Undiagnosed invasive candidiasis: incorporating non-culture diagnostics into rational prophylactic and preemptive antifungal strategies

The insensitivity of blood cultures for diagnosing invasive candidiasis fuels prophylactic and preemptive antifungal treatment. Assays like serum beta-D-glucan or mannan/anti-mannan detection can identify blood culture-negative invasive candidiasis, but their roles in guiding antifungal therapy are undefined. We propose that non-culture tests can be incorporated into rational management strategies, based on clinical setting. As an example, beta-D-glucan sensitivity/specificity for blood culture-negative, deep-seated candidiasis is approximately 60/75%. In intensive care units with <1 or 3% invasive candidiasis rates, positive/negative predictive values are <2/>99% and 6/98%, respectively. With pre-test likelihoods of 10 and 33%, positive/negative predictive values are 20/94% and 54/79%, respectively. Based on these data, negative and positive beta-D-glucan results likely will be most useful for discontinuing prophylaxis among low-risk to moderate-risk patients (pre-test likelihoods similar to 3-10%), and triggering preemptive therapy among moderate-risk to high-risk patients (pre-test likelihoods similar to 10-25%), respectively. In extremely high-risk patients, universal prophylaxis is likely to be the best strategy.