scholarly journals Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size

2018 ◽  
Author(s):  
Loïc Marrec ◽  
Anne-Florence Bitbol
Keyword(s):  
Antimicrobial Resistance ◽  
Microbial Population ◽  
Fitness Landscape ◽  
Resistant Bacteria ◽  
Fixed Size ◽  
Variable Environment ◽  
Resistance Evolution ◽  
Evolution Of Resistance ◽  
The Impact ◽  
Analytical Approaches

AbstractThe evolution of antimicrobial resistance often occurs in a variable environment, as antimicrobial is given periodically to a patient or added and removed from a medium. This environmental variability has a huge impact on the microorganisms’ fitness landscape, and thus on the evolution of resistance. Indeed, mutations conferring resistance often carry a fitness cost in the absence of antimicrobial, which may be compensated by subsequent mutations. As antimicrobial is added or removed, the relevant fitness landscape thus switches from a fitness valley to an ascending landscape or vice-versa.Here, we investigate the effect of these time-varying patterns of selection within a stochastic model. We focus on a homogeneous microbial population of fixed size subjected to a periodic alternation of phases of absence and presence of an antimicrobial that stops growth. Combining analytical approaches and stochastic simulations, we quantify how the time necessary for fit resistant bacteria to take over the microbial population depends on the period of the alternations. We demonstrate that fast alternations strongly accelerate the evolution of resistance, and that a plateau is reached once the period gets sufficiently small. Besides, the acceleration of resistance evolution is stronger for larger populations. For asymmetric alternations, featuring a different duration of the phases with and without antimicrobial, we shed light on the existence of a broad minimum of the time taken by the population to fully evolve resistance. At this minimum, if the alternations are sufficiently fast, the very first resistant mutant that appears ultimately leads to full resistance evolution within the population. This dramatic acceleration of the evolution of antimicrobial resistance likely occurs in realistic situations, and can have an important impact both in clinical and experimental situations.

scholarly journals Resist or perish: fate of a microbial population subjected to a periodic presence of antimicrobial

2019 ◽  
Author(s):  
Loïc Marrec ◽  
Anne-Florence Bitbol
Keyword(s):  
Antimicrobial Resistance ◽  
Stochastic Model ◽  
Death Rate ◽  
Microbial Population ◽  
Threshold Value ◽  
Microbial Populations ◽  
Population Composition ◽  
Resistance Evolution ◽  
Rare Mutations ◽  
The Impact

AbstractThe evolution of antimicrobial resistance can be strongly affected by variations of antimicrobial concentration. Here, we study the impact of periodic alternations of absence and presence of antimicrobial on resistance evolution in a microbial population, using a stochastic model that includes variations of both population composition and size, and fully incorporates stochastic population extinctions. We show that fast alternations of presence and absence of antimicrobial are inefficient to eradicate the microbial population and strongly favor the establishment of resistance, unless the antimicrobial increases enough the death rate. We further demonstrate that if the period of alternations is longer than a threshold value, the microbial population goes extinct upon the first addition of antimicrobial, if it is not rescued by resistance. We express the probability that the population is eradicated upon the first addition of antimicrobial, assuming rare mutations. Rescue by resistance can happen either if resistant mutants preexist, or if they appear after antimicrobial is added to the environment. Importantly, the latter case is fully prevented by perfect biostatic antimicrobials that completely stop division of sensitive microorganisms. By contrast, we show that the parameter regime where treatment is efficient is larger for biocidal drugs than for biostatic drugs. This sheds light on the respective merits of different antimicrobial modes of action.Author summaryAntimicrobials select for resistance, which threatens to make antimicrobials useless. Understanding the evolution of antimicrobial resistance is therefore of crucial importance. Under what circumstances are microbial populations eradicated by antimicrobials? Conversely, when are they rescued by resistance? We address these questions employing a stochastic model that incorporates variations of both population composition and size. We consider periodic alternations of absence and presence of antimicrobial, which may model a treatment. We find a threshold period above which the first phase with antimicrobial fully determines the fate of the population. Faster alternations strongly select for resistance, and are inefficient to eradicate the microbial population, unless the death rate induced by the treatment is large enough. For longer alternation periods, we calculate the probability that the microbial population gets eradicated. We further demonstrate the different merits of biostatic antimicrobials, which prevent sensitive microbes from dividing, and of biocidal ones, which kill sensitive microbes.

scholarly journals Antimicrobial resistance three ways: healthcare crisis, major concepts and the relevance of biofilms

2019 ◽  
Vol 95 (8) ◽  
Author(s):  
Paula Jorge ◽  
Andreia Patrícia Magalhães ◽  
Tânia Grainha ◽  
Diana Alves ◽  
Ana Margarida Sousa ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Mechanisms ◽  
Resistant Bacteria ◽  
Adaptive Resistance ◽  
Considerable Research ◽  
Ecological Aspects ◽  
The Social ◽  
Healthcare Crisis ◽  
The Impact ◽  
First World

ABSTRACTWorldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem of antimicrobial resistance (AMR). The social and economic burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this minireview, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely their main resistance and tolerance mechanisms, are elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.

scholarly journals Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial

2021 ◽  
Author(s):  
Harry Pickering ◽  
John D. Hart ◽  
Sarah Burr ◽  
Richard Stabler ◽  
Ken Maleta ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Diarrhoeal Disease ◽  
Childhood Mortality ◽  
Resistant Bacteria ◽  
Clinical Benefits ◽  
The Impact

AbstractBackgroundMass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities.MethodsThis study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.FindingsThe proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.InterpretationThe impacts of MDA with azithromycin, including increased carriage of macrolide-resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.FundingBill and Melinda Gates Foundation

scholarly journals Mechanism and challenges associated with adaptation and evolution of drug-resistant bacteria: an overview

2020 ◽  
pp. 1-18
Author(s):  
Shikha Kapil ◽  
Tarun Kumar ◽  
Vipasha Sharma
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Random Mutation ◽  
Protein Carriers ◽  
Drug Resistant Bacteria ◽  
Global Issue ◽  
Evolution Of Resistance ◽  
Vertical Evolution

Antimicrobial resistance is one of the leading challenges in the human healthcare segment. Advances in antimicrobial resistance studies have revealed various intrinsic, adaptive or acquired factors to be involved for pathogenicity. Antimicrobial agents are either bactericidal or bacteriostatic in action and prescribed according to the mode of action. Various factors are confined for the antimicrobial activity of these agents via biochemical, mechanical, physiological and molecular mechanisms. Microbial cell expresses a number of alternates responsible for the evolution of resistance against these agent activities involving cell surface modifications, enzyme inhibitions, modifications in efflux system, protein carriers and mutations in nucleic acids. Apart from this, the successful adaptations of such microbes have also been observed with the transfer of responsible genes through miscellaneous operations such as vertical evolution, horizontal gene transfer, co-selection, compensatory and random mutation. In addition, alterations or modifications in biochemical and physiological mechanisms at cellular levels are also responsible for antibiotic resistance. This article briefly shows the present scenario of antimicrobial resistance and the alternatives to overcome this global issue in future.

De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock

2020 ◽  
Vol 75 (12) ◽  
pp. 3665-3674 ◽  
Author(s):  
Christina Routsi ◽  
Aikaterini Gkoufa ◽  
Kostoula Arvaniti ◽  
Stelios Kokkoris ◽  
Alexandros Tourtoglou ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Therapy ◽  
Sofa Score ◽  
Multivariate Regression Analysis ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Number Of Patients ◽  
Observational Cohort ◽  
The Impact

Abstract Background De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. Objectives To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. Methods Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. Results A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11–0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14–0.70, P = 0.005). Conclusions In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

scholarly journals Adapt or Perish: Evolutionary Rescue in a Gradually Deteriorating Environment

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 573-583
Author(s):  
Loïc Marrec ◽  
Anne-Florence Bitbol
Keyword(s):  
Antimicrobial Resistance ◽  
Carrying Capacity ◽  
Microbial Population ◽  
Stochastic Simulations ◽  
Extinction Time ◽  
Resistance Evolution ◽  
Mutation Probability ◽  
Evolutionary Rescue ◽  
Population Sizes ◽  
Environment Degradation

We investigate the evolutionary rescue of a microbial population in a gradually deteriorating environment, through a combination of analytical calculations and stochastic simulations. We consider a population destined for extinction in the absence of mutants, which can survive only if mutants sufficiently adapted to the new environment arise and fix. We show that mutants that appear later during the environment deterioration have a higher probability to fix. The rescue probability of the population increases with a sigmoidal shape when the product of the carrying capacity and of the mutation probability increases. Furthermore, we find that rescue becomes more likely for smaller population sizes and/or mutation probabilities if the environment degradation is slower, which illustrates the key impact of the rapidity of environment degradation on the fate of a population. We also show that our main conclusions are robust across various types of adaptive mutants, including specialist and generalist ones, as well as mutants modeling antimicrobial resistance evolution. We further express the average time of appearance of the mutants that do rescue the population and the average extinction time of those that do not. Our methods can be applied to other situations with continuously variable fitnesses and population sizes, and our analytical predictions are valid in the weak-to-moderate mutation regime.

scholarly journals A Model to Investigate the Impact of Farm Practice on Antimicrobial Resistance in UK Dairy Farms

2021 ◽  
Vol 83 (4) ◽  
Author(s):  
Christopher W. Lanyon ◽  
John R. King ◽  
Dov J. Stekel ◽  
Rachel L. Gomes
Keyword(s):  
Antimicrobial Resistance ◽  
Management Practices ◽  
Animal Husbandry ◽  
Antibiotic Use ◽  
Health Impact ◽  
Multidrug Resistant ◽  
Equation Model ◽  
Resistant Bacteria ◽  
Waste Management Practices ◽  
The Impact

AbstractThe ecological and human health impact of antibiotic use and the related antimicrobial resistance (AMR) in animal husbandry is poorly understood. In many countries, there has been considerable pressure to reduce overall antibiotic use in agriculture or to cease or minimise use of human critical antibiotics. However, a more nuanced approach would consider the differential impact of use of different antibiotic classes; for example, it is not known whether reduced use of bacteriostatic or bacteriolytic classes of antibiotics would be of greater value. We have developed an ordinary differential equation model to investigate the effects of farm practice on the spread and persistence of AMR in the dairy slurry tank environment. We model the chemical fate of bacteriolytic and bacteriostatic antibiotics within the slurry and their effect on a population of bacteria, which are capable of resistance to both types of antibiotic. Through our analysis, we find that changing the rate at which a slurry tank is emptied may delay the proliferation of multidrug-resistant bacteria by up to five years depending on conditions. This finding has implications for farming practice and the policies that influence waste management practices. We also find that, within our model, the development of multidrug resistance is particularly sensitive to the use of bacteriolytic antibiotics, rather than bacteriostatic antibiotics, and this may be cause for controlling the usage of bacteriolytic antibiotics in agriculture.

scholarly journals 313. Using a Clinical Decision Prediction Tool to Improve Empirical Antimicrobial Therapy in Ceftriaxone-Resistant Enterobacterales Bloodstream Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S153-S153
Author(s):  
Elizabeth McDougal ◽  
Julie Ann Justo ◽  
Joseph Kohn ◽  
P B Bookstaver ◽  
Hana R Winders ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Real Time ◽  
Antimicrobial Stewardship ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Therapy ◽  
Bloodstream Infections ◽  
Prediction Score ◽  
Resistant Bacteria ◽  
The Impact ◽  
Mean Time

Abstract Background There are several clinical tools for prediction of antimicrobial resistance. However, their utility in management of bloodstream infections (BSI) due to resistant bacteria remains unclear. This quasi-experimental cohort examined the impact of utilization of the extended-spectrum beta-lactamase (ESBL) prediction score on time to initiation of appropriate antimicrobial therapy (AAT) in BSI due to ceftriaxone-resistant (CRO-R) Enterobacterales. Methods Adults with first episodes of monomicrobial BSI due to CRO-R Enterobacterales at Prisma Health-Midlands Hospitals in South Carolina from January 2010 to December 2017 were included. Antimicrobial stewardship intervention was implemented in January 2014 consisting of real-time alerts for positive blood cultures and rapid diagnostics for identification of bloodstream isolates. The ESBL prediction score was used to stratify risk of resistance prior to conventional antimicrobial susceptibility results. Student’s t-test was used to compare mean time to AAT before and after intervention. Results Among 92 patients with BSI due to CRO-R Enterobacterales, median age was 66 years, 52 (57%) were men, 68 (74%) had community-onset BSI, and 52 (57%) had urinary source of infection. Escherichia coli 52 (57%) and Klebsiella species 27 (29%) were the most common bloodstream isolates and the majority 63 (68%) produced ESBLs. There were no significant differences in demographics or clinical characteristics of patients before (n=45) and after (n=47) antimicrobial stewardship intervention. Mean time to AAT was 3.2 days prior and 1.7 days after utilization of ESBL prediction score (p=0.021). Results were consistent among ESBL-producing Enterobacterales (time to AAT 2.8 before and 1.8 days after intervention, p=0.025). Conclusion Utilization of the ESBL prediction score as part of a real-time antimicrobial stewardship intervention significantly reduced time to AAT in BSI due to CRO-R and ESBL-producing Enterobacterales. The ESBL prediction score represents a viable tool to improve antimicrobial management in clinical settings that lack access to multiplex PCRs for detection of antimicrobial resistance genes and novel methods for rapid phenotypic antimicrobial susceptibility testing. Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau)

scholarly journals Travel-Related Antimicrobial Resistance: A Systematic Review

2021 ◽  
Vol 6 (1) ◽  
pp. 11
Author(s):  
Hamid Bokhary ◽  
Krisna N. A. Pangesti ◽  
Harunor Rashid ◽  
Moataz Abd El Ghany ◽  
Grant A. Hill-Cawthorne
Keyword(s):  
Antimicrobial Resistance ◽  
Low Income ◽  
Medical Tourism ◽  
Bacterial Species ◽  
Human Movement ◽  
International Travel ◽  
Low Income Countries ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
The Impact

There is increasing evidence that human movement facilitates the global spread of resistant bacteria and antimicrobial resistance (AMR) genes. We systematically reviewed the literature on the impact of travel on the dissemination of AMR. We searched the databases Medline, EMBASE and SCOPUS from database inception until the end of June 2019. Of the 3052 titles identified, 2253 articles passed the initial screening, of which 238 met the inclusion criteria. The studies covered 30,060 drug-resistant isolates from 26 identified bacterial species. Most were enteric, accounting for 65% of the identified species and 92% of all documented isolates. High-income countries were more likely to be recipient nations for AMR originating from middle- and low-income countries. The most common origin of travellers with resistant bacteria was Asia, covering 36% of the total isolates. Beta-lactams and quinolones were the most documented drug-resistant organisms, accounting for 35% and 31% of the overall drug resistance, respectively. Medical tourism was twice as likely to be associated with multidrug-resistant organisms than general travel. International travel is a vehicle for the transmission of antimicrobial resistance globally. Health systems should identify recent travellers to ensure that adequate precautions are taken.

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