 |
Rhodococcus equi is the most serious cause of pneumonia in foals 1–5 mo old. It is not the most common cause of pneumonia in this age group; however, it has significant economic consequences due to mortality, prolonged treatment, surveillance programs for early detection, and relatively expensive prophylactic strategies. Clinical disease is rare in horses >8 mo old. Compelling epidemiologic data indicate pulmonary infection probably originates within the first week of life.
Etiology and Pathogenesis
R equi is a gram-positive, facultative intracellular pathogen that is nearly ubiquitous in soil. Only certain types (vapA, vapB, vapC) are pathogenic. The incidence of clinical disease on a specific premises is not correlated to environmental bacterial load or magnitude of bacterial shedding by the dam. Development of clinical disease does appear related to immunocompetency of individual foals; foals that produce little to no detectable γ interferon (IFN-γ) are at risk of developing pneumonia. Inhalation of dust particles laden with virulent R equi is the major route of pneumonic infection. Manure from pneumonic foals is a major source of virulent bacteria contaminating the environment. Foals with pulmonary infections swallow sputum laden with R equi, which readily replicates in their intestinal tract. The pathogenicity of R equi is linked to its ability to survive intracellularly, which hinges on failure of phagosome-lysosomal fusion in infected macrophages and failure of functional respiratory burst upon phagocytosis of R equi.
Clinical Findings and Lesions
R equi infection is slowly progressive with acute to subacute clinical manifestations. Clinical signs of disease are difficult to detect until pulmonary infection reaches a critical mass, resulting in decompensation of the foal. Pulmonary lesions are relatively consistent and include subacute to chronic suppurative bronchopneumonia, pulmonary abscessation, and suppurative lymphadenitis. At the onset of clinical signs, most foals are lethargic, febrile, and tachypneic. Cough is a variable clinical sign; purulent nasal discharge is less common. Thoracic auscultation reveals crackles and wheezes with asymmetric/regional distribution. Pulmonary regions with marked consolidation lack breath sounds and exhibit dull resonance on thoracic percussion. Diarrhea is observed in many foals due to colonic microabscessation.
Intestinal and mesenteric abscesses are the most common extrapulmonary sites of infection. Foals with abdominal involvement often present with fever, depression, anorexia, weight loss, colic, and diarrhea. Intestinal lesions are characterized by multifocal, ulcerative enterocolitis and typhlitis involving Peyer's patches with granulomatous or suppurative inflammation of the mesenteric and/or colonic lymph nodes. The prognosis for foals with abdominal forms of R equi is less favorable than for those with pulmonary disease. Septic physitis and osteomyelitis are less common extrapulmonary sites of infection. Vertebral osteomyelitis may result in pathologic vertebral fracture and spinal cord compression, and is a devastating manifestation of R equi osteomyelitis. Panophthalmitis, guttural pouch empyema, sinusitis, pericarditis, nephritis, nonseptic uveitis and synovitis, and hepatic and renal abscessation with R equi have been reported.
Diagnosis
Routine laboratory evaluation of CBC and serum chemistry reveals nonspecific abnormalities consistent with infection and inflammation. Neutrophilic leukocytosis and hyperfibrinogenemia are common, and the severity of these findings relates to prognosis. Thoracic radiographic evaluation may reveal a pattern of perihilar alveolization, consolidation, and abscessation. The presence of nodular lung lesions and mediastinal lymphadenopathy in foals 1–5 mo old is highly suggestive of R equi. Bacterial culture of transtracheal wash samples is required for definitive diagnosis. Cytologic evaluation of transtracheal wash samples reveals intracellular coccobacilli, indicating that appropriate antimicrobial therapy should be started pending culture results.
Treatment and Prognosis
The combination of erythromycin (25 mg/kg, PO, qid; esters or salts) and rifampin (5–10 mg/kg, PO, bid) has historically been the treatment of choice for R equi infections in foals. These antimicrobials may be bacteriostatic, but their activity is synergistic, and the combination has markedly improved survival of foals with R equi pneumonia. Rifampin is lipid soluble (able to penetrate abscess material) and is concentrated in phagocytic cells. Erythromycin is concentrated in granulocytes and alveolar macrophages; however, its antimicrobial activity is somewhat inhibited by intracellular pH. Adverse reactions are relatively common in foals treated with the erythromycin-rifampin combination. Diarrhea, idiosyncratic hyperthermia, tachypnea, anorexia, bruxism, and salivation can occur with erythromycin administration, and antimicrobial resistance of R equi to erythromycin-rifampin has been reported.
Azithromycin is a newer generation macrolide with higher bioavailability than erythromycin, and it achieves higher drug concentrations in phagocytic cells and tissues. Azithromycin produces less GI adverse events in human patients. It is administered orally (10 mg/kg), once daily until clinical signs stabilize, followed by every other day until disease resolves. The principal advantage of azithromycin-rifampin over erythromycin-rifampin is the convenience of once-per-day dosing.
Clarithromycin is the macrolide of choice for foals with severe disease, given the most favorable minimum inhibitory concentration against R equi isolates obtained from pneumonic foals (90% of isolates are inhibited at 0.12, 0.25, and 1.0 μg/mL for clarithromycin, erythromycin, and azithromycin, respectively). In foals with R equi pneumonia, the combination of clarithromycin (7.5 mg/kg, PO, bid) and rifampin is superior to erythromycin-rifampin and azithromycin-rifampin. Foals treated with clarithromycin-rifampin have improved survival rates and fewer febrile days than foals treated with erythromycin-rifampin and azithromycin-rifampin. Reported adverse effects of clarithromycin-rifampin include diarrhea in treated foals. The duration of antimicrobial therapy typically is 3–8 wk.
Supportive therapy includes provision of a clean, comfortable environment and highly palatable, dust-free feeds. Judicial IV fluid therapy and saline nebulization facilitates expectoration of pulmonary exudates. NSAID should be administered as needed to maintain rectal temperature <103.5°F (39.7°C). Nasal insufflation with oxygen is necessary in foals with severe respiratory compromise. Bronchodilator therapy may or may not improve arterial oxygenation. Prophylactic antiulcer medication is indicated in foals that are stressed by respiratory difficulty, pain, frequent handling, hospitalization, and transportation.
The survival rate of R equi pneumonia is ~70–90% with appropriate therapy. The case fatality rate without therapy (or with inappropriate antimicrobial therapy) is ~80%. Parameters for discontinuation of medical therapy include clinical signs, serum fibrinogen concentration, and radiographic resolution of pulmonary consolidation and abscessation. Life-threatening, antibiotic-induced enterocolitis, due to Clostridium difficile, has been observed in the dams of nursing foals treated with all 3 macrolide preparations.
Prevention
There are several strategies to decrease the incidence of R equi pneumonia on endemic farms: early detection of clinical cases, enhanced passive immunity for neonatal foals, and enhanced nonspecific immunity for neonatal foals. Foals should be maintained in well-ventilated, dust-free areas, avoiding dirt paddocks and overcrowding. Pneumonic foals should be isolated and their manure composted. Herd surveillance programs for early detection of pneumonic foals on endemic farms include twice weekly physical examination and auscultation, and monthly CBC and fibrinogen concentration. Foals with a WBC count >14,000 cells/μL should be further evaluated via ultrasonographic examination for R equi. Administration of hyperimmune plasma might reduce the incidence and severity of R equi within the herd, but it is not completely effective in preventing disease. Hyperimmune plasma (1 L) is administered IV within the first week of life, followed by a second liter at ~25 days of age. Foals with low IFN-γ production in the first month of age appear more susceptible to development of clinical disease. Administration of a nonspecific immunostimulant may enhance IFN-γ production and protect this susceptible population. A unique strategy in development uses gallium maltolate as an iron mimic to disrupt replication of the iron-dependent R equi. Gallium (20 mg/kg) is administered to neonatal foals via nasogastric tube, which produces serum concentrations sufficient to suppress growth or kill intracellular R equi.
Last full review/revision March 2012 by Bonnie R. Rush, DVM, MS, DACVIM
| |
|
