Frontiers in antibiotics最新文献

The rise in antimicrobial resistance and the decline in new antibiotics has created a great need for novel approaches to treat drug resistant bacterial infections. Increasing the burden of antimicrobial resistance, bacterial virulence factors allow for survival within the host, where they can evade host killing and antimicrobial therapy within their intracellular niches. Repurposing host directed therapeutics has great potential for adjuvants to allow for more effective bacterial killing by the host and antimicrobials. To this end, phosphoinositide 3-kinase inhibitors are FDA approved for cancer therapy, but also have potential to eliminate intracellular survival of pathogens. This review describes the PI3K pathway and its potential as an adjuvant target to treat bacterial infections more effectively.

Antibiotic resistance is a major danger to public health that threatens to claim the lives of millions of people per year within the next few decades. Years of necessary administration and excessive application of antibiotics have selected for strains that are resistant to many of our currently available treatments. Due to the high costs and difficulty of developing new antibiotics, the emergence of resistant bacteria is outpacing the introduction of new drugs to fight them. To overcome this problem, many researchers are focusing on developing antibacterial therapeutic strategies that are "resistance-resistant"-regimens that slow or stall resistance development in the targeted pathogens. In this mini review, we outline major examples of novel resistance-resistant therapeutic strategies. We discuss the use of compounds that reduce mutagenesis and thereby decrease the likelihood of resistance emergence. Then, we examine the effectiveness of antibiotic cycling and evolutionary steering, in which a bacterial population is forced by one antibiotic toward susceptibility to another antibiotic. We also consider combination therapies that aim to sabotage defensive mechanisms and eliminate potentially resistant pathogens by combining two antibiotics or combining an antibiotic with other therapeutics, such as antibodies or phages. Finally, we highlight promising future directions in this field, including the potential of applying machine learning and personalized medicine to fight antibiotic resistance emergence and out-maneuver adaptive pathogens.

Introduction: Globally, the demand for animal protein for human consumption has beenQ7 Q6increasing at a faster rate in the last 5 to 10 decades resulting in increasedantimicrobial consumption in food producing animals. Antimicrobials arefrequently used as part of modern methods of animal production, which mayput more pressure on evolution of antibiotic resistant bacteria. Despite theserious negative effects on animal and human health that could result fromusing antibiotics, there are no assessment of antimicrobials consumed by thelivestock sector in Fiji as well as other Pacific Island Countries. The objective ofthis study was to quantify antimicrobials imported for consumption in foodanimals into Fiji from 2017 to 2021.

Methods: Data on imported antimicrobials, whichwere finished products, was obtained from Biosecurity Authority Fiji (BAF).Imported antimicrobials were then analyzed by antimicrobial class, andimportance to veterinary and human medicine.

Results: An average of 92.86 kg peryear (sd = 64.12) of antimicrobials as a net weight was imported into Fiji in the2017-2021 study period. The mean amount of imported active antimicrobialingredients after adjusting for animal biomass was 0.86 mg/kg (sd = 0.59). Fromthe total antimicrobial imports during the years 2017 to 2021, penicillins(69.72%) and tetracycline (15.95%) were the most imported antimicrobialclasses. For animal health 96.48% of the antimicrobial imports wereveterinary critically important antimicrobials. For human healthfluroquinolones, macrolides, aminoglycosides, and penicillins were theimported critically important antimicrobials.

Discussion: The study concluded that use ofantimicrobials in food producing animals is low but monitoring of antimicrobialconsumption and antimicrobial resistance was critical in Fiji due to overrelianceon critically important antimicrobials.

Background: Antimicrobial resistance (AMR) has emerged as a leading global health and economic threat of the 21st century, with Africa bearing the greatest burden of mortality from drug-resistant infections. Optimization of the use of antimicrobials is a core strategic element of the response to AMR, addressing misuse and overuse as primary drivers. Effectively, this requires the whole society comprising not only healthcare professionals but also the public, as well as the government, to engage in a bottom-up and a top-down approach. We determined the progress of African national governments in optimizing antimicrobial drug use.

Methods: From September 2021 to June 2022, all 47 member states of the World Health Organization African region (WHO AFRO) were invited to participate in a survey determining the implementation of strategies to optimize antimicrobial use (AMU). We used the WHO antimicrobial stewardship (AMS) assessment tool, National core elements-A checklist to guide the country in identifying existing national core elements for the implementation of AMS Programs, to obtain information from national AMR focal persons. The tool consists of four sections-national plans and strategies; regulations and guidelines; awareness, training, and education; and supporting technologies and data-with a total of 33 checklist items, each graded from 0 to 4. The responses were aggregated and analyzed using Microsoft Excel 2020^®.

Results: Thirty-one (66%) of the 47 countries returned completed forms. Only eight (25.8%) countries have developed a national AMS implementation policy incorporating defined goals, targets, and operational plans. There are no budget lines for AMS activities in 23 (74.2%) countries. The WHO Access, Watch, Reserve (AWaRe) classification of optimizing AMU has been integrated into the national essential medicines list or formulary in 19 (61.3%) countries, while the incorporation of the AMS principles and WHO AWaRe classification into national clinical guidelines for the management of infections is present in only 12 (38.7%) and 11 (34.5%) countries, respectively. Although regulations on the prescription-only sale/dispensing of antibiotics are present in 68% of countries, their enforcement is poor. Systems identifying pathogens and antibiotic susceptibility for optimal use of antibiotics are lacking in 38% of countries.

Conclusion: In Africa, wide gaps exist in the governments' implementation of the core elements of optimizing antimicrobial drug use. Responding to AMR constitutes a long journey, and technical and financial support needs to be deployed to optimize the use of antimicrobials.

Of all animal derived-food, the demand for poultry meat is the most dynamic. The poultry sector can meet this demand only by introducing intensive production where antimicrobial use is inevitable. Bacterial infection prevention and control is an important factor in intensive livestock production. Antibiotics are an effective and relatively inexpensive means of preventing and controlling infections, thus maintaining animal health and productivity. The aim of this study was to gain insight into the costs and benefits of various scenarios of antimicrobial use reduction at broiler farms in Dar es Salaam, Tanzania. This study focused on the economic impact of an average broiler farm. Costs and benefits for various scenarios of antimicrobial use reduction levels were projected by a partial budget framework using the Mclnerney model. The disease cost of the current situation was US$225. On reduction of antimicrobial use by 20% the avoidable disease cost was US$ 31, by 50% was US$ 83 and by 100% was US$ 147. A reduction in antibiotic use can only be achieved if better alternatives are available to combat disease. In conclusion, the model predicts that reducing antibiotic use increases production costs. Future studies on antimicrobial use reduction's impact on morbidity and mortality and the efficiency of additional control and other measures of producing poultry meat without high concentrations of antibiotics are necessary.

Antimicrobial resistance (AMR) is a significant threat to global public health. Specifically, excessive usage of antimicrobials in food animal production is one significant reason for AMR development in humans. Therefore, it is essential to identify the trends of AMR in fish and poultry and develop better surveillance strategies for the future. Despite this imperative need, such information is not well documented, especially in Africa. This study used a systematic review to assess AMR trend, spatial distribution, and incidence in fish and poultry research in Nigeria, Egypt, and South Africa. A literature assessment was conducted for published studies on AMR between 1989 and 2021 using the Scopus and Web of Science databases. One hundred and seventy-three relevant articles were obtained from the database search. Egypt was the leading exponent of antimicrobial resistance research (43.35%, 75 studies), followed by Nigeria (39.31%, 68 studies), then South Africa (17.34%, 30 studies). The majority of the antimicrobial resistance studies were on poultry in Egypt (81%, 61 studies), Nigeria (87%, 59 studies), and South Africa (80%, 24 studies). Studies on fish were 17% (13 studies), 9% (6 studies), and 10% (3 studies) in Egypt, Nigeria, and South Africa, respectively. Antimicrobial resistance patterns showed multiple drug resistance and variations in resistant genes. AMR research focused on sulfamethoxazole groups, chloramphenicol, trimethoprim, tetracycline, erythromycin, and ampicillin. Most studies employed the disk diffusion method for antimicrobial susceptibility tests. Among the four mechanisms of AMR, limiting drug uptake was the most reported in this study (both in fish and poultry). The findings reveal public and environmental health threats and suggest that it would be useful to promote and advance AMR research, particularly for countries on the global hotspot for antimicrobial use.

Enterococci are a normal flora of the gastrointestinal tracts of humans and animals. Enterococci can also cause life-threatening nosocomial infections. Antimicrobial-resistant Enterococcus species have been reported in the feedlot and dairy cattle productions and in meat and milk products, suggesting their foodborne importance. Cow-calf operations represent a significant segment in the beef production system by producing weaned calves. Weaned calves are brought into the feedlot to be finished for meat, and culled cows are also slaughtered for beef, primarily for ground beef products. Infection dynamics in the cow-calf operation can contribute to meat contamination. This study evaluated the effects of age and wheat grazing on the concentration and prevalence of a macrolide antibiotic erythromycin (ERY^r) and tetracycline (TET^r) resistant enterococci, associated resistance genes and species distribution in a cow-calf production system. In 2017 and 2018, 32 Angus breed cow-calf pairs were randomly assigned to feed on tall fescue or wheat pasture in two independent field experiments. During the grazing experiments of 2-3 weeks, fecal samples were collected weekly and cultured to enumerate, isolate and identify ERY^r, TET^r, and generic enterococci, using media supplemented with erythromycin, tetracycline or non-supplemented media, respectively. The two main species frequently associated with human illnesses, Enterococcus faecium and E. faecalis, were widely distributed in the cow-calf groups. Generic and TET^r- enterococci were prevalent (96-100% prevalence) and abundant (3.2-4.9 log₁₀ CFU/g) in the cow-calf population; however, ERY^r enterococci were enumerable by direct plating only from a single cow despite being detected in at least 40% of the fecal samples after enrichment, showing their low abundance. TET- and ERY-resistance were mainly conferred by tet(M) and erm(B), respectively. Wheat grazing reduced the concentration of TET^r enterococci and modified enterococcal species and resistance gene distributions. Hence, it is necessary to further investigate wheat grazing in cow-calf production as a potential strategy to mitigate antimicrobial resistance.

Antibiotic resistance causes higher morbidity and mortality and higher healthcare costs. One of the factors influencing the emergence of antibiotic resistance is the inappropriate use of antibiotics. Clinical practitioners' incorrect prescription patterns and a disregard for antibiotic usage recommendations are the leading causes of this resistance. This study examined the antibiotic prescription patterns among hospitalized patients at the Kiambu Level 5 hospital (KL5) to find potential for hospital quality improvement. This study was conducted in July 2021, and all patients hospitalized on the study day were included. The information was extracted from patient medical records using a World Health Organization Point Prevalence Survey (PPS) instrument. Anonymized data was gathered, entered, and then SPSS version 26 was used for analysis. Among the 308 surveyed patients, 191 (62%) received antibiotic medication, and 60.1% of the total were female. The pediatric ward, which had an antibiotic prescription rate of 94.1%, had the highest rate of antibiotic usage, followed by the medical ward (69.2%) and gynecological ward (65.6%). Over 40% of antibiotic prescriptions had a prophylactic medical indication. Penicillin G was the most prescribed antibiotic for community-acquired infections (32.2%), followed by 3rd generation cephalosporins (27.6%) and aminoglycosides (17.2%). Based on the AWaRe classification, 57% of the prescribed antibiotics were in the Access class while 42% were in the Watch class. Incomplete site of indication, lack of a method of administration, and length of administration are some of the conformities that were missing in the medical records. This study shows that antibiotic prescription rates are high, particularly for young patients, and there is a higher risk of antibiotic misuse. The data makes a compelling justification for using antibiotic stewardship practices in Kenyan hospitals.

A healthy development is denied to millions of children worldwide as harsh life conditions manifest themselves in an altered inflammation-prone microbiome crosstalk environment. Keynote of this tragedy is that insufficient nutritious amino acid blocks lipids-intake to sustain diverse microbiota, and promotes the generalist strategy followed by Escherichia coli -besides other proteobacteria- of shifting gut metabolism, subverting the site specificity of first immune reaction. Furthermore, it could be hypothesized that selective success lies in their ability to induce inflammation, since this phenomenon also fuels horizontal gene transfer (HGT). In this review, we dilucidate how immune mechanisms of environmental enteric dysfunction affect overgrowth restriction, infectious morbidity rate, and acquired lifelong risks among severe acute malnourished children. Also, despite acknowledging complexities of antimicrobial resistant enrichment, we explore and speculate over the links between virulence regulation and HGT as an indissociable part in the quest for new inflammatory niches by open genome bacteria, particularly when both collide in the most vulnerable.

The increasing global expansion of antimicrobial resistant infections warrants the development of effective antibiotic alternative therapies, particularly for use in livestock production, an agricultural sector that is perceived to disproportionately contribute to the antimicrobial resistance (AMR) crisis by consuming nearly two-thirds of the global antibiotic supply. Probiotics and probiotic derived compounds are promising alternative therapies, and their successful use in disease prevention, treatment, and animal performance commands attention. However, insufficient or outdated probiotic screening techniques may unintentionally contribute to this crisis, and few longitudinal studies have been conducted to determine what role probiotics play in AMR dissemination in animal hosts and the surrounding environment. In this review, we briefly summarize the current literature regarding the efficacy, feasibility, and limitations of probiotics, including an evaluation of their impact on the animal microbiome and resistome and their potential to influence AMR in the environment. Probiotic application for livestock is often touted as an ideal alternative therapy that might reduce the need for antibiotic use in agriculture and the negative downstream impacts. However, as detailed in this review, limited research has been conducted linking probiotic usage with reductions in AMR in agricultural or natural environments. Additionally, we discuss the methods, including limitations, of current probiotic screening techniques across the globe, highlighting approaches aimed at reducing antibiotic usage and ensuring safe and effective probiotic mediated health outcomes. Based on this information, we propose economic and logistical considerations for bringing probiotic therapies to market including regulatory roadblocks, future innovations, and the significant gaps in knowledge requiring additional research to ensure probiotics are suitable long-term options for livestock producers as an antibiotic alternative therapy.