The Epidemiology and Diagnosis of Invasive Candidiasis Among Premature Infants

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Key points

  • Invasive candidiasis occurs primarily in extremely premature infants and is associated with substantial morbidity and mortality.

  • The incidence of invasive candidiasis is strongly related to gestational age and birth weight, but most cases are preventable.

  • The diagnosis of invasive candidiasis relies on clinical suspicion and detection of Candida in blood culture or cultures from other normally sterile sites.

  • Several methods were recently developed that can shorten the time needed for the

Background

Invasive candidiasis is a leading infectious cause of morbidity and mortality in extremely premature infants. It affects 4% to 8% of extremely low-birth-weight (ELBW; birth weight <1000 g) infants and is associated with 30% mortality.1, 2, 3, 4, 5, 6, 7, 8 Infants with invasive candidiasis who survive frequently have long-term neurological impairment, including cerebral palsy, blindness, hearing impairment, cognitive deficits, and periventricular leukomalacia.2, 5, 9, 10, 11

The incidence of

Pathogenesis

Candida species are yeast that frequently colonize skin, the gastrointestinal (GI) tract, and the female genitourinary tract.16 Infants admitted to the NICU are colonized by Candida rapidly after birth, with the GI and respiratory tracts being the most frequent sites during the first 2 weeks of life.17, 18, 19, 20, 21 Colonization during this age period may be related to the birthing process; infants delivered vaginally have higher rates of colonization than infants born by Caesarean section,

Risk factors

Neonatal candidiasis generally occurs after the first 2 weeks of life in the setting of extreme prematurity or among infants of any gestational age with GI processes.35 Over the past decade, investigators identified risk factors for invasive candidiasis in several large cohorts of infants.

Microbiology

Although there are more than 150 species of Candida, most cases of invasive candidiasis among infants are caused by relatively few species. C albicans is generally the most commonly isolated species, accounting for 45% to 55% of episodes of invasive candidiasis among infants.2, 3, 8, 13, 57 In most cohorts, C parapsilosis is the most frequent nonalbicans Candida species (20%–35%), followed by C tropicalis (1%–6%).3, 13, 39, 58 Nonalbicans species may be responsible for a growing proportion of

Diagnosis

Delayed initiation of appropriate antifungal therapy is associated with increased mortality from invasive candidiasis.61, 62 However, the identification of infants with candidiasis is challenging, as infants typically have nonspecific symptoms and diagnostic capabilities are currently limited.

Treatment

Indications and neonatal dosing for specific antifungal agents are discussed in detail elsewhere in this issue. However, for the bedside clinician, 2 aspects of invasive candidiasis warrant special consideration: (1) involvement of the kidneys should guide the choice of antifungal therapy and (2) central nervous system involvement should be presumed in the infant with invasive candidiasis. More specifically, liposomal formulations of amphotericin B should not be used for infants with renal

Summary

Although improved recognition of risk factors led to a substantial reduction in neonatal candidiasis over the past decade, this infection remains a barrier to achieving further reductions in the morbidity and mortality associated with extreme prematurity. The diagnosis of invasive candidiasis continues to rely on clinical suspicion and the detection of candidemia. Several methods were recently developed that can shorten the duration of time needed for the identification of yeast from positive

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      The reported rates of invasive Candida infections in NICU settings range between 0.5 and 2%, depending on the gestational age and birth weight of patients in the cohorts. The risk is greatest among preterm infants with extremely low birth weight (<1000 g).24,25 Antibiotic prophylaxis was not administered in any of the centers, but antifungal prophylaxis was performed in 74.1% of the centers.

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    Conflicts of interest: Dr D.K. Benjamin receives support from the US government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-05, 1K24HD058735-05, UL1TR001117, and National Institute of Child Health and Human Development contract HHSN275201000003I) and the nonprofit organization Thrasher Research Fund for his work in neonatal candidiasis (www.thrasherresearch.org); he also receives research support from industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). Dr. P.B. Smith receives consultant fees from Astellas Pharma, GlaxoSmithKline, and Pfizer.

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