scholarly journals Mathematical modeling links benefits of short and long antibiotic treatment to details of infection

2019 ◽  
Author(s):  
Francisco F. S. Paupério ◽  
Vitaly V. Ganusov ◽  
Erida Gjini

AbstractAntibiotics are the major tool for treating bacterial infections. With rising antibiotic resistance in microbes, strategies that limit further evolution and spread of drug resistance are urgently needed, in individuals and populations. While classical recommendations favor longer and aggressive treatments, more recent studies and clinical trials advocate for moderate regimens. In this debate, two axes of aggressive treatment have typically been conflated: treatment intensity and treatment duration, the latter being rarely addressed by mathematical models. Here, by using a simple mathematical model of a generic bacterial infection, controlled by host’s immune response, we investigate the role of treatment timing and antibiotic efficacy in determining optimal duration of treatment. We show that even in such simple mathematical model, it is impossible to select for universally optimal treatment duration. In particular, short (3 day) or long (7 day) treatments may be both beneficial depending on treatment onset, on the criterion used, and on the antibiotic efficacy. This results from the dynamic trade-off between immunity and resistance in acute, self-limiting infections, and uncertainty relating symptoms to the start of infection. We find that treatment timing can shift the trend between resistance selection and length of antibiotic exposure in individual hosts. We propose that major advances in predicting impact of antibiotics on bacterial infections must come from deeper experimental understanding of bacterial infection dynamics in humans. To guide rational therapy, mathematical models need to be constrained by data, including details of pathology and symptom thresholds in patients, and of host immune control of infection.

2020 ◽  
Vol 2020 (1) ◽  
pp. 249-263
Author(s):  
Erida Gjini ◽  
Francisco F S Paupério ◽  
Vitaly V Ganusov

Abstract Antibiotics are the major tool for treating bacterial infections. Rising antibiotic resistance, however, calls for a better use of antibiotics. While classical recommendations favor long and aggressive treatments, more recent clinical trials advocate for moderate regimens. In this debate, two axes of ‘aggression’ have typically been conflated: treatment intensity (dose) and treatment duration. The third dimension of treatment timing along each individual’s infection course has rarely been addressed. By using a generic mathematical model of bacterial infection controlled by immune response, we examine how the relative effectiveness of antibiotic treatment varies with its timing, duration and antibiotic kill rate. We show that short or long treatments may both be beneficial depending on treatment onset, the target criterion for success and on antibiotic efficacy. This results from the dynamic trade-off between immune response build-up and resistance risk in acute, self-limiting infections, and uncertainty relating symptoms to infection variables. We show that in our model early optimal treatments tend to be ‘short and strong’, while late optimal treatments tend to be ‘mild and long’. This suggests a shift in the aggression axis depending on the timing of treatment. We find that any specific optimal treatment schedule may perform more poorly if evaluated by other criteria, or under different host-specific conditions. Our results suggest that major advances in antibiotic stewardship must come from a deeper empirical understanding of bacterial infection processes in individual hosts. To guide rational therapy, mathematical models need to be constrained by data, including a better quantification of personal disease trajectory in humans. Lay summary: Bacterial infections are becoming more difficult to treat worldwide because bacteria are becoming resistant to the antibiotics used. Addressing this problem requires a better understanding of how treatment along with other host factors impact antibiotic resistance. Until recently, most theoretical research has focused on the importance of antibiotic dosing on antibiotic resistance, however, duration and timing of treatment remain less explored. Here, we use a mathematical model of a generic bacterial infection to study three aspects of treatment: treatment dose/efficacy (defined by the antibiotic kill rate), duration, and timing, and their impact on several infection endpoints. We show that short and long treatment success strongly depends on when treatment begins (defined by the symptom threshold), the target criterion to optimize, and on antibiotic efficacy. We find that if administered early in an infection, “strong and short” therapy performs better, while if treatment begins at higher bacterial densities, a “mild and long” course of antibiotics is favored. In the model host immune defenses are key in preventing relapses, controlling antibiotic resistant bacteria and increasing the effectiveness of moderate intervention. In order to improve rational treatments of human infections, we call for a better quantification of individual disease trajectories in bacteria-immunity space.


2020 ◽  
Author(s):  
Yulii D. Shikhmurzaev ◽  
Vladislav D. Shikhmurzaev

AbstractA new approach to formulating mathematical models of increasing complexity to describe the dynamics of viral epidemics is proposed. The approach utilizes a map of social interactions characterizing the population and its activities and, unifying the compartmental and the stochastic viewpoints, offers a framework for incorporating both the patterns of behaviour studied by sociological surveys and the clinical picture of a particular infection, both for the virus itself and the complications it causes. The approach is illustrated by taking a simple mathematical model developed in its framework and applying it to the ongoing pandemic of SARS-CoV-2 (COVID-19), with the UK as a representative country, to assess the impact of the measures of social distancing imposed to control its course.


2019 ◽  
Vol 2 (1) ◽  
pp. 1-3
Author(s):  
Attabak Toofani Milani ◽  
Mahshid Mohammadian ◽  
Sadegh Rostaminasab ◽  
Roghayeh Paribananaem ◽  
Zohre Ahmadi ◽  
...  

Conventional diagnostic test have limitations to deferential diagnosis in clinical suspicion ofbacterial infection cases, that in some cases lead to inappropriate antibiotic therapy and increases antibiotic resistance. A new diagnostic insight is procalcitonin (PCT) test to improve diagnosis of bacterial infections and to guide antibiotic therapy. Serum PCT levels are of useful test as a biomarker in patients with bacterial infections for several reasons. Initial rise of PCT levels due to bacterial infection, subsequent sequential PCT levels can be used to assess the effectiveness and duration of antibiotic therapy. Based on clinical researches results, in bacterial infections, promising good results obtained when use of PCT used as differential diagnostic test. But further intervention studies are needed before use of PCT in clinical routine tests. The goal of this review is to study the PCT reliability as infections diagnostic biomarker.


2018 ◽  
Vol 15 (1) ◽  
pp. 39-55
Author(s):  
V. B. Rudakov ◽  
V. M. Makarov ◽  
M. I. Makarov

The article considers the problem of determining the rational plans of the input sampling reliability and technical parameters of components of space technology, the totality of which is supplied to the Assembly plants for the manufacture of complex products of space technology. Problem statement and mathematical model based on the minimization of the economic costs of control and losses related to the risks of taking wrong decisions, are given in the article. The properties of the mathematical models are investigated, the algorithm for its optimization is developed. The result is an optimal plan for the sampling of sets of components, which includes: an optimal product mix subject to mandatory control of the aggregate and optimum risks of first and second kind, when acceptance number of statistical plan is zero. The latter circumstance is due to the high requirements of reliability and technical parameters of products of space technology.


2021 ◽  
pp. 104320
Author(s):  
Maocheng Cao ◽  
Junjing Wang ◽  
Chunfeng Wu ◽  
Aseel Takshe ◽  
Bishr. Muhamed Muwafak

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Allen Abbing ◽  
Vasiliki Koretsi ◽  
Theodore Eliades ◽  
Spyridon N. Papageorgiou

Abstract Objectives Adults with fixed orthodontic appliances are increasing nowadays. Compared with adolescents, adults present biological differences that might influence treatment duration. Therefore, the aim of the study was to compare duration of treatment with fixed appliances between adults and adolescents. Materials and methods Eight databases were searched up to September 2019 for randomized and non-randomized clinical studies comparing treatment duration with fixed appliances in adolescents and adult patients. After duplicate study selection, data extraction, and risk of bias assessment with the Cochrane ROBINS-I tool, random effects meta-analyses of mean differences (MD) and their 95% confidence intervals (CIs) were performed, followed by assessment of the quality of evidence with GRADE. Results A total of 11 unique studies (one prospective and 10 retrospective non-randomized) with 2969 adolescents and 1380 adult patients were finally included. Meta-analysis of 7 studies found no significant difference in the duration of comprehensive treatment with fixed appliances (MD = − 0.8 month; 95% CI = − 4.2 to 2.6 months; P = 0.65; I2 = 92%) between adults and adolescents. Similarly, both distalization of upper first molars with skeletal anchorage for class II correction and the retraction of canines into the premolar extraction spaces lasted similarly long among adults and adolescents. On the other hand, alignment of palatally displaced canines lasted considerably longer in adults compared to adolescents (1 study; MD = 3.8 months; 95% CI = 1.4 to 6.2 months; P = 0.002). The quality of evidence for the meta-analysis was low due to the inclusion of non-randomized studies with considerable risk of bias. Conclusions While existing evidence does not indicate a difference in the overall duration of treatment with fixed appliances between adults and adolescents, the alignment of palatally displaced canines lasted significantly longer in adults. However, our confidence in these estimates is low due to the risk of bias in the included studies. Trial registration PROSPERO: (CRD42019148169)


Author(s):  
Chenyang Yin ◽  
Zekun Wang ◽  
Xiaoyuan Ding ◽  
Xiaoqing Chen ◽  
Jingyuan Wang ◽  
...  

Photodynamic antibacterial therapy employs nanocomposites as an alternative to traditional antibiotics for the treatment of bacterial infections. However, many of these antibacterial materials are less effective towards bacteria than traditional...


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