CASE STUDY Cortical Osteitis of The Humeral Diaphysis Caused by Rhodococcus Equi Maureen Kelleher, DVM, and Dave MacDonald, DVM, DACVS
ABSTRACT Infection with Rhodococcus equi is a common cause of pneumonia in foals. Extrapulmonary manifestations occur, including gastrointestinal disease such as enterocolitis, musculoskeletal disease such as osteomyelitis, as well as other aberrant regions of abscess. Osteomyelitis predominately occurs in the metaphyseal or epiphyseal regions of long bones because of low-pressure blood flow through the sinusoids of these regions of the bone. In this report, a case of cortical, diaphyseal osteitis of the humerus caused by Rhodococcus equi and subsequent medical and surgical management is described. Keywords: Rhodococcus equi; Osteitis; Foal; Humerus
CASE DETAILS A 75-day-old Quarter Horse colt was referred to Pioneer Equine Hospital (PEH) for a grade 3 of 5 lameness of the right forelimb. The owner and referring veterinarian reported a right forelimb lameness at approximately 14 days of age, which resolved without medical therapy. At 30 days of age, the colt was not lame but classified as unthrifty. No audible lung abnormalities were identified; however, a complete blood count (CBC) was performed. Leukocytosis (14,000 cell/ml; reference range 4,500–11,400 cell/ml) and hyperfibrinogenemia (800 mg/dl; reference range 100–400 mg/dL) prompted the initiation of a short course of gentamicin sulfate (6.6 mg/kg [3.0 mg/lb], IV, every 24 hours) by the referring veterinarian. At 75 days of age, the colt was referred to PEH for upper limb radiography with an acute onset right forelimb lameness and CBC abnormalities, consisting of leukocytosis (13,400 cells/ml) and hyperfibrinogenemia (800 mg/dl). At presentation, the colt had normal vital parameters and a body condition score of 4 of 9. The colt had a grade 3 of 5 right forelimb lameness, with difficulty advancing the limb. No palpable abnormalities were identified associated with the right forelimb, but the foal was resentful of manipulation of the upper limb. Because of the foal’s difficulty advancing the limb and tendency to drag the toe with From Oakdale, CA. Reprint requests: M. Kelleher, DVM, 115 Sutter Street, Woodland, CA 95695.
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advancement of the limb, radiography of the right elbow and shoulder joints was performed and revealed no abnormalities. Radiography of the right humerus revealed a cortical lucency at the caudal aspect of the humeral diaphysis, with sequestra present proximal and distal to the cortical focus (Fig. 1). The colt had no audible thoracic abnormalities, but radiography of the thorax was performed based on a history of rhodococcal disease on the farm where the foal resided. Thoracic radiographs revealed an interstitial pattern. The colt displayed no signs of respiratory disease at admission or during hospitalization. Antimicrobial therapy was initiated with procaine penicillin G (22,000 IU/kg, IM, every 12 hours) and gentamicin sulfate (6.6 mg/kg, IV, every 24 hours). Treatment with flunixin meglumine (1.1 mg/kg, IV, every 12 hours) and omeprazole (4.4 mg/kg, PO, every 24 hours) also was initiated. Based on radiographic findings, surgical exploration of the right humerus was elected. Two days after presentation, the colt was anesthetized and positioned in left lateral recumbency for surgical debridement of the lesion. An 18-gauge spinal needle was placed into the caudal humeral musculature and surgical approach was mapped to the lesion using digital radiography. A 10-cm skin incision was made parallel to the long axis of the right humerus, starting approximately 5 cm proximal and cranial to the 18-gauge spinal needle and extending in a distal and caudal direction. Dissection through muscle planes, centered near the 18gauge spinal needle, to the caudal aspect of the humerus revealed an area of abscess and surrounding necrotic tissue. A 11-cm cavitation at the caudal aspect of the humeral diaphysis was palpable. A sample of purulent material from the abscess site was obtained and submitted for bacteriological culture. A combination of curettage and lavage with sterile saline was used to debride and remove necrotic bone fragments and muscle tissue, leaving the cavitated region of humerus smoothed to healthy bone tissue. A solution of 500 mg enrofloxacin diluted in 60 ml sterile saline was lavaged into the area of abscess before closure of the musculature and skin. The incision was closed in several layers, using 0 Vicryl for fascia and subcutaneous tissues. Skin was closed with 2–0 Ethilon in a simple interrupted pattern. Therapy with procaine penicillin G, gentamicin sulfate, flunixin meglumine, and omeprazole was continued. The colt became transiently febrile (rectal temperature, 40.48C [104.88F]) after surgery, but responded favorably to flunixin meglumine. Ambulation was improved by 1 day postoperatively. Antimicrobial treatment was changed 317
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Fig. 1. Lateromedial radiograph of the right humerus depicting a cortical lesion at the caudal aspect of the diaphysis of the bone. to chloramphenicol (44 mg/kg, PO, every 6 hours) at day 2 postoperatively, because of the colt’s intolerance of continued intramuscular injections. Bacteriological culture was finalized 5 days postoperatively with a pure growth of Rhodococcus equi. Antimicrobial sensitivity was not performed because the slow growth of Rhodococcus equi does not allow for formulation of a broth used in standardized susceptibility testing. No further testing, such as identification of virulent associated plasmid (VAP), was performed on the isolate obtained from the culture. The foal was discharged, at day 5 postoperatively, with instruction for continued antimicrobial therapy with clarithromycin (7.5 mg/kg, PO, every 12 hours) and rifampin (5 mg/kg, PO, every 12 hours) for 7 days then every other day for 3 weeks. The colt was evaluated again 24 days postoperatively. No lameness was detected at the walk or trot. Radiographs of the right humerus showed a decrease in the overall size of the cortical lucency with a thickened rim of sclerosis surrounding the site of abscess (Fig. 2). No periosteal reaction was present, nor was there any evidence of sequestration. The colt was discharged with instruction for continued antimicrobial therapy with clarithromycin (7.5 mg/kg, PO, every 12 hours) and rifampin (5 mg/kg, PO, every 12 hours), every other day, for an additional 21 days. At 12 weeks postoperatively, the owner reported that the colt was thriving and turned out with other colts in pasture, with no observable lameness.
DISCUSSION Rhodococcus equi is an intracellular pathogen that predominately causes pyogranulomatous pneumonia in foals aged 1 to 6 months. Gastrointestinal involvement also is common and is seen clinically as enterocolitis. Extrapulmonary,
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Fig. 2. Lateromedial radiograph of the right humerus taken 21 days post-operatively. The lesion has decreased in size and is surrounded by a thick rim of sclerosis. extraintestinal disease is much less common; however, nonseptic polysynovitis, septic arthritis, osteomyelitis, as well as other aberrant sites of abscess, have been reported.1 In foals, osteomyelitis is primarily seen at less than 4 months of age. Proposed routes of bone infection include extension of joint sepsis, hematogenous spread from another site of infection such as the lungs, gastrointestinal tract or umbilicus, or via local spread from an infected cutaneous wound.2 Bacteremia with settling of organisms at points of low blood flow and pressure through sinusoids of the epiphysis and metaphysis is the most common mechanism of hematogenous infection to bone. Immune system immaturity is also thought to play a role in development of osteomyelitis in foals. Osteomyelitis caused by Rhodococcus equi is more commonly reported affecting the vertebra,3-5 but metatarsal, radial, femoral, pelvic, scapular, and humeral cases also have been noted in the literature.6-11 In this case, abscess involved the diaphyseal cortex of the humerus. The outer third of the diaphyseal cortex is supplied blood via penetration of periosteal arteries. In adult horses, diaphyseal infections most commonly occur secondary to fracture repair, whereas cortical osteitis occurs because of contaminated traumatic, cutaneous wounds, with disruption of periosteal blood flow and bruising of surrounding tissues. Although this colt had no visible evidence of trauma to the right forelimb at 2 weeks of age, likely trauma played a role in the lameness, which initially resolved without medical therapy. Trauma to the right upper limb at age 2 weeks resulted in an area of hemorrhage and disruption of periosteal blood supply, a nidus of infection at a time when bacteremia was likely. Cohen et al12 theorized that foals are likely exposed to and have an
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increased susceptibility to Rhodococcus equi in the first 3 days to 2 weeks of life, and this foal, raised on a farm with a history of rhodococcal disease, was exposed to the bacteria via the respiratory or gastrointestinal tract. With bacteremia from a pulmonary or intestinal source, an area of blunt trauma to the right forelimb may have allowed bacteria to settle in or near the cortical, diaphyseal bone, resulting in abscess formation. Disseminated, hematogenous bacteremia did not lead to multiple sites of infection, or infection at a point of low blood flow, such as a metaphysis or epiphysis. However, with a suspicion of right forelimb trauma, the sequelae of impact provided an environment suitable for bacterial settling and proliferation. Of the nine reported cases of nonvertebral osteomyelitis caused by Rhodococcus equi, four cases are independent of joint involvement. Of these four cases, abscess was localized to the metatarsus, radius, pelvis, and scapula.6,8,9,11 Localization within the bone was the metaphysis for the radial and metatarsal infections, pubic symphysis in the pelvis, and not reported in the scapula. No reported cases exist of rhodococcal cortical osteitis involving the diaphysis, as was seen in the current case. None of the nonvertebral, nonsynovial cases report a history of trauma; however, hematogenous translocation of bacteria was speculated in all cases, with pulmonary involvement confirmed in one case. Surgical management with antibiotic therapy was attempted and successful in two cases (metatarsus, pelvis). In this case, surgical debridement of bacterial material and necrotic bone debris in combination with long-term antimicrobial therapy proved to be a successful treatment combination. Treatment of choice for Rhodococcus equi infection in foals is combination therapy of rifampin and a macrolide, such as erythromycin or clarithromycin, or a related azalide, azithromycin. Daily therapy with rifampin and clarithromycin was initiated at the time of identification of Rhodococcus equi as the bacterial cause of abscess. Everyother-day therapy was initiated, after an initial daily course of therapy for 7 days, based on dosing regimens for azithromycin, an azalide similar to the macrolide clarithromycin. Azithromycin, typically given orally once a day for 5 days, persists in bronchoalveolar cells above minimum inhibitory concentrations for Rhodococcus equi, allowing for continued therapy on an every-other-day basis.13 For this foal, clarithromycin was selected based on availability as well as evidence that it is more effective than erythromycin or azithromycin, with rifampin, in treating rhodococcal infections in foals.14 The dose used in this foal was extrapolated from the azithromycin dosing regimen. Although treatment was successful with this foal, evidence now indicates that clarithromycin does not persist in bronchoalveolar cells, as azithromycin does, so in this foal the clarithromycin should have been given continually on an every day basis.15 The authors are unaware of any scientific research regarding the persistence of azithromycin or clarithromycin in the musculoskeletal system of foals. Although pneumonia and enterocolitis are the more common sequelae to Rhodococcus equi infection, cortical
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osteitis caused by this bacteria should be considered a possible cause of severe lameness in foals. Osteitis should be suspected in foals that may have had trauma early in life, at a period when exposure to Rhodococcus equi is likely, and immune response to the bacteria is immature. Radiographic evaluation can be used successfully to differentiate other causes of significant lameness in foals. Surgical debridement of the lesion enables accurate diagnosis as well as a means of potentially successful therapy. Prognosis for return to soundness in cases without joint involvement treated with aggressive surgical removal of abscess material and appropriate antimicrobial therapy is very favorable. REFERENCES 1. Giguere S. Rhodococcus equi pneumonia. Proceedings 47th Annual Meeting American Association of Equine Practitioners 2001;47: 456–467. 2. Hance SR. Hematogenous infections of the musculoskeletal system in foals. Proceedings 44th Annual Meeting American Association of Equine Practitioners 1998;44:159–166. 3. Olchowy TWJ. Vertebral body osteomyelitis due to Rhodococcus equi in two Arabian foals. Equine Vet J 1994;26:79–82. 4. Giguere S, Lavoie JP. Rhodococcus equi vertebral osteomyelitis in 3 Quarter Horse colts. Equine Vet J 1994;26:74–77. 5. Chaffin MK, Honnas CM, Crabill MR, Schneiter HL, Brumbaugh GW, Briner RP. Cauda equine syndrome, diskospondylitis, and a paravertebral abscess caused by Rhodococcus equi in a foal. J Am Vet Med Assoc 1995;206:215–220. 6. Desjardins MR, Vachon AM. Surgical management of Rhodococcus equi metaphysitis in a foal. J Am Vet Med Assoc 1990;197:608–612. 7. Collatos C, Clark ES, Reef VB, Morris DD. Septicemia, atrial fibrillation, cardiomegaly, left atrial mass, and Rhodococcus equi septic osteoarthritis in a foal. J Am Vet Med Assoc 1990;197:1039–1042. 8. Firth EC, Alley MR, Hodge H. Rhodococcus equi-associated osteomyelitis in foals. Aust Vet J 1993;70:304–307. 9. Clark-Price SC, Rush BR, Gaughan EM, Cox JH. Osteomyelitis of the pelvis caused by Rhodococcus equi in a two-year-old horse. J Am Vet Med Assoc 2003;222:969–972. 10. Loesch DA, Bryant JE, Lopez-Martinez A. Septic coxofemoral arthritis with extension into the abdominal cavity in a foal. Equine Vet Educ 2003;15:15–18. 11. Paradis MR. Cutaneous and musculoskeletal manifestations of Rhodococcus equi infection in foals. Equine Vet J 1997;9:266–270. 12. Cohen ND, Horowitz ML, Takai S, Becu T, Chaffin MK, Magdesian KG, et al. Evidence that foals with Rhodococcus equi pneumonia become infected early in life. Proceedings 47th Annual Meeting American Association of Equine Practitioners 2001;47:403–406. 13. Jacks S, Giguere S, Gronwall R, Brown MP, Merritt KA. Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals. Am J Vet Res 2001;62:1870–1875. 14. Giguere S, Jacks S, Roberts GD, Hernandez J, Long MT, Ellis C. Retrospective comparison of azithromycin, clarithromycin, and erythromycin for the treatment of foals with Rhodococcus equi pneumonia. J Vet Intern Med 2004;18:568–573. 15. Womble AY, Giguere S, Lee EA, Vickroy TW. Pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar cells in foals. Am J Vet Res 2006;67:1681–1686.