Equi Pneumonia Research Articles

Monitoring of inflammatory blood biomarkers in foals with Rhodococcus Equi pneumonia during antimicrobial treatment

Rhodococcus equi (R. equi), a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals and represents a major cause of disease and death. The aim of the present study was to investigate the time-depended changes in White Blood Cells (WBC), basophils (Baso), neutrophils (Neu), lymphocytes (Lymf), monocytes (Mon), eosinophils (Eos), platelet (PLT) counts, fibrinogen (Fbg) concentration, interferon (IFN-α, IFN-γ) and interleukins (IL-2 and IL-10) in foals with clinical R. equi pneumonia. The main treatment was with azithromycin-rifampicin for 14 days. Blood was sampled prior to, 7 and 14 days after starting therapy. Treatment was associated with significantly decreased counts of WBC, (25.6 ± 6.7 and 14.2 ± 2,7 × 103/ml), Neu (18.6 ±6.2 and 10.7 ± 3.1 × 103/ml), Mon (1.5 ± 0.5 and 0.9 ± 0.2 × 103/ml) and Fbg (539 ± 124 and 287 ± 26 g/dl) between day 0 and day 14. IL-2 and IL-10 concentrations were significantly increased (P = 0.028, P = 0.013, respectively) after treatment, whereas IFN-α and IFN-γ concentrations were not. The diagnostic potentials of INF-α, INF-γ, IL-2 and IL-10 per se seems not very high, however, the study suggests that the activity change of selected interleukins in the course of the disease may be associated with amelioration. We concluded that patterns of serum concentration changes of INF-α, INF-γ, IL-2 and IL-10 may help in the study of the innate immune response in foals during infection and treatment of R. equi pneumonia.

The N-terminal domain is required for cell surface localisation of VapA, a member of the Vap family of Rhodococcus equi virulence proteins.

Rhodococcus equi pneumonia is an important cause of mortality in foals worldwide. Virulent equine isolates harbour an 80-85kb virulence plasmid encoding six virulence-associated proteins (Vaps). VapA, the main virulence factor of this intracellular pathogen, is known to be a cell surface protein that creates an intracellular niche for R. equi growth. In contrast, VapC, VapD and VapE are secreted into the intracellular milieu. Although these Vaps share very high degree of sequence identity in the C-terminal domain, the N-terminal domain (N-domain) of VapA is distinct. It has been proposed that this domain plays a role in VapA surface localization but no direct experimental data provides support to such hypothesis. In this work, we employed R. equi 103S harbouring an unmarked deletion of vapA (R. equi ΔvapA) as the genetic background to express C-terminal Strep-tagged Vap-derivatives integrated in the chromosome. The surface localization of these proteins was assessed by flow cytometry using the THE2122;-NWSHPQFEK Tag FITC-antibody. We show that VapA is the only cell surface Vap encoded in the virulence plasmid. We present compelling evidence for the role of the N-terminal domain of VapA on cell surface localization using fusion proteins in which the N-domain of VapD was exchanged with the N-terminus of VapA. Lastly, using an N-terminally Strep-tagged VapA, we found that the N-terminus of VapA is exposed to the extracellular environment. Given the lack of a lipobox in VapA and the exposure of the N-terminal Strep-tag, it is possible that VapA localization on the cell surface is mediated by interactions between the N-domain and components of the cell surface. We discuss the implications of this work on the light of the recent discovery that soluble recombinant VapA added to the extracellular medium functionally complement the loss of VapA.

Evaluation of oxidative stress in foals with Rhodococcus equi infection-induced pneumonia for the judgment of therapeutic effect.

Forty-five foals with Rhodococcus equi infection and pneumonia symptoms were classified into a surviving group and a dead group. Using serum samples, the oxidative stress index (OSI) was determined at the first visit and the follow-up visit. The OSI of the surviving group was significantly lower at the follow-up than that at the first visit. No significant difference was observed between the OSI of the dead group at the first and follow-up visits. In the surviving group, treatment at the first visit mitigated inflammation and reduced OSI. However, in the dead group, poor response to the treatment provided at the first visit led to continued inflammation, and no change was observed the OSI.

Evaluation of serum concentration of acute-phase proteins (haptoglobin and serum amyloid A) in the affected Arabian foals with rhodococcosis.

Early detection of Rhodococcus equi pneumonia in foals is essential for horse health and for veterinarians. This study aimed to demonstrate the usefulness of assessing the serum concentration of acute-phase proteins (APPs) in the early diagnosis of pneumonia. The study evaluated APPs in 19 Arabian foals with R. equi pneumonia and compared them with 18 normal Arabian foals in equestrian clubs in Tabriz, Iran. Affected foals were identified through history, clinical findings and bacterial culture of tracheal washing. Biochemical methods and polymerase chain reaction tests were performed by examining the 16S rRNA and vapA genes to confirm the diagnosis of bacterial isolates. Blood samples were taken from all sick and healthy horses, and their serum was isolated. APPs in the serum were measured in all the samples. Rhodococcosis increased the serum concentration of haptoglobin (Hp) and serum amyloid A (SAA) (p < 0.001). The relationship between SAA and Hp was meaningful in the infected group (r = 0.933) but not in the healthy group. In cases where there are clinical findings of R. equi pneumonia, the concentration of SAA and Hp can help the effectiveness of treatment. Serum concentration analysis of APPs can be helpful in early diagnosis and successfully treating foals with R. equi pneumonia.

Transfusion of hyperimmune plasma for protecting foals against Rhodococcus equi pneumonia.

The bacterium Rhodococcus equi causes pneumonia in foals that is prevalent at breeding farms worldwide. In the absence of an effective vaccine, transfusion of commercial plasma from donor horses hyperimmunised against R. equi is used by many farms to reduce the incidence of pneumonia among foals at farms where the disease is endemic. The effectiveness of hyperimmune plasma for controlling R. equi pneumonia in foals has varied considerably among reports. The purposes of this narrative review are: (1) to review early studies that provided a foundational basis for the practice of transfusion of hyperimmune plasma that is widespread in the United States and in many other countries; (2) to summarise current knowledge of hyperimmune plasma for preventing R. equi pneumonia; (3) to provide an interpretive summary of probable explanations for the variable results among studies evaluating the effectiveness of transfusion of hyperimmune plasma for reducing the incidence of R. equi pneumonia; (4) to review mechanisms by which hyperimmune plasma might mediate protection; and (5) to consider risks of transfusing foals with hyperimmune plasma. Although the weight of evidence supports the practice of transfusing foals with hyperimmune plasma to prevent R. equi pneumonia, many important gaps in our knowledge of this topic remain including the volume/dose of hyperimmune plasma to be transfused, the timing(s) of transfusion, and the mechanism(s) by which hyperimmune plasma mediates protection. Transfusing foals with hyperimmune plasma is expensive, labour-intensive, and carries risks for foals; therefore, alternative approaches for passive and active immunisation to prevent R. equi pneumonia are greatly needed.

Rhodococcus equi foal pneumonia: Update on epidemiology, immunity, treatment and prevention.

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 in North America. Correlates of protective immunity for R. equi infections of foals remain elusive, but recent evidence indicates that innate immune responses are important both for mediating killing and orchestrating adaptive immune responses. A macrolide antimicrobial in combination with rifampin remains the recommended treatment for foals with R. equi pneumonia. Great need exists to identify which antimicrobial combination is most effective for treating foals with R. equi pneumonia and to limit emergence of antimicrobial-resistant strains. In the absence of an effective vaccine against R. equi, passive immunisation remains the only commercially available method for effectively reducing the incidence of R. equi pneumonia. Because passive immunisation is expensive, labour-intensive and carries risks for foals, great need exists to develop alternative approaches for passive and active immunisation.

Birth month associated with tracheal colonization of Rhodococcus equi in newborn foals on horse-breeding farms with sporadic rhodococcosis in Japan

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 observation, 9/30 foals (30.0 %) born in February showed the first clinical signs at 56 ± 8 d old, 21/61 foals (34.4 %) born in March showed the signs at 37 ± 3 d old, 15/49 foals (30.6 %) born in April showed the signs at 39 ± 2 d old, and 7/30 foals (23.3 %) born in May showed signs at 44 ± 3 d old. Two sick foals (6.7 %) born in February, 19 sick foals (31.1 %) born in March, 15 sick foals (30.6 %) born in April, and 6 sick foals (20.0 %) born in May showed a positive culture of R. equi at 28 or 35 d old. The present study revealed that birth month is associated with the initial colonization of R. equi in the trachea of newborn foals on farms with sporadic rhodococcosis in Japan. Therefore, birth month might be a risk factor for developing R. equi pneumonia in foals.

Randomized, controlled trial comparing Rhodococcus equi and poly-N-acetyl glucosamine hyperimmune plasma to prevent R equi pneumonia in foals.

BackgroundHyperimmune 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.HypothesisTransfusion with PNAG HIP will be superior to RE HIP in foals for protection against R equi pneumonia in a randomized, controlled, blinded clinical trial.AnimalsFour hundred sixty Quarter Horse and Thoroughbred foals at 5 large breeding farms in the United States.MethodsA randomized, controlled, blinded clinical trial was conducted in which foals were transfused within 24 hours after birth with 2 L of either RE HIP or PNAG HIP. Study foals were monitored through weaning for clinical signs of pneumonia by farm veterinarians. The primary outcome was the proportion of foals that developed pneumonia after receiving each type of plasma.ResultsThe proportion of foals that developed pneumonia was the same between foals transfused with RE HIP (14%; 32/228) and PNAG HIP (14%; 30/215).Conclusions and Clinical ImportanceResults indicate that PNAG HIP was not superior to a commercially available, United States Department of Agriculture‐licensed RE HIP product for protecting foals against R equi pneumonia under field conditions.

Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.

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 determined by ELISA, and then associated with either clinical pneumonia at Farm A (n = 119) or subclinical pneumonia at Farm B (n = 114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C՛1q deposition, respectively. Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C՛1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.

Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia

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 in BAL fluid and alveolar macrophages after ex vivo infection with R. equi. Then, the in vivo effects of PUL-042 on clinical signs of pneumonia were examined in 22 additional foals after intrabronchial challenge with R. equi. Foals infected and nebulized with PUL-042 or vehicle alone had a shorter duration of clinical signs of pneumonia and smaller pulmonary lesions when compared to non-nebulized foals. Our results demonstrate that host-directed therapy can enhance neonatal immune responses against respiratory pathogens and reduce the duration and severity of R. equi pneumonia.

Changing policy to treat foals with Rhodococcus equi pneumonia in the later course of disease decreases antimicrobial usage without increasing mortality rate.

There is a lack of data on the efficacy of treatment of Rhodococcus equi pneumonia in association with an optimised selection of foals. To evaluate whether targeted treatment protocols resulting in decreased antimicrobial use impact foal mortality rates. Retrospective study. Three hundred and thirty foals with pneumonia per year were randomly selected from 2008 to 2016. All foals were examined once weekly from birth until weaning. A physical examination of the respiratory tract, body temperature, haematology and an ultrasonographic examination of the lungs was included. Sonography areas with visible consolidation were measured and added to calculate an 'abscess score' which represents the extent of pulmonary damage. All weekly medical data were analysed retrospectively. In the period from 2008 to 2011, every foal with pulmonary abscesses was treated. The treatment protocol was changed in 2012 when only foals with larger lesions were treated. Between the two time periods 2008-2011 and 2012-2016, the abscess score at the beginning of treatment increased from a median of 4-11.5cm. From all foals that developed Requi pneumonia, 81.5% received antibiotic treatment in 2008-2011 (n=1215) compared with 50.9% in 2012-2016 (n=1541). The percentage of foals that died from pneumonia or Requi infections did not differ significantly between 2008-2011 and 2012-2016 (0.4% vs 0.6% respectively; P=.6). There was some lack of clarity in old data because this was a retrospective study; therefore, some foals had to be excluded from data analysis. Alteration of treatment criteria, to exclude antibiotic treatment of foals with smaller lesions, has significantly decreased the number of foals being treated without a significant increase in mortality from Requi pneumonia.

Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA

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 < 0.05). Seventy-six percent (76%) of farms yielded resistant R. equi, and resistance to macrolides and rifampicin was associated with their use at farms. The present study is the first to report the prevalence and distribution of resistant isolates in the environment of farms in Kentucky, USA. Collectively, previous reports and the data presented herein provide irrefutable evidence of emerging antimicrobial resistance in R. equi with alarming prevalence. Widespread dissemination and maintenance of resistance genes in the environment where many other pathogenic bacteria exist is a concern for both animal and human health.

Transfusion With 2 L of Hyperimmune Plasma is Superior to Transfusion of 1 L or Less for Protecting Foals Against Subclinical Pneumonia Attributed to Rhodococcus equi

Transfusing foals with Rhodococcus equi hyperimmune plasma (REHIP) is a standard practice at many horse-breeding farms to help prevent R. equi pneumonia. At many large breeding farms, pneumonia is most commonly recognized as subclinical based on thoracic ultrasonography findings. The efficacy of REHIP transfusion and the impact of the volume of plasma transfused for reducing the cumulative incidence of subclinical R. equi pneumonia are unknown. A retrospective cohort study was conducted among foals born and residing through weaning at a large breeding farm. Foals were transfused with either 0 L (n = 2 foals), 1 L (n = 85 foals), or 2 L (n = 62 foals) of REHIP within 36 hours of birth. Volume transfused was principally based on intended use of the foals. All foals at the ranch were routinely screened using thoracic ultrasonography at 5, 7, and 9 weeks of age to detect subclinical pneumonia attributed to R. equi based on farm history. The proportion of the foals receiving < 1 L REHIP that developed subclinical pneumonia (32%; 26/82) was significantly (P = .0068; chi-squared test) greater than that among foals transfused with 2 L of REHIP (12%; 8/68). Despite the important limitations of this observational study, it provides evidence supporting the need for well-designed clinical trials to evaluate the impact of the use and dose of REHIP for preventing subclinical pneumonia. Reducing the incidence of subclinical pneumonia is important because reducing antibiotic treatment of subclinical cases will decrease selection pressure for antimicrobial resistance in R. equi.

Foal-Level Risk Factors Associated With Development of Rhodococcus equi Pneumonia at a Quarter Horse Breeding Farm

The occurrence of Rhodococcus equi at farms varies, with disease occurring endemically at some farms, but only sporadically, or not at all at other farms. Only some foals residing on endemic farms develop clinical signs of disease. Limited evidence is available regarding foal-level risk factors for the development of R. equi pneumonia. The purpose of this study was to identify foal-level risk factors associated with the development of R. equi pneumonia among foals at a large breeding farm in Texas with a recurrent problem of R. equi pneumonia. A retrospective cohort study was conducted using data from foals born at the farm from January 2009 through December 2011 that met the criteria for inclusion. Dam-level, foal-level, and health-related data were collected from all foals. Independent variables were analyzed with logistic regression, controlling for the effect of year. Data from 787 foals born at the farm were included, of which 209 (27%) developed R. equi pneumonia. The cumulative incidence of disease at the farm varied significantly by year. Foals that were diagnosed with a prior morbidity besides R. equi were less likely to develop R. equi pneumonia.

Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi.

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 conjugate vaccine targeting the highly conserved microbial surface polysaccharide, poly-N-acetyl glucosamine (PNAG). We ascertained antibody was transferred to foals via colostrum, the only means for foals to acquire maternal antibody. Horses lack transplacental antibody transfer. Next, a randomized, controlled, blinded challenge was conducted by inoculating at ~4 weeks of age ~106 cfu of R. equi via intrabronchial challenge. Eleven of 12 (91%) foals born to immune mares did not develop clinical R. equi pneumonia, whereas 6 of 7 (86%) foals born to unvaccinated controls developed pneumonia (P = 0.0017). In a confirmatory passive immunization study, infusion of PNAG-hyperimmune plasma protected 100% of 5 foals against R. equi pneumonia whereas all 4 recipients of normal horse plasma developed clinical disease (P = 0.0079). Antibodies to PNAG mediated killing of extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms depended on antibody recognition of surface expression of PNAG on infected cells, along with complement deposition and PMN-assisted lysis of infected macrophages. Peripheral blood mononuclear cells from immune and protected foals released higher levels of interferon-γ in response to PNAG compared to controls, indicating vaccination also induced an antibody-dependent cellular release of this critical immune cytokine. Overall, antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against diseases caused by intracellular bacterial pathogens.

Rhodococcus equi Pneumonia in Kidney Transplant Recipient Affected by Acute Intermittent Porphyria: A Case Report

Rhodococcus equi is a gram-positive coccobacillus responsible for severe infections in patients with weakened immune systems. R equi generally causes pnumonia that may evolve into fatal systemic infection if left untreated. Here, we present a case of a 67-year-old woman affected by acute intermittent porphyria (AIP) who developed R equi pneumonia 7 months after kidney transplantation. Although clinical features at presentation were nonspecific, lung computed tomography showed right perihilar consolidation with a mass-like appearance causing bronchial obstruction. Appropriate antibiotic including intravenous meropenem and oral azithromycin that was then switched to oral levofloxacin and oral azithromycin along with reduction of immunosuppressive therapy resolved pneumonia without provoking an acute attack of porphyria. AIP limited the choice of antibiotics for the treatment of R equi infection because some potentially porphyrinogenic antibacterial agents were avoided. Based on this experience, azithromycin and meropenem can be safely administered for the treatment of R Equi infection in patients with AIP.

Differential distribution of vapA-positive Rhodococcus equi in affected and unaffected horse-breeding farms

Rhodococcus equi causes pulmonary and extrapulmonary infections in animals and humans, with endemic situations and significant young foal mortality in horse-breeding farms worldwide (von Bargen and Haas 2009, Muscatello 2012,...

Prevention and treatment of Rhodococcus equi infection in foals: an update

Rhodococcus equiis a Gram-positive facultative intracellular bacterial pathogen that primarily infects macrophages. It is considered to be the most important cause of pneumonia in foals aged three weeks to five...

Use of Serial Quantitative PCR of the vapA Gene of Rhodococcus equi in Feces for Early Detection of R. equi Pneumonia in Foals.

BackgroundCurrent screening tests for Rhodococcus equi pneumonia in foals lack adequate accuracy for clinical use. Real‐time, quantitative PCR (qPCR) for virulent R. equi in feces has not been systematically evaluated as a screening test.ObjectiveThe objective of this study was to evaluate the accuracy of qPCR for vapA in serially collected fecal samples as a screening test for R. equi pneumonia in foals.AnimalsOne hundred and twenty‐five foals born in 2011 at a ranch in Texas.MethodsFecal samples were collected concurrently with thoracic ultrasonography (TUS) screening examinations at ages 3, 5, and 7 weeks. Affected (pneumonic) foals (n = 25) were matched by age and date‐of‐birth to unaffected (n = 25) and subclinical (ie, having thoracic TUS lesions but no clinical signs of pneumonia) foals (n = 75). DNA was extracted from feces using commercial kits and concentration of virulent R. equi in feces was determined by qPCR.ResultsSubsequently affected foals had significantly greater concentrations of vapA in feces than foals that did not develop pneumonia (unaffected and subclinical foals) at 5 and 7 weeks of age. Accuracy of fecal qPCR, however, was poor as a screening test to differentiate foals that would develop clinical signs of pneumonia from those that would remain free of clinical signs (including foals with subclinical pulmonary lesions attributed to R. equi) using receiver operating characteristic (ROC) methods.Conclusions and Clinical ImportanceIn the population studied, serial qPCR on feces lacked adequate accuracy as a screening test for clinical R. equi foal pneumonia.

Successful management of multiple extrapulmonary complications associated with Rhodococcus equi pneumonia in a foal

SummaryThis report describes the diagnosis and successful treatment of multiple extrapulmonary sequelae of Rhodococcus equi (R. equi) pneumonia in a 3‐month‐old filly. Bilateral uveitis and hyphaema, haemolytic anaemia and polysynovitis developed in this foal and were likely due to immune‐mediated mechanisms. The challenges associated with diagnosis and treatments of these extrapulmonary disorders are discussed. The filly was treated initially with clarithromycin and rifampin; however, a blood transfusion and immunosuppressive therapy with dexamethasone were required due to progressive haemolysis and for treatment of uveitis and polysynovitis. Bilateral hyphaema was successfully treated with intracameral injections of a recombinant tissue plasminogen activator. The development of antimicrobial resistance in R. equi was an additional challenge encountered in the management of this case and emphasises the importance of culture and in vitro antimicrobial susceptibility testing of isolates from foals with R. equi pneumonia. Extrapulmonary disorders associated with R. equi pneumonia are likely underdiagnosed and associated with a poor prognosis. This case highlights the importance of thorough and ongoing diagnostic assessment of foals with R. equi pneumonia and demonstrates that a successful outcome can be achieved with appropriate and directed treatment.