Abstract
Blood cultures are positive for Candida species in < 50% and < 20% of hematogenously disseminated and intra-abdominal candidiasis, respectively. Non-culture tests such as mannan, anti-mannan antibody, Candida albicans germ tube antibody (CAGTA), 1,3-β-d-glucan (BDG), the T2Candida nanodiagnostic panel, and polymerase chain reaction (PCR) are available for clinical use, but their roles in patient care are uncertain. Sensitivity/specificity of combined mannan/anti-mannan, BDG, T2Candida and PCR for candidemia are ~80%/80%, ~80%/80%, ~90%/98%, and ~90%/90%, respectively. Limited data for intra-abdominal candidiasis suggest CAGTA, BDG sensitivity/specificity of ~65%/75% and PCR sensitivity of ~85–90%. PCR specificity has varied widely for intra-abdominal candidiasis (33–97%), and T2Candida data are lacking. Tests will be useful if restricted to cases in which positive and negative predictive values (PPVs, NPVs) differ in a clinically meaningful way from the pre-test likelihood of invasive candidiasis. In some patients, PPVs are sufficient to justify antifungal treatment, even if blood cultures are negative. In most patients, NPVs of each test are excellent, which may support decisions to withhold antifungal therapy. If test results are not interpreted judiciously, non-culture diagnostics may have unintended consequences for stewardship and infection prevention programs. In particular, discrepant non-culture test-positive/culture-negative results may promote inappropriate antifungal treatment of patients who are unlikely to have candidiasis, and lead to spurious reporting of hospital-acquired infections. In conclusion, non-culture Candida diagnostics have potential to advance patient care, but this promise will be realized only if users understand tests’ strengths and limitations, and plan proactively for how best to employ them at their hospitals.
Highlights
Candida species are among the most common causes of nosocomial bloodstream infections, and of invasive infections in intensive care units (ICUs)
Results are reported as positive or negative for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis, groupings that are based on typical antifungal susceptibility patterns
Food and Drug Administration (FDA) clearance of T2Candida was based on data from the multi-center DIRECT trial, which included >1500 control patients with Candida-negative blood cultures, 6 patients with Candida-positive blood cultures, and 250 contrived blood specimens spiked with C. albicans, C. glabrata, C. parapsilosis, C. tropicalis or C. krusei at concentrations ranging from 1–100 CFU/mL [20]
Summary
Candida species are among the most common causes of nosocomial bloodstream infections, and of invasive infections in intensive care units (ICUs). Fungi 2018, 4, 27 most commonly as abscesses and/or peritonitis; mortality ranges from 20–80%, depending on the disease manifestations [3] For both candidemia and intra-abdominal candidiasis, the institution of timely antifungal therapy and source control are crucial determinants of good outcomes [2,3]. 2–3 days for growth to be evident), and the fact that they often turn positive late in the course of infection For these reasons, the development and validation of non-culture diagnostic tests for candidemia, intra-abdominal candidiasis, and other types of invasive candidiasis is a top medical priority [1,4]. The objectives of this paper are to provide updates on new data from studies of non-culture tests for candidemia and intra-abdominal candidiasis, discuss how these tests might improve patient care, and consider unintended consequences of testing for stewardship and infection prevention programs. We will focus on testing of whole blood or blood fractions, since data for other types of samples are scant or absent
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