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

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Trends in the etiology of infectious corneal ulcers at the F. I. Proctor Foundation.

OBJECTIVE: We analyzed laboratory results from corneal ulcers seen from 1976 to 1999 at the Francis I. Proctor Foundation, a referral center in San Francisco, to determine the relative frequencies of pathogens and to analyze for trends in frequencies of the most common pathogens. The results were compared with a previous study of corneal ulcers seen from 1948 to 1976 at the same institution. METHODS: Ulcers presenting to the Proctor Foundation were Gram stained and cultured using standard techniques. Herpetic corneal ulcers were excluded from the study. RESULTS: Organisms were isolated from 427 ulcers, 38% of all cases. Two hundred seventy-eight (59%) isolates were gram-positive bacteria, 145 (31%) gram-negative bacteria, 16 (3%) Acanthamoeba spp., and 36 (8%) fungi. Staphylococcus aureus was the most common organism, composing 20% of all isolates, followed by viridans group streptococci (12%), Streptococcus pneumoniae (11%), Pseudomonas aeruginosa (6%), Moraxella spp. (5%), and Serratia marcescens (4%). Over the 24-year study period the proportion of positive cultures decreased and the incidence of S. marcescens increased significantly. Comparing the period of 1948-1976 to 1976-1999, the frequency of S. pneumoniae and P. aeruginosa decreased, and that of S. marcescens increased significantly. CONCLUSION: The common pathogens associated with corneal ulcers have changed over the past 50 years in Northern California, with S. pneumoniae and P. aeruginosa being isolated relatively less often and S. marcescens being isolated with increasing frequency. The decrease in isolation of organisms over the 1976-1999 period may have resulted from increasing empiric antibiotic treatment by referring ophthalmologists.