Septic Arthritis and NECC Steroid Injections

The CDC recommendations for treatment of septic arthritis for NECC steroid patients are based on evidence that Exserohilum rostratum (a brown-black mold) is the predominant pathogen in this outbreak. According to the CDC, expert opinion and published literature indicate that voriconazole may be effective in treating infections due to brown-black molds as well as infections due to Aspergillus species, another fungus that has been found in NECC steroid patients.

The following is CDC information:

This is interim guidance for treatment of adult patients with septic arthritis associated with intra-articular injections with potentially contaminated steroid products from the New England Compounding Center.  Interim guidance may change as new information becomes available.

• Consult an infectious diseases physician to assist with diagnosis, management, and follow–up, which may be complex and prolonged.
• Thorough diagnostic evaluation is essential, and should include collection of synovial fluid and/or synovial tissue, prior to initiation of treatment. Samples should be sent for fungal culture, molecular testing, and histopathological examination, in addition to the standard tests for bacterial infection and crystal-induced disease.
• Routine empiric antibacterial therapy should be used according to the judgment of the physician while awaiting results of the diagnostic studies.
• In clinically stable patients, at the discretion of the provider, it may be reasonable to wait 48-72 hours before initiating empiric antifungal therapy, to allow time for identification of alternative diagnoses (e.g., bacterial arthritis, crystal-induced arthritis, etc.).
• When empiric antifungal therapy is initiated,  the following regimen is suggested until the etiology of the patient’s septic arthritis has been identified:
  • Voriconazole, beginning with a loading dose of 6 mg/kg every 12 hours for two doses, followed by 4 mg/kg every 12 hours¹for the duration of treatment.
    • Regular monitoring of serum voriconazole concentrations (e.g., at a weekly interval) is recommended, aiming for trough levels of 2-5 mcg/ml.
    • Patients with more severe joint infection and/or clinical instability should be started on voriconazole IV. The above target serum levels of voriconazole are readily achievable using the oral form but may require a slightly higher dose and make take longer to achieve if unforeseen problems with gastro-intestinal intolerance or poor absorption are encountered.
    • Patients with mild joint infection may be started on oral voriconazole at the provider’s discretion.
    • Patients initially started on IV voriconazole therapy may be transitioned to oral therapy after they are clinically stable or improving, as long as no contraindications to oral therapy exist.
    • Providers and patients should be aware of and monitor for potential adverse effects of voriconazole, including (but not limited to) hepatic toxicity and neurotoxicity.
    • Providers should carefully consider and manage the potential for voriconazole drug interactions in all patients.
  • A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily should be considered in addition to voriconazole in patients with severe joint infection and/or clinical instability. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity. Providers and patients should be aware of and monitor for potential adverse effects of amphotericin B formulations.
  • Alternate therapies to consider for patients who are unable to tolerate treatment with voriconazole include lipid formulations of amphotericin B, posaconazole and itraconazole. Therapeutic drug monitoring should be performed for patients treated with posaconazole or itraconazole. Consultation with an infectious diseases physician should be sought regarding dosages and monitoring of these agents. Fluconazole should NOT be used.
• Arthroscopy with joint lavage and/or debridement should be considered in consultation with an orthopedic surgeon.
• Consideration should be given to obtaining joint imaging studies in patients for whom osteomyelitis is a concern. Osteomyelitis will prolong the duration of treatment.
• Adequate duration of antifungal treatment is unknown, but it is likely that patients will require prolonged therapy (e.g., months), tailored by the clinical response to treatment. Individual management decisions, including choice of long-term antifungal regimen, should be made in consultation with infectious diseases physicians experienced in the treatment of fungal infections. Although the adequate duration of therapy is unknown and will likely vary substantially depending upon individual patient circumstances, a minimum of 3 months of antifungal treatment should be considered. Treatment may need to continue for longer than 3 months in patients with more severe disease, bone infection, underlying immunosuppression, etc. Clinicians should be vigilant for potential relapse of infection after completion of therapy.