抗生素耐药防控的One Health策略

抗生素耐药作为威胁公共卫生的巨大挑战已经制约了世界经济发展。我国抗生素使用量大,是世界上抗生素滥用最严重的国家之一。文中对人群、食用动物、环境中抗生素耐药产生的原因以及抗生素耐药现状进行综述,针对我国目前抗生素使用与耐药情况,从One Health理念提出了促进抗生素的科学使用、积极探索新型抗生素研发、建立抗生素立体监测网络系统、推广抗生素耐药教育、预防感染等措施,呼吁建立跨学科、跨部门、跨地域的交流与合作,推进我国抗生素耐药防控工作进一步开展,加强环境保护,维护人类与动物的共同健康。     

Qualitative analysis of models with different treatment protocols to prevent antibiotic resistance

This paper is concerned with the qualitative analysis of two models [S. Bonhoeffer, M. Lipsitch, B.R. Levin, Evaluating treatment protocols to prevent antibiotic resistance, Proc. Natl. Acad. Sci. USA 94 (1997) 12106] for different treatment protocols to prevent antibiotic resistance. Detailed qualitative analysis about the local or global stability of the equilibria of both models is carried out in term of the basic reproduction number R₀. For the model with a single antibiotic therapy, we show that if R₀ < 1, then the disease-free equilibrium is globally asymptotically stable; if R₀ > 1, then the disease-endemic equilibrium is globally asymptotically stable. For the model with multiple antibiotic therapies, stabilities of various equilibria are analyzed and combining treatment is shown better than cycling treatment. Numerical simulations are performed to show that the dynamical properties depend intimately upon the parameters.     

Correlation of in vitro and in vivo resistance development to antimicrobial agents

Preclinical in vitro and in vivo determinations of the likelihood of an antibiotic to develop resistance can and has proven predictive of their likelihood of resistance development in patients. Problematic antibiotic/bacterial species combinations are often associated with high frequencies of single-step resistance development in that species. Thus, treatment of organisms with rapid in vitro emergence of drug resistance should be monitored carefully. In vitro studies, however, are limited in predicting resistance mediated through acquisition of a resistance plasmid.The frequency of resistance development to a drug is dependent on factors such as the drug used for selections, the concentration (i.e., dosing) of the drug, the bacterium, and the site of infection. Organisms intrinsically less susceptible to an antibiotic develop resistance rapidly due to their low therapeutic ratios. Since cross-resistance often occurs within an antibiotic class, it may be desirable to initiate therapy with a drug with low resistance-selecting potential. Optimal dosing regimens are especially critical when treating bacterial species likely to develop drug resistance. Though combination drug therapies have proven affective in experimental animal infections and in man, they do not prevent resistant variants from emerging. Understanding of drug-resistance development will contribute to our management of infectious diseases.     

The derivation of theoretical resistance mechanisms to antibacterial agents

The elucidation of molecular mechanisms whereby bacterial cells become resistant to the inhibitory effects of antibacterial agents is of importance in the design and development of new agents. Using a reaction path model to describe the interaction between a hypothetical drug and a susceptible cell-system, an extensive range of theoretical mechanisms of resistance are derived. It is presumed that such resistances are genome-mediated and the intention is to define the subcellular mechanisms resulting from genotype alterations. The derivation of such an extensive range of potential mechanisms provides the investigator of unknown mechanisms with a detailed analysis of the range of options available. It is suggested that the principles involved are applicable to drug-resistance studies in any chemotherapeutic context, irrespective of the type of organism involved.     

Kinetic resistance to anticancer agents

Adherent epithelial cancer cells, such as colon cancer cells, are much more resistant to anthracyclines and to many other major anticancer agents when the cell population reaches confluence. Our purpose is to analyze the mechanisms of this confluence dependent resistance (CDR) that is probably the major cause of the natural resistance of solid tumors to chemotherapy. Some drugs (anthracyclines, etoposide and vincristine) but not others (cisplatin, melphalan and 5-fluorouracil) accumulate less in confluent than in nonconfluent cells. A decrease of the passive transmembrane drug transport in confluent cells is associated to a reduced membrane fluidity. However, the predominant mechanism of CDR is an increase in the intrinsic resistance of the DNA to the drug-induced damage. This mechanism is now relatively well understood for anthracyclines and etoposide that act mainly through an inhibition of the topoisomerase II: as the enzyme level is low in slowly proliferating confluent cells, the number of drug-induced DNA strand breaks is lower than in rapidly growing nonconfluent cells which highly express the topoisomerase II gene. Mechanisms of CDR for the other drugs are less clear and could involve an increase in the ability to repair damaged DNA. Attempts to circumvent CDR could consist in the stimulation of the cell proliferation by hormones or growth factors, or in the recruitment of quiescent cells into the S and G2 phases by previous treatment of confluent cells with infratoxic concentration of DNA-damaging agents.     

Glyconanoparticles as tools to prevent antimicrobial resistance

The increased phenomenon of antimicrobial resistance and the slow pace of development of new antibiotics are at the base of a global health concern regarding microbial infections. Antibiotic resistance kills an estimated 700,000 people each year worldwide, and this number is expected to increase dramatically if efforts are not made to develop new drugs or alternative containment strategies. Increased vaccination coverage, improved sanitation or sustained implementation of infection control measures are among the possible areas of action. Indeed, vaccination is one of the most effective tools of preventing infections. Starting from 1970s polysaccharide-based vaccines against Meningococcus, Pneumococcus and Haemophilus influenzae type b have been licensed, and provided effective protection for population. However, the development of safe and effective vaccines for infectious diseases with broad coverage remains a major challenge in global public health. In this scenario, nanosystems are receiving attention as alternative delivery systems to improve vaccine efficacy and immunogenicity. In this report, we provide an overview of current applications of glyconanomaterials as alternative platforms in the development of new vaccine candidates. In particular, we will focus on nanoparticle platforms, used to induce the activation of the immune system through the multivalent-displacement of saccharide antigens.

Graphical abstract

     

The biological cost of antibiotic resistance.

The frequency and rates of ascent and dissemination of antibiotic resistance in bacterial populations are anticipated to be directly related to the volume of antibiotic use and inversely related to the cost that resistance imposes on the fitness of bacteria. The data available from recent laboratory studies suggest that most, but not all, resistance-determining mutations and accessory elements engender some fitness cost, but those costs are likely to be ameliorated by subsequent evolution.     

The epidemiology of antibiotic resistance in Campylobacter

Antibiotic resistance, particularly with the fluoroquinolones and macrolide antibiotics, has now emerged globally with thermophilic campylobacters, including Campylobacter jejuni and C. coli, giving rise to concerns about how these organisms have acquired such resistance characteristics, as well as consequences for human and animal treatment. This review examines (i) the clinical epidemiology of antibiotic resistance in human and animal thermophilic campylobacters, (ii) an update on resistance rates globally, (iii) surveillance of antimicrobial resistance in campylobacters originating from animals, particularly poultry, (iv) the role of the environment in the acquisition and transmission of antibiotic-resistant campylobacters, as well as (v) issues of biocide resistance in campylobacters.     

The food safety perspective of antibiotic resistance

Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic and sub-therapeutic antimicrobials to animals, due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been the subject of heated debates for many years, however, there is still no complete consensus on the significance of antimicrobial use in animals, or resistance in bacterial isolates from animals, on the development and dissemination of antibiotic resistance among human bacterial pathogens. In fact, the debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 years, beginning with the release of the Swann report in the United Kingdom. The latest report released by the National Research Council (1998) confirmed that there were substantial information gaps that contribute to the difficulty of assessing potential detrimental effects of antimicrobials in food animals on human health. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including expanded-spectrum cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of these antimicrobial resistant phenotypes is gained from extra-chromosomal genes that may impart resistance to an entire antimicrobial class. In recent years, a number of these resistance genes have been associated with large, transferable, extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, such as transposons and integrons. These DNA mobile elements have been shown to transmit genetic determinants for several different antimicrobial resistance mechanisms and may account for the rapid dissemination of resistance genes among different bacteria. The increasing incidence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. Although much scientific information is available on this subject, many aspects of the development of antimicrobial resistance still remain uncertain. The emergence and dissemination of bacterial antimicrobial resistance is the result of numerous complex interactions among antimicrobials, microorganisms, and the surrounding environments. Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, debate still continues whether this role is significant enough to merit further regulation or restriction.     

Adhesiveness and antibiotic resistance of the causative agents of salmonella infection in Gomel' region

The adhesive capacity, resistance to antibiotics and biological properties of Salmonella strains of different serogroups, circulating in the Gomel region, were under study. Resistance to antibiotics and changes in biological properties were accompanied by an increased adhesiveness of these strains. A high degree of adhesiveness was noted in S. hadar, a new for Belarus strains.