Macrolides are a class of antibiotics frequently used in equine medicine to treat bacterial infections, particularly those caused by Rhodococcus equi in foals. These antibiotics function by inhibiting bacterial protein synthesis, thereby limiting the growth and proliferation of bacteria. Common macrolides used in horses include erythromycin, clarithromycin, and azithromycin. While effective against certain pathogens, macrolides can also cause side effects such as colitis in adult horses due to disruption of the gut microbiota. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetics, therapeutic applications, and potential adverse effects of macrolide antibiotics in equine health.
Zúñiga MP, Badillo E, Abalos P, Valencia ED, Marín P, Escudero E, Galecio JS.Rhodococcus equi is responsible for foal pneumonia worldwide, with a significant economic impact on the production and breeding of horses. In Chile, the first case was reported in 2000, and since then, its incidence has been increasing. Distinctive characteristics of R. equi as an intracellular pathogen in macrophages, emergence of virulence plasmids encoding surface lipoprotein antigens, and appearance of antibiotic resistance against macrolides and rifampicin have significantly complicated the treatment of R. equi pneumonia in foals. Therefore, in vitro susceptibility studies of first-line a...
Narváez SÁ, Fernández I, Patel NV, Sánchez S. is an important veterinary pathogen that takes the lives of many foals every year. With the emergence and spread of MDR to current antimicrobial treatment, new tools that can provide a fast and accurate diagnosis of the disease and antimicrobial resistance profile are needed. Here, we have developed and analytically validated a multiplex qPCR for the simultaneous detection of and related macrolide resistance genes in equine respiratory samples. The three sets of oligos designed in this study to identify housekeeping gene and macrolide resistance genes (46) and (51) showed high analytic se...
Patterson Rosa L, Mallicote MF, MacKay RJ, Brooks SA.Macrolide drugs are the treatment of choice for infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration-pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin...
Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA.Clonal multidrug resistance recently emerged in Rhodococcus equi, complicating the therapeutic management of this difficult-to-treat animal- and human-pathogenic actinomycete. The currently spreading multidrug-resistant (MDR) "2287" clone arose in equine farms upon acquisition, and coselection by mass macrolide-rifampin therapy, of the pRErm46 plasmid carrying the (46) macrolide-lincosamide-streptogramin resistance determinant, and of an mutation. Here, we screened a collection of susceptible and macrolide-resistant strains from equine clinical cases using a panel of 15 antimicrobials agains...
Huber L, Giguère S, Hart KA, Slovis NM, Greiter ME, Dailey CA, Cohen ND.To compare soil concentrations of macrolide- and rifampicin-resistant strains (MRRE) on horse-breeding farms that used thoracic ultrasonographic screening (TUS) to identify foals with subclinical pneumonia combined with subsequent administration of macrolides and rifampin to affected foals (TUS farms) versus soil concentrations on farms that did not (non-TUS farms), determine whether the combined use of TUS and antimicrobial treatment of subclinically affected foals was associated with soil concentration of MRRE, and assess whether there were temporal effects on soil concentrations of MRRE du...
Álvarez-Narváez S, Giguère S, Berghaus LJ, Dailey C, Vázquez-Boland JA.Conjugation is one of the main mechanisms involved in the spread and maintenance of antibiotic resistance in bacterial populations. We recently showed that the emerging macrolide resistance in the soilborne equine and zoonotic pathogen is conferred by the (46) gene carried on the 87-kb conjugative plasmid pRErm46. Here, we investigated the conjugal transferability of pRErm46 to 14 representative bacteria likely encountered by in the environmental habitat. mating experiments demonstrated conjugation to different members of the genus as well as to and spp. at frequencies ranging from ∼10...
Erol E, Locke S, Saied A, Cruz Penn MJ, Smith J, Fortner J, Carter C.Mainstay therapy for rhodococcosis in foals is the combination of rifampicin and a macrolide. While emergence of resistance to rifampicin and macrolides has been reported, studies demonstrating the development of resistance to such drugs is limited in necropsied foals with rhodococcosis. In this study, the foal necropsy records between 01/01/2011 and 08/30/2019 were reviewed for culture-positive R. equi with MICs and, whether or not the affected foals received any mainstay dual therapy before their deaths. Resistance to antimicrobials in the R. equi isolates from necropsied foals were then com...
Álvarez-Narváez S, Logue CM, Barbieri NL, Berghaus LJ, Giguère S.Rhodococcus equi (R. equi) infections are endemic in many horse facilities in the United States resulting significant economic loses annually. Currently, there is no commercial vaccine available and the emergence of isolates that are resistant to the current treatment and prophylaxis using antibiotics prompts closer surveillance of this pathogen. Objective: This study compares three different genotyping techniques, Pulsed Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST) and whole genome SNP-based phylogeny to determine the most accurate method to monitor the spread of macrol...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S.The soil-dwelling, saprophytic actinomycete is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in t...
Huber L, Giguère S, Cohen ND, Slovis NM, Hanafi A, Schuckert A, Berghaus L, Greiter M, Hart KA.The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. 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 genera...
Huber L, Giguère S, Slovis NM, Carter CN, Barr BS, Cohen ND, Elam J, Erol E, Locke SJ, Phillips ED, Smith JL.The objective of this study was to determine the prevalence of strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the bacterium was cultured and tested for susceptibility to erythromycin or rifampin. susceptibility testing to erythromycin was available for 2,169 isolates of , while s...
Giguère S, Berghaus LJ, Willingham-Lane JM.Pneumonia caused by remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin has been the recommended treatment for foals with clinical signs of infection caused by since the early 1980s with, until recently, only rare reports of resistance. Resistance to macrolides and rifampin in isolates of cultured from horses is increasing, with isolates resistant to all macrolides and rifampin now being cultured from up to 40% of infected foals at some farms. This text reviews the available data regarding ant...
Giguère S.Pneumonia caused by Rhodococcus equi remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin remains the recommended therapy for foals with clinical signs of infection caused by R equi. Most foals with small, subclinical ultrasonographic pulmonary lesions associated with R equi recover without therapy, and administration of antimicrobial agents to these subclinically affected foals does not hasten lesion resolution relative to administration of a placebo. Resistance to macrolides and rifampin in isol...
Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I, Cohen ND, Roberts MC, Vazquez-Boland JA.The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. Methods: Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR w...
Cohen ND, Slovis NM, Giguère S, Baker S, Chaffin MK, Bernstein LR.Macrolide-resistant isolates of Rhodococcus equi are emerging, prompting the search for clinically effective alternative antimicrobials. Objective: The proportion of foals with ultrasonographic evidence of pneumonia presumed to be caused by R. equi that had a successful outcome when administered gallium maltolate (GaM) PO would not be more than 10% inferior (ie, lower) than that of foals receiving standard treatment. Methods: Fifty-four foals with subclinical pulmonary abscesses among 509 foals at 6 breeding farms in Kentucky. Methods: Controlled, randomized, prospective noninferiority study. ...
Carlson KL, Kuskie KR, Chaffin KM, Libal MC, Giguère S, Lawhon SD, Cohen ND.This study determined the antimicrobial activity of tulathromycin against Rhodococcus equi in vitro. Ninety-eight virulent isolates of R. equi from equine clinical cases were examined, of which 20 isolates were macrolide resistant. A custom 96-well antimicrobial susceptibility testing plate was used, allowing 14 additional antimicrobials to be tested against R. equi. Isolates were cultured with various concentrations of antimicrobials, and minimal inhibitory concentration (MIC) values were determined. Tulathromycin was found to have poor activity in vitro against R. equi isolates susceptible o...
Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N, Martens RJ, Franklin RP, Clark CC, Slovis NM.To determine the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and to describe treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. Methods: Cross-sectional study. Methods: 38 isolates classified as resistant to macrolide antimicrobials or rifampin received from 9 veterinary diagnostic laboratories between January 1997 and December 2008. Methods: For each isolate, the minimum inhibitory concentration of macrolide antimicrobials (ie, azithromycin, erythromycin, and clarithromycin) and rifampin was dete...
Giguère S, Lee E, Williams E, Cohen ND, Chaffin MK, Halbert N, Martens RJ, Franklin RP, Clark CC, Slovis NM.To determine the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and to describe treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. Methods: Cross-sectional study. Methods: 38 isolates classified as resistant to macrolide antimicrobials or rifampin received from 9 veterinary diagnostic laboratories between January 1997 and December 2008. Methods: For each isolate, the minimum inhibitory concentration of macrolide antimicrobials (ie, azithromycin, erythromycin, and clarithromycin) and rifampin was dete...
Giguère S, Berghaus LJ, Willingham-Lane JM.Pneumonia caused by remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin has been the recommended treatment for foals with clinical signs of infection caused by since the early 1980s with, until recently, only rare reports of resistance. Resistance to macrolides and rifampin in isolates of cultured from horses is increasing, with isolates resistant to all macrolides and rifampin now being cultured from up to 40% of infected foals at some farms. This text reviews the available data regarding ant...
Giguère S.Pneumonia caused by Rhodococcus equi remains an important cause of disease and death in foals. The combination of a macrolide (erythromycin, azithromycin, or clarithromycin) with rifampin remains the recommended therapy for foals with clinical signs of infection caused by R equi. Most foals with small, subclinical ultrasonographic pulmonary lesions associated with R equi recover without therapy, and administration of antimicrobial agents to these subclinically affected foals does not hasten lesion resolution relative to administration of a placebo. Resistance to macrolides and rifampin in isol...
Anastasi E, Giguère S, Berghaus LJ, Hondalus MK, Willingham-Lane JM, MacArthur I, Cohen ND, Roberts MC, Vazquez-Boland JA.The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. Methods: Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR w...
Huber L, Giguère S, Slovis NM, Carter CN, Barr BS, Cohen ND, Elam J, Erol E, Locke SJ, Phillips ED, Smith JL.The objective of this study was to determine the prevalence of strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the bacterium was cultured and tested for susceptibility to erythromycin or rifampin. susceptibility testing to erythromycin was available for 2,169 isolates of , while s...
Huber L, Giguère S, Cohen ND, Slovis NM, Hanafi A, Schuckert A, Berghaus L, Greiter M, Hart KA.The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0...
Cohen ND, Slovis NM, Giguère S, Baker S, Chaffin MK, Bernstein LR.Macrolide-resistant isolates of Rhodococcus equi are emerging, prompting the search for clinically effective alternative antimicrobials. Objective: The proportion of foals with ultrasonographic evidence of pneumonia presumed to be caused by R. equi that had a successful outcome when administered gallium maltolate (GaM) PO would not be more than 10% inferior (ie, lower) than that of foals receiving standard treatment. Methods: Fifty-four foals with subclinical pulmonary abscesses among 509 foals at 6 breeding farms in Kentucky. Methods: Controlled, randomized, prospective noninferiority study. ...
Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA.Clonal multidrug resistance recently emerged in Rhodococcus equi, complicating the therapeutic management of this difficult-to-treat animal- and human-pathogenic actinomycete. The currently spreading multidrug-resistant (MDR) "2287" clone arose in equine farms upon acquisition, and coselection by mass macrolide-rifampin therapy, of the pRErm46 plasmid carrying the (46) macrolide-lincosamide-streptogramin resistance determinant, and of an mutation. Here, we screened a collection of susceptible and macrolide-resistant strains from equine clinical cases using a panel of 15 antimicrobials agains...
Erol E, Locke S, Saied A, Cruz Penn MJ, Smith J, Fortner J, Carter C.Mainstay therapy for rhodococcosis in foals is the combination of rifampicin and a macrolide. While emergence of resistance to rifampicin and macrolides has been reported, studies demonstrating the development of resistance to such drugs is limited in necropsied foals with rhodococcosis. In this study, the foal necropsy records between 01/01/2011 and 08/30/2019 were reviewed for culture-positive R. equi with MICs and, whether or not the affected foals received any mainstay dual therapy before their deaths. Resistance to antimicrobials in the R. equi isolates from necropsied foals were then com...
Álvarez-Narváez S, Giguère S, Berghaus LJ, Dailey C, Vázquez-Boland JA.Conjugation is one of the main mechanisms involved in the spread and maintenance of antibiotic resistance in bacterial populations. We recently showed that the emerging macrolide resistance in the soilborne equine and zoonotic pathogen is conferred by the (46) gene carried on the 87-kb conjugative plasmid pRErm46. Here, we investigated the conjugal transferability of pRErm46 to 14 representative bacteria likely encountered by in the environmental habitat. mating experiments demonstrated conjugation to different members of the genus as well as to and spp. at frequencies ranging from ∼10...
Huber L, Giguère S, Hart KA, Slovis NM, Greiter ME, Dailey CA, Cohen ND.To compare soil concentrations of macrolide- and rifampicin-resistant strains (MRRE) on horse-breeding farms that used thoracic ultrasonographic screening (TUS) to identify foals with subclinical pneumonia combined with subsequent administration of macrolides and rifampin to affected foals (TUS farms) versus soil concentrations on farms that did not (non-TUS farms), determine whether the combined use of TUS and antimicrobial treatment of subclinically affected foals was associated with soil concentration of MRRE, and assess whether there were temporal effects on soil concentrations of MRRE du...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S. 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 genera...
Carlson KL, Kuskie KR, Chaffin KM, Libal MC, Giguère S, Lawhon SD, Cohen ND.This study determined the antimicrobial activity of tulathromycin against Rhodococcus equi in vitro. Ninety-eight virulent isolates of R. equi from equine clinical cases were examined, of which 20 isolates were macrolide resistant. A custom 96-well antimicrobial susceptibility testing plate was used, allowing 14 additional antimicrobials to be tested against R. equi. Isolates were cultured with various concentrations of antimicrobials, and minimal inhibitory concentration (MIC) values were determined. Tulathromycin was found to have poor activity in vitro against R. equi isolates susceptible o...
Narváez SÁ, Fernández I, Patel NV, Sánchez S. is an important veterinary pathogen that takes the lives of many foals every year. With the emergence and spread of MDR to current antimicrobial treatment, new tools that can provide a fast and accurate diagnosis of the disease and antimicrobial resistance profile are needed. Here, we have developed and analytically validated a multiplex qPCR for the simultaneous detection of and related macrolide resistance genes in equine respiratory samples. The three sets of oligos designed in this study to identify housekeeping gene and macrolide resistance genes (46) and (51) showed high analytic se...
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S.The soil-dwelling, saprophytic actinomycete is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in t...
Álvarez-Narváez S, Logue CM, Barbieri NL, Berghaus LJ, Giguère S.Rhodococcus equi (R. equi) infections are endemic in many horse facilities in the United States resulting significant economic loses annually. Currently, there is no commercial vaccine available and the emergence of isolates that are resistant to the current treatment and prophylaxis using antibiotics prompts closer surveillance of this pathogen. Objective: This study compares three different genotyping techniques, Pulsed Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST) and whole genome SNP-based phylogeny to determine the most accurate method to monitor the spread of macrol...
Patterson Rosa L, Mallicote MF, MacKay RJ, Brooks SA.Macrolide drugs are the treatment of choice for infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration-pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin...
Zúñiga MP, Badillo E, Abalos P, Valencia ED, Marín P, Escudero E, Galecio JS.Rhodococcus equi is responsible for foal pneumonia worldwide, with a significant economic impact on the production and breeding of horses. In Chile, the first case was reported in 2000, and since then, its incidence has been increasing. Distinctive characteristics of R. equi as an intracellular pathogen in macrophages, emergence of virulence plasmids encoding surface lipoprotein antigens, and appearance of antibiotic resistance against macrolides and rifampicin have significantly complicated the treatment of R. equi pneumonia in foals. Therefore, in vitro susceptibility studies of first-line a...
