DeNegre Ashley A, Myers Kellen, Fefferman Nina H
Department of Ecology, Evolution and Natural Resources, Rutgers University, New Brunswick, NJ 08901, USA.
The Command, Control and Interoperability Center for Advanced Data Analysis (CCICADA), Rutgers University, New Brunswick, NJ 08901, USA.
Antibiotics (Basel). 2020 Mar 7;9(3):114. doi: 10.3390/antibiotics9030114.
Despite the risk of emerging drug resistance that occurs with the frequent use of antimicrobial agents, targeted and prophylactic antibiotics have been considered crucial to opportunistic infection management among the HIV/AIDS-immunocompromised. As we recently demonstrated, the disrupted selective pressures that occur in AIDS-prevalent host populations increase the probability of novel emergence. This effect is concerning, given that bacterial strains unresponsive to first-line antibiotics can be particularly dangerous to hosts whose immune response is insufficient to fight infection in the absence of antibiotic support. While greater host susceptibility within a highly immunocompromised population may offer a fitness advantage to drug-resistant bacterial strains, this advantage could be mitigated by increased morbidity and mortality among the AIDS-immunocompromised. Using a Susceptible-Exposed-Infectious-Recovered (SEIR) epidemiological model parameterized to reflect conditions in an AIDS-prevalent host population, we examine the evolutionary relationship between drug-sensitive and -resistant strains of . We explore this relationship when the fitness of the resistant strain is varied relative to that of the sensitive strain to investigate the likely long-term multi-strain dynamics of the AIDS-mediated increased emergence of drug resistance.
尽管频繁使用抗菌药物会出现新的耐药风险,但针对性和预防性抗生素一直被认为对于管理艾滋病毒/艾滋病免疫功能低下者的机会性感染至关重要。正如我们最近所证明的,艾滋病流行宿主群体中被打乱的选择压力增加了新菌株出现的可能性。鉴于对一线抗生素无反应的细菌菌株对免疫反应不足以在没有抗生素支持的情况下抵抗感染的宿主可能特别危险,这种影响令人担忧。虽然在高度免疫功能低下的人群中宿主易感性增加可能会给耐药细菌菌株带来适应性优势,但这种优势可能会因艾滋病免疫功能低下者发病率和死亡率的增加而减弱。我们使用一个易感-暴露-感染-康复(SEIR)流行病学模型,该模型经过参数化以反映艾滋病流行宿主群体中的情况,来研究[具体细菌名称]的药敏菌株和耐药菌株之间的进化关系。当耐药菌株的适应性相对于敏感菌株有所变化时,我们探究这种关系,以研究艾滋病介导的耐药性增加出现的可能长期多菌株动态。