**10. Diagnosis of Invasive** *Candida* **Infections**

Diagnosis of ICIs is very difficult in newborns, as clinical signs and symptoms of ICIs can be nonspecific and often subtle. For this clinical, radiological, and mycological evaluations should be carried out simultaneously. In addition to microbiological cultures (blood, urine, cerebrospinal fluid, peritoneal fluid, tracheal aspirate), laboratory techniques for diagnosing ICIs also include the direct microscopic examination, the histological examination of the involved tissues, the evaluation of fungal antibodies and fungal antigens (galactomannan, 1,3-beta-D-glucan) by enzyme-linked immunosorbent assay (ELISA) or by immunofluorescence, and the detection of fungal DNA by polymerase chain reaction (PCR) in blood and/or other biologic fluids. While fungi grow readily in culture media, their identification requires large volumes of blood, which are difficult to collect, especially in preterm infants. Therefore, blood cultures can be negative in a large number of patients with fungal sepsis. In addition, up to 50% of infants with positive cerebrospinal fluid (CSF) for *Candida albicans* or *Candida parapsilosis* may have negative blood cultures within seven days. This explains the complexity of diagnosing ICIs in the newborn and the need for a prompt empirical therapy at the time of diagnostic suspicion [92].

In particular, two new diagnostic molecular tools seem to be particularly promising to early diagnose ICIs, especially in the cases where a previous antifungal prophylaxis or empirical therapy could have reduced the possibility of a positive blood culture:


However, to best of our knowledge, there are still no studies in literature that evaluated the performance of these tests in the neonatal age only.
