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1.
PeerJ ; 12: e16917, 2024.
Article in English | MEDLINE | ID: mdl-38426146

ABSTRACT

Background: The emergence and spread of antibiotic-resistant pathogens have led to the exploration of antibiotic combinations to enhance clinical effectiveness and counter resistance development. Synergistic and antagonistic interactions between antibiotics can intensify or diminish the combined therapy's impact. Moreover, these interactions can evolve as bacteria transition from wildtype to mutant (resistant) strains. Experimental studies have shown that the antagonistically interacting antibiotics against wildtype bacteria slow down the evolution of resistance. Interestingly, other studies have shown that antibiotics that interact antagonistically against mutants accelerate resistance. However, it is unclear if the beneficial effect of antagonism in the wildtype bacteria is more critical than the detrimental effect of antagonism in the mutants. This study aims to illuminate the importance of antibiotic interactions against wildtype bacteria and mutants on the deacceleration of antimicrobial resistance. Methods: To address this, we developed and analyzed a mathematical model that explores the population dynamics of wildtype and mutant bacteria under the influence of interacting antibiotics. The model investigates the relationship between synergistic and antagonistic antibiotic interactions with respect to the growth rate of mutant bacteria acquiring resistance. Stability analysis was conducted for equilibrium points representing bacteria-free conditions, all-mutant scenarios, and coexistence of both types. Numerical simulations corroborated the analytical findings, illustrating the temporal dynamics of wildtype and mutant bacteria under different combination therapies. Results: Our analysis provides analytical clarification and numerical validation that antibiotic interactions against wildtype bacteria exert a more significant effect on reducing the rate of resistance development than interactions against mutants. Specifically, our findings highlight the crucial role of antagonistic antibiotic interactions against wildtype bacteria in slowing the growth rate of resistant mutants. In contrast, antagonistic interactions against mutants only marginally affect resistance evolution and may even accelerate it. Conclusion: Our results emphasize the importance of considering the nature of antibiotic interactions against wildtype bacteria rather than mutants when aiming to slow down the acquisition of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Humans , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Models, Theoretical , Bacteria
2.
PeerJ ; 10: e14353, 2022.
Article in English | MEDLINE | ID: mdl-36540805

ABSTRACT

Background: Human behaviour, economic activity, vaccination, and social distancing are inseparably entangled in epidemic management. This study aims to investigate the effects of various parameters such as stay-at-home restrictions, work hours, vaccination, and social distance on the containment of pandemics such as COVID-19. Methods: To achieve this, we have developed an agent based model based on a time-dynamic graph with stochastic transmission events. The graph is constructed from a real-world social network. The edges of graph have been categorized into three categories: home, workplaces, and social environment. The conditions needed to mitigate the spread of wild-type COVID-19 and the delta variant have been analyzed. Our purposeful agent based model has carefully executed tens of thousands of individual-based simulations. We propose simple relationships for the trade-offs between effective reproduction number (R e), transmission rate, working hours, vaccination, and stay-at-home restrictions. Results: We have found that the effect of a 13.6% increase in vaccination for wild-type (WT) COVID-19 is equivalent to reducing four hours of work or a one-day stay-at-home restriction. For the delta, 20.2% vaccination has the same effect. Also, since we can keep track of household and non-household infections, we observed that the change in household transmission rate does not significantly alter the R e. Household infections are not limited by transmission rate due to the high frequency of connections. For the specifications of COVID-19, the R e depends on the non-household transmissions rate. Conclusions: Our findings highlight that decreasing working hours is the least effective among the non-pharmaceutical interventions. Our results suggest that policymakers decrease work-related activities as a last resort and should probably not do so when the effects are minimal, as shown. Furthermore, the enforcement of stay-at-home restrictions is moderately effective and can be used in conjunction with other measures if absolutely necessary.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2/genetics , Physical Distancing , Pandemics
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