The Etest Performed Directly on Blood Culture Bottles Is a Reliable Tool for Detection of Fluconazole-Resistant Candida albicans Isolates.

We assessed the ability of the Etest performed directly on positive blood cultures (ETDIR) to detect fluconazole susceptibility in 6 fluconazole-resistant and 12 fluconazole-susceptible Candida albicans isolates, according to CLSI M27-A3 and EUCAST EDef 7.2 procedures. Categorical agreement between ETDIR and broth microdilution was 100% when the trays were incubated at 25°C and trailing effect was ruled out. ETDIR is a reliable procedure when screening for the presence of fluconazole resistance in C. albicans.

Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment.

OBJECTIVES: Initiation of empirical antifungal therapy for invasive candidiasis (IC) is usually based on clinical suspicion. Serological biomarkers have not yet been studied as a means of ruling out IC. We evaluated the potential role of two combined biomarkers in stopping unnecessary antifungals in patients at risk of IC in the ICU and in other wards. METHODS: This was a prospective observational study including adults starting empirical antifungal treatment for suspected IC, at Gregorio Marañón Hospital, Madrid (Spain). Patients were stratified according to admission department (ICU or other wards) and final diagnosis (no IC or proven or probable IC). Type of candidiasis (candidaemia or deep-seated candidiasis) was also considered. The Candida albicans germ tube antibody (CAGTA) test and the ß-d-glucan (BDG) test were performed on serum samples collected by venepuncture on days 0, 3 and 5 after starting empirical antifungal therapy. RESULTS: Sixty-three ICU patients and 37 non-ICU patients were included. High-risk gastrointestinal surgery and sepsis in non-surgical patients were the main indications for empirical treatment (30% each). Patients had no IC (58%), proven IC (30%) or probable IC (12%). Overall, sensitivity and negative predictive value of the combination of both the CAGTA test and the BDG test were 97% for the entire population. The best performance was observed in ICU patients (sensitivity and negative predictive value of 100%). Among patients without IC, all biomarkers were negative in 31 patients. CONCLUSIONS: Serial determination of CAGTA/BDG during empirical antifungal therapy has a high sensitivity and negative predictive value. If properly confirmed, this strategy could be used to discontinue antifungal treatment in at least 31% of patients as a complementary tool in antifungal stewardship programmes.

Candida biomarkers in patients with candidaemia and bacteraemia.

OBJECTIVES: Microbiological strategies are necessary to help clinicians discontinue empirical antifungal therapy in patients with suspected invasive candidiasis. Culture methods and biomarkers each show low sensitivity. We analysed the value of combining different biomarkers as a decision-making tool for discontinuing empirical antifungal treatment. METHODS: We studied stored serum samples from 31 patients with candidaemia (Candida albicans 40%, Candida tropicalis 20%, Candida parapsilosis 18%, Candida glabrata 12% and other 10%) and 50 patients with bacteraemia at Gregorio Marañón Hospital, Madrid, Spain. C. albicans germ tube antibody (CAGTA), mannan antigens (MN), antimannan antibodies (AMN) and (1→3)-ß-d-glucan (BDG) were assayed using the manufacturer's and alternative cut-offs to improve the accuracy of the tests. RESULTS: The sensitivity of the biomarkers when used alone was low (58%-84%), but specificity was high (65.8%-92.0%). The best combinations were CAGTA and BDG using cut-offs of 1/80 and 80 pg/mL, respectively (sensitivity 96.8% and specificity 84%), and CAGTA and MN using cut-offs of 1/80 and 75 pg/mL, respectively (sensitivity 93.5% and specificity 86.0%). The sensitivity of both combinations was 100% for C. albicans, C. tropicalis and C. parapsilosis, but only combinations including BDG detected Candida krusei. The negative predictive values (NPVs) of both combinations were, respectively, 97.7% and 95.6% (prevalence of candidaemia, 23.6%). For a prevalence of candidaemia of 5% and 10%, the NPV reached 99.8% and 99.6%. CONCLUSIONS: The combinations of CAGTA and BDG or CAGTA and MN had a very high NPV at the alternative cut-offs and could be used in antifungal stewardship programmes as a decision-making tool for discontinuing unnecessary empirical therapy in patients with suspected candidaemia.

Potential role of Candida albicans germ tube antibody in the diagnosis of deep-seated candidemia.

Patients with candidemia may have transient or catheter-related infections without involvement of deep tissues or deep-seated candidiasis. Clinical differentiation of these entities may not be evident with conventional microbiological and imaging methods. Our aim was to determine if the detection of Candida albicans germ tube-specific antibody (CAGTA) in patients with candidemia was related to the extent of the disease. This study was conducted from 2003 to 2012 with 50 patients diagnosed as having candidemia, that is, 29 with deep-seated candidiasis and 21 with non-deep-seated candidiasis. The most common species recovered from samples obtained from these patients were C. albicans, 40%; C. tropicalis, 20%; C. parapsilosis, 18%; and C. glabrata, 12%. Serum samples were processed according to the manufacturer's recommendations (Vircell Microbiologist S.L., Granada, Spain). The CAGTA tests were positive in 1/21 non-deep-seated candidemias (DSCs; 4.76%) and 20/29 DSCs (68.96%; P < 0.01). Accordingly, the values for specificity and positive predictive values of CAGTA for identifying DSC were 95%. We concluded that the presence of a positive CAGTA test in a sample from a patient with candidemia suggests deep-seated candidiasis. Extension screening studies should be considered and origins other than catheters should be searched. Prospective studies are needed to determine the clinical implications of this finding and its potential use in defining the optimal duration of therapy.