scholarly journals Competition and diversity determine vaccine impact on antibiotic resistance evolution

2019 ◽  
Author(s):  
Nicholas G. Davies ◽  
Stefan Flasche ◽  
Mark Jit ◽  
Katherine E. Atkins
Keyword(s):  
Antibiotic Resistance ◽  
Pneumococcal Vaccination ◽  
Antibiotic Use ◽  
Relative Strength ◽  
Antibiotic Resistant ◽  
Resistance Evolution ◽  
Pneumococcal Carriage ◽  
Bacterial Transmission ◽  
Vaccine Impact ◽  
The Impact

Bacterial vaccines can protect recipients from contracting potentially antibiotic-resistant infections. But by altering the selective balance between sensitive and resistant strains, vaccines may also help suppress—or spread—antibiotic resistance among unvaccinated individuals. Predicting the outcome requires knowing the drivers of resistance evolution. Using mathematical modelling, we identify competition and diversity as key mediators of resistance evolution. Specifically, we show that the frequency of penicillin resistance in Streptococcus pneumoniae (pneumococcus) across 27 European countries can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or within-host competition. We use our calibrated model to predict the impact of universal pneumococcal vaccination upon the prevalence of carriage, incidence of disease, and frequency of resistance for S. pneumoniae. The relative strength and directionality of competition between resistant and sensitive pneumococcal strains determines whether vaccination promotes, inhibits, or has little effect on the evolution of antibiotic resistance. Finally, we find that differences in overall bacterial transmission and carriage alter predictions, suggesting that evidence-based policies for managing resistance with vaccines must be tailored to both pathogen and setting.One sentence summaryCompetition and diversity are key to antibiotic resistance evolution and determine whether vaccines will prevent or increase resistant infections.

scholarly journals Quantifying the impact of treatment history on plasmid-mediated resistance evolution in human gut microbiota

2019 ◽  
Vol 116 (46) ◽  
pp. 23106-23116 ◽  
Author(s):  
Burcu Tepekule ◽  
Pia Abel zur Wiesch ◽  
Roger D. Kouyos ◽  
Sebastian Bonhoeffer
Keyword(s):  
Antibiotic Resistance ◽  
Gut Microbiota ◽  
Drug Exposure ◽  
Center Of Mass ◽  
Antibiotic Use ◽  
Resistance Evolution ◽  
Treatment History ◽  
Resistant Infection ◽  
The Impact

To understand how antibiotic use affects the risk of a resistant infection, we present a computational model of the population dynamics of gut microbiota including antibiotic resistance-conferring plasmids. We then describe how this model is parameterized based on published microbiota data. Finally, we investigate how treatment history affects the prevalence of resistance among opportunistic enterobacterial pathogens. We simulate treatment histories and identify which properties of prior antibiotic exposure are most influential in determining the prevalence of resistance. We find that resistance prevalence can be predicted by 3 properties, namely the total days of drug exposure, the duration of the drug-free period after last treatment, and the center of mass of the treatment pattern. Overall this work provides a framework for capturing the role of the microbiome in the selection of antibiotic resistance and highlights the role of treatment history for the prevalence of resistance.

scholarly journals Impact of existing vaccines in reducing antibiotic resistance: Primary and secondary effects

2018 ◽  
Vol 115 (51) ◽  
pp. 12896-12901 ◽  
Author(s):  
Keith P. Klugman ◽  
Steven Black
Keyword(s):  
Antibiotic Resistance ◽  
Influenza Vaccination ◽  
Direct Reduction ◽  
Antibiotic Use ◽  
The United States ◽  
Antibiotic Usage ◽  
Secondary Effect ◽  
Antibiotic Resistant ◽  
Vaccination Programs ◽  
The Impact

Vaccines impact antibiotic-resistant infections in two ways: through a direct reduction in the organisms and strains carrying resistant genes that are specifically targeted by the vaccine and also via a secondary effect through a reduction in febrile illnesses that often lead to the use of antibiotics. We review here the impact of pneumococcal conjugate vaccines (PCVs) on the prevalence of antibiotic-resistant disease and antibiotic usage as an example of the direct effect of vaccines on antibiotic resistance and the impact of influenza vaccination on antibiotic usage as an example of a secondary effect. A prelicensure study of a PCV in Africa demonstrated 67% fewer penicillin-resistant invasive disease episodes in the PCV group compared with controls. Similar studies in the United States and Europe demonstrated reductions in antibiotic use consistent with the vaccines’ impact on the risk of otitis media infections in children. Postlicensure reductions in the circulation of antibiotic-resistant strains targeted by the vaccines have been dramatic, with virtual elimination of these strains in children following vaccine introduction. In terms of a secondary effect, following influenza vaccination reductions of 13–50% have been observed in the use of antibiotics by individuals receiving influenza vaccine compared with controls. With the demonstrated effectiveness of vaccination programs in impacting the risk of antibiotic-resistant infections and the increasing threat to public health that these infections represent, more attention needs to be given to development and utilization of vaccines to address antibiotic resistance.

scholarly journals Modeling the effect of vaccination on selection for antibiotic resistance in Streptococcus pneumoniae

2021 ◽  
Vol 13 (606) ◽  
pp. eaaz8690
Author(s):  
Nicholas G. Davies ◽  
Stefan Flasche ◽  
Mark Jit ◽  
Katherine E. Atkins
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Bacterial Pathogens ◽  
Pneumococcal Vaccination ◽  
Pathogen Transmission ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Selection For ◽  
The Impact

Vaccines against bacterial pathogens can protect recipients from becoming infected with potentially antibiotic-resistant pathogens. However, by altering the selective balance between antibiotic-sensitive and antibiotic-resistant bacterial strains, vaccines may also suppress—or spread—antibiotic resistance among unvaccinated individuals. Predicting the outcome of vaccination requires knowing what drives selection for drug-resistant bacterial pathogens and what maintains the circulation of both antibiotic-sensitive and antibiotic-resistant strains of bacteria. To address this question, we used mathematical modeling and data from 2007 on penicillin consumption and penicillin nonsusceptibility in Streptococcus pneumoniae (pneumococcus) invasive isolates from 27 European countries. We show that the frequency of penicillin resistance in S. pneumoniae can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or frequency-dependent selection brought about by within-host competition between antibiotic-resistant and antibiotic-sensitive S. pneumoniae strains. We used our calibrated models to predict the impact of non–serotype-specific pneumococcal vaccination upon the prevalence of S. pneumoniae carriage, incidence of disease, and frequency of S. pneumoniae antibiotic resistance. We found that the relative strength and directionality of competition between drug-resistant and drug-sensitive pneumococcal strains was the most important determinant of whether vaccination would promote, inhibit, or have little effect upon the evolution of antibiotic resistance. Last, we show that country-specific differences in pathogen transmission substantially altered the predicted impact of vaccination, highlighting that policies for managing antibiotic resistance with vaccines must be tailored to a specific pathogen and setting.

The Future of Antibiotics and Meat

2016 ◽  
pp. 178-200 ◽  
Author(s):  
Talia Raphaely ◽  
Dora Marinova ◽  
Mira Marinova
Keyword(s):  
Antibiotic Resistance ◽  
Food Chain ◽  
Animal Husbandry ◽  
Meat Consumption ◽  
Antibiotic Use ◽  
Meat Production ◽  
Livestock Industry ◽  
Antibiotic Resistant ◽  
New Challenges ◽  
Food Animals

This chapter discusses antibiotic use in the livestock industry and potential ramifications for human health. Antibiotics are routinely administered to food animals, primarily at sub-therapeutic levels. The extensive use of antibiotics in global animal husbandry in quantities greater than used for humans is creating antibiotic resistance. There is evidence that antibiotic resistant organisms emerging in food animals transfer to humans through the food chain, environmental contamination, direct association with animals or through mobile resistant genetic elements resulting in co-resistance to other antibiotics. No new classes of antibiotics have been developed since the 1980s. Intensifying use of existing antibiotics for meat production poses new challenges for treating humans, needs to be taken seriously and dealt with urgently. This chapter argues that reduced meat consumption is an under-considered but essential part in any suite of solutions aimed at preserving the use of antibiotics for human treatment.

scholarly journals Comparison of different approaches to antibiotic restriction in food-producing animals: stratified results from a systematic review and meta-analysis

2019 ◽  
Vol 4 (4) ◽  
pp. e001710 ◽  
Author(s):  
Karen L Tang ◽  
Niamh P Caffrey ◽  
Diego B Nóbrega ◽  
Susan C Cork ◽  
Paul E Ronksley ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antibiotic Resistance ◽  
Meta Analysis ◽  
Antibiotic Use ◽  
Growth Promoter ◽  
Antibiotic Resistant ◽  
Random Effects Models ◽  
Differential Effectiveness ◽  
Different Types ◽  
Meta Analyses

BackgroundWe have previously reported, in a systematic review of 181 studies, that restriction of antibiotic use in food-producing animals is associated with a reduction in antibiotic-resistant bacterial isolates. While informative, that report did not concretely specify whether different types of restriction are associated with differential effectiveness in reducing resistance. We undertook a sub-analysis of the systematic review to address this question.MethodsWe created a classification scheme of different approaches to antibiotic restriction: (1) complete restriction; (2) single antibiotic-class restriction; (3) single antibiotic restriction; (4) all non-therapeutic use restriction; (5) growth promoter and prophylaxis restriction; (6) growth promoter restriction and (7) other/undetermined. All studies in the original systematic review that were amenable to meta-analysis were included into this substudy and coded by intervention type. Meta-analyses were conducted using random effects models, stratified by intervention type.ResultsA total of 127 studies were included. The most frequently studied intervention type was complete restriction (n=51), followed by restriction of non-therapeutic (n=33) and growth promoter (n=19) indications. None examined growth promoter and prophylaxis restrictions together. Three and seven studies examined single antibiotic-class and single antibiotic restrictions, respectively; these two intervention types were not significantly associated with reductions in antibiotic resistance. Though complete restrictions were associated with a 15% reduction in antibiotic resistance, less prohibitive approaches also demonstrated reduction in antibiotic resistance of 9%–30%.ConclusionBroad interventions that restrict global antibiotic use appear to be more effective in reducing antibiotic resistance compared with restrictions that narrowly target one specific antibiotic or antibiotic class. Importantly, interventions that allow for therapeutic antibiotic use appear similarly effective compared with those that restrict all uses of antibiotics, suggesting that complete bans are not necessary. These findings directly inform the creation of specific policies to restrict antibiotic use in food-producing animals.

scholarly journals Within-host dynamics explain patterns of antibiotic resistance in commensal bacteria

2017 ◽  
Author(s):  
Nicholas G. Davies ◽  
Stefan Flasche ◽  
Mark Jit ◽  
Katherine E. Atkins
Keyword(s):  
Antibiotic Resistance ◽  
Management Strategies ◽  
Resistance Management ◽  
Population Level ◽  
Antibiotic Consumption ◽  
Mathematical Framework ◽  
Host Immune Responses ◽  
Resistance Evolution ◽  
Resistant Strains ◽  
The Impact

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Empirically, resistant strains gradually increase in prevalence as antibiotic consumption increases, but current mathematical models predict a sharp transition between full sensitivity and full resistance. In other words, we do not understand what drives persistent coexistence between resistant and sensitive strains of disease-causing bacteria in host populations. Without knowing what drives patterns of resistance, we cannot accurately predict the impact of potential strategies for managing resistance. Here, we show that within-host dynamics—bacterial growth, strain competition, and host immune responses—promote frequency-dependent selection for resistant strains, explaining patterns of resistance at the population level. By capturing these processes in a parsimonious mathematical framework, we resolve a long-standing conflict between theory and observation. Our models capture widespread coexistence for multiple bacteria-drug combinations across 30 European countries and explain associations between carriage prevalence and resistance prevalence among bacterial subtypes. A mechanistic understanding of resistance evolution is needed to accurately forecast the impact and effectiveness of resistance-management strategies.

Effectiveness of antimicrobial stewardship programmes in neonatology: a systematic review

2020 ◽  
Vol 105 (6) ◽  
pp. 563-568
Author(s):  
André Ricardo Araujo da Silva ◽  
Amanda Marques ◽  
Clara Di Biase ◽  
Monique Faitanin ◽  
Indah Murni ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Stewardship ◽  
Broad Spectrum ◽  
Neonatal Intensive Care ◽  
Antiviral Agents ◽  
Final Analysis ◽  
Antibiotic Use ◽  
Antibiotic Consumption ◽  
Multi Centre Study ◽  
The Impact

IntroductionAntimicrobial stewardship programmes (ASPs) are recommended to improve antibiotic use in healthcare and reduce antimicrobial resistance (AMR). Our aim was to investigate the effectiveness of ASPs in reducing antibiotic consumption, use of broad-spectrum/restricted antibiotics, antibiotic resistance and healthcare-associated infections (HAIs) in neonates.MethodsWe searched PUBMED, SCIELO, EMBASE and the Cochrane Database (January 2000–April 2019) to identify studies on the effectiveness of ASPs in neonatal wards and/or neonatal intensive care units (NICUs). Outcomes were as follows: reduction of antibiotic consumption overall and of broad-spectrum/target antibiotics, inappropriate antibiotic use, antibiotic resistance and HAIs. ASPs conducted in settings other than acute care hospitals, for children older than 1 month, and ASPs addressing antifungal and antiviral agents, were excluded.ResultsThe initial search identified 53 173 titles and abstracts; following the application of filters and inclusion criteria, a total of six publications were included in the final analysis. All studies, of which one was multi-centre study, were published after 2010. Five studies were conducted exclusively in NICUs. Four articles applied multimodal interventions. Reduction of antibiotic consumption overall and/or inappropriate antibiotic use were reported by four articles; reduction of broad-spectrum/targeted antibiotics were reported by four studies; No article evaluated the impact of ASPs on AMR or the incidence of HAI in neonates.ConclusionASPs can be effectively applied in neonatal settings. Limiting the use of broad-spectrum antibiotics and shorting the duration of antibiotic treatment are the most promising approaches. The impact of ASPs on AMR and HAI needs to be evaluated in long-term studies.

The Future of Antibiotics and Meat

2016 ◽  
pp. 1335-1357
Author(s):  
Talia Raphaely ◽  
Dora Marinova ◽  
Mira Marinova
Keyword(s):  
Antibiotic Resistance ◽  
Food Chain ◽  
Animal Husbandry ◽  
Meat Consumption ◽  
Antibiotic Use ◽  
Meat Production ◽  
Livestock Industry ◽  
Antibiotic Resistant ◽  
New Challenges ◽  
Food Animals

This chapter discusses antibiotic use in the livestock industry and potential ramifications for human health. Antibiotics are routinely administered to food animals, primarily at sub-therapeutic levels. The extensive use of antibiotics in global animal husbandry in quantities greater than used for humans is creating antibiotic resistance. There is evidence that antibiotic resistant organisms emerging in food animals transfer to humans through the food chain, environmental contamination, direct association with animals or through mobile resistant genetic elements resulting in co-resistance to other antibiotics. No new classes of antibiotics have been developed since the 1980s. Intensifying use of existing antibiotics for meat production poses new challenges for treating humans, needs to be taken seriously and dealt with urgently. This chapter argues that reduced meat consumption is an under-considered but essential part in any suite of solutions aimed at preserving the use of antibiotics for human treatment.

GENERAL PRINCIPLES OF ANTIBIOTIC RESISTANCE EVOLUTION IN BACTERIA (REVIEW OF LITERATURE)

2020 ◽  
Vol 65 (6) ◽  
pp. 387-393
Author(s):  
N. V. Davidovich ◽  
Natalya Nilolaevna Kukalevskaya ◽  
E. N. Bashilova ◽  
T. A. Bazhukova
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Molecular Genetic ◽  
Antibiotic Resistance Genes ◽  
Human Pathogens ◽  
Intrinsic Resistance ◽  
Resistance Evolution ◽  
Genes Encoding ◽  
The Impact

Currently, the impact of antibiotic resistance on human health is a worldwide problem and its study is of great interest from a molecular genetic, environmental and clinical view-point. This review summarizes the latest data about antibiotic resistance, the classification of microorganisms as sensitive and resistant to the action of antibiotics, reveals the concept of minimum inhibitory concentration from modern positions. The resistance of microorganisms to antibacterial agents can be intrinsic and acquired, as well as being one of the examples of evolution that are currently available for study. Modern methods of whole-genome sequencing and complex databases of nucleotide-tagged libraries give an idea of the multifaceted nature of the mechanisms of intrinsic resistance to antibiotics and are able to provide information on genes encoding metabolic enzymes and proteins that regulate the basic processes of the physiology of bacteria. The article describes the main ways of spreading the resistance of microorganisms, reflects the concepts of “founder effect” and the fitness cost of bacteria, which underlie the emergence and evolution of antibiotic resistance. It is shown that the origin of antibiotic resistance genes that human pathogens currently possess can be traced by studying the surrounding not only clinical, but also non-clinical (ecological) habitats. As well as microorganisms of the surrounding ecosystems are the donors of resistance genes in horizontal gene transfer.

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