern Microbiological Methods to Detect Biofilm Formation in Orthopedy and Suggestions for Antibiotic Therapy, with Particular Emphasis on Prosthetic Joint Infection (PJI).

Biofilm formation is a serious problem that relatively often causes complications in orthopedic surgery. Biofilm-forming pathogens invade implanted foreign bodies and surrounding tissues. Such a condition, if not limited at the appropriate time, often requires reoperation. This can be partially prevented by selecting an appropriate prosthesis material that prevents the development of biofilm. There are many modern techniques available to detect the formed biofilm. By applying them we can identify and visualize biofilm-forming microorganisms. The most common etiological factors associated with biofilms in orthopedics are: Staphylococcus aureus, coagulase-negative Staphylococci (CoNS), and Enterococcus spp., whereas Gram-negative bacilli and Candida spp. also deserve attention. It seems crucial, for therapeutic success, to eradicate the microorganisms able to form biofilm after the implantation of endoprostheses. Planning the effective targeted antimicrobial treatment of postoperative infections requires accurate identification of the microorganism responsible for the complications of the procedure. The modern microbiological testing techniques described in this article show the diagnostic options that can be followed to enable the implementation of effective treatment.

Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1H-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a ß-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a-j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Drug Utilization Review of Monitored Parenteral Antimicrobials in a Tertiary Care Private Hospital in Cebu City.

Background: Based on the 2017-2020 annual report of the Department of Health-Antimicrobial Resistance Surveillance Program, significant resistance patterns have been observed for common disease-causing pathogens. In the hospital setting, antimicrobial stewardship programs have been implemented to optimize the use of antimicrobials. Drug utilization review studies provide essential feedback to improve prescribing and use of medications. Objectives: This study aimed to review drug utilization of monitored parenteral antimicrobials among patients admitted from January to December 2019. Methods: The study employed a retrospective, cross-sectional, descriptive research design. A retrospective chart review of drugs administered to patients was conducted. Results: A total of 821 patients charts met the inclusion criteria. The patients' ages ranged from 18 to 98 years old and 52% were females. General Internal Medicine practitioners (28%) were the top prescribers of monitored parenteral antimicrobials primarily for the management of moderate-risk community-acquired pneumonia (39%). They were mostly indicated for empirical treatment of infections (94%) and were given for an average of 5.73 days.Only 58% of the total cases had orders for culture and sensitivity testing. Of which, principally 47% had colony cultures. Blood (29%) and sputum (27%) were the most common specimens taken for culture and sensitivity testing. The microorganisms often isolated were Escherichia coli (19%), Klebsiella pneumoniae (18%), and Staphylococcus aureus (9%). In addition, extended-spectrum beta lactamase-producing gram-negative pathogens (4%) and methicillin-resistant S. aureus (1%) were also isolated. All the microorganisms isolated showed most resistance to ampicillin (81%) and most susceptibility to colistin (100%). There were drug therapy-related problems encountered. There was one case of an adverse drug reaction (0.1%) and two cases of contraindications (0.2%). Therapeutic duplication was also observed in 5% of the cases. Moreover, 39% had instances of drug-drug interactions.Piperacillin-tazobactam had the highest consumption (79.50 defined daily doses/1,000-patient days) among the monitored parenteral antimicrobials.Some prescriptions were deemed inappropriate upon evaluation. 12% of cases were inappropriate based on the justification indicator. As for the critical indicators, duration of therapy (78%) was the main reason. Only four components of the DUE criteria indicators have met or exceeded the established threshold level.The cost analysis indicated that the total actual cost of therapy with the monitored parenteral antimicrobials amounted to ₱17,645,601.73. Considering Department of Health National Antibiotic Guidelines recommendations, ideal total cost of treatment was ₱14,917,214.29. Potential cumulative cost savings of ₱2,728,387.44 could have been achieved for patients admitted last 2019. Conclusion: Consumption of piperacillin-tazobactam was relatively high as compared to the other monitored parenteral antimicrobials covered in this study. Physicians at the study site seldom prescribe monitored parenteral antimicrobials as recommended by the National Antibiotic Guidelines. This is evidenced in the incidence of inappropriate therapy regimens, with inapt duration of therapy as the leading explanation.From the patient's perspective, the main economic implication was on the direct medical costs, particularly the increased cost of the actual antimicrobial therapy prescribed to manage various infections. Adherence of physicians to the established guidelines and selection of the most cost-effective therapy could have resulted in considerable cost savings.

The escalating threat of human-associated infectious bacteria in surface aquatic resources: Insights into prevalence, antibiotic resistance, survival mechanisms, detection, and prevention strategies.

Anthropogenic activities and climate change profoundly impact water quality, leading to a concerning increase in the prevalence and abundance of bacterial pathogens across diverse aquatic environments. This rise has resulted in a growing challenge concerning the safety of water sources, particularly surface waters and marine environments. This comprehensive review delves into the multifaceted challenges presented by bacterial pathogens, emphasizing threads to human health within ground and surface waters, including marine ecosystems. The exploration encompasses the intricate survival mechanisms employed by bacterial pathogens and the proliferation of antimicrobial resistance, largely driven by human-generated antibiotic contamination in aquatic systems. The review further addresses prevalent pathogenic bacteria, elucidating associated risk factors, exploring their eco-physiology, and discussing the production of potent toxins. The spectrum of detection techniques, ranging from conventional to cutting-edge molecular approaches, is thoroughly examined to underscore their significance in identifying and understanding waterborne bacterial pathogens. A critical aspect highlighted in this review is the imperative for real-time monitoring of biomarkers associated with waterborne bacterial pathogens. This monitoring serves as an early warning system, facilitating the swift implementation of action plans to preserve and protect global water resources. In conclusion, this comprehensive review provides fresh insights and perspectives, emphasizing the paramount importance of preserving the quality of aquatic resources to safeguard human health on a global scale.

Vaginal microbes alter epithelial transcriptome and induce epigenomic modifications providing insight into mechanisms for susceptibility to adverse reproductive outcomes.

The cervicovaginal microbiome is highly associated with women's health, with microbial communities dominated by Lactobacillus species considered optimal. Conversely, a lack of lactobacilli and a high abundance of strict and facultative anaerobes, including Gardnerella vaginalis, have been associated with adverse reproductive outcomes. However, how host-microbial interactions alter specific molecular pathways and impact cervical and vaginal epithelial function remains unclear. Using RNA-sequencing, we characterized the in vitro cervicovaginal epithelial transcriptional response to different vaginal bacteria and their culture supernatants. We showed that G. vaginalis upregulates genes associated with an activated innate immune response. Unexpectedly, G. vaginalis specifically induced inflammasome pathways through activation of NLRP3-mediated increases in caspase-1, IL-1ß and cell death, while live L. crispatus had minimal transcriptomic changes on epithelial cells. L. crispatus culture supernatants resulted in a shift in the epigenomic landscape of cervical epithelial cells that was confirmed by ATAC-sequencing showing reduced chromatin accessibility. This study reveals new insights into host-microbe interactions in the lower reproductive tract and suggests potential therapeutic strategies leveraging the vaginal microbiome to improve reproductive health.

Direct prediction of antimicrobial resistance in Pseudomonas aeruginosa by metagenomic next-generation sequencing.

Objective: Pseudomonas aeruginosa has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of P. aeruginosa isolates and clinical samples by genotype is helpful for timely antibiotic treatment. Methods: In the study, whole genome sequencing (WGS) data of 494 P. aeruginosa isolates were used to screen key anti-microbial resistance (AMR)-associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in P. aeruginosa by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of P. aeruginosa to four antibiotics by the AMR-associated features screened, we collected 74 P. aeruginosa positive sputum samples to sequence by metagenomics next-generation sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model. Results: We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in P. aeruginosa. The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of P. aeruginosa, in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance. Conclusion: In summary, mNGS can predict the resistance of P. aeruginosa by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria.

Antimicrobial Activity of Crude Metabolites of Vitis vinifera using Methanol Extract against the Clinical Pathogens.

Background: The Vitis vinifera, also known as grapevine, is one of the most widely grown fruit crops in the world and is renowned for producing wine and grapes. Other than their importance in gastronomy and ecology, certain sections of the V. vinifera plant have shown promising bioactive qualities. The numerous phytochemicals in this plant, including flavonoids, stilbenes, and phenolic acids, are what gives its antibacterial and antifungal properties though the antimicrobial properties of seed extract have to be studied, however in this present study we focus on screening and its biological compatibility of seed extracts of V. vinifera. Methods: The commercial power of seed (V. vinifera) obtained from local market near Poonamallee, Chennai, India. and the extraction of crude metabolites was done by direction extraction method, the antimicrobial activity was done by well diffusion method, and Minimum Inhibitory concentration was done by CLSI guideline. To check the biocompatibility of crude metabolites was done by hemolytic assay. Results: Studies have demonstrated that grapevine extracts and their separated components have potent antibacterial and antifungal effects against a variety of pathogenic microorganisms, including bacterial strains that are resistant to antibiotics. The Minimum Inhibitory Concentration of the plant's extracts have demonstrated potential 128 µg/mL for S. aureus, and 256 µg/mL E. faecalis and C. albicans as the best inhibitory concentration. The biological compatibility of crude metabolites shows 3 % of lysis at 512 µg/mL. Conclusion: V. vinifera is a prospective source for the creation of novel antimicrobial drugs because of its antibacterial capabilities. To completely understand the chemicals' mode of action and to create efficient treatments for microbial illnesses, more research is necessary.