Abstract
BackgroundLaboratory 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.Methods and FindingsWe 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.ConclusionsAlthough 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.
Highlights
Streptococcus pneumoniae is the leading cause of serious illness in children and adults worldwide [1]
Conclusions: 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
The diversity and adaptability of S. pneumoniae is facilitated in large part by active DNA import and extensive genomic repeats that greatly increase the likelihood of intra- and interspecific homologous recombination [3]
Summary
Streptococcus pneumoniae is the leading cause of serious illness in children and adults worldwide [1]. Despite the availability of a vaccine to combat the disease, rates of colonization remain high, as vaccine-induced immunity often results in replacement of targeted strains as other pneumococcal serotypes fill the newly opened ecological niche [2]. This antigenic diversity renders eradication nearly impossible, emphasizing the importance of antibiotic treatment for control of invasive pneumococcal disease, and illuminating the necessity for understanding and predicting long-term trends in resistance. 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
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