Emergence of rifampin-resistant Rhodococcus equi in an infected foal

Abstract

To investigate the emergence of rifampin resistance in Rhodococcus equi strains isolated from foals and their environment in Japan, we compared the in vitro antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals and 98 soil isolates from their horse-breeding farms. As a control, 39 human isolates from patients with and without AIDS were also tested for susceptibility to rifampin. All of the isolates showed rifampin sensitivity, except isolates from one infected foal and two patients with AIDS that showed rifampin resistance. To investigate the emergence of rifampin-resistant R. equi in the infected foal, which had received rifampin monotherapy for a month before euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the intestinal contents of the one foal with rifampin-resistant organisms were analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99 isolates from the lesions, all of which were virulent R. equi strains containing a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin resistant (MIC, м12.5 g/ml). On the other hand, of the 20 isolates from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC, м25 g/ml), and 5 of them were avirulent R. equi strains. Among these 101 rifampin-resistant R. equi isolates with and without virulence plasmids characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III, and 12 were type IV. These results demonstrated that at least eight different rifampin-resistant R. equi strains emerged concurrently and respectively from the different lesions and intestinal contents of the infected foal.

Emergence of Resistance to Macrolides and Rifampin in Clinical Isolates of Rhodococcus equi from Foals in Central Kentucky, 1995 to 2017

“…During the introduction of the combination of a macrolide and rifampin for the treatment of infections caused by R. equi in foals in the 1980s and the early 2000s, resistance to rifampin was extremely rare, and there was only one report of resistance to a macrolide (4)(5)(6). In a more recent study, 12 of 328 (3.7%; 95% CI, 1.9% to 6.3%) isolates of R. equi cultured from foals in Texas and Florida between 1999 and 2008 were resistant to macrolides and rifampin.…”

“…The majority (77.8%) of macrolide-resistant isolates in this study were also resistant to rifampin. Rifampin resistance in R. equi is the result of mutations in the rpoB gene, and there are no known mechanisms of cross-resistance between macrolides and rifampin (4,6,12). The selection pressure caused by the combined use of rifampin with macrolide for the prevention and treatment of R. equi infection in foals might have coselected for the acquisition of erm(46) along with rpoB mutations.…”

Molecular and infection biology of the horse pathogenRhodococcus equi

“…Treatment often consists of combined application of macrolides such as erythromycin and rifampicin (Giguere, 2000), which are concentrated in granulocytes and macrophages (Giguere & Prescott, 1997;Heidmann et al, 2006). However, the minimal inhibitory concentrations of rifampin and erythromycin for R. equi strains isolated within the last 10 years have been rising (Buckley et al, 2007), and the emergence of some strains resistant to different antibiotics have been reported (Nordmann et al, 1992;Takai et al, 1997;Asoh et al, 2003;Niwa et al, 2006). These findings highlight the need for strategies alternative to antibiotic treatment to prevent or cope with R. equi infection, such as application of gallium nitrate (Harrington et al, 2006).…”

Controversies in therapy of infections caused by Rhodococcus equi in foals

“…Most macrolide-resistant isolates of R. equi that have been identified to date are also resistant to rifampin. Rifampin resistance in R. equi is the result of mutations in the rpoB gene (Takai et al 1997;Fines et al 2001;Asoh et al 2003;Riesenberg et al 2014).…”