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Catalytic Production of Erythromycin Against COVID-19
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The outbreak of COVID-19 and the need to alleviate the virus’s symptoms prompted the scientific community to explore alternative treatment methods, aiming to surpass the effectiveness of traditional medicine. This study examines the overall structure and catalytic mechanism of erythromycin’s synthesis, as well as its industrial production, emphasizing its value against infectious diseases like COVID-19. Key points include the discovery of erythromycin, its broad clinical applications, and the pivotal role of P450eryF in its production. The significance of erythromycin and its biosynthesis catalyst, P450eryF, has led to collaboration between many countries with the World Health Organization (WHO) and the health industry. Between 2011 and 2021, erythromycin production increased globally. In particular, in Asia, South America, and Africa, the exportation of erythromycin antibiotics rose during the COVID-19 outbreak. In 2021, China was the top exporter of erythromycin (USD 185 M). Meanwhile, the leading importers were India (USD 104 M), with Japan and Croatia following. In the same decade, 60,046 erythromycin-related patents were published worldwide, with the U.S. holding the largest share at 36.88%. This analysis utilizes current production rates and published patents to review the latest statistics, highlighting global collaboration in erythromycin’s production and its critical role in addressing global health challenges, as it remains a crucial antibiotic for treating diverse infectious diseases.

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A Survey of Antimicrobial Usage/Consumption in Animal Production: a Cross-Sectional Study of Kaduna Metropolis, Nigeria
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BACKGROUND: The use of antimicrobials in animals is a global practice against infections and for the enhancement of productivity. This study was aimed at monitoring antimicrobial usage/consumption (AMU/AMC) in animal production in Kaduna metropolis. Measuring AMU in animal production can provide useful data for monitoring AMU over time, which will assist in setting benchmarks to promote antimicrobial resistance (AMR) reduction.

METHOD: This study involved the daily collation and validation of active primary drug sales and prescription data from thirty-two veterinary pharmaceutical outlets and clinics out of forty-one (41) pre-identified points within Kaduna metropolis (78%) over a 12-week period.

RESULTS: Classes and types of antimicrobials that were identified included macrolides, quinoxalines, polypeptides, streptogramins, glycolipids, oligosaccharides, phosphonic acids, and polymeric compounds. In total, 83.7% of the identified antimicrobials were in the forms of oral medication, and most were registered antibiotics (52.8%). Parenteral and topical forms were also identified, with 94% also being antibiotics. The estimated AMU/AMC was 282mg/kg population correction unit (PCU). Poultry were the most significant population, constituting 99% (31,502,004) of the study population. The class-specific AMU/AMC was antibiotics, with 274mg/kg PCU (with the terramycines constituting 24.1%). The antiprotozoal AMU/AMC was 418mg/kg PCU, of which triazenetriones (17.1%) were mainly applied in the treatment of coccidia infections. The anthelminthic AMU/AMC was the highest at 576mg/kg PCU, with albendazole, piperazine, and levamisole being the most commonly used. These constituted 95.8% of the volume of anthelminthics and 16.5% of the volume of antimicrobials that were used in animals in the study. Oxytetracycline had the highest sale/usage for a single active agent at 9.6% of the volume.

CONCLUSION: This study has provided useful and practical information on the trends in antimicrobial usage in animals, with poultry being the most important animal population involved in AMU/AMC and oxytetracycline being the most abused antibiotic in animal production. Antimicrobial stewardship (AMS) should be targeted at poultry populations, with an emphasis on reducing antibiotic usage/consumption.

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Prescribing Patterns and the Pharmacoeconomic Evaluation Of Antibiotics in the Pediatric Population Of A Tertiary Care Teaching Hospital—A Prospective, Observational Study

Background: Antibiotics are the most commonly prescribed drugs in pediatrics, which focuses on the medical treatment of newborns, children, and adolescents. Understanding and monitoring antibiotic prescribing patterns are crucial to ensuring their appropriate use, maximizing their benefits and minimizing harm. Cost minimization analysis is an effective tool for evaluating cost-effective strategies in pediatric healthcare. Methodology: This prospective observational study was conducted over ten months at Parul Sevashram Hospital, Vadodara, Gujarat. Following institutional ethics committee approval, 155 participants were enrolled based on the study-specific inclusion criteria. Data collected from the participants were evaluated against the WHO core prescribing indicators. A cost minimization analysis was performed on the antibiotic data. Statistical analyses were conducted using MS Excel and GraphPad Prism, and the findings were presented through percentages, tables, and graphical formats. Results: Our study involving 155 participants at Parul Sevashram Hospital, Vadodara, observed a higher proportion of males (65.16%) compared to females (34.84%). Most of the participants were aged 2 to 11 years (60.65%). Amoxicillin and Potassium Clavulanate were the most commonly prescribed antibiotics, with E. Coli being a prevalent pathogen. Polypharmacy was evident, with an average of 10.87 medications per prescription and many patients receiving more than three antibiotics. Injectable antibiotics were frequently used, though generic prescribing was below the WHO recommendations. The cost analysis revealed a significant price difference of 26% between the prescribed brands (INR 572,929.14/USD 6,851.20) and the suggested brands (INR 425,329.61/USD 5,086.05). This highlights the importance of cost-effective antibiotic choices. Conclusion: This study analyzed the antibiotic use in pediatric patients, focusing on the WHO's core indicators and pharmacoeconomic factors. It highlights polypharmacy and the prevalence of parenteral antibiotic treatment. Despite using generic names, the hospital does not meet the WHO's recommended range of antibiotics. A cost minimization analysis revealed significant differences between the prescribed and suggested brand formulations, highlighting opportunities for cost savings through generic or recommended substitutes.

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Biofilm Formation and Antibiotic Resistance in Pseudomonas Aeruginosa Isolated From Blood and Cerebrospinal Fluid of Children
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Background: Gram-negative bloodstream and central nervous system infections in children in intensive care units are among the most dangerous complications, leading to complications in therapy and often to fatal outcomes.

Aim: We aimed to determine antibiotic resistance, the ability to form biofilms on abiotic surfaces, and biofilm formation genes.

Methods: Antibiotic sensitivity was determined by a broth microdilution method; biofilms were grown in polystyrene plates, followed by fixation, staining, and elution, and biofilm formation genes were determined by PCR.

Results: During the period from 2014 to 2023, we studied 34 isolates of P. aeruginosa, isolated from the blood and cerebrospinal fluid of children. Resistance to carbapenems was 76%, to aminoglycosides and fluoroquinolones it was 68%, to aztreonam it wa 26%, and to protected cephalosporins it was 74%. All strains were sensitive to colistin. When determining the resistance phenotype, we identified 35% of multi-drug-resistant (MDR) isolates and 38% of extremely drug-resistant (XDR) isolates. When studying the ability to form biofilms, we determined that the majority formed high-intensity (47%) and moderate-intensity (32.5%) biofilms, while 20.5% of isolates formed low-intensity biofilms. It is noteworthy that isolates with moderate biofilm formation ability were mostly MDR (5/11), while isolates with high biofilm formation ability were more often XDR (8/16).

Genes responsible for biofilm formation, pilA and pilB, were identified in 12% and 41% of 34 isolates, respectively. Moreover, they were most often found in isolates with high and moderate biofilm-formation ability.

Conclusion: We found widespread resistance to antibiotics, especially carbapenems and protected cephalosporins. The intensity of biofilm formation correlated with the resistance of isolates. Genes responsible for biofilm formation were more often found in isolates with high and moderate biofilm formation.

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Antimicrobial Susceptibilities of Salmonella and Shigella species isolates in stool culture in British Columbia, Canada, 2020-2023
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Introduction: Hospital microbiology laboratories do not routinely allow for testing for community gastrointestinal stool pathogens in hospitalized patients who develop diarrhea after day 3 of hospitalization. In contrast, community microbiology laboratories routinely collect data on gastrointestinal stool pathogens, including their antimicrobial susceptibility profiles. To assist community antimicrobial stewardship, the current study aimed to summarize the susceptibilities of Salmonella and Shigella isolates in stool cultures performed in regional community microbiology laboratories in British Columbia (BC), Canada.

Methods: LifeLabs BC microbiology laboratories, connected with 129 collection centres in urban and rural communities in the province, provided the laboratory data for the Salmonella and Shigella species that were isolated in stool cultures. An audit was conducted from January 1, 2020, to December 31, 2023.

Results:

Table 1: Antimicrobial Susceptibilities of Salmonella and Shigella species isolates in stool culture in British Columbia, Canada, 2020-2023

https://drive.google.com/file/d/1sA8xTisYM553KEtKpLtFiPi1z00R8kqH/view?usp=sharing

(Results could be skewed for antibiotic susceptibility results with <30 isolates.)

Conclusion: Salmonella Paratyphi A and Salmonella Typhi isolates in stool were universally susceptible to ampicillin, trimethoprim-sulfamethoxazole, azithromycin, and ceftriaxone. Choosing an oral antimicrobial agent for Shigella species is a challenge, as the sensitivities of oral agents were <50%. However, Shigella boydii, Shigella flexneri, and Shigella sonnei were >80% susceptible to intravenous ceftriaxone.

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Immersive Technologies in Healthcare: Virtual Reality's Role in Addressing Antibiotic Resistance
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Antibiotic resistance is an escalating global public health issue that requires innovative strategies for reduction. Virtual reality (VR) is being utilised as a cutting-edge technology for medical training, patient education, and drug development. In this study, we aimed to review the role of VR in combating antibiotic-resistant infections by improving antibiotic administration, infection control methods, and surgical plans for resistant infections. VR-based simulations provide medical professionals with authentic training environments to improve their clinical decision-making and avoid antibiotic abuse. VR-inspired health-tech helps model bacterial resistance and new drug candidates, optimizing the antibiotic detection process. The combination of virtual reality (VR) with artificial intelligence (AI) and big data analytics enables real-time diagnosis, personalized treatment planning, and precision medicine. Additionally, using VR in public health initiatives improves patients' compliance with infection control measures. It has great potential but also drawbacks, such as high cost, availability issues, and the need to validate interventions affected by VR. The current review provides a perspective on the latest advances, challenges, and future methods for the implementation of VR in the treatment of infectious diseases. The use of VR can change the way in which we fight antibiotic resistance and pave the way for improved and more sustainable health solutions around the world.

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Bio-absorbable Antibiotic Beads for Vascular Graft Infection Management: Challenges and Future Prospects
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Vascular stenosis and occlusion are the key causes of cardiovascular diseases, which are major contributors to global mortality. Surgical revascularization remains one of the most sought-after treatment options for long-term vessel restoration. However, surgical site infections pose serious concerns, especially when synthetic scaffold materials are in use. Bio-absorbable antibiotic beads represent a promising solution to combat vascular graft infections. These beads facilitate localized delivery of high antibiotic dosages, leading to minimized systemic toxicity with targeted therapeutic effects. This review aims to evaluate the strength of evidence concerning the efficacy of antibiotic beads for vascular intervention. A comprehensive literature search across PubMed, MedlinePlus, and Embase identified relevant studies while excluding conventional surgical interventions. Modern alternatives, i.e., silver-coated grafts and stem cell therapy, were also excluded. Polymethyl methacrylate (PMMA) beads were the most commonly used formulation, with growing interest in biodegradable formulations such as calcium sulfate beads. The search strategy included keywords such as “Vascular Surgery,” “Vascular Grafts,” “Vascular Graft Infections,” and “Antibiotic Beads.” Evidence indicates that bio-absorbable antibiotic beads could be highly beneficial in vascular surgery for infection prevention and to reduce systemic complications. Future studies should focus on the effectiveness of beads based on different microbial factors to attain the best possible outcomes.

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Correlation between use of antibiotics and prevalence of resistant strains of coagulase-positive staphylococci (S. aureus) in dairy farms in Apulia (Southern Italy)
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The spread of multidrug-resistant bacteria is a concerning problem worldwide. This preliminary study investigated the correlation between antibiotic consumption and the antimicrobial resistance trends of coagulase-positive Staphylococci (S. aureus) in raw milk from 154 dairy farms located in two provinces of the Apulia region in Southern Italy: Bari and Taranto.
Data concerning antibiotic consumption expressed in DDDAit (Defined Daily Dose Animal for Italy) were extracted from the VETINFO portal. Data on antibiotic resistance (percentage of antibiotic-intermediate or -resistant isolates) were obtained from raw milk analysis performed at the laboratory of the Istituto Zooprofilattico Sperimentale di Puglia e Basilicata, Putignano (BA).
The data collected suggest a strong correlation between the quantities of some antibiotics used (i.e. penicillins, aminoglycosides, cephalosporins, macrolides, lincosamides, fluoroquinolones and third-generation cephalosporins) and the prevalence of Staphylococcus aureus strains resistant to the molecules used (i.e. oxacillin, ampicillin, penicillin, amoxicillin/clavulanic acid, rifampicin, kanamycin, gentamicin, cefazolin, erythromycin, pirlimycin, enrofloxacin and ceftiofur). These data are in agreement with a previous study by Parisi et al. (2016) and may indicate a possible positive correlation between the use of antibiotics and the development of antibiotic resistance. This study, although preliminary, must be interpreted in the broader context of safeguarding public health: the presence of antimicrobial-resistant bacteria in dairy products, particularly those produced from raw milk, poses a potential risk of infection and/or colonization for humans, with limited treatment options and complications in treatment outcome. The overall data present a discrete indicator of antibiotic use and resistance patterns in Apulian dairy farms. A continued review of databases and a more rigorous use of antimicrobials therefore appear critical to minimizing the risk of the emergence of resistant organisms.

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Artificial Intelligence in Antibiotic Stewardship: Optimising Prescribing Processes and Overcoming Ethical Challenges

The overuse and misuse of antibiotics increases antibiotic resistance (AMR), limiting treatment options and placing a major economic and clinical burden on healthcare systems (Ribers & Ullrich, 2019) (Price, 2016). According to WHO/ECDC's 2023 report, resistance to broad-spectrum beta-lactam antibiotics has reached critical levels in Europe. In the United States, more than 2.8 million resistant infections occur each year, and more than 35,000 people die. If no measures are taken, it is estimated that AMR-related deaths will reach 10 million annually by 2050. Against this threat, artificial intelligence (AI)-based clinical decision support systems (CDSSs) offer an innovative approach to optimise antibiotic prescribing processes. By analysing patient data, microbial profiles, and local antibiotic resistance patterns, personalised and targeted antibiotic recommendations can be provided (Ribers & Ullrich, 2019) (Tran et al., 2022). However, AI-assisted prescribing systems should not only improve the technical efficiency, but also comply with ethical principles. The utilitarian approach is proposed as the most appropriate ethical framework, as it aims to minimise the development of resistance while maximising patient benefit (Bolton et al., 2022). WHO launched the ‘Antimicrobial Resistance (AMD) Call to Action’ in 2021, accelerating the global response with the participation of 113 countries and 38 organisations. With the lessons of COVID-19, the WHO and the UN have identified AMR as a ‘Silent Tsunami’ and committed to take measures under the 2030 Agenda for Sustainable Development. As a result, AI-based strategies have great potential in combating antibiotic resistance (Pascucci et al., 2021). AI-powered systems can protect public health by reducing unnecessary antibiotic use. However, transparency, ethical standards, and regulatory frameworks are required for its successful implementation. Future research can contribute to sustainable antibiotic stewardship by improving the accuracy of AI models.

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Environmental dissemination of multidrug-resistant Klebsiella spp.: evidence from genomic surveillance of surface water

Klebsiella spp. are opportunistic pathogens capable of acquiring antimicrobial resistance genes, posing a public health concern. Surface water can act as a reservoir for resistant bacteria, facilitating their dissemination in the environment. This study aimed to identify Klebsiella species in surface water and characterize their antimicrobial resistance and virulence profiles through whole-genome sequencing.

Water samples were collected from 77 sites in the Douro River Basin, Portugal, including rivers, streams, wells, and fountains. Water was filtered through a 0.45 μm membrane and incubated in BHI broth at 37°C for 24 h. Cultures were plated on Chromogenic Coliform Agar and subcultured on HiChrome Klebsiella Selective Agar. Purple colonies were subcultured on BHI agar and identified by MALDI-TOF MS. Antimicrobial susceptibility was evaluated using the Kirby–Bauer disk diffusion method, while whole-genome sequencing was conducted to identify resistance and virulence genes, along with clonal lineages.

Out of the 77 samples, 21 (27.3%) Klebsiella spp. were isolated. Among the isolates, thirteen K. pneumonia, five K. aerogenes, two K. michiganensis, and one K. oxytoca were identified. Among K. pneumoniae, blaCTX-M-15, blaTEM-1, blaSHVvariants, and blaKPC-3 (3/13) were detected. Aminoglycoside resistance genes (aph(3'')-Ib, aph(6)-Id) and fluoroquinolone resistance genes (qnrB1, qnrS1) were present. All isolates carried fosA and heavy-metal resistance genes (sil, pco). Regarding the molecular typing, K. pneumoniae isolates belonged to a wide ranges of sequence types, including ST34, ST716, ST45, ST198, ST39, ST234, ST276, ST422, ST6, and ST37, while K. oxytoca was ascribed to ST155. K. aerogenes harbored ampC, fosA9, and efflux pump regulators (ramA, marA, baeR). K. michiganensis carried blaOXY-1, fosA, and qnrS1 (1/2), while K. oxytoca had blaOXY-2-8, fosA, and oqxA/B efflux genes.

These findings highlight the presence of multidrug-resistant Klebsiella species in surface water, emphasizing the potential role of aquatic environments in the dissemination of antimicrobial resistance genes.

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