Effect of Macrolide and Rifampin Resistance on the Fitness of Rhodococcus equi.

is a leading cause of severe pneumonia in foals. Standard treatment is dual antimicrobial therapy with a macrolide and rifampin, but the emergence of macrolide- and rifampin-resistant isolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness of Three unique isogenic sets were created, each consisting of four strains, as follows: a susceptible parent isolate, strains resistant to macrolides or rifampin, and a dual macrolide- and rifampin-resistant strain. Each isogenic set's bacterial growth curve was generated in enriched medium, minimal medium (MM), and minimal medium without iron (MM-I). Bacterial survival in soil was analyzed over 12 months at -20°C, 4°C, 25°C, and 37°C, and the ability of these strains to retain antimicrobial resistance during sequential subculturing was determined. Insertion of the mobile element conferring macrolide resistance had minimal effect on growth. However, two of three mutations conferring rifampin resistance resulted in a decreased growth rate in MM. In soil, macrolide- or rifampin-resistant strains exhibited limited growth compared to that of the susceptible isolate at all temperatures except -20°C. During subculturing, macrolide resistance was lost over time, and two of three mutations reverted to the wild-type form. The growth of rifampin-resistant colonies is delayed under nutrient restriction. In soil, possession of rifampin or macrolide resistance results in decreased fitness. Both macrolide and rifampin resistance can be lost after repeated subculturing. This work advances our understanding of the opportunistic environmental pathogen , a disease agent affecting horses and immunocompromised people. is one of the most common causes of severe pneumonia in young horses. For decades, the standard treatment for pneumonia in horses has been dual antimicrobial therapy with a macrolide and rifampin; effective alternatives to this combination are lacking. The World Health Organization classifies these antimicrobial agents as critically important for human medicine. Widespread macrolide and rifampin resistance in isolates is a major emerging problem for the horse-breeding industry and might also adversely impact human health if resistant strains infect people or transfer resistance mechanisms to other pathogens. This study details the impact of antimicrobial resistance on fitness, a vital step for understanding the ecology and epidemiology of resistant isolates, and will support development of novel strategies to combat antimicrobial resistance.