The fitness cost of antibiotic resistance in Streptococcus pneumoniae: insight from the field

• Published in: PloS one 2012-01, Vol.7 (1), p.e29407-e29407
• Main Authors: Maher, M Cyrus, Alemayehu, Wondu, Lakew, Takele, Gaynor, Bruce D, Haug, Sara, Cevallos, Vicky, Keenan, Jeremy D, Lietman, Thomas M, Porco, Travis C
• Format: Article
• Language: English
• Subjects: Algorithms; Analysis; Analysis of Variance; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Azithromycin; Azithromycin - therapeutic use; Bacteria; Bacterial Proteins - genetics; Biology; Cross-resistance; Data processing; Development and progression; Disease transmission; Drug dosages; Drug resistance; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; Epidemiology; Ethics; Ethiopia - epidemiology; Eye; Eye diseases; Fitness; Genetic Association Studies - statistics & numerical data; Genotype & phenotype; Humans; Macrolide antibiotics; Mass distribution; Medicine; Membrane Proteins - genetics; Microbial drug resistance; Microbial Viability - drug effects; Microbial Viability - genetics; Models, Genetic; Observational studies; Pneumococcal Infections - drug therapy; Pneumococcal Infections - epidemiology; Pneumococcal Infections - microbiology; Pneumonia; Prescriptions (Drugs); Prevalence; Reproductive fitness; Strains (organisms); Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - genetics; Studies; Towns; Trachoma; Trachoma - microbiology; Trachoma - prevention & control; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0029407

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.