Rhodococcus equi is a significant cause of pneumonia in young horses and a common opportunistic pathogen in immunocompromised humans. For over a decade, control strategies on endemic horse farms have involved early detection of subclinical pulmonary disease using thoracic ultrasonography, followed by antimicrobial treatment before clinical signs emerge. While this approach has been suggested to reduce mortality from R. equi pneumonia, a potential consequence is the development of drug resistance. This article details the emergence of macrolide and rifampin resistance among R. equi isolates from a specific Horse Breeding Farm following the implementation of such a screening and treatment program.
Background on Rhodococcus equi and Antimicrobial Use
Rhodococcus equi poses a substantial threat to equine health, particularly in foals. The common practice of utilizing macrolides and rifampin for treating subclinical pulmonary lesions, detected via ultrasonography, has raised concerns about the rise of antimicrobial resistance. The temporal association between widespread use of these drugs and an observed increase in drug-resistant R. equi isolates in recent years suggests this practice may have unintended negative consequences. This study investigates the development of resistance on a farm that adopted an ultrasonographic screening program and subsequently initiated widespread treatment of foals with subclinical lesions.
The Study: Investigating Drug Resistance on a Kentucky Breeding Farm
This investigation took place at a Thoroughbred horse breeding farm in Kentucky, USA. In 2001, the farm implemented an ultrasonographic screening program aimed at reducing R. equi-related pneumonia deaths by enabling early diagnosis and treatment of foals with subclinical lesions. Between March and July 2010, the farm reported nine foals infected with macrolide- and rifampin-resistant R. equi. This prompted a comprehensive disease investigation. The study involved retrospective data collection, environmental air sampling in September 2010 to assess the prevalence of resistant R. equi, and prospective culturing of pulmonary lesions from all foals in 2011 before initiating antimicrobial therapy.
The farm’s ultrasonographic screening program, introduced in 2001, coincided with the first identification of R. equi isolates resistant to macrolides and rifampin in 2008. Notably, no isolates were found to be resistant to only a macrolide or rifampin individually. Air sampling from the farm yielded 82 R. equi isolates, of which 15 (18%) were virulent (containing the virulence plasmid) and 67 (82%) were avirulent. In vitro antimicrobial drug susceptibility testing and genotyping were performed on these isolates. Two (5%) of the 38 isolates tested exhibited resistance to azithromycin, clarithromycin, erythromycin, and rifampin. One resistant isolate was virulent and recovered from an outdoor paddock housing foals diagnosed with drug-resistant R. equi pneumonia, while the other resistant, avirulent isolate was found in an air sample from an indoor barn.
During the 2011 breeding season, 132 foals were born. Ultrasonography revealed pulmonary disease in 27 foals (20%). Pre-treatment tracheobronchial aspirate cultures from these foals identified R. equi in 25 cases (93%). Among these pretreatment isolates, 6 (24%) were resistant to macrolides and rifampin. Twenty-four foals received clarithromycin and rifampin treatment. Follow-up cultures two weeks post-therapy from 19 foals yielded R. equi in 13 instances (68%). Critically, 8 of these 13 posttreatment isolates (62%) were resistant to macrolides and rifampin. While all foals diagnosed with R. equi pneumonia in 2011 survived, some received additional antimicrobial agents (gentamicin or doxycycline).
Repetitive sequence–based PCR genotyping revealed distinct clusters of R. equi isolates. In 2010, all macrolide- and rifampin-resistant isolates from five foals and one air sample grouped into a single main cluster. [cite:0, cite:1] In 2011, resistant isolates from foals formed four distinct clusters, with the largest containing seven isolates. [cite:0, cite:2] Analysis of 11 foals with both pre- and post-treatment samples indicated that five had similar isolates between sampling points, while six had different pretreatment and posttreatment isolates, highlighting the dynamic nature of resistance. [cite:0, cite:3]
Conclusions and Recommendations
The development of macrolide resistance in clinically significant pathogens is a growing concern in both human and animal populations with intensive antimicrobial use. This study documented the occurrence of macrolide- and rifampin-resistant R. equi isolates just seven years after the implementation of an ultrasonographic screening program that led to the treatment of all foals with subclinical pulmonary lesions.
Research in other pathogens, such as Campylobacter jejuni and Streptococcus pneumoniae, suggests that macrolide resistance can impair pathogen fitness and transmission, potentially leading to a decrease in prevalence when the selective pressure of antimicrobial drugs is removed. However, the elimination of resistance in R. equi may require a significant period and strict absence of antimicrobial selection pressure.
A recent study indicated no difference in recovery rates between foals treated with azithromycin and rifampin and those given a placebo for R. equi-associated pulmonary lesions detected by ultrasonography. This finding, coupled with the increased prevalence of macrolide- and rifampin-resistance demonstrated here, strongly supports the cessation of mass macrolide treatment for subclinical R. equi infections in foals on breeding farms. The focus should shift towards accurately identifying the small subset of subclinically infected foals that are truly likely to develop disease and thus require treatment.
Acknowledgments
The authors express their gratitude to Kristen M. Guldbech and Tina Elam for their assistance. Funding for this study was provided by the Hodgson Equine Research Endowment of the University of Georgia and the Link Equine Research Endowment of Texas A&M University. The air sampler utilized was acquired through a grant from the Grayson-Jockey Club Research Foundation.
Biography
Dr. Burton, a graduate research assistant at the University of Georgia, focuses her research on infectious diseases in horses, with a particular emphasis on infections caused by R. equi.
References
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