Do We Have New Data for Optimal Treatments of Candida-Related Prosthetic Joint Infections?
The choice between debridement and implant exchange affects treatment outcomes for Candida-related prosthetic joint infections, highlighting the need for standardized guidelines and further research.
Prosthetic joint infections (PJIs) are among the most common complications of arthroplasties. Most PJIs are caused by bacteria and most commonly by Staphylococcus species, whereas only 1% to 2% are caused by fungi.1 Among these rare fungal PJIs, Candida species are the most isolated pathogens, with Candida albicans being the most prevalent, followed by non–C albicans species such as Candida parapsilosis, Candida glabrata, and Candida tropicalis.2 Candida species, particularly C albicans, tend to adhere to host surfaces and medical devices, causing biofilm formation that leads to high morbidity and mortality.3 Special patient populations, including those with immunocompromised status, overuse or inappropriate use of antibiotics in the past, or indwelling catheters, are at higher risk of acquiring such mycotic infections.4
Candida PJIs represent a diagnostic challenge because fever rarely occurs in these patients, and single specimens growing Candida may be considered a contaminant. To date, there are no established guidelines for the treatments of fungal PJIs, possibly due to their rare incidence and challenges in accurate diagnosis.1 Polymicrobial PJIs are also possible, and past cases have shown that 15% to 20% of fungal PJIs may have concurrent bacterial infections.1 Systemic reviews of the literature have been published; however, the quality of evidence is still limited by the availability of case reports, small case series, and very small retrospective cohorts.1,2,4-9 Therefore, the optimal medical and surgical management, choice of antimicrobials, and duration of treatment for fungal PJIs remain uncertain. In the setting of a general lack of highquality literature on the management of candidal PJIs, Dinh et al conducted a large, retrospective, multinational observational cohort study to bridge this gap.10 This study evaluated patients diagnosed with Candidarelated PJI across 19 hospitals from 7 countries from 2010 to 2021. Patients who met European Bone and Joint Infection Society PJI criteria, had Candida spp in 2 or more sterile samples, and had clinical signs and symptoms of PJI such as fever, pain, or other inflammatory indicators were included. In terms of outcomes, the cohort was divided into cure and treatment failure groups, where the cure was defined as not having any signs and symptoms of infection after 2 years of follow-up and treatment failure was defined as a composite of relapse/recurrence, need for suppressive treatment, or death. Overall, 269 patients were included in the cohort; 10.8% had immunocompromised status, and 75.8% had previous infection at the same site. Statistically significant baseline patient characteristics are summarized in the TABLE.
From a clinical signs and symptoms standpoint, approximately half of patients (50.6%) had local inflammatory signs, followed by fistulas (33.8%) and dehiscence (30.9%). C albicans and C parapsilosis were the most frequent isolated pathogens at 55.8% and 29.4%, respectively. Bacterial coinfection was identified in 51.3% of cases, with coagulase-negative staphylococci being the most common (34.2%), followed by Enterobacterales (23.4%), Staphylococcus aureus (20.4%), and Enterococcus spp (12.6%). Regarding antifungal treatment, the most used antifungal agents were azoles (75.8%) followed by echinocandins (30.9%), and the median treatment duration was 92 days. Notably, only 9.1% of patients received a combination of antifungals.
The choice of antifungal did not affect rates of treatment failure. Treatment success occurred in 58% of patients, with only the removal of the implant demonstrating a statistically significant impact on treatment success. The procedure of debridement and irrigation with implant retention (DAIR) without prosthesis exchange was associated with treatment failure (OR, 1.946; 95% CI, 1.157-3.285), but there was no difference comparing 1- to 2-stage exchange. In addition, age of more than 70 years was associated with treatment failure (OR, 1.811; 95% CI, 1.079-3.072). In comparison, C parapsilosis infections were associated with better outcomes (OR, 0.546; 95% CI, 0.305-0.958) than C albicans infections.
Findings from this study suggest that among patients with Candida PJIs, the primary predictor of treatment failure is the method of surgical intervention. Either 1- or 2-stage prosthesis exchange should be favored over DAIR without prosthesis exchange to reduce the risk of treatment failure. The choice of antifungal therapy did not affect treatment success. However, the study may have been underpowered to detect a difference between agents, as most (75.8%) patients received an azole. The strength of this study is its relatively larger sample sizes compared with existing relevant studies in the literature; however, its applicability is still limited by retrospective design, possible increasing risk of confounding variables over a more extended 2-year follow-up period, and lack of clear conclusion on the optimal antifungal choice and treatment duration. More studies, namely prospective randomized trials with larger sample sizes, are required to further explore the effectiveness and safety of various medical treatment options given these limitations.
HIGHLIGHTED ARTICLE Dinh A, McNally M, D’Anglejan E, et al; European Society of Clinical Microbiology and Infectious Diseases Study Group on Implant-Associated Infections (ESGIAI). Prosthetic joint infections due to Candida species: a multicenter international study. Clin Infect Dis. Published online August 27, 2024. doi:10.1093/cid/ciae395
References
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10.Dinh A, McNally M, D’Anglejan E, et al; European Society of Clinical Microbiology and Infectious Diseases Study Group on Implant Associated Infections (ESGIAI). Prosthetic joint infections due to Candida species: a multicenter international study. Clin Infect Dis. Published online August 27, 2024.
