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.

scholarly journals Mathematical Basis for the Assessment of Antibiotic Resistance and Administrative Counter-Strategies

2020 ◽  
Author(s):  
Hans H. Diebner ◽  
Anna Kather ◽  
Ingo Roeder ◽  
Katja de With
Keyword(s):  
Antibiotic Resistance ◽  
Control Strategies ◽  
Antibiotic Consumption ◽  
University Hospital ◽  
Mathematical Framework ◽  
Mathematical Basis ◽  
Antibiotic Resistant ◽  
Administrative Control ◽  
Spatial Changes ◽  
The Impact

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

scholarly journals Mixtures as a Fungicide Resistance Management Tactic

2014 ◽  
Vol 104 (12) ◽  
pp. 1264-1273 ◽  
Author(s):  
Frank van den Bosch ◽  
Neil Paveley ◽  
Femke van den Berg ◽  
Peter Hobbelen ◽  
Richard Oliver
Keyword(s):  
At Risk ◽  
Disease Control ◽  
Fungicide Resistance ◽  
Management Strategies ◽  
Resistance Management ◽  
Relative Effect ◽  
Resistance Evolution ◽  
Modes Of Action ◽  
Selection For ◽  
Effective Life

We have reviewed the experimental and modeling evidence on the use of mixtures of fungicides of differing modes of action as a resistance management tactic. The evidence supports the following conclusions. 1. Adding a mixing partner to a fungicide that is at-risk of resistance (without lowering the dose of the at-risk fungicide) reduces the rate of selection for fungicide resistance. This holds for the use of mixing partner fungicides that have either multi-site or single-site modes of action. The resulting predicted increase in the effective life of the at-risk fungicide can be large enough to be of practical relevance. The more effective the mixing partner (due to inherent activity and/or dose), the larger the reduction in selection and the larger the increase in effective life of the at-risk fungicide. 2. Adding a mixing partner while lowering the dose of the at-risk fungicide reduces the selection for fungicide resistance, without compromising effective disease control. The very few studies existing suggest that the reduction in selection is more sensitive to lowering the dose of the at-risk fungicide than to increasing the dose of the mixing partner. 3. Although there are very few studies, the existing evidence suggests that mixing two at-risk fungicides is also a useful resistance management tactic. The aspects that have received too little attention to draw generic conclusions about the effectiveness of fungicide mixtures as resistance management strategies are as follows: (i) the relative effect of the dose of the two mixing partners on selection for fungicide resistance, (ii) the effect of mixing on the effective life of a fungicide (the time from introduction of the fungicide mode of action to the time point where the fungicide can no longer maintain effective disease control), (iii) polygenically determined resistance, (iv) mixtures of two at-risk fungicides, (v) the emergence phase of resistance evolution and the effects of mixtures during this phase, and (vi) monocyclic diseases and nonfoliar diseases. The lack of studies on these aspects of mixture use of fungicides should be a warning against overinterpreting the findings in this review.

The effects of local selection versus dispersal on insecticide resistance patterns: longitudinal evidence from diamondback moth (Plutella xylostella (Lepidoptera: Plutellidae)) in Australia evolving resistance to pyrethroids

2008 ◽  
Vol 98 (2) ◽  
pp. 145-157 ◽  
Author(s):  
N.M. Endersby ◽  
P.M. Ridland ◽  
A.A. Hoffmann
Keyword(s):  
Gene Flow ◽  
Plutella Xylostella ◽  
Diamondback Moth ◽  
Management Strategies ◽  
Resistance Management ◽  
Synthetic Pyrethroids ◽  
Forage Crops ◽  
Microsatellite Variation ◽  
Resistance Evolution ◽  
Local Selection

AbstractWhen strong directional selection acts on a trait, the spatial distribution of phenotypes may reflect effects of selection, as well as the spread of favoured genotypes by gene flow. Here we investigate the relative impact of these factors by assessing resistance to synthetic pyrethroids in a 12-year study of diamondback moth, Plutella xylostella, from southern Australia. We estimated resistance levels in populations from brassicaceous weeds, canola, forage crops and vegetables. Differences in resistance among local populations sampled repeatedly were stable over several years. Levels were lowest in samples from weeds and highest in vegetables. Resistance in canola samples increased over time as insecticide use increased. There was no evidence that selection in one area influenced resistance in adjacent areas. Microsatellite variation from 13 populations showed a low level of genetic variation among populations, with an AMOVA indicating that population only accounted for 0.25% of the molecular variation. This compared to an estimate of 13.8% of variation accounted for by the resistance trait. Results suggest that local selection rather than gene flow of resistance alleles dictated variation in resistance across populations. Therefore, regional resistance management strategies may not limit resistance evolution.

scholarly journals Cytochrome P450 metabolic resistance (CYP6P9a) to pyrethroids imposes a fitness cost in the major African malaria vector Anopheles funestus

Heredity ◽  
2020 ◽  
Vol 124 (5) ◽  
pp. 621-632 ◽  
Author(s):  
Magellan Tchouakui ◽  
Jacob Riveron Miranda ◽  
Leon M. J. Mugenzi ◽  
Doumani Djonabaye ◽  
Murielle J. Wondji ◽  
...  
Keyword(s):  
Malaria Vector ◽  
Management Strategy ◽  
Management Strategies ◽  
Resistance Management ◽  
Anopheles Funestus ◽  
Fitness Cost ◽  
Malaria Vectors ◽  
Hybrid Strain ◽  
Metabolic Resistance ◽  
The Impact

Abstract Metabolic resistance threatens the sustainability of pyrethroid-based malaria control interventions. Elucidating the fitness cost and potential reversal of metabolic resistance is crucial to design suitable resistance management strategies. Here, we deciphered the fitness cost associated with the CYP6P9a (P450-mediated metabolic resistance) in the major African malaria vector Anopheles funestus. Reciprocal crosses were performed between a pyrethroid susceptible (FANG) and resistant (FUMOZ-R) laboratory strains and the hybrid strains showed intermediate resistance. Genotyping the CYP6P9a-R resistance allele in oviposited females revealed that CYP6P9a negatively impacts the fecundity as homozygote susceptible mosquitoes (CYP6P9a-SS) lay more eggs than heterozygote (OR = 2.04: P = 0.01) and homozygote resistant mosquitoes. CYP6P9a also imposes a significant fitness cost on the larval development as homozygote resistant larvae (CYP6P9a-RR) developed significantly slower than heterozygote and homozygote susceptible mosquitoes (χ2 = 11.2; P = 0.0008). This fitness cost was further supported by the late pupation of homozygote resistant than susceptible mosquitoes (OR = 2.50; P < 0.01). However, CYP6P9a does not impact the longevity as no difference was observed in the life span of mosquitoes with different genotypes (χ2 = 1.6; P = 0.9). In this hybrid strain, a significant decrease of the resistant CYP6P9a-RR genotype was observed after ten generations (χ2 = 6.6; P = 0.01) suggesting a reversal of P450-based resistance in the absence of selection. This study shows that the P450-mediated metabolic resistance imposes a high fitness cost in malaria vectors supporting that a resistance management strategy based on rotation could help mitigate the impact of such resistance.

Modeling Glyphosate Resistance Management Strategies for Palmer Amaranth (Amaranthus palmeri) in Cotton

2011 ◽  
Vol 25 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Paul Neve ◽  
Jason K. Norsworthy ◽  
Kenneth L. Smith ◽  
Ian A. Zelaya
Keyword(s):  
Weed Management ◽  
Management Strategies ◽  
Resistance Management ◽  
Glyphosate Resistance ◽  
Palmer Amaranth ◽  
Case Scenario ◽  
Management Options ◽  
Worst Case ◽  
Resistance Risk ◽  
Resistance Evolution

A simulation model is used to explore management options to mitigate risks of glyphosate resistance evolution in Palmer amaranth in glyphosate-resistant cotton in the southern United States. Our first analysis compares risks of glyphosate resistance evolution for seven weed-management strategies in continuous glyphosate-resistant cotton monoculture. In the “worst-case scenario” with five applications of glyphosate each year and no other herbicides applied, evolution of glyphosate resistance was predicted in 74% of simulated populations. In other strategies, glyphosate was applied with various combinations of preplant, PRE, and POST residual herbicides. The most effective strategy included four glyphosate applications with a preplant fomesafen application, and POST tank mixtures of glyphosate plusS-metolachlor followed by glyphosate plus flumioxazin. This strategy reduced the resistance risk to 12% of populations. A second series of simulations compared strategies where glyphosate-resistant cotton was grown in one-to-one rotations with corn or cotton with other herbicide resistance traits. In general, crop rotation reduced risks of resistance by approximately 50% and delayed the evolution of resistance by 2 to 3 yr. These analyses demonstrate that risks of glyphosate resistance evolution in Palmer amaranth can be reduced by reducing glyphosate use within and among years, controlling populations with diverse herbicide modes of action, and ensuring that population size is kept low. However, no strategy completely eliminated the risk of glyphosate resistance.

scholarly journals Survival and Development of Striacosta albicosta (Smith) (Lepidoptera: Noctuidae) Immature Stages on Dry Beans, non-Bt, Cry1F, and Vip3A Maize

Insects ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 343 ◽  
Author(s):  
Débora G. Montezano ◽  
Thomas E. Hunt ◽  
Alexandre Specht ◽  
Priscila M. C. Luz ◽  
Julie A. Peterson
Keyword(s):  
Management Strategies ◽  
Resistance Management ◽  
The United States ◽  
Economic Damage ◽  
Immature Stages ◽  
Dry Beans ◽  
Bt Maize ◽  
Emergence Period ◽  
Striacosta Albicosta ◽  
The Impact

Striacosta albicosta is a crop pest that causes economic damage in the United States and Canada. Only maize and dry beans are shown to be suitable hosts, since larval development is incomplete on other hosts. The objective of this study was to describe the developmental parameters of immature stages of S. albicosta feeding on dry beans, non-Bt, Cry1F, and Vip3A maize. For Vip3A, mortality was 100% after 24 h. Larvae feeding on non-Bt maize had the highest larval survival (70.6%) compared to the other hosts. Maize expressing Cry1F had higher survival (31.3%) than dry beans (26.0%). Larvae feeding on dry beans had a significantly faster total development time (74.8 days), compared to 92.5 days for non-Bt and 96.2 days for Cry1F. All larvae developed through seven instars. Pupae from larvae that had fed on non-Bt maize were significantly heavier than pupae from other hosts. An understanding of S. albicosta immature development on various host plants is needed to improve recommendations for effective scouting, treatment timing, and economic thresholds. Differential development can result in an extended adult emergence period, and possibly result in assortative mating between Bt susceptible and resistant populations, which violates the assumption of random mating necessary for current resistance management strategies for Bt maize. Therefore, understanding the impact of host plant and transgenic traits on aspects of pest biology will aid in developing effective integrated pest management and insect resistance management strategies for this pest.

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.

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.

Correlation between the reproductive potential and the pyrethroid resistance in an Indian strain of filarial vector, Culex quinquefasciatus Say (Diptera: Culicidae)

2010 ◽  
Vol 101 (1) ◽  
pp. 25-31 ◽  
Author(s):  
S. Kumar ◽  
M.K.K. Pillai
Keyword(s):  
Culex Quinquefasciatus ◽  
Egg Production ◽  
Pyrethroid Resistance ◽  
Management Strategies ◽  
Resistance Management ◽  
Reproductive Potential ◽  
Reproductive Fitness ◽  
Egg Hatchability ◽  
Deltamethrin Resistance ◽  
Resistant Strains

AbstractThe laboratory studies were conducted to uncover the correlation between the levels of pyrethroid resistance and the reproductive potential of parent (SS) and resistant strains of Culex quinquefasciatus (RR) originating from Delhi, India and selected with deltamethrin (RDL) or the combination of deltamethrin and PBO (1:5) (RDP) at the larval stage and selected with deltamethrin at the adult stage (RDA). The reproductive potential was evaluated in terms of fecundity, fertility, egg hatchability and longevity of gonotrophic cycles. The RR strains exhibited 68–74% reduced duration of the gonotrophic cycles when compared with that of SS strain. The considerable decrease in the egg production, ranging from 45.4% to 61.6%, observed in the selected strains as compared to the SS strain, indicates the possible positive correlation between the levels of deltamethrin resistance and the reproduction disadvantage. This correlation was further confirmed by 24.6% to 53.6% decrease in the hatchability of eggs of the selected strains with respect to that of the parent strain. A worth-mentioning observation of the reduced reproductive fitness in RDP strains suggests the effectiveness of synergized deltamethrin selections in reducing the frequency of resistant individuals. The reproductive disadvantage in adult-selected strains possessing negligible resistance to deltamethrin implicates the efficacy of deltamethrin as an adulticide rather than as a larvicide against Cx. quinquefasciatus. The results suggest that the reduced reproductive fitness of resistant genotypes in the population can eliminate heterozygotes and resistant homozygotes by implementing different resistance-management strategies against Cx. quinquefasciatus.

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.

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