Candida osteomyelitis: analysis of 207 pediatric and adult cases (1970-2011)

Abstract

Background: The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood.

Methods: Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases.

Results: Median age was 30 years (range, ≤ 1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04-.25), rib, and sternum; for pediatric patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4-48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response.

Conclusions: Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6-12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome.

Figure 1.

Number of reported cases of Candida osteomyelitis per decade, 1970–2011.

Figure 2.

A and B, Representative pathological specimens from a patient with proven Candida species osteomyelitis. All photomicrographs shown are at ×20 magnification under hematoxylin-eosin staining. A, Depicts lamellar bone with scalloped edges and inflammatory infiltration of the marrow space, as well as surrounding bone. B, Depicts fungal forms consistent with Candida species within the necrotic bone. C, Anteroposterior radiograph of the hips from a patient with proven Candida glabrata osteomyelitis and prosthetic joint infection demonstrates markedly demineralized, sclerotic bone with destruction of the femoral head and neck. Attempted placement of a cement spacer resulted in a femoral fracture with protrusion of the rod component through the midshaft.