Intensive Care Antifungal Stewardship Programme Based on T2Candida PCR and Candida Mannan Antigen: A Prospective Study

Abstract

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non-neutropenic sepsis and a high risk of IC from two large tertiary ICUs were prospectively included, during a one-year period. IC was classified as proven, likely, possible or unlikely. The AFSP, diagnostic values of T2Candida and MAg, and the consumption of antifungals were evaluated. An amount of 219 patients with 504 T2Candida/MAg samples were included. IC was classified as proven in 29 (13.2%), likely in 7 (3.2%) and possible in 10 (5.5%) patients. Sensitivity/specificity/PPV/NPV values, comparing proven/likely versus unlikely IC, were 47%/100%/94%/90% for BC alone, 50%/97%/75%/90% for T2Candida alone, and 39%/96%/67%/88% for MAg alone. For the combination of T2Candida/MAg taken ≤3 days after AFT initiation, sensitivity/specificity/PPV/NPV was 70%/90%/63%/93%. T2Candida/MAg contributed to early (<3 days) AFT initiation in 13%, early AFT discontinuation in 25% and abstaining from AFT in 24% of patients. No reduction in overall use of AFT during the study period compared with the previous year was observed. An AFSP based on T2Candida and MAg screening contributed to a reduction of unnecessary treatment, but not overall AFT use. The diagnostic performance of T2Candida was lower than previously reported, but increased if T2Candida was combined with MAg.

T2Candida assay: diagnostic performance and impact on antifungal prescribing

“…We present the first UK data on the diagnostic performance and impact of T2Candida on management of patients at risk of IC. In line with other studies 7 , 8 , 9 , 14 , T2Candida demonstrated a high specificity (>85%) and NPV (>95%) informing cessation of antifungal therapy in approximately one-third of patients, demonstrating the utility of T2Candida as an aid to antifungal stewardship (AFS), and a comparable impact to that of a negative BDG result. Diagnostic-driven strategies, especially through non-culture-based testing, can improve AFS, 15 and contribute to reducing unnecessary antifungal treatment.…”

“…Diagnostic-driven strategies, especially through non-culture-based testing, can improve AFS, 15 and contribute to reducing unnecessary antifungal treatment. 7 , 16 Given the significant toxicity and cost of antifungals, 17 the AFS benefits of the T2Candida test may even offset its upfront costs.…”

“…Subsequent studies have also observed high NPV (80%–100%), indicating T2Candida can have a role in discontinuing antifungals. 7–9 It has also been assessed as a tool for early initiation antifungal therapy, with earlier detection of Candida compared with BC in complicated candidaemia, 10 and reduced time to targeted antifungal therapy compared with BC. 11 However, some studies have reported lower sensitivity (42.8%) for diagnosing IC (with or without candidaemia), 12 33.3% for the diagnosis of intra-abdominal candidiasis 13 and 59% for the diagnosis of proven/probable IC.…”

Evaluation of a stewardship program of antifungal use at a Brazilian tertiary care hospital

“… 3 Most of the stewardship programs have focused on antibiotics, with less initiatives in IFD and use of antifungal agents. 4 , 5 , 6 , 7 , 8 In this study we evaluated the quality of antifungal prescriptions in a tertiary care hospital and tested if a simple educational activity could improve the quality of prescriptions.…”