By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Prosthetic valve endocarditis due to Candida spp. is associated with high mortality, but is curable — or at least controllable.

SOURCE: Rivoisy C, Vena A, Schaeffer L, et al; French Mycoses Study Group and Grupo de Apoyo al Manejo de las Endocarditis en España (GAMES). Prosthetic valve Candida spp. endocarditis: New insights into long-term prognosis — The ESCAPE Study. Clin Infect Dis 2018;66:825-832.

Rivoisy and colleagues reviewed the prospectively collected records of 46 patients from 41 centers in France and Spain with prosthetic valve endocarditis (PVE) due to Candida spp. Ten cases were judged by the Duke criteria to be possible endocarditis and 36 were proven endocarditis. Candida PVE, 60% involving a bioprosthesis, occurred 4-27.2 months (median, 8.9 months) after native valve replacement surgery. Almost half (48%), including all nine intravenous drug users, had experienced a previous episode of endocarditis after a median interval of 338 days. In five of these 22 patients, the initial episode had been due to Candida of the same species as was isolated subsequently during the second episode of valve infection, and each had involved a native valve.

Presentation with one or more embolic complications occurred in 21 (46%) patients. Among these, pulmonary emboli occurred in four (36%) of 11 with right-sided endocarditis, while cerebral emboli occurred in 10 (21.7%) patients, and seven (15.2%) had splenic emboli.

Infection was due to Candida parapsilosis in 19 (41%) patients, followed by Candida albicans in 16 (35%), Candida tropicalis in five (10.9%), Candida glabrata in four (8.7%), and Candida guilliermondii in two (4.3%). None were found to be resistant to standard antifungals, including amphotericin B (although there are no official breakpoints for this drug), flucytosine, fluconazole, voriconazole, and caspofungin.

All patients received antifungal therapy, with 19 (41%) also undergoing surgical intervention; 27 patients received antifungal therapy alone. Twelve (71%) and 19 (66%) patients, respectively, survived. A contraindication was present in 15 of the 27 who did not undergo surgery, while three refused surgery and, in the remaining nine, surgery was deemed not necessary by their physicians.

Combination antifungal therapy, most often liposomal amphotericin B (L-amB) plus 5-flucytosine, was administered to 31 (67%) patients. The duration of induction antifungal therapy ranged from 24 to 69 days (median 40 days). In univariate analysis, survival was associated with younger age, L-amB-based treatment, long-term receipt of fluconazole, and being an intravenous drug user. Patients who received monotherapy with L-amB had better survival at six months than those who received caspofungin monotherapy (adjusted odds ratio [aOR], 13.52; 95% confidence interval [CI], 1.03-838.10).

The overall in-hospital mortality was 30%, but increased to 56% during the entire period of follow-up, with 18 (69%) deaths due to Candida PVE. Of the 31 patients who were alive at the end of induction therapy, 21 (68%) received maintenance fluconazole therapy and four (19%) of these had a relapse of their infection, as did five (50%) of the 10 who did not receive maintenance therapy.

COMMENTARY

The 2016 Infectious Diseases Society of America (IDSA) guidelines recommend initial treatment of Candida PVE with L-amB with or without flucytosine or an echinocandin given in high dose (e.g., caspofungin at 150 mg daily) together with valve replacement with continued induction antifungal therapy for a minimum of six weeks post-operatively.1 This is to be transitioned to chronic administration of 400 to 800 mg (6-12 mg/kg) fluconazole daily.1 However, it should be noted that all the IDSA recommendations are graded as strong, but based on low-quality evidence.

Although the IDSA guideline indicates that echinocandin and L-amB are each first-line treatment choices, the study reviewed here found that treatment with L-amB was statistically marginally superior to treatment with caspofungin. However, no information is provided regarding the doses administered, and it is possible that the higher-than-usual caspofungin doses recommended by IDSA were not used in these patients.

Somewhat surprisingly, Rivoisy and colleagues found outcomes of Candida PVE to be similar to those reported for Candida native valve endocarditis. However, they did confirm that the relapse rate is higher with the former infection. Of note is that the relapse rate was higher in those who received only 200 mg fluconazole daily — lower than recommended.

Mortality was similar in patients with possible and probable endocarditis. The finding of similar outcomes for patients with and without surgical intervention seems surprising to me and raises the question of whether some of the latter group did not, in fact, have Candida PVE. I would think twice about recommending against valve replacement for a patient with this infection.

REFERENCE

  1. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-50.