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Fusobacterium osteomyelitis in a child with sickle cell disease

2002; Lippincott Williams & Wilkins; Volume: 21; Issue: 10 Linguagem: Inglês

10.1097/00006454-200210000-00020

1532-0987

Sandra J. Murray, Jay M. Lieberman,

Infectious Diseases and Tuberculosis

Children who have sickle cell disease are at increased risk for osteomyelitis caused by Salmonella spp. and Staphylococcus aureus. We report a case of anaerobic osteomyelitis caused by Fusobacterium nucleatum in a child with sickle cell disease. The infection did not resolve with antibiotic therapy alone, but was cured after surgical debridement and hyperbaric oxygen therapy. Children who have sickle cell disease are at increased risk for bacterial infections because of functional asplenia and a defect in the alternate complement pathway. They are also at increased risk for osteomyelitis due to vasoocclusive episodes that can result in bone necrosis and form a nidus for infection. The most common cause of osteomyelitis in children with sickle cell disease is Salmonella followed by Staphylococcus aureus. 1–3 Anaerobes are uncommon causes of osteomyelitis in children. This is the first reported case of Fusobacterium nucleatum osteomyelitis in a child with sickle cell disease. Case report. The patient was a 7-year-old African-American boy with sickle cell disease who presented with a 1-month history of left leg pain, which initially was thought to be a result of vasoocclusive crisis. Two weeks before this admission, he was hospitalized for fever and leg pain. He was treated with ceftriaxone, the fever resolved and he was discharged after blood cultures were negative. Despite treatment with acetaminophen with codeine, ibuprofen and hydroxyzine, the left leg pain persisted, and swelling and redness of the leg developed during the week before admission. A radiograph revealed periosteal elevation of the left proximal tibia, and the child was hospitalized for treatment of osteomyelitis. On admission the patient was afebrile and walked with a very mild limp. The left leg was warm, erythematous and tender over the anterior proximal tibia. The remainder of the physical examination was normal. The peripheral white blood cell count was 15 600/mm3 with 79% neutrophils, 12% lymphocyte and 8% monocytes. The erythrocyte sedimentation rate was 30 mm/h and C-reactive protein was 2.7 mg/dl. A bone aspirate was obtained under fluoroscopy before antibiotic therapy with nafcillin and ceftriaxone was initiated. Gram stain of the bone aspirate revealed many polymorphonuclear cells but no organisms. The aspirate subsequently grew a pure culture of F. nucleatum, which was identified based on its characteristic colony morphology (a spindle-shaped Gram-negative bacillus) and biochemical analysis using the RapID ANA II System (REMEL, Inc., Norcross, GA). The organism did not grow on subculture for susceptibility testing but was beta-lactamase-negative. The nafcillin and ceftriaxone were discontinued, and intravenous clindamycin (40 mg/kg/day divided every 6 h) was started. The patient improved with a decrease in swelling and erythema of the left leg, and he was able to resume walking without a limp. The erythrocyte sedimentation rate and C-reactive protein decreased to 14 mm/h and 0.3 mg/dl, respectively, by Day 4 of clindamycin therapy. After 3 weeks of clindamycin therapy, however, the leg remained very tender, and a repeat radiograph demonstrated progression of the central medullary and subcortical hypolucency and a linear periosteal reaction in the proximal left tibia. The decision was made to surgically debride the infected bone. Cultures obtained at the time of surgery were sterile, and pathology demonstrated "bone fragments with prominent necrosis consistent with infarct, along with prominent new bone formation, marked marrow fibrosis and minimal chronic inflammation." Daily hyperbaric oxygen treatment was initiated, and iv clindamycin was continued for an additional 3 weeks. At the conclusion of therapy the leg was nontender and without swelling or erythema, and the patient had resumed his full activities. Discussion. F. nucleatum is an anaerobic Gram-negative rod that belongs to the family Bacteroidaceae. The organism is a common inhabitant of the oral, intestinal and genitourinary tract flora. Fusobacterium spp. are pathogenic anaerobes that can cause a variety of diseases including bacteremia, abdominal and genital tract infections, brain abscess and bone and joint infections. The role of anaerobes as etiologic agents of osteomyelitis has been recognized since the early 1900s. 4, 5 As the ability to collect, transport and grow anaerobic organisms improved, the frequency of anaerobic isolates from patients with osteomyelitis increased. 6, 7 Most cases of osteomyelitis caused by anaerobes are polymicrobial infections, with a mixture of aerobic and anaerobic or mixed anaerobic organisms. Infections with a single anaerobic organism are rare and usually result from hematogenous spread. 8, 9 Anaerobic osteomyelitis of long bones is usually a consequence of bacteremia, trauma or a prosthetic device. Fusobacterium osteomyelitis most commonly occurs in the facial bones, 4, 5 but infections in vertebral, pubic, leg, hand and foot bones have been reported. These infections have followed human bites, fractures or oral infections or occurred in association with vascular insufficiency or neuropathic disease. 4, 8–10 Our patient had no history of recent dental work, otitis media, sinusitis or trauma. His vasoocclusive episode likely progressed to bone infarction. We hypothesize that intravascular sickling of the bowel vessels resulted in bowel ischemia and mucosal barrier breakdown, which led to a transient bacteremia and hematogenous spread of F. nucleatum to the site of infarction. 3, 11 F. nucleatum has historically been susceptible to penicillin, but beta-lactamase-producing isolates have been reported with increasing frequency since the 1980s. 12 Treatment with clindamycin, piperacillin, cefoxitin, imipenem, metronidazole or a penicillin with a beta-lactamase inhibitor is recommended for Fusobacterium infections. 7, 13, 14 Clindamycin is often used for treatment of osteomyelitis because of its excellent bone penetration. The duration of treatment for anaerobic osteomyelitis in the literature ranges from 3 to 6 weeks. Surgical debridement is necessary when continued pain, swelling, fever or persistent elevation of the white blood cell count and sedimentation rate indicate that the infection has not responded to antibiotics alone. 2, 7, 13 Debridement is essential to remove necrotic and ischemic tissue that sustains anaerobic conditions as well as to drain any foci of persistent infection. 2, 8, 14 The Undersea and Hyperbaric Medicine Society recognizes refractory osteomyelitis as an indication for the use of adjunctive hyperbaric oxygen (HBO). The oxygen content of infected bone is decreased compared with normal bone tissue. HBO increases the oxygen content of infected bone, which aids healing by several mechanisms. Fibroblasts in a hypoxic environment do not divide or synthesize collagen; increased oxygen improves the activity of fibroblasts and speeds healing. Phagocytic killing of S. aureus improves with increased oxygenation, and the bactericidal action of aminoglycosides is augmented by HBO. In addition increased oxygen tension is lethal to strict anaerobes and some microaerophilic organisms, making HBO especially helpful as adjunctive therapy for anaerobic osteomyelitis. 15, 16 Anaerobic osteomyelitis in children is uncommon but should be considered when the infection results from bites or decubitus ulcers, it occurs in skull and facial bones, there is a foul smelling exudate or the infection does not respond to standard therapy. Proper collection, transport and culture techniques are absolutely necessary for the isolation of anaerobes. All bone specimens obtained from patients with osteomyelitis should be sent for anaerobic as well as aerobic culture.