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Alternative therapeutics for self-limiting infections-An indirect approach to the antibiotic resistance challenge.

ABSTRACT: Alternative therapeutics for infectious diseases is a top priority, but what infections should be the primary targets? At present there is a focus on therapies for severe infections, for which effective treatment is most needed, but these infections are hard to manage, and progress has been limited. Here, we explore a different approach. Applying an evolutionary perspective to a review of antibiotic prescription studies, we identify infections that likely make a large contribution to resistance evolution across multiple taxa but are clinically mild and thus present easier targets for therapeutics development. Alternative therapeutics for these infections, we argue, would save lives indirectly by preserving the high efficacy of existing antibiotics for the patients who need them the most.

SUBMITTER: Wollein Waldetoft K

PROVIDER: S-EPMC5746204 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Alternative therapeutics for self-limiting infections-An indirect approach to the antibiotic resistance challenge.

Wollein Waldetoft Kristofer K Brown Sam P SP

PLoS biology 20171228 12

Alternative therapeutics for infectious diseases is a top priority, but what infections should be the primary targets? At present there is a focus on therapies for severe infections, for which effective treatment is most needed, but these infections are hard to manage, and progress has been limited. Here, we explore a different approach. Applying an evolutionary perspective to a review of antibiotic prescription studies, we identify infections that likely make a large contribution to resistance ...[more]

PMID: 29283999

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Project description:BackgroundClinical guidelines (CG) are used to reduce variability in practice when the scientific evidence is sparse or when multiple therapies are available. The development and implementation of evidence-based CG is intended to organize and provide the best available evidence to support clinical decision making in order to improve quality of care. Upper respiratory tract infections (URTI) are the leading cause of misuse of antibiotics and a CG may reduce the unnecessary antibiotic prescription.MethodsThe aim of this quasi-experimental, before-after study was to analyze the short- and long-term effects of the implementation of a CG to decrease the rate of antibiotic prescription in URTI cases in the emergency department of a third level private hospital in Quito, Ecuador. The study included 444 patients with a main diagnosis of URTI. They were distributed in three groups: a baseline cohort 2011 (n = 114), a first post-implementation cohort 2011 (n = 114), and a later post-implementation cohort 2018 (n = 216). The implementation strategy consisted of five key steps: acceptance of the need for implementation of the CG, dissemination of the CG, an educational campaign, constant feedback, and sustainability of the strategy through continuous training.ResultsThe results of this study show a 42.90% of antibiotic prescription rate before the CG implementation. After the implementation of the CG, the prescription rate of antibiotics was significantly reduced by 24.5% (42.9% vs 18.4%, p<0.0001) and the appropriate antibiotic prescription rate was significantly increased by 44.2% (22.4% vs 66.6%, p<0.0001) in the first post-implementation cohort 2011. There was not a significant difference in antibiotic prescription rate and appropriate antibiotic prescription rate between two post-implementation cohorts: 18.4% vs 25.9% (p = 0.125) and 66.6% vs 50% (p = 0.191), respectively.ConclusionsThe implementation of CGs decreases the rate of antibiotic prescription in URTI cases. The results are remarkable after early implementation, but the effect persists over time. The emphasis must shift from guideline development to strategy implementation.

Project description:BackgroundThe fall armyworm, Spodoptera frugiperda, is a significant and widespread pest of maize, sorghum, rice, and other economically important crops. Successful management of this caterpillar pest has historically relied upon application of synthetic insecticides and through cultivation of genetically engineered crops expressing insecticidal proteins (Bt crops). Fall armyworm has, however, developed resistance to both synthetic insecticides and Bt crops, which risks undermining the benefits delivered by these important crop protection tools. Previous modelling and empirical studies have demonstrated that releases of insecticide- or Bt-susceptible insects genetically modified to express conditional female mortality can both dilute insecticide resistance and suppress pest populations.ResultsHere, we describe the first germline transformation of the fall armyworm and the development of a genetically engineered male-selecting self-limiting strain, OX5382G, which exhibits complete female mortality in the absence of an additive in the larval diet. Laboratory experiments showed that males of this strain are competitive against wild-type males for copulations with wild-type females, and that the OX5382G self-limiting transgene declines rapidly to extinction in closed populations following the cessation of OX5382G male releases. Population models simulating the release of OX5382G males in tandem with Bt crops and non-Bt 'refuge' crops show that OX5382G releases can suppress fall armyworm populations and delay the spread of resistance to insecticidal proteins.ConclusionsThis article describes the development of self-limiting fall armyworm designed to control this pest by suppressing pest populations, and population models that demonstrate its potential as a highly effective method of managing resistance to Bt crops in pest fall armyworm populations. Our results provide early promise for a potentially valuable future addition to integrated pest management strategies for fall armyworm and other pests for which resistance to existing crop protection measures results in damage to crops and impedes sustainable agriculture.

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Alternative therapeutics for self-limiting infections-An indirect approach to the antibiotic resistance challenge.

Publications

Alternative therapeutics for self-limiting infections-An indirect approach to the antibiotic resistance challenge.

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