Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2012;7(1):e29407. doi: 10.1371/journal.pone.0029407. Epub 2012 Jan 17.
Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates.
We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone.
Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance.
实验室研究表明，抗生素耐药性可能导致携带该耐药性的细菌适应性降低。观察性研究支持这一观点，但由于伦理和实际考虑，很少能够对抗生素处方率进行实验控制。
我们分析了一项为期 54 个月的纵向试验的数据，该试验在每年两次大规模分发阿奇霉素以消除致盲眼病沙眼期间和之后监测肺炎球菌的药物耐药性。在世界的这个地区，很少有开阿奇霉素和能与之产生交叉耐药性的抗生素的处方。因此，我们能够在不受未测量的抗生素使用影响的情况下跟踪耐药性的趋势。使用这些数据，我们拟合了一个概率疾病传播模型，其中包括两种耐药菌株，分别对应于两种对大环内酯类抗生素的主要耐药模式。我们估计这两种菌株的相对适应性为 0.86（95%置信区间为 0.80 至 0.90）和 0.88（95%置信区间为 0.82 至 0.93），相对于抗生素敏感菌株。然后，我们使用这些估计值预测，在最后一次抗生素治疗后的 5 年内，仅通过种内竞争就有 95%的机会消除大环内酯类耐药性。
尽管大环内酯类耐药性的适应性成本很可能足以确保其最终在没有抗生素选择的情况下消除，但这一过程需要时间，在与耐药性的斗争中，预防可能是最好的策略。
