Rhodococcus equi pleuropneumonia in an adult horse

Abstract

A 10-year-old warmblood gelding was evaluated for intermittent pyrexia, dullness, weight loss, and progressive respiratory disease. Multifocal necrotic pneumonia and pleuritis due to Rhodococcus equi infection was diagnosed. Case management is discussed, as well as factors that may have led to this rare cause of pleuropneumonia in an adult horse.

Rhodococcus equi is an important cause of a pyogranulomatous pneumonia in foals between 1 and 6 mo of age (1,2), with most cases occurring in foals younger than 4 mo. Less common manifestations of R. equi infection in foals are intestinal disease, immune-mediated polysynovitis, septic arthritis and osteomyelitis, and soft tissue infections (1,2). Rhodococcus equi is a soil organism, the growth of which is increased by herbivore manure (1,2,3); it can cause infection in wide variety of mammals, often following immunosuppression (2). It is an important opportunistic pathogen in immunosuppressed humans, such as with acquired immuno deficiency syndrome (AIDS) patients or organ transplantation patients who are receiving immunosuppressive therapy (2,4).

Disease due to R. equi is rare in adult horses (1). It manifests itself as an illness similar to that in foals, involving the lungs or the colon and related lymph nodes, or, rarely, as a uterine or wound infection (1,5,6,7,8). Acquired immunodeficiency of unknown cause in an adult horse that was complicated by R. equi septicemia with lung abscessation, reported by Freestone et al (5), and chronic pyogranulomatous lymphadenitis and enteritis caused by R. equi in a mare, reported by Genetzky et al (6), are the only cases described in detail.

A 10-year-old warmblood gelding (511 kg) was presented to the Ontario Veterinary College (OVC) with a 3-week history of recurrent fever, dullness, weight loss, and progressive respiratory disease following prolonged transportation. The horse had been transported to Ontario from New York State for a sale. Initial examination by the referring veterinarian 10 d prior to presentation at the OVC had revealed weight loss, increased lung sounds, and occasional cough. The horse was treated parenterally with trimethoprim-sulfadiazine, penicillin, and a thyroid supplement (dosages unknown). Response to treatment was poor, and 3 d prior to presentation at the OVC, the horse refused to eat and became more lethargic. Mild anemia, leukocytosis, hyperglobulinemia, and increased serum glucose were blood abnormalities reported prior to referral. The horse had no other major health problem in the 5 y prior to its present problem.

On admission, the horse was depressed and in poor body condition with a dry, dull hair coat. Rectal temperature (39.2°C), heart rate (60 beats/min), and respiratory rate (32 breaths/min) were all elevated. Mucous membranes were dark pink with normal capillary refill time. The animal was subjectively estimated to be 5% dehydrated. The lung sounds were absent bilaterally ventrally, indicative of lung consolidation, the presence of excess pleural fluid, or a space-occupying lesion. Percussion of the left lung field indicated a fluid line. It was not possible to characterize a definite fluid line on the right side. Thoracic radiographs revealed consolidation of the pulmonary parenchyma in the ventral pulmonary field and a heavy interstitial pattern of increased pulmonary radiopacity in the rest of the lungs. Thoracic ultrasonography showed the presence of pleural effusion with pleural roughening in the left hemithorax and minimal amount of pleural fluid and consolidation of lung tissue in the right hemithorax. A temporary chest drain was placed in the 7th intercostal space, 5 cm dorsal to the costochrondral junction, and samples of pleural fluid for bacteriologic culture and cytologic examination were obtained. Approximately 4 L of yellow cloudy fluid was drained from the left pleural space. Thoracocentesis of the right 6th intercostal space with a teat cannula, 2 cm dorsal to the costochondral junction, yielded no fluid. Cytologic examination of the fluid from the left pleural space revealed an increased cellularity (17.4 × 10⁹/L cells; normal < 10 × 10⁹/L cells), consisting mostly of degenerating neutrophils. No bacteria were identified microscopically or in cultures. The pleural fluid had a high protein concentration (47 g/L, normal < 30 g/L), a low glucose concentration (2.8 mmol/L; normal > 3.7 mmol/L), and a normal concentration of lactate dehydrogenase (459 U/L; normal < 1000 U/L). Its pH was 7.0. Clinical pathological findings of pleural fluid were suggestive of a septic inflammatory reaction.

Blood analysis revealed a mild leukopenia (4.2 × 10⁹ leukocytes/L; normal 4.9 to 14 × 10⁹ leukocytes/L), likely due to inflammatory cells being recruited to the site of infection. The lymphocyte count was 0.13 × 10⁹ cells/L (normal 1.3 to 4.7 × 10⁹ cells/L) and the monocyte count was 0.08 × 10⁹ cells/L (normal 0.1 to 0.8 × 10⁹ cells/L). Total serum protein was within normal range (67 g/L), but the albumin:globulin ratio was low (0.60, normal 0.8 to1.3), due to low serum albumin concentration (25 g/L, normal 30 to 37 g/L) and mildly increased serum globulin concentration (42 g/L, normal 26 to 41 g/L). The hypoalbuminemia was attributed to the formation of a high-protein effusion into the pleural space and the mild hyperglobulinemia to the increased production of immunoglobulins. Plasma fibrinogen concentration was high at 6.7 g/L (normal 1.6 to 2.9 g/L). These findings were supportive of an ongoing, active inflammatory process. Arterial blood gas of the resting horse (breathing room air) was analyzed and yielded PaO₂ at 87.2 mmHg (normal 100 to 112 mmHg) and PaCO₂ at 34.4 mmHg (normal 42 to 47 mmHg).

Endoscopic examination of the airways showed moderate amounts of thick, brownish fluid in the ventral aspect of the trachea. At the level of the carina, a large amount of thick, brown purulent exudate, traceable from the 2nd bronchus of the right lung, was collected with a sterile indwelling catheter for laboratory evaluation. A small amount of exudate was also recovered with a sterile indwelling catheter from the left terminal bronchus. Cytologic examination of the tracheal and bronchial aspirates revealed high numbers of lytic neutrophils, consistent with marked suppurative infectious inflammation. Based on these initial tests, a diagnosis of severe septic pleuropneumonia with intrapulmonary abscesses was made. A β-hemolytic Streptococcus spp. infection with gram-negative bacterial complication was suspected. Anaerobic infection was also considered. Initial therapy, therefore, consisted of IV fluid therapy with lactated Ringer's solution, (5 mL/kg body weight (BW)/h); penicillin G sodium (Penicillin G Sodium for Injection; Novopharm Limited, Toronto, Ontario), 22 000 IU/kg BW, IV, q6h; gentamicin (Gentamicin Sulphate Injection; The Veterinary Pharmacy, Guelph, Ontario), 6.6 mg/kg BW, IV, q24h; flunixin meglumine (Flunazine; Bimeda-MTC Animal Health, Cambridge, Ontario), 1.1 mg/kg BW, IV, q12h; and metronidazole (Apo-Metronidazole; Apotex Inc., Toronto, Ontario), 20 mg/kg BW, PO, q6h. The horse's condition worsened over the 48 h of hospitalization. Due to the poor response to the treatment and financial constraints, the horse was euthanized.

The bacterial cultures of tracheal and bronchial fluid samples obtained by lung endoscopy were reported only after the horse's death. They were positive for large numbers of R. equi in pure culture.

Postmortem examination revealed that the ventral region of the right caudal lung lobe was diffusely consolidated. Throughout the rest of the lung, there were small, firm, round, 3- to 5-cm tan nodules. On the cut surface, some of these were solid and tan-white, while others contained caseous material. Fibrin tags were on the pleural surface and clear red fluid was in the pleural space. Histologic examination of lung revealed marked, multifocal, obliterative inflammation comprised of large numbers of lymphocytes, plasmacytes, and neutrophils. There were marked amounts of mature, organized fibrous tissue interspersed in areas with increased numbers of fibroblasts, indicating chronic pneumonia. In some areas, the normal lung parenchyma was completely destroyed, with a few protein-filled alveolar spaces on the periphery. There were multiple foci of necrotic debris throughout the affected tissue. No abnormalities were identified in other organs.

Bacterial culture of the contents of the lung nodules revealed heavy infection with R. equi, with scanty numbers of Escherichia coli. The R. equi isolate was virulence associated protein A-positive (VapA) on Western blot analysis. Restriction enzyme digestion analysis of the virulence plasmid showed that this isolate possessed an 85 kb type I virulence plasmid, the commonest virulence plasmid type in foal isolates from Canada and the United States (9).

Clinical and laboratory findings were consistent with diagnosis of chronic, ongoing multifocal necrotic pneumonia and pleuritis due to R. equi infection. Escherichia coli, which commonly complicates pneumonia (10), was considered to be a less important factor in this case. No anaerobic bacteria were isolated.

Rhodococcus equi is a rare and uncommon etiologic agent of respiratory disease in the adult horse (11). Roberts et al (7) reported R. equi pleuropneumonia in an 18-year-old gelding, diagnosed after several weeks of debilitating disease. Other reports of R. equi infection in adult horses described infection that incorporated different organ systems (5,6). The case presented here is the first detailed report of R. equi respiratory infection in an adult horse. The distribution of lesions in the lungs was suggestive of aerosol infection (3). This is also the first report of the isolation of a virulence plasmid-positive R. equi expressing VapA from an adult horse with pleuropneumonia.

Foals are believed to be exposed to R. equi early in life and that immunologic memory from the exposure protects them throughout their adult life, an immunity probably reinforced by repeated exposure from the environment (12). In humans, infection with R. equi is almost invariably associated with immunosuppression, associated mainly with human immunodeficiency virus (HIV) infection or the use of immunosuppressive drugs. However, there are reports in human medicine of R. equi being a pathogen capable of producing primary disease in the immuno-competent patient (4,13).

Cell-mediated immunity is critical to protecting against R. equi infection (12). Because a diagnosis of R. equi infection was made only after the horse was dead, his immune status was not investigated. The hyperglobulinemia suggests that B cell function was intact, but the mild lymphopenia that was present only after admission to the OVC suggests that there was dysfunction in other lymphocyte populations. Lymphopenia is often recognized in the leukogram of sick animals. In this case, the lesion was limited to pulmonary tissue, which may negate the presence of immunodeficiency. Although a majority of isolates of R. equi from patients with AIDS and from the intestinal tract and environment of horses do not possess the virulence plasmid, a proportion have virulence plasmids (9), as did the isolate from this horse. As happened in this case, R. equi infection in adult horses may be overlooked, clinically, and easily mistaken for other clinically similar pulmonary infections. Standard antimicrobial therapy that targets common aerobic and anaerobic bacteria most often associated with pleuropneumonia, as used in this case, is not effective in the treatment of severe infections with R. equi (14,15). If circumstances had allowed the horse to remain hospitalized, the antibiotic treatment of choice after the bacteriology report had been received, would have been a combination of erythromycin estolate or phosphate and rifampin. The treatment with trimethoprim sulfadiazine and penicillin prior to development of pleuropneumonia might have enabled a selection of bacteria that allowed proliferation and overgrowth of R. equi. However, this is not the usual behavior of R. equi and has never been described.

The prevalence of R. equi infection in immunocompromised humans increases (4). However, to evaluate the prevalence and clinical importance of primary or secondary R. equi infection in adult horses, more in-depth case reports, such as this, are needed. CVJ