The Antimicrobial Activity of Human Defensins at Physiological Non-Permeabilizing Concentrations Is Caused by the Inhibition of the Plasma Membrane H+-ATPases.

Human defensins are cysteine-rich peptides (Cys-rich peptides) of the innate immune system. Defensins contain an ancestral structural motif (i.e., γ-core motif) associated with the antimicrobial activity of natural Cys-rich peptides. In this study, low concentrations of human α- and ß-defensins showed microbicidal activity that was not associated with cell membrane permeabilization. The cell death pathway was similar to that previously described for human lactoferrin, also an immunoprotein containing a γ-core motif. The common features were (1) cell death not related to plasma membrane (PM) disruption, (2) the inhibition of microbicidal activity via extracellular potassium, (3) the influence of cellular respiration on microbicidal activity, and (4) the influence of intracellular pH on bactericidal activity. In addition, in yeast, we also observed (1) partial K+-efflux mediated via Tok1p K+-channels, (2) the essential role of mitochondrial ATP synthase in cell death, (3) the increment of intracellular ATP, (4) plasma membrane depolarization, and (5) the inhibition of external acidification mediated via PM Pma1p H+-ATPase. Similar features were also observed with BM2, an antifungal peptide that inhibits Pma1p H+-ATPase, showing that the above coincident characteristics were a consequence of PM H+-ATPase inhibition. These findings suggest, for the first time, that human defensins inhibit PM H+-ATPases at physiological concentrations, and that the subsequent cytosolic acidification is responsible for the in vitro microbicidal activity. This mechanism of action is shared with human lactoferrin and probably other antimicrobial peptides containing γ-core motifs.

Decoding the biochemical dialogue: metabolomic insights into soybean defense strategies against diverse pathogens.

Soybean, a crucial global leguminous crop, confronts persistent threats from diverse pathogens, exerting a profound impact on global yields. While genetic dimensions of soybean-pathogen interactions have garnered attention, the intricate biochemical responses remain poorly elucidated. In this study, we applied targeted and untargeted liquid chromatography coupled to mass spectrometry (LC-MS) metabolite profiling to dissect the complex interplay between soybeans and five distinct pathogens. Our analysis uncovered 627 idMS/MS spectra, leading to the identification of four main modules, encompassing flavonoids, isoflavonoids, triterpenoids, and amino acids and peptides, alongside other compounds such as phenolics. Profound shifts were observed in both primary and secondary metabolism in response to pathogenic infections. Particularly notable were the bidirectional changes in total flavonoids across diverse pathogenic inoculations, while triterpenoids exhibited a general declining trend. Noteworthy among the highly inducible total flavonoids were known representative anti-pathogen compounds (glyceollin I), backbone forms of isoflavonoids (daidzein, genistein, glycitein, formononetin), and newly purified compounds in this study (prunin). Subsequently, we delved into the biological roles of these five compounds, validating their diverse functions against pathogens: prunin significantly inhibited the vegetative growth and virulence of Phytophthora sojae; genistein exhibited a pronounced inhibitory effect on the vegetative growth and virulence of Phomopsis longicolla; daidzein and formononetin displayed significant repressive effects on the virulence of P. longicolla. This study underscores the potent utility of metabolomic tools, providing in-depth insights into plant-pathogen interactions from a biochemical perspective. The findings not only contribute to plant pathology but also offer strategic pathways for bolstering plant resistance against diseases on a broader scale.

Antimicrobial assay and controlled drug release studies with novel eugenol imprinted p(HEMA)-bacterial cellulose nanocomposite, designed for biomedical applications.

In this study, a novel bio-composite material that allow sustained release of plant derived antimicrobial compound was developed for the biomedical applications to prevent the infections caused by microorganisms resistant to commercial antimicrobials agents. With this aim, bacterial cellulose (BC)-p(HEMA) nanocomposite film that imprinted with eugenol (EU) via metal chelated monomer, MAH was prepared. Firstly, characterization studies were utilized by FTIR, SEM and BET analysis. Then antimicrobial assays, drug release studies and in vitro cytotoxicity test were performed. A significant antimicrobial effect against both Gram (+) Staphylococcus aureus and Gram (-) Escherichia coli bacteria and a yeast Candida albicans were observed even in low exposure time periods. When antimicrobial effect of EU compared with commercially used agents, both antifungal and antibacterial activity of EU were found to be higher. Then, sustained drug release studies showed that approximately 55% of EU was released up to 50 h. This result proved the achievement of the molecular imprinting for an immobilization of molecules that desired to release on an area in a long-time interval. Finally, the in vitro cytotoxicity experiment performed with the mouse L929 cell line determined that the synthesized EU-imprinted BC nanocomposite was biocompatible.

Antibiotic stewardship in the emergency department setting: Focus on oral antibiotic selection for adults with skin and soft tissue infections.

PURPOSE: An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting. SUMMARY: While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations. Convening a team of experts locally to establish institution-specific guidelines as part of a comprehensive antibiotic stewardship program can ensure patients receive the most appropriate oral therapy for the outpatient treatment of SSTIs in patients visiting the ED. CONCLUSION: SSTI treatment considerations for antibiotic selection in the ED supported by current, evidence-based guidelines, including guidance on optimal oral antibiotic selection for patients discharged for outpatient treatment, are a useful tool to improve the quality and efficiency of care, enhance patient-centric outcomes and satisfaction, decrease healthcare costs, and reduce overuse of antibiotics.

Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Antibiotic resistance trends in high-risk lineages of Salmonella enterica serovar Typhi: A study spanning pre to post COVID-19 pandemic.

OBJECTIVES: The aim of this study was to understand the status of extensively drug-resistance (XDR) genotype in Salmonella enterica serotype Typhi (S. Typhi) recovered during the pre to post COVID-19 pandemic period using Multiplex PCR. METHODS: A longitudinal descriptive study was carried out during five years. Antibiotic susceptibility testing was performed according to the Clinical Laboratory Standards Institute antimicrobial susceptibility testing guidelines. The identification of S. Typhi, the detection of their high-risk lineages and XDR genotype was done using single nucleotide polymorphism-based multiplex PCR. RESULTS: A total of four hundred nine (n = 409) S. Typhi isolates were recovered during pre to post COVID-19 pandemic period. Among them, 30.81% belonged to the pre COVID-19 period while 69.19% to the post COVID-19 period. Different trends in antibiotic resistance in S. Typhi isolates with high prevalence of XDR-S. Typhi were observed. However, there was comparatively different frequency of their occurrence among the S. Typhi isolates recovered during pre to post COVID-19 pandemic period. Multiplex PCR showed that the majority of S. Typhi isolates were the H58 haplotype or genotype 4.3.1 which contained XDR genotype. CONCLUSIONS: The increasing episodes of XDR-S. Typhi causing typhoid fever in endemic areas is alarming. The antibiotic resistance in food and water borne pathogens greatly contribute to the dissemination of the antimicrobial resistance in pathogenic bacteria, which has now been considered as a global concern.

Coptis rhizome extract influence on Streptococcus pneumoniae through autolysin activation.

This study investigated the antibacterial properties of Coptis rhizome, a plant traditionally used for respiratory infections, against Streptoccus pneumonia (S. pneumoniae), for which there has been minimal empirical evidence of effectiveness. The study particularly examined autolysis, indirectly associated with antibacterial resistance, when using Coptis rhizome for bacterial infections. In our methodology, Coptis rhizome was processed with ethanol and distilled water to produce four different extracts: CRET30, CRET50, CRET70, and CRDW. The antibacterial activity of these extracts were tested through Minimum Inhibitory Concentration (MIC) assays, disk diffusion tests, and time-kill assays, targeting both standard (ATCC 49619) and resistant (ATCC 70067) strains. The study also evaluated the extracts' biofilm inhibition properties and monitored the expression of the lyt gene, integral to autolysis. The results prominently showed that the CRET70 extract demonstrated remarkable antibacterial strength. It achieved an MIC of 0.125 µg/mL against both tested S. pneumoniae strains. The disk diffusion assay recorded inhibition zones of 22.17 mm for ATCC 49619 and 17.20 mm for ATCC 70067. Impressively, CRET70 resulted in a 2-log decrease in bacterial numbers for both strains, showcasing its potent bactericidal capacity. The extract was also effective in inhibiting 77.40% of biofilm formation. Additionally, the significant overexpression of the lytA gene in the presence of CRET70 pointed to a potential mechanism of action for its antibacterial effects. The outcomes provided new perspectives on the use of Coptis rhizome in combating S. pneumoniae, especially significant in an era of escalating antibiotic resistance.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights.

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.

Repeated doxycycline treatment among patients with neuroborreliosis: a nationwide, population-based, registry-based, matched cohort study.

OBJECTIVES: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms. METHODS: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 106/l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5-85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9-6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7-1.3; ≥1 years HR 1.2, 95%CI: 0.9-1.5). CONCLUSIONS: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general.

Screening of Antimicrobial, Antibiofilm, and Cytotoxic Activities of Some Medicinal Plants from Balikesir Province, Türkiye: Potential Effects of Allium paniculatum Flower.

Objectives: Plant extracts are important natural resources that may have antimicrobial and antibiofilm effects against pathogens. This study was conducted to investigate the in vitro antimicrobial activities of methanol extracts of some medicinal plants (Achillea nobilis subspecies neilreichii (A. Kern.) Velen., Aetheorhiza bulbosa (L.) Cass, Allium paniculatum L, Asphodelus aestivus Brot., Ballota nigra L., Cistus laurifolius L., Cistus salviifolius L., Dioscorea communis (L.) Caddick and Wilkin, Galium verum L., Hypericum triquetrifolium Turra, Paliurus spina-christi Mill., Primula vulgaris Huds. subspecies rubra (Sm.) Arcang., Ranunculus arvensis L. and Teucrium polium L.) from Balikesir province in Türkiye. Materials and Methods: Preliminary antimicrobial activity screening was conducted for all extracts. Antibiofilm activity studies were conducted on mature Candida albicans biofilms. Moreover, the cytotoxicities of A. paniculatum flower extract on A549 and Vero cell lines were determined using a colorimetric tetrazolium-based assay. Results: A. paniculatum flower, P. vulgaris root, C. laurifolius, C. salviifolius, and A. nobilis displayed good activity [minimum inhibitory concentrations (MIC): 9.75, 156, 312, 312 and 312 µg/mL, respectively] against C. albicans American Type Culture Collection 10231. Biofilm studies were conducted on these plant extracts. The methanol extract of A. paniculatum flower decreased the number of C. albicans [colony-forming unit (CFU)/mL] in mature biofilm statistically at 32 x MIC and higher concentrations (p < 0.01). A. paniculatum flower extract had a cytotoxic effect (killing more than 50% of cells) at high concentrations, and its effect on Vero cells was similar to that on A549 cells. Conclusion: This study demonstrated the importance of the methanol extract of A. paniculatum flower as a natural alternative against C. albicans infections, including biofilms.

Intestinal biofilms: pathophysiological relevance, host defense, and therapeutic opportunities.

SUMMARYThe human intestinal tract harbors a profound variety of microorganisms that live in symbiosis with the host and each other. It is a complex and highly dynamic environment whose homeostasis directly relates to human health. Dysbiosis of the gut microbiota and polymicrobial biofilms have been associated with gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel diseases, and colorectal cancers. This review covers the molecular composition and organization of intestinal biofilms, mechanistic aspects of biofilm signaling networks for bacterial communication and behavior, and synergistic effects in polymicrobial biofilms. It further describes the clinical relevance and diseases associated with gut biofilms, the role of biofilms in antimicrobial resistance, and the intestinal host defense system and therapeutic strategies counteracting biofilms. Taken together, this review summarizes the latest knowledge and research on intestinal biofilms and their role in gut disorders and provides directions toward the development of biofilm-specific treatments.

Applications of machine learning on electronic health record data to combat antibiotic resistance.

There is growing excitement about the clinical use of artificial intelligence and machine learning technologies. Advancements in computing and the accessibility of machine learning frameworks enable researchers to easily train predictive models using electronic health record data. However, there are several practical factors that must be considered when employing machine learning on electronic health record data. We provide a primer on machine learning and approaches commonly taken to address these challenges. To illustrate how these approaches have been applied to address antimicrobial resistance, we review the use of electronic health record data to construct machine learning models for predicting pathogen carriage or infection, optimizing empiric therapy, and aiding antimicrobial stewardship tasks. Machine learning shows promise in promoting the appropriate use of antimicrobials, although clinical deployment is limited. We conclude by describing potential dangers of, and barriers to, implementation of machine learning models in the clinic.

Eradication Therapy for Helicobacter pylori Infection in Patients Receiving Hemodialysis: Review.

Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2-1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48-1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93-5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23-6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2-1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.

Chemical composition, cytotoxicity, antimicrobial, antibiofilm, and anti-quorum sensing potential of Mentha Piperita essential oil against the oral pathogen Streptococcus mutans.

Dental caries is a highly prevalent oral disease affecting billions of individuals globally. The disease occurs chemically as a result of breakdown of the tooth surface attributed to metabolic activity in colonizing biofilm. Biofilms, composed of exopolysaccharides and proteins, protect bacteria like Streptococcus mutans, which is notable for its role in tooth decay due to its acid-producing abilities. While various antimicrobial agents may prevent biofilm formation, these drugs often produce side effects including enamel erosion and taste disturbances. This study aimed to examine utilization of the Mentha piperita essential oil as a potential antibiofilm activity agent against S. mutans. M. piperita oil significantly (1) reduced bacterial biofilm, (2) exhibited a synergistic effect when combined with chlorhexidine, and (3) did not induce cell toxicity. Chemical analysis identified the essential oil with 99.99% certainty, revealing menthol and menthone as the primary components, constituting approximately 42% and 26%, respectively. Further, M. piperita oil eradicated preformed biofilms and inhibited biofilm formation at sub-inhibitory concentrations. M. piperita oil also interfered with bacterial quorum sensing communication and did not produce any apparent cell toxicity in immortalized human keratinocytes (HaCaT). M. piperita represented an alternative substance for combating S. mutans and biofilm formation and a potential combination option with chlorhexidine to minimize side effects. An in-situ performance assessment requires further studies.

Investigating the Variability among Indicators for Quantifying Antimicrobial Use in the Intensive Care Units: Analysis of Real-world Evidence.

This study investigated variability among four indicators for quantifying antimicrobial use in intensive care units (ICUs): defined daily doses (DDD), prescribed daily doses (PDD), duration of therapy (DOT), and length of therapy (LOT) and recommended the most clinically relevant approach. Retrospective data from patients who had received at least one antimicrobial was analyzed. Patients whose records were incomplete or expired were excluded. Duration of therapy (24433/1000 PDs) and LOTs (12832/1000 PDs) underestimated the overall consumption of antimicrobials compared with DDD of 28391/1000 PDs. Whereas PDD (46699/1000 PDs) overestimated it. Comparison analysis detected % differences of 13.94, 23.92, and 54.80% between DDD and DOT, DDD and PDD, and DDD and LOT, indicators respectively. Linear regression revealed stronger (r 2 = 0.86), moderate (r 2 = 0.50), and moderate (r 2 =0.60) correlation between DDD and DOT, DDD and PDD and DDD and LOT indicators respectively. According to findings, combining DOT and DDD is a more practical method to quantify antimicrobial consumption in hospital ICUs. How to cite this article: Deshwal PR, Tiwari P. Investigating the Variability among Indicators for Quantifying Antimicrobial Use in the Intensive Care Units: Analysis of Real-world Evidence. Indian J Crit Care Med 2024;28(7):662-676.

Antimicrobial use, residues and resistance in fish production in Africa: systematic review and meta-analysis.

In low- and middle-income countries, data on antimicrobial use (AMU) and antimicrobial resistance (AMR) in aquaculture are scarce. Therefore, summarizing documented data on AMU, antimicrobial residue (AR), and AMR in aquaculture in Africa is key to understanding the risk to public health. Google Scholar, PubMed, African Journals online, and Medline were searched for articles published in English and French following the PRISMA guidelines. A structured search string was used with strict inclusion and exclusion criteria to retrieve and screen the articles. The pooled prevalence and 95% confidence intervals were calculated for each pathogen-antimicrobial pair using random effects models. Among the 113 full-text articles reviewed, 41 met the eligibility criteria. The majority of the articles reported AMR (35; 85.4%), while a few were on AMU (3; 7.3%) and AR (3; 7.3%) in fish. The articles originated from West Africa (23; 56.1%), North Africa (8; 19.7%), and East Africa (7; 17.1%). Concerning the antimicrobial agents used in fish farming, tetracycline was the most common antimicrobial class used, which justified the high prevalence of residues (up to 56.7%) observed in fish. For AMR, a total of 69 antimicrobial agents were tested against 24 types of bacteria isolated. Bacteria were resistant to all classes of antimicrobial agents and exhibited high levels of multidrug resistance. Escherichia coli, Salmonella spp., and Staphylococcus spp. were reported in 16, 10, and 8 studies, respectively, with multidrug resistance rates of 43.1% [95% CI (32.0-55.0)], 40.3% [95% CI (24.1-58.1)] and 31.3% [95% CI (17.5-49.4)], respectively. This review highlights the high multidrug resistance rate of bacteria from aquaculture to commonly used antimicrobial agents, such as tetracycline, ampicillin, cotrimoxazole, gentamicin, and amoxicillin, in Africa. These findings also highlighted the lack of data on AMU and residue in the aquaculture sector, and additional efforts should be made to fill these gaps and mitigate the burden of AMR on public health in Africa.

Building an antimicrobial stewardship model for a public-sector hospital: a pre-implementation study.

Introduction. Antimicrobial resistance (AMR) is recognized as an important global health risk, associated with increased mortality, morbidity and healthcare costs. Antimicrobial stewardship (AMS) involves a coherent set of processes that promote the rational use of antimicrobials.Gap statement. An AMS programme should be adapted and developed according to the available resources of a facility. This requires an analysis of the core AMS elements that are already in place and the resources available.Aim. This study aimed to assess the readiness of a tertiary healthcare facility and staff towards implementing an antimicrobial stewardship programme (ASP).Methodology. This study focused on two aspects during an AMS pre-implementation phase. A situational or strengths, weaknesses, opportunities, and threats analysis was conducted based on (1) a questionnaire on attitudes and perceptions of pharmacists, clinicians and nurses towards AMR and AMS and (2) a situational analysis on the readiness of the facility.Results. The questionnaire, which was available for completion between September 2021 and December 2021, was sent to a total of 3100 healthcare professionals (HCPs). Thirty-two (1.0 %) HCPs comprising 2 pharmacists, 16 clinicians and 14 nurses completed the questionnaire. Of the total participants, 31 (96.9 %) viewed AMR as a problem in South African hospitals and 29 (90.6 %) perceived AMR as a problem at their facility. The majority (n = 29, 90.6 %) of the participants were familiar with the term AMS, and 26 (81.3 %) participants agreed to willingly participate in any initiatives involving antimicrobial use at the facility. The situational analysis depicted existing strengths in terms of AMS structures such as the formation of an AMS committee and information and technology systems at the HCP's disposal. Weaknesses included the limited number of AMS activities being carried out and poor participation from HCPs within the AMS team.Conclusion. A pre-implementation phase in the building of an ASP can greatly assist in finding gaps for improvement, which can then be addressed in the implementation phase. Furthermore, the pre-implementation phase provides a baseline to measure improvements once the implementation phase has been instituted.

Unlocking the Potential: PEGylation and Molecular Weight Reduction of Ionenes for Enhanced Antifungal Activity and Biocompatibility.

Numerous synthetic polymers, imitating natural antimicrobial peptides, have demonstrated potent antimicrobial activity, positioning them as potential candidates for new antimicrobial drugs. However, the high activity of these molecules often comes at the cost of elevated toxicity against eukaryotic organisms. In this study, a series of cationic ionenes with varying molecular weights to assess the influence of polymer chain length on ionene activity is investigated. To enhance polymer antimicrobial activity and limit toxicity a PEG side chain is introduced into the repeating unit. The resulting molecules consistently exhibited high activity against three model organisms: E. coli, S. aureus and C. albicans. The incorporation of side PEG chain improves antifungal properties and biocompatibility, regardless of molecular weight. The most important finding of this work is that the reduction of polymer molecular mass led to increased antifungal activity and reduced cytotoxicity against HMF and MRC-5 cell lines simultaneously. As a result, the best-performing molecules reported herein displayed minimal inhibitory concentrations (MIC) as low as 2 and 0.0625 µg mL1 for C. albicans and C. tropicalis respectively, demonstrating exceptional selectivity. It is plausible that some of described herein molecules can serve as potential lead candidates for new antifungal drugs.

Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies.

The rapid emergence and global spread of antimicrobial resistance in recent years have raised significant concerns about the future of modern medicine. Superbugs and multidrugresistant bacteria have become endemic in many parts of the world, raising the specter of untreatable infections. The overuse and misuse of antimicrobials over the past 80 years have undoubtedly contributed to the development of antimicrobial resistance, placing immense pressure on healthcare systems worldwide. Nonetheless, the molecular mechanisms underlying antimicrobial resistance in bacteria have existed since ancient times. Some of these mechanisms and processes have served as the precursors of current resistance determinants, highlighting the ongoing arms race between bacteria and their antimicrobial adversaries. Moreover, the environment harbors many putative resistance genes, yet we cannot still predict which of these genes will emerge and manifest as pathogenic resistance phenotypes. The presence of antibiotics in natural habitats, even at sub-inhibitory concentrations, may provide selective pressures that favor the emergence of novel antimicrobial resistance apparatus and, thus, underscores the need for a comprehensive understanding of the factors driving the persistence and spread of antimicrobial resistance. As the development of antimicrobial strategies that evade resistance is urgently needed, a clear perception of these critical factors could ultimately pave the way for the design of innovative therapeutic targets.

Revolutionizing Antibacterial Strategies: Lipid Nanoparticles as Game-Changers in Combatting Multi-Drug-Resistant Infections.

To overcome the limits of traditional antibiotic medications, novel approaches are needed to combat the growing global epidemic of Multidrug-resistant (MDR) infections. As drug-resistant bacteria develop, the importance of innovative antimicrobial methods is underscored by antibiotic abuse and misuse. The global threat of MDR microorganisms is increasing, which calls for a coordinated global response. Lipid Nanoparticles (LNPs) possess several characteristics that make them attractive choices for managing multidrug resistant (MDR) infections, as well as potential delivery systems for antimicrobial agents. Thus, LNPs improve drug solubility, stability, and targeted delivery, thereby mitigating the drawbacks of conventional antibiotic therapy. Several characteristics of LNPs, which stop MDR bacteria from developing resistance mechanisms, serve as guidelines for precision medicine. It presents a powerful approach for combating the growing concern of MDR bacteria by increasing Anti-Microbial Peptides (AMPs) bioavailability and targeting distribution to bacterial cells. LNPs have the potential to redefine antibacterial treatments for MDR illnesses in the context of this study. Further, it discusses LNP use in larger applications, such as fighting Anti-Microbial Resistance (AMR) and MDR. A complete understanding of the unique features, many uses, and importance of collaborative efforts to overcome the global challenge of antibiotic resistance are also conveyed in the study.