Infectious Diseases in Clinical Practice:
Abstract: Although community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an increasingly important pathogen in skin and soft tissue infections, the organism has rarely been reported to cause osteomyelitis secondary to a hematogenous source in adults. A review of the literature found 5 published reports of adult CA-MRSA osteomyelitis secondary to a presumed hematogenous source, all of which involve severe destructive infections of the long bones in immunocompetent patients. Three of the 5 cases presented with radiographic findings initially suggestive of primary bone malignancy. We present a similar case of CA-MRSA osteomyelitis of the femur that mimicked osteosarcoma radiographically and summarize the existing literature to alert clinicians to consider CA-MRSA osteomyelitis in the differential diagnosis of destructive bone lesions.
Departments of *Radiology and †Internal Medicine, University of South Florida College of Medicine, Tampa, FL.
Address correspondence and reprint requests to Charles M. Edwards, MD, FACP, 2-A Columbia Dr, 6th Floor, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33606. E-mail: firstname.lastname@example.org.
A recent study indicates that community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and soft tissue infections presenting to US emergency rooms.1 Although most cases remain superficial, invasive CA-MRSA is becoming increasingly frequent in young, otherwise healthy patients and is associated with significant morbidity and mortality.2 We present a case of necrotizing osteomyelitis caused by CA-MRSA with an aggressive radiographic appearance that was initially diagnosed as a primary bone tumor and review the current literature of CA-MRSA osteomyelitis.
A 34-year-old white man in good health presented with severe pain in the right thigh which had progressively worsened over 3 weeks. He denied fever, chills, and night sweats. The patient had no history of trauma, intravenous drug use, or contact with hospitalized patients. Physical examination revealed marked tenderness of the proximal right lower extremity with no erythema, warmth, or palpable mass. Distal neurovascular status was intact. In addition, a right axillary furuncle was discovered on physical examination which the patient reported to have developed 4 weeks before presentation.
Plain radiographs of the hip and femur demonstrated no abnormalities. White blood cell count was 13,800/μL with a normal differential; erythrocyte sedimentation rate was 72 mm/h; and C-reactive protein was 30.2 mg/L. Other laboratory values were within normal limits. Computed tomography scan of the right lower extremity demonstrated a destructive lesion of the posteromedial femoral diaphysis with cortical erosion and irregular periosteal reaction which was concerning for primary bone malignancy (Fig. 1). Subsequent magnetic resonance imaging revealed diffuse abnormal marrow signal throughout the right femoral diaphysis extending to the distal metaphysis. Because of the concern for malignancy, incisional biopsy was performed. Surgical exploration revealed purulent material, and frozen sections demonstrated extensive inflammation suggestive of osteomyelitis. The area was debrided intraoperatively. Bone cultures from surgical specimens as well as subsequent blood cultures yielded MRSA. Final pathology revealed no evidence of malignancy. A transesophageal echocardiogram demonstrated no evidence of cardiac vegetation. Evaluation for immunodeficiency including HIV testing was negative. Based on sensitivities, antimicrobial therapy with vancomycin and rifampin was initiated, resulting in sterilization of blood cultures by the fourth hospital day. An intramedullary femoral rod was subsequently placed to avoid pathological fracture given the extent of bony destruction. The patient completed 12 weeks of intravenous vancomycin and oral rifampin, with resolution of his symptoms and no evidence of recurrence after 6 months of follow-up.
We performed an English-language search of the MEDLINE database for CA-MRSA osteomyelitis using the terms "methicillin-resistant Staphylococcus aureus" ("community acquired" or "community associated") and "osteomyelitis," disregarding reports involving patients younger than 18 years. Five cases were found of hematogenous osteomyelitis caused by CA-MRSA in adults2-4 (Table 1). All cases involved the metaphysis or diaphysis of long bones, regions of greatest blood flow. This location is consistent with hematogenous spread of the organism, which is a common source of osteomyelitis in children but unusual in adults for whom direct extension from a local soft tissue infection is typical. Although positive blood cultures were documented in only one half of the cases, transient bacteremia was presumed in all cases as the source of spread. All cases had a history of recent skin infection which likely provided the organism's portal of entry. A common feature of all 5 cases was the severe destructive nature of the infection. Three cases presented with radiographic findings initially suggestive of primary bone malignancy. Two cases required intramedullary fixation due to present or impending pathological fracture, and all but one required surgical debridement.
The severity of invasive CA-MRSA infections is largely attributed to the Panton-Valentine leukocidin (PVL) virulence factor, a cytotoxin that is frequently carried by CA-MRSA strains but rarely found in health care-associated strains.5 Panton-Valentine leukocidin has been shown to mediate leukocyte destruction and tissue necrosis and has been clearly implicated in necrotizing soft tissue infections and pneumonias.6,7 Although genetic analysis was not performed on all of the reported isolates, the 3 organisms that were tested all demonstrated the PVL gene. Another virulence factor, bone sialoprotein adhesion gene (bbp), is felt to specifically contribute to CA-MRSA osteomyelitis because it promotes Staphylococcus adhesion to bone proteins. Interestingly, this gene has not yet been demonstrated in the continent-specific US CA-MRSA strains.8
In a relatively short period, invasive CA-MRSA disease has expanded to include conditions such as endocarditis, necrotizing pneumonia, and necrotizing fasciitis.2,9-12 This report and review of the literature alert the clinician to include destructive osteomyelitis in the broadening spectrum of potentially life-threatening manifestations of CA-MRSA.
1. Moran G, Krishnadasan A, Gorwitz R, et al. Methicillin-resistant S. aureus
infections among patients in the emergency department. N Engl J Med
2. Crum N. The emergence of severe, community-acquired methicillin-resistant Staphylococcus aureus
infections. Scand J Infect Dis
3. Gelfand MS, Cleveland KO, Heck RK, et al. Pathological fracture in acute osteomyelitis of long bones secondary to community-acquired methicillin-resistant Staphylococcus aureus
: two cases and review of the literature. Am J Med Sci
4. Seybold U, Talati N, Kizilbash Q, et al. Hematogenous osteomyelitis mimicking osteosarcoma due to community associated methicillin-resistant Staphylococcus aureus
5. Vandenesch F, Naimi T, Enright M, et al. Community-acquired methicillin-resistant Staphylococcus aureus
carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis
6. Lina G, Piédmont Y, Godaíl-Gamot F, et al. Involvement of Panton-Valentine leukocidin producing Staphylococcus aureus
in primaryskin infections and pneumonia. Clin Infect Dis
7. Naimi T, LeDell K, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus
8. Otsuka T, Saito K, Dohmae S, et al. Key adhesin gene in community-acquired methicillin resistant Staphylococcus aureus
. Biochem Biophys Res Commun
9. Millar B, Prendergast B, Moore J, et al. Community-associated MRSA (CA-MRSA): an emerging pathogen in infective endocarditis. J Antimicrob Chemother
. October 25, 2007; e-pub ahead of print.
10. Castaldo E, Yang E. Severe sepsis attributable to community-associated methicillin-resistant Staphylococcus aureus
: an emerging fatal problem. Am Surg
11. Francis J, Doherty M, Lopatin U, et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus
carrying the Panton-Valentine leukocidin genes. Clin Infect Dis
12. Miller L, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus
in Los Angeles. N Engl J Med