Rhodococcus equi is a bacterial pathogen that primarily affects foals, leading to pneumonia and other systemic infections. It is a significant concern in equine health due to its impact on the respiratory system of young horses. The bacterium is found in soil and can be inhaled by foals, leading to infection. Clinical signs of Rhodococcus equi infection in foals include coughing, fever, and respiratory distress. Diagnosis is typically confirmed through bacterial culture or polymerase chain reaction (PCR) testing. Management of the disease involves antimicrobial therapy and supportive care. This page compiles peer-reviewed research studies and scholarly articles that explore the pathogenesis, diagnosis, treatment, and prevention of Rhodococcus equi infections in horses.
Cohen ND, Flores-Ahlschewde P, Gonzales GM, Kahn SK, da Silveira BP, Bray JM, King EE, Blair CC, Bordin AI.Diagnostic accuracy of real-time, quantitative PCR (qPCR) assays to quantify virulent Rhodococcus equi using rectal swab samples has not been systematically evaluated. Objective: To evaluate the accuracy of qPCR of rectal swab samples to differentiate foals with pneumonia from healthy foals of similar age from the same environment. Methods: One hundred privately owned foals born in 2021 from 2 farms in New York. Methods: An incident case-control study design was used. Rectal swabs were collected from all foals diagnosed with R. equi pneumonia at 2 horse-breeding farms (n = 47). Eligible pneu...
Suzuki Y, Takai S, Kubota H, Hasegawa N, Ito S, Yabuuchi Y, Sasaki Y, van Duijkeren E, Kakuda T.Rhodococcus equiis the causative agent of pyogenic pneumonia in foals, and a virulence-associated protein A (VapA) encoded on the pVAPA virulence plasmid is important for its pathogenicity. In this study, we analyzed the virulence of R. equi strain U19, originally isolated in the Netherlands in 1997 and the genetic characteristics of the pVAPA_U19 plasmid. U19 expressed VapA that was regulated by temperature and pH and underwent significant intracellular proliferation in macrophages. The restriction fragment length polymorphism of pVAPA_U19 digested with EcoRI was similar to that of pREAT701 (...
Espíndola JP, Machado G, Diehl GN, Dos Santos LC, de Vargas AC, Gressler LT.Microbiological diagnosis of equine respiratory infections is essential for disease management. However, reliable diagnosis can be a challenge due to colonization of the upper respiratory tract (URT) by a diverse microbial population, and because there is a lack of studies with samples from healthy animals. Aiming to guide adequate URT culture, this work reports culturable microbial population from the URT of 1,010 apparently healthy horses from 341 farms in Southern Brazil and identifies the putative presence of pathogenic microorganisms. Nasal swabs were cultured in 5% blood agar, and the is...
Cohen ND, Kahn SK, Bordin AI, Gonzales GM, da Silveira BP, Bray JM, Legere RM, Ramirez-Cortez SC.Intragastric administration of virulent Rhodococcus equi protects foals against subsequent experimental intrabronchial (IB) infection, but it is unknown whether R. equi naturally ingested by foals contributes to their susceptibility to pneumonia. Objective: Fecal concentration of virulent R. equi before IB infection with R. equi is positively associated with protection from pneumonia in foals. Methods: Twenty-one university-owned foals. Methods: Samples were collected from experimental studies. Five foals were gavaged with live, virulent R. equi (LVRE) at age 2 and 4 days; the remaining 16 f...
Bordin AI, Huber L, Sanz MG, Cohen ND.Pneumonia in foals caused by the bacterium Rhodococcus equi has a worldwide distribution and is a common cause of disease and death for foals. The purpose of this narrative review was to summarise recent developments pertaining to the epidemiology, immune responses, treatment, and prevention of rhodococcal pneumonia of foals. Screening tests have been used to implement earlier detection and treatment of foals with presumed subclinical R. equi pneumonia to reduce mortality and severity of disease. Unfortunately, this practice has been linked to the emergence of antimicrobial-resistant R. equi i...
Mouncey R, Arango-Sabogal JC, de Mestre AM, Foote AK, Verheyen KL.Enhanced understanding of reasons for, and timings of, mortality in Thoroughbreds prior to entering race training is warranted to provide insight into this population's health status. The aims of this study were to describe pathologies diagnosed at post-mortem (PM) examination in Thoroughbreds aged from birth to 18 months and investigate associations between age and pathology. Reports from a pathology laboratory in Newmarket, UK, were used to identify eligible cases examined between January 2006 and December 2020. Reported pathologies were extracted and categorised where appropriate. Comorbidi...
Takai S, Yoda A, Sasaki Y, Kakuda T, Suzuki Y, Oikawa M.Tracheal washing fluid was collected from 170 foals at 28 and 35 d old from February to July in a foaling season on horse-breeding farms with sporadic rhodococcosis in Japan and was investigated by quantitative culture. The history of the 170 foals followed up for the next few months. The proportion of R. equi-positive foals at 28 and 35 d old was significantly increased according to the birth month. Furthermore, the mean number of R. equi in the tracheal washing fluid of each month group increased according to their birth month with the rise in outside temperature. During the follow-up observ...
Rivolta AA, Pittman DC, Kappes AJ, Stancil RK, Kogan C, Sanz MG.The efficacy of Rhodococcus equi-specific hyperimmune plasma (HIP) is usually evaluated in vitro. Anticoagulants (AC) used for plasma collection can negatively impact bacterial replication but their effect on R. equi growth has not been evaluated. The aim of this study was to establish the effect that AC routinely used in veterinary medicine (ACD, KEDTA, Li Heparin, and Na Citrate) have on in vitro R. equi growth. To assess this, in vitro assays commonly used to test HIP efficacy (direct effect on microorganism and macrophage infection), were performed using each AC and non-treated bacteria. R...
Nielsen SS, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ.... () was identified among the most relevant antimicrobial-resistant (AMR) bacteria in the EU for horses in a previous scientific opinion. Thus, it has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on its eligibility to be listed, Annex IV for its categorisation according to disease prevention and control rules as in Article 9 and Article 8 for listing animal species related to the bacterium. The assessment has been performed following a methodology previously published. The outcome is the med...
Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Flores-Ahlschwede P, Metcalfe LL, Nevill M, Vinacur M, Sutter PJ, Meyer SC....Hyperimmune plasma raised against β-1→6-poly-N-acetyl glucosamine (PNAG HIP) mediates more opsonophagocytic killing of Rhodococcus equi (R equi) than does R equi hyperimmune plasma (RE HIP) in vitro. The relative efficacy of PNAG HIP and RE HIP to protect foals against R equi pneumonia, however, has not been evaluated. Objective: Transfusion with PNAG HIP will be superior to RE HIP in foals for protection against R equi pneumonia in a randomized, controlled, blinded clinical trial. Methods: Four hundred sixty Quarter Horse and Thoroughbred foals at 5 large breeding farms in the Un...
Takai S, Sudo M, Sakai M, Suzuki K, Sasaki Y, Kakuda T, Suzuki Y.Rhodococcus equi was isolated from the gastrointestinal contents of earthworms (family Megascolecidae) and their surrounding soil collected from pastures of two horse-breeding farms in Aomori Prefecture, outdoor pig pens, forest in Towada campus, orange groves and forest where wild boars (Sus scrofa) are established in Tanabe, Wakayama Prefecture. The number of R. equi in the lower gastrointestinal contents of 23 earthworms collected from our campus was significantly larger than that of the upper gastrointestinal content. The mean numbers of R. equi from the gastrointestinal contents of earthw...
Erol E, Shaffer CL, Lubbers BV.The alarming increase in rifampin and macrolide resistance among Rhodococcus equi isolates highlights the need to identify alternative therapeutic options that can effectively control rhodococcosis in foals while limiting the further development of drug resistance. Objective: To evaluate bacterial killing, antibiotic synergism and mutant prevention concentrations (MPCs) of clarithromycin alone and in combination with doxycycline, minocycline or rifampin against clinical isolates of R equi. Methods: In vitro experiments. Methods: Bacterial time-kill, fractional inhibitory concentration (checker...
Żychska M, Witkowski L, Klementowska A, Rzewuska M, Kwiecień E, Stefańska I, Czopowicz M, Szaluś-Jordanow O, Mickiewicz M, Moroz A, Bonecka J.... infection is commonly known in equine medicine to cause frequently fatal rhodococcosis. Infections in other species and people are also reported. Clinical manifestation in goats is relatively similar to horses and humans, but data regarding bacterium prevalence are scarce. Thus, the study aimed to estimate the occurrence of in goats. Methods: During post mortem examination, submandibular, mediastinal, and mesenteric lymph nodes were collected. Standard methods were used for bacteria isolation and identification. Results: A total of 134 goats were examined, and 272 lymph node samples were col...
Vail KJ, da Silveira BP, Bell SL, Cohen ND, Bordin AI, Patrick KL, Watson RO.Rhodococcus equi is a major cause of foal pneumonia and an opportunistic pathogen in immunocompromised humans. While alveolar macrophages constitute the primary replicative niche for R. equi, little is known about how intracellular R. equi is sensed by macrophages. Here, we discovered that in addition to previously characterized pro-inflammatory cytokines (e.g., Tnfa, Il6, Il1b), macrophages infected with R. equi induce a robust type I IFN response, including Ifnb and interferon-stimulated genes (ISGs), similar to the evolutionarily related pathogen, Mycobacterium tuberculosis. Follow up studi...
Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Vinacur M, Cortez-Ramirez SC, Sutter PJ, Meyer SC, Bordin AI, Vlock DR, Pier GB....The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C՛1q) onto PNAG were d...
Cohen ND, Kahn SK, Cywes-Bentley C, Ramirez-Cortez S, Schuckert AE, Vinacur M, Bordin AI, Pier GB.Rhodococcus equi is a prevalent cause of pneumonia in foals worldwide. Our laboratory has demonstrated that vaccination against the surface polysaccharide β-1→6-poly-N-acetylglucosamine (PNAG) protects foals against intrabronchial infection with R. equi when challenged at age 28 days. However, it is important that the efficacy of this vaccine be evaluated in foals when they are infected at an earlier age, because foals are naturally exposed to virulent R. equi in their environment from birth and because susceptibility is inversely related to age in foals. Using a randomized, blind experim...
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...
Allegro AR, Barhoumi R, Bordin AI, Bray JM, Cohen ND.Rhodococcus equi is a soil saprophytic bacterium and intracellular pathogen that causes pneumonia in foals. Strains of R. equi that are virulent in foals contain a plasmid that encodes a virulence-associated protein A (VapA) necessary for replication in macrophages. Because other intracellular pathogens survive and replicate inside amoebae, we postulated that the VapA-bearing plasmid (pVAPA) confers a survival advantage for R. equi against environmental predators like amoebae. To test this hypothesis, we compared phagocytosis by and survival in Acanthamoeba castellanii of isogenic strains of p...
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...
Knych HK, Magdesian KG.Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence-based clinical decision-making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra-label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. P...
Miller AB, Loynachan AT, Barker VD, Adams AA.In order to better understand the influence of age on innate immune function in horses, blood was collected from twelve adult horses (aged 10-16 years; mean: 13 years) and ten geriatric horses (aged 18-26 years; mean: 21.7 years) for analysis of plasma myeloperoxidase, complete blood counts, and cytokine and receptor expression in response to in vitro stimulation with heat-inactivated Rhodococcus equi, heat-inactivated Escherichia coli, and PMA/ionomycin. Gene expression was measured using RT-PCR for IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-12α, IL-13, IL-17α, TLR2, TLR4, and TNFα. Endocrine fu...
Sanclemente JL, Rivera-Velez SM, Dasgupta N, Horohov DW, Wood PL, Sanz MG.Many foals that develop thoracic ultrasonographic lesions as a result of Rhodococcus equi infection heal on their own. However, most of these foals receive antimicrobials because foals at risk of developing clinical pneumonia cannot be identified. Untargeted lipidomics is useful to identify candidate biomarkers. Objective: (a) To describe the changes that occur in foal lipidomics as a result of ageing (birth to 8 weeks) and (b) To compare these results with those observed in foals after experimental infection with R. equi. Methods: Experimental study. Methods: Healthy newborn foals (n = 9) ...
Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M.Pneumonia caused by the intracellular bacterium Rhodococcus equi is an important cause of disease and death in immunocompromised hosts, especially foals. Antibiotics are the standard of care for treating R. equi pneumonia in foals, and adjunctive therapies are needed. We tested whether nebulization with TLR agonists (PUL-042) in foals would improve innate immunity and reduce the severity and duration of pneumonia following R. equi infection. Neonatal foals (n = 48) were nebulized with either PUL-042 or vehicle, and their lung cells infected ex vivo. PUL-042 increased inflammatory cytokines...
Álvarez-Narváez S, Giguère S, Cohen N, Slovis N, Vázquez-Boland JA.Multidrug resistance has been detected in the animal and zoonotic human pathogen Rhodococcus equi after mass macrolide/rifampin antibioprophylaxis in endemically affected equine farms in the United States. Multidrug-resistant (MDR) R. equi emerged upon acquisition of pRERm46, a conjugative plasmid conferring resistance to macrolides, lincosamides, streptogramins, and, as we describe, tetracycline. Phylogenomic analyses indicate that the increasing prevalence of MDR R. equi since it was first documented in 2002 is caused by a clone, R. equi 2287, attributable to coselection of pRErm46 with a ch...
Harvey AB, Bordin AI, Rocha JN, Bray JM, Cohen ND.Evidence regarding the efficacy of equine hyperimmune plasma to prevent pneumonia in foals caused by Rhodococcus equi is limited and conflicting. Objective: Opsonization with R. equi-specific hyperimmune plasma (HIP) will significantly increase phagocytosis and decrease intracellular replication of R. equi by alveolar macrophages (AMs) compared to normal plasma (NP). Methods: Fifteen adult Quarter Horses were used to collect bronchoalveolar lavage cells. Methods: In the first experiment, AMs from 9 horses were pretreated (incubated) with either HIP, NP, or media only (control) and then infecte...
Punsmann S, Hoppe J, Klopfleisch R, Venner M.Acute interstitial pneumonia in foals has been sparsely described in literature, and the individual authors disagree on the underlying aetiology. Histopathological follow-up from surviving foals is not available. Objective: Description of clinical and histopathological findings in the course of acute interstitial pneumonia and in recovery. Investigating the aetiology and possible triggering factors of acute interstitial pneumonia. Methods: Case series. Methods: Post-mortem examination of nine affected foals; seven died during the acute phase, and two had recovered from acute interstitial pneum...
Rakowska A, Cywinska A, Witkowski L.The aim of this review was to summarize studies on equine rhodococcosis over the last decade. For many years has remained one of the major health challenges in the equine breeding industry worldwide. Recently, many novel approaches and ideas have been described and some of them were initially implemented into the clinical practice. This study reviews a variety of new information about neonatal susceptibility, clinical appearance, considered and applied diagnostic procedures and treatment alternatives, factors limiting accurate prognosis, ideas regarding environmental management and prophylax...
Petry S, Sévin C, Kozak S, Foucher N, Laugier C, Linster M, Breuil MF, Dupuis MC, Hans A, Duquesne F, Tapprest J.Study of the rifampicin resistance of Rhodococcus equi strains isolated from French horses over a 20-year period. Rifampicin susceptibility was tested by disk diffusion (DD) and broth macrodilution methods, and rpoB gene sequencing and MLST were performed on 40 R. equi strains, 50.0% of which were non-susceptible to rifampicin. Consistency of results was observed between rifampicin susceptibility testing and rpoB sequencing. Strains non-susceptible to rifampicin by DD had a substitution at one of the sites (Asp516, His526 and Ser531) frequently encountered and conferring rifampicin resistance....
Bianchi MV, Mello LS, Ribeiro PR, Wentz MF, Stolf AS, Lopes BC, de Andrade CP, Snel GGM, Sonne L, Driemeier D, Pavarini SP.We document the causes and pathological findings in 50 cases of equine pneumonia and pleuritis in Southern Brazil. Suppurative (17/50), pyogranulomatous (14/50), aspiration (5/50), mycotic (4/50), bronchointerstitial (3/50), embolic (3/50) and eosinophilic granulomatous pneumonia (1/50) and pleuritis (3/50) were the main conditions identified. Streptococcus spp. were identified in 11 cases of suppurative pneumonia. Suppurative pneumonia was further divided into acute (8/17), subacute (6/17) and chronic (3/17) based on the morphological pattern of lesions. Rhodococcus equi was identified in all...
Kalinowski M, Jarosz Ł, Grądzki Z.Rhodococcus equi is an opportunistic, intracellular saprophyte that causes severe pyogranulomatous pneumonia in foals. The bacterium displays in vitro susceptibility to many antibiotics. The highest efficacy against R. equi in vitro and in vivo is achieved by using a combination of rifampicin and macrolide antibiotics. Recent years have seen an upward trend in the minimum inhibitory concentration (MIC) of rifampicin and erythromycin, suggesting increasing resistance of R. equi to these antibiotics. The aim of the study was to determine the antimicrobial activity of 24 selected antibiotics...
Yager JA.The pathogenesis of Rhodococcus equi pneumonia in foals is reviewed. The main routes of infection are respiratory and alimentary. The latter is probably the chief route of exposure in all foals and probably leads to development of specific immunity. Susceptible foals, those whose maternal immunity wanes before generation of their own immune response, readily develop disease if exposed aerogenously to sufficient numbers of R. equi. Management and environmental circumstances have a major role to play in determining the magnitude of this challenge and, therefore, in the prevalence of the disease....
Kanaly ST, Hines SA, Palmer GH.Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often fatal granulomatous pneumonia in young horses and in humans with AIDS. The inability of host alveolar macrophages to kill intracellular R. equi results in the development of granulomas and progressive loss of pulmonary parenchyma. Clearance of the organism from the lung requires functional CD4+ T cells. The purpose of this study was to identify the cytokine effector mechanisms that mediate clearance of R. equi from the lung. Mice were treated with monoclonal antibodies (MAbs) to either gamma interferon (IFN-gamma) o...
Cywes-Bentley C, Rocha JN, Bordin AI, Vinacur M, Rehman S, Zaidi TS, Meyer M, Anthony S, Lambert M, Vlock DR, Giguère S, Cohen ND, Pier GB.Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equi, that causes granulomatous pneumonia in horse foals, we devised and tested an experimental system relying solely on antibody-mediated protection against this host-specific etiologic agent. Immunity was induced by vaccinating pregnant mares 6 and 3 weeks prior to predicted parturition with a conjug...
Martens RJ, Martens JG, Fiske RA, Hietala SK.The immunoprophylactic capacity of specific immune plasma was evaluated in pony foals infected experimentally with Rhodococcus equi. Immune plasma, produced by repeated parenteral administration of viable R. equi to adult horses, was harvested and frozen. Group I (six control foals) and Group II (six principal foals) received lactated Ringers solution and immune plasma respectively at three and five days of age. R. equi were aerosolised into a caudal lung lobe of all foals at seven days of age. Clinical signs, haematological alterations, immune responses, thoracic radiographs and technetium99m...
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...
Barton MD, Hughes KL.A selective broth enrichment technique was used to study the distribution of Rhodococcus equi in soil and grazing animals. Rhodococcus equi was isolated from 54% of soils examined and from the gut contents, rectal faeces and dung of all grazing herbivorous species examined. Rhodococcus equi was not isolated from the faeces or dung of penned animals which did not have access to grazing. The isolation rate from dung was much higher than from other samples and this was found to be due to the ability of R. equi to multiply more readily in dung. Delayed hypersensitivity tests were carried out on ho...
Jacks SS, Giguère S, Nguyen A.The objective of this study was to determine in vitro activities of azithromycin (AZM), clarithromycin (CLR), and 20 other antimicrobial agents against Rhodococcus equi and other common equine bacterial pathogens. A total of 201 bacterial isolates from various equine clinical samples were examined. CLR was more active than AZM against R. equi, with MICs at which 90% of the isolates were inhibited of 0.12 and 1.0 micro g/ml, respectively. Other antimicrobial agents highly active against at least 90% of R. equi isolates in vitro included rifampin, gentamicin, and imipenem. Both AZM and CLR showe...
Woolcock JB, Farmer AM, Mutimer MD.The development of a selective medium for the isolation of Corynebacterium equi is described. The medium has been used to examine fecal samples from 127 horses of which 90 have been found to carry the organism.
Wada R, Kamada M, Anzai T, Nakanishi A, Kanemaru T, Takai S, Tsubaki S.Twelve foals, between 27 and 83 days old, were infected with 2 strains of Rhodococcus equi by intratracheal administration. Ten of the 12 foals were inoculated with 10(4)-10(10) colony forming units (cfu) of ATCC 33701 strain. The other 2 foals were inoculated with 10(9) cfu of a plasmid-cured derivative of the ATCC 33701 strain (ATCC 33701P-). All of the 10 foals challenged with the ATCC 33701 strain showed clinical signs of pulmonary disease within 5-13 days, such as gross lesions associated with acute bronchopneumonia and microscopic lesions associated with granulomatous pneumonia. The two ...
Hines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC.Rhodococcus equi is a gram-positive bacterium that infects alveolar macrophages and causes rhodococcal pneumonia in horses and humans. The virulence plasmid of R. equi appears to be required for both pathogenicity in the horse and the induction of protective immunity. An understanding of the mechanisms by which virulent R. equi circumvents protective host responses and by which bacteria are ultimately cleared is important for development of an effective vaccine. Six adult horses were challenged with either virulent R. equi or an avirulent, plasmid-cured derivative. By using a flow cytometric m...
Nordengrahn A, Rusvai M, Merza M, Ekström J, Morein B, Belák S.Equine herpesvirus type 2 (EHV-2), a member of the Gammaherpesvirinae subfamily, was studied in a two-phase respiratory disease complex of young foals as a predisposing factor for the secondary bacterial invasion of lungs with Rhodococcus equi (R. equi). Foals were immunized against EHV-2 on a farm where R. equi pneumonia regularly occurred during the last years. The immunizations were performed by using a subunit vaccine which selectively presents envelope glycoproteins of EHV-2 in a multimeric form of immunostimulating complexes (iscoms). The etiological role of EHV-2 was estimated by observ...
Muscatello G, Anderson GA, Gilkerson JR, Browning GF.The ecology of virulent strains of Rhodococcus equi on horse farms is likely to influence the prevalence and severity of R. equi pneumonia in foals. This study examined the association between the ecology of virulent R. equi and the epidemiology of R. equi pneumonia by collecting air and soil samples over two breeding seasons (28 farm-year combinations) on Thoroughbred breeding farms with different reported prevalences of R. equi pneumonia. Colony blotting and DNA hybridization were used to detect and measure concentrations of virulent R. equi. The prevalence of R. equi pneumonia was associate...
Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA.Rhodococcus equi infects and causes pneumonia in foals between 2 and 4 months of age but does not induce disease in immunocompetent adults, which are immune and remain clinically normal upon challenge. Understanding the protective response against R. equi in adult horses is important in the development of vaccine strategies, since those mechanisms likely reflect the protective phenotype that an effective vaccine would generate in the foal. Twelve adult horses were challenged with virulent R. equi and shown to be protected against clinical disease. Stimulation of cells obtained from bronchoalve...
Muscatello G.Rhodococcus equi pneumonia is a worldwide infectious disease of major concern to the equine breeding industry. The disease typically manifests in foals as pyogranulomatous bronchopneumonia, resulting in significant morbidity and mortality. Inhalation of aerosolised virulent R. equi from the environment and intracellular replication within alveolar macrophages are essential components of the pathogenesis of R. equi pneumonia in the foal. Recently documented evidence of airborne transmission between foals indicates the potential for an alternative contagious route of disease transmission. In the...
Álvarez-Narváez S, Berghaus LJ, Morris ERA, Willingham-Lane JM, Slovis NM, Giguere S, Cohen ND.The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (...
Cohen ND.Pneumonia caused by Rhodococcus equi is an important cause of disease and death in foals. This article reviews current knowledge of the epidemiology, clinical signs, diagnosis, treatment, prevention, and control of R equi pneumonia in foals.
Giguère S, Jacks S, Roberts GD, Hernandez J, Long MT, Ellis C.The objective of this retrospective study was to compare the efficacy of azithromycin-rifampin, clarithromycin-rifampin, and erythromycin-rifampin for the treatment of pneumonia caused by Rhodococcus equi in foals. Eighty-one foals with naturally acquired pneumonia caused by R. equi were included in the study. Information on age, sex, breed, physical examination findings, laboratory testing, and thoracic radiography was abstracted from each medical record. Foals were divided in 3 groups based on the antimicrobial agent selected for therapy. Short-term (discharge from the hospital) and long-ter...
Giguère S, Lee EA, Guldbech KM, Berghaus LJ.There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, ami...
Venner M, Astheimer K, Lämmer M, Giguère S.Mass antimicrobial treatment of foals with small subclinical ultrasonographic pulmonary lesions is empirical practice on many farms with endemic disease caused by Rhodococcus equi. Objective: Mass antimicrobial treatment of foals with subclinical ultrasonographic pulmonary lesions is unnecessary. Methods: One hundred and eight foals on a farm endemic for infections caused by R. equi. Methods: Controlled, randomized, and double-blinded prospective study. Foals with ultrasonographic evidence of pulmonary abscesses 5.0-10 cm in diameter (n = 108) were randomly allocated in 5 treatment groups: (1)...
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...
Sweeney CR, Sweeney RW, Divers TJ.Case records of 48 foals with pneumonia due to Rhodococcus equi were reviewed. Twenty of the 48 foals survived and 28 died or were euthanized. There was no significant difference between the survivors and non-survivors in the age of onset of illness, duration of illness prior to admission, the mean white blood cell (WBC) count, or the mean plasma fibrinogen content. All foals had R. equi isolated from a tracheobronchial aspirate or lung specimens obtained at necropsy. All organisms were susceptible in vitro (Kirby-Bauer) to erythromycin and gentamicin. Susceptibilities to other drugs were: tri...
Álvarez-Narváez S, Giguère S, Cohen N, Slovis N, Vázquez-Boland JA.Multidrug resistance has been detected in the animal and zoonotic human pathogen Rhodococcus equi after mass macrolide/rifampin antibioprophylaxis in endemically affected equine farms in the United States. Multidrug-resistant (MDR) R. equi emerged upon acquisition of pRERm46, a conjugative plasmid conferring resistance to macrolides, lincosamides, streptogramins, and, as we describe, tetracycline. Phylogenomic analyses indicate that the increasing prevalence of MDR R. equi since it was first documented in 2002 is caused by a clone, R. equi 2287, attributable to coselection of pRErm46 with a ch...
Riesenberg A, Feßler AT, Erol E, Prenger-Berninghoff E, Stamm I, Böse R, Heusinger A, Klarmann D, Werckenthin C, Schwarz S.The aim of this study was to determine the MICs of 32 antimicrobial agents for 200 isolates of Rhodococcus equi of animal origin by applying a recently described broth microdilution protocol, and to investigate isolates with distinctly elevated rifampicin MICs for the genetic basis of rifampicin resistance. Methods: The study included 200 R. equi isolates, including 160 isolates from horses and 40 isolates from other animal sources, from the USA and Europe. MIC testing of 32 antimicrobial agents or combinations thereof followed a recently published protocol. A novel PCR protocol for the joint ...
Garton NJ, Gilleron M, Brando T, Dan HH, Giguère S, Puzo G, Prescott JF, Sutcliffe IC.Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and (1)H and (31)P and two-dimensional heteronuclear nuclear magnetic resonance studies. Key structural features of the lipoglycan are a linear alph...
Halbert ND, Reitzel RA, Martens RJ, Cohen ND.To evaluate sensitivity and specificity of a multiplex polymerase chain reaction (PCR) assay for simultaneous detection of Rhodococcus equi and differentiation of strains that contain the virulence-associated gene (vapA) from strains that do not. Methods: 187 isolates of R equi from equine and nonequine tissue and environmental specimens and 27 isolates of bacterial species genetically or morphologically similar to R equi. Methods: The multiplex PCR assay included 3 gene targets: a universal 311-bp bacterial 16S ribosomal RNA amplicon (positive internal control), a 959-bp R equi-specific targe...
Tripathi VN, Harding WC, Willingham-Lane JM, Hondalus MK.Rhodococcus equi is a facultative intracellular, Gram-positive, soilborne actinomycete which can cause severe pyogranulomatous pneumonia with abscessation in young horses (foals) and in immunocompromised people, such as persons with AIDS. All strains of R. equi isolated from foals and approximately a third isolated from humans contain a large, ~81-kb plasmid which is essential for the intramacrophage growth of the organism and for virulence in foals and murine in vivo model systems. We found that the entire virulence plasmid could be transferred from plasmid-containing strains of R. equi (dono...
Gustafsson A, Båverud V, Gunnarsson A, Rantzien MH, Lindholm A, Franklin A.In Sweden there are several reports of mares developing acute colitis while their foals were being treated orally for Rhodococcus equi pneumonia with the combination of erythromycin and rifampicin. In this study 6 adult horses were given low oral dosages of these antibiotics, singly or in combination. Within 3 days post administration of erythromycin, in one case in combination with rifampicin, 2 horses developed severe colitis (one fatal). Clostridium difficile was isolated from one of the horses, whereas no specific pathogens were isolated from the other. Both horses had typical changes in b...
Giguère S, Gaskin JM, Miller C, Bowman JL.To determine efficacy of a commercially available hyperimmune plasma product for prevention of naturally acquired pneumonia caused by Rhodococcus equi in foals. Methods: Randomized clinical trial. Methods: 165 foals. Methods: Foals were randomly assigned to 1 of 2 groups (hyperimmune plasma or nontreated controls). Foals with failure of passive transfer (FPT) of immunity were treated with hyperimmune plasma and evaluated as a third group. Foals that received plasma were given 950 ml between 1 and 10 days of age and between 30 and 50 days of age. A tracheobronchial aspirate was obtained from fo...
Horowitz ML, Cohen ND, Takai S, Becu T, Chaffin MK, Chu KK, Magdesian KG, Martens RJ.The distributions of the incubation periods for infectious and neoplastic diseases originating from point-source exposures, and for genetic diseases, follow a lognormal distribution (Sartwell's model). Conversely, incubation periods in propagated outbreaks and diseases with strong environmental components do not follow a lognormal distribution. In this study Sartwell's model was applied to the age at onset and age at death of foals with Rhodococcus equi pneumonia. The age at onset of clinical signs and age at death were compiled for 107 foals that had been diagnosed with R. equi pneumonia at b...
