Disseminated Fungal Infections in Very Low-Birth-Weight Infants: Therapeutic Toxicity

The improved survival of very low-birth-weight infants, who require prolonged hospitalization and many invasive procedures, increases the risks for nosocomial illnesses, such as disseminated fungal infections. In a 2-year period, systemic fungal infections were clinically diagnosed in ten infants. This necessitated the institution of antifungal therapy in extremely premature infants (mean birth weight 788 g, mean gestational age 28 weeks) despite the paucity of knowledge about the pharmacokinetics and toxicity of these drugs in the very immature patient. Despite the absence of reported toxicity in infants and older children, severe nephrotoxicity was commonly observed with oliguria/anuria, temporally related to the administration of amphotericin B in seven of these infants. Additional evidence of nephrotoxicity included either a rise in creatinine levels (≥1.3 mg/dL), an increase in BUN (≥30 mg/dL), hypokalemia (≤2.9 mEq/L), or hyperkalemia (≥6.0 mEq/L). Six of these seven drug-toxic infants died. Interruption of amphotericin B therapy, with reinstitution at a lower dose, was the most successful factor in alleviating the anuria. There is an urgent need for detailed pharmacokinetic and toxicity studies of antifungal agents in immature infants.