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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success
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Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

机译：在一个类别中升级抗生素的使用：抵抗力与治疗成功之间的权衡

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Increasing resistance to antibiotics creates the need for prudent antibiotic use. When resistance to various antibiotics within a class is driven by stepwise accumulation of mutations, a dilemma may exist in regard to replacing an antibiotic that is losing effectiveness due to resistance with a new drug within the same class. Such replacement may enhance treatment success in the short term but promote the spread of highly resistant strains. We used mathematical models to quantify the tradeoff between minimizing treatment failures (by switching early) and minimizing the proliferation of the highly resistant strain (by delaying the switch). Numerical simulations were applied to investigate the cumulative prevalence of the highly resistant strain (Resistance) and the cumulative number of treatment failures (Failure) that resulted from following different antibiotic use policies. Whereas never switching to the new drug always minimizes Resistance and maximizes Failure, immediate switching usually maximizes Resistance and minimizes Failure. Thus, in most circumstances, there is a strict tradeoff in which early use of the new drug enhances treatment effectiveness while hastening the rise of high-level resistance. This tradeoff is most acute when acquired resistance is rare and the highly resistant strain is readily transmissible. However, exceptions occur when use of the new drug frequently leads to acquired resistance and when the highly resistant strain has substantial "fitness cost"; these circumstances tend to favor an immediate switch. We discuss the implications of these considerations in regard to antibiotic choices for Streptococcus pneumoniae.
机译：对抗生素的抗药性增强，因此需要谨慎使用抗生素。当突变的逐步积累驱动一类对各种抗生素的抗药性时，在替换由于同一类中的新药的抗药性而失去效力的抗生素时，可能会出现困境。这种替代可以在短期内提高治疗成功率，但会促进高抗性菌株的传播。我们使用数学模型来量化在最小化治疗失败（通过早期切换）和最小化高抗性菌株的扩散（通过延迟切换）之间的权衡。应用数值模拟研究了高耐药菌株的累积患病率（抗药性）和因遵循不同的抗生素使用政策而导致的治疗失败的累积数（失败）。永不切换到新药总是使抵抗力最小化并最大程度地减少失败，而立即切换通常使抵抗力最大化并最大程度地减少失败。因此，在大多数情况下，存在一个严格的权衡，即尽早使用新药可以增强治疗效果，同时又可以加速高水平耐药性的上升。当获得的抗性很少且高抗性菌株易于传播时，这种权衡是最严重的。但是，当新药的使用经常导致获得性抗药性以及高度抗药性菌株具有相当大的“适应性成本”时，就会发生例外。这些情况倾向于立即转换。我们讨论这些考虑因素对肺炎链球菌的抗生素选择的影响。

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