Management of osteoarticular fungal infections in the setting of immunodeficiency

ABSTRACT

Introduction: Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendations based on low quality evidence. Furthermore, the differences between the management of immunocompromised and immunocompetent patients are not distinct. This is a narrative review after a literature search in PubMed, up to November 2019.

Areas covered: The major fungal groups causing osteomyelitis and/or arthritis are Candida spp., Aspergillus spp., non-Aspergillus filamentous fungi, non-Candida yeasts and endemic dimorphic fungi. Their epidemiology is briefly analyzed with emphasis on immunodeficiency and other risk factors. Management of OAFIs includes appropriate antifungal drug therapy (liposomal amphotericin B, triazoles or echinocandins), local surgery and immunotherapy for primary immunodeficiencies. Cessation of immunosuppressive drugs is also mandated.

Expert opinion: Management of OAFIs includes affordable and available options and approaches. However, research on therapeutic practices is urgently required to be further improved, due to the rarity of affected patients. Evolution is expected to translate into novel antifungal drugs, less invasive and precise surgical approaches and targeted enhancement of immunoregulatory pathways in defense of challenging fungal pathogens.

KEYWORDS:

• Antifungals
• fungi
• immunodeficiency
• osteoarticular
• surgery

Article Highlights

• Osteoarticular fungal infections (OAFIs) include osteomyelitis, septic arthritis and prosthetic joint infection.

• Good quality evidence arising from randomized clinical trials, systematic reviews and meta-analyses regarding the treatment of OAFIs is lacking.

• Patients with primary (congenital) or secondary (acquired) immunodeficiencies are at increased risk to suffer from OAFIs.

• Candida species and Aspergillus species are the most prevalent pathogens. Other groups are non-Aspergillus filamentous fungi, non-Candida yeasts and endemic dimorphic fungi.

• Management of OAFIs consists of antifungal drug therapy (either systemic or regional or both), surgery, augmentation of the immune system, treatment of underlying conditions and cessation of immunosuppressive drugs, where applicable.

• Location, extent, and severity of the infection, patient comorbidities and identification of the pathogen at species level, as well as antifungal drug susceptibility determine the optimal therapeutic approach.

Declaration of Interest

E Rolidies has received research grants from Gilead Sciences, Merck, Pfizer and Astellas, is or has been a consultant to Astellas, Merck, Gilead and Pfizer, and served at the speaker’s bureau of Astellas, Gilead, Merck and Pfizer. T Walsh has received grants for experimental and clinical antimicrobial pharmacology and therapeutics to his institution from Allergan, Amplyx, Astellas, Lediant, Medicines Company, Merck, Scynexis, and Tetraphase and has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Lediant, Medicines Company, Merck, Methylgene, Pfizer, and Scynexis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

No funding was used for the writing of this article. T Walsh was supported in part as a Scholar of the Henry Schueler Foundation.