Invasive Fungal Infections in Newborns and Current Management Strategies

Shilpa Hundalani; Mohan Pammi


Expert Rev Anti Infect Ther. 2013;11(7):709-721. 

In This Article

Clinical Manifestations

Systemic Candidiasis

Neonatal candidemia occurs typically due to catheter-related or localized infections that disseminate to the kidneys, CNS and other organs. The most common presentation is similar to that of bacterial sepsis with lethargy, feeding intolerance, hyperbilirubinemia, apnea, cardiovascular instability and/or respiratory distress.[56,57] Persistent thrombocytopenia is strongly associated with candidemia and, if present, a diagnosis of candidemia should be considered.[58] Skin abscesses, which appear as clusters of painless pustules on an erythematous base or nodules, have been described in neonates with candidemia and are thought to be caused by septic emboli.[59]

Catheter-related Infections Without Multiorgan Involvement

Infants who have indwelling catheters in place are at risk of developing a catheter-related Candida infection.[12,13] An infected thrombus or fungal ball can form on the catheter tip, which consumes platelets and is a source of septic emboli.

Invasive Focal Infection

Invasive focal infection is generally due to seeding of the individual organ system from hematogenous dissemination. Although any organ can be involved, the most common sites include the eye, urinary tract, heart and the CNS.[60]

Urinary Tract Infection A Candida urinary tract infection (UTI) is present if there is greater than 103 CFU/ml in a urine specimen collected by suprapubic aspiration or greater than 104 CFU/ml in a urine specimen collected by catheterization.[61,62] Other investigators have diagnosed Candida UTI more conservatively as >106 CFU/l from a suprapubic aspirate or >107 CFU/l from a bladder catheter specimen.[63] Risk factors for Candida UTI include congenital anomalies of the kidney and urinary tract, obstruction, urinary stasis and the presence of an indwelling bladder catheter.[62,64] In several case series, the reported renal involvement ranged from 5 to 33% of infants with candidemia.[65–67] Ultrasonography is useful to detect any renal parenchymal infiltration, calyceal mycetoma or fungal masses in the urinary tract. In a retrospective review of neonates with candidemia, abdominal ultrasonography detected abnormalities due to Candida in the kidneys in three out of 65 (5%).[66] In infants with oliguria, obstruction due to discrete fungal masses can be detected by ultrasonography.[62]

CNS Infection Meningitis is the most common CNS presentation with others including brain abscesses, ventriculitis, vasculitis and fungal masses within the subarachnoid space.[56] CNS involvement in infants with disseminated candidiasis ranges from 10 to 64%.[68,69] This variability may be due to differences in the degree and thoroughness of investigations to detect CNS disease. Clinical signs may be the same as in acute bacterial meningitis. Findings on CSF are variable and relate to the type of CNS involvement (meningeal vs parenchymal disease). Normal CSF chemistries, cell count and Gram stain do not exclude CNS involvement because the inflammatory response may be limited or delayed, and the inoculum of the organism may be low.[70,71] In some infants, parenchymal abscesses may be the initial diagnosis detected by cranial imaging.[72] Complications after CNS infection include obstructive hydrocephalus requiring shunt placement, cerebral atrophy and poor neurodevelopmental outcomes.[71]

Peritonitis Case reports and case series have reported Candida peritonitis in VLBW with necrotizing enterocolitis (NEC) or focal gastrointestinal perforations.[73–75] In particular, spontaneous intestinal perforation may be associated with disseminated Candida infection. This was illustrated in a small case series of premature infants with spontaneous intestinal perforation, in which 33% of the affected infants had Candida isolated from a culture of blood, peritoneal fluid, CSF or urine.[74] It is unclear whether perforation is due to a primary Candida invasion of the mucosa, or whether Candida is only a colonizing organism that invades the bowel wall already damaged from a primary insult.[56]

Endopthalmitis Ocular candidiasis is used to describe both Candida chorioretinitis (minimal or no vitreous inflammation) and endophthalmitis (marked vitritis). The reported incidence varies from 6 to 50% of premature infants with disseminated candidiasis.[66,69,76] Indirect ophthalmoscopy examination may detect focal, glistening, white, infiltrative, often mound-like lesions on the retina with indistinct borders. Vitreous extension occurs occasionally and can be seen as a vitreal haze or as fluffy white balls ('snowballs') within in the vitreous. Candidemia without endophthalmitis appears to be associated with an increased risk of developing severe retinopathy of prematurity (ROP).[77,78] Although the study by Karlowicz et al. did not find any association with ROP after controlling for gestational age,[79] several other studies have shown an association between candidal sepsis and ROP requiring laser surgery.[77,80]

Osteoarticular Infections Candida osteomyelitis or arthritis rarely occurs as an isolated event and typically occurs after disseminated infection.[81,82] The signs and symptoms are similar to those that occur in septic arthritis or osteomyelitis caused by bacteria with swelling and decreased range of motion of the extremity. Fungal infection is confirmed by the isolation of Candida from either cultures of the synovial fluid or bone aspirate.

Endocarditis In a retrospective review of 86 infants with candidemia, echocardiogram demonstrated thrombi or vegetations in 11 out of 72 infants (15%).[66] Infants with fungemia that lasted 5 or more days were more likely to have cardiac lesions, as well as renal or ophthalmologic abnormalities.