Severe primary cutaneous aspergillosis refractory to amphotericin B and the successful treatment with systemic voriconazole in two premature infants with extremely low birth weight

Abstract

Primary cutaneous aspergillosis is a rare, life-threatening, infectious complication in premature infants that may result in fulminant sepsis and subsequent multi-organ failure. In the past decade, the incidence of primary aspergillosis has increased significantly, whereas the high morbidity and mortality of invasive aspergillosis remains unaltered. In vitro studies reveal that more and more Aspergillus species seem to be refractory to the classical treatment with fluconazole or amphotericin B. This case report presents two extremely low birth weight infants (ELBW) with primary cutaneous aspergillosis, which was refractory to amphotericin B. Both patients were successfully treated with systemic voriconazole, an extendedspectrum triazole antifungal, supported by topical care. This paper provides the clinical manifestation, diagnostics and pharmacotherapy of primary cutaneous aspergillosis, as well as pharmacokinetic aspects of voriconazole in ELBW infants.

Primary cutaneous aspergillosis in a preterm neonate

“…We chose to treat with a high dose of liposomal amphotericin recommended for invasive fungal infections and for a total of 14 days. In cases of PCA refractory to amphotericin, successful treatment with voriconazole has been reported in the literature 8 9. Owing to an immediate clinical response, our patient did not need additional antifungal treatment.…”

Deep cutaneous fungal infections in immunocompromised children

“…Although PCA is rare and reportedly more common with trauma and burns, it has been described in premature neonates with increasing frequency, particularly over the last decade. 5,[22][23][24][25] Interestingly, 16 of 17 of the PCA cases reviewed by Woodruff and Hebert 24 occurred after 1990; 15 of 17 were in premature neonates. In our group, no cases of primary or secondary aspergillosis were encountered in neonates.…”

Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections

“…Another case study examined 2 preterm infants with invasive aspergillosis where difficulty reaching voriconazole therapeutic trough concentrations was once again noted. Despite neither patient achieving that threshold (all troughs <0.8 mg/L), both showed clinical improvement after approximately one month of voriconazole treatment [113].…”