The Fitness Cost of Antibiotic Resistance in Streptococcus pneumoniae: Insight from the Field

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.

Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo

“…Other studies have reported similar changes in S. pneumoniae colonization and macrolide resistance following community-based mass administration of azithromycin for trachoma [17,27,28]. Seemingly, the fitness cost of macrolide resistance for S. pneumoniae ensures its replacement by susceptible strains when antibiotic selection pressure is removed [29].…”

Analysis of Neisseria gonorrhoeae Azithromycin Susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013

“…Apart from three case reports that demonstrated azithromycin MIC increases after treatment with azithromycin monotherapy (15,23,24) and studies that selected for macrolide resistance using erythromycin (25, 26), we are not aware of published data on mutational frequency with in vitro azithromycin exposure or on the stability of the mutants. Related to this, reduced azithromycin susceptibility may be acquired at a fitness cost that limits transmissibility, as appears to be the case with Streptococcus pneumoniae and Campylobacter jejuni (27)(28)(29). This may explain the sporadicity of the detection of isolates with reduced azithromycin susceptibility observed at individual geographic sites in the GISP.…”

Review of Antimicrobial Resistance in the Environment and Its Relevance to Environmental Regulators

“…However, many other chemicals, natural [e.g., plant-derived (Friedman, 2015)], and xenobiotic [e.g., solvents such as octanol, hexane and toluene (Ramos et al, 2002; Fernandes, 2003)], are also known to select for resistance genes. The prevalence of resistance genes in the environment are the result of a complex combination of factors, that reflect a dynamic balance of fitness costs and benefits: costs of carrying the ARG in the context of the host genome and environment (Maher et al, 2012; Roux et al, 2015); relative to the severity and frequency of hazard (Gullberg et al, 2011, 2014); relative to some physical environmental factors, such as temperature (Gifford et al, 2016) and microbial ecology (Amini et al, 2011), among others.…”