Successful treatment of Candida glabrata peritonitis with fluconazole plus flucytosine in a premature infant following in vitro fertilization

Although Candida is an increasingly common cause of neonatal infections, particularly in very-low-birth-weight infants, Candida glabrata has rarely been reported as a causative agent. We describe here a case of C. glabrata neonatal peritonitis that occurred in a premature infant following preterm rupture of membranes and chorioamnionitis. The infant had been conceived with in vitro fertilization and embryo transfer. The mother was immunocompetent and was not diabetic. This was her sixth pregnancy. In this case, preterm rupture of membranes occurred at 21 weeks’ gestation, and a Candida sp. was isolated from four consecutive vaginal samples collected at that time. Due to the rupture, prophylactic antimicrobial chemotherapy with ceftriaxone, metronidazole and netilmicin was started. Bethamethasone was also given for fetal lung maturation. At gestational week 25, Cesarean section was required because of antepartum hemorrhage and maternal fever. Following the procedure, the maternal outcome was satisfactory. The infant was born with a birth weight of 680 g. Mechanical ventilatory support was required for managing hyaline membrane disease, and the outcome was favorable. An intravenous (i.v.) amoxicillin–amikacin combination was started but discontinued after 48 h when blood cultures were found to be sterile. C. glabrata was isolated from the neonatal gastric aspirate sample taken on admission to the neonatal intensive care unit, and from the venous and arterial umbilical catheter tips that had been removed on day 3 after admission. Pneumoperitoneum, probably due to spontaneous intestinal perforation occurred on day 11. There were no radiological signs of pneumatosis intestinalis. Empirical i.v. fluconazole (7 mg/kg/day) was started immediately following the detection of gastrointestinal tract colonization with C. glabrata. On day 15 of hospitalization a sub-phrenic collection with documented C. glabrata was drained under ultrasound guidance. On day 27, given the persistence of the collection on ultrasound imaging and the continued growth of C. glabrata detected in three consecutive samples, in combination with the results of E-test susceptibility testing (AB Biodisk, Solna, Sweden) revealing an MIC of 32 mg/l for fluconazole and 0.023 mg/l for flucytosine, the antimicrobial regimen was changed to i.v. flucytosine (100 mg/kg/day) combined with i.v. fluconazole (10 mg/kg/day). Blood cultures performed on day 26 were negative. On day 36 the peritoneal drain was removed. The total duration of intravenous antifungal treatment was 43 days. No relapses occurred in the infant thereafter. Histologic examination of the placental membranes after hematoxylin eosin staining showed acute chorioamnionitis. Retrospective Grocott staining of the placental membranes revealed small yeast cells lacking pseudo-hyphae that, together with the prior identification of the cultured yeast isolates, confirmed the diagnosis of C. glabrata chorioamnionitis. All yeast isolates from the mother were retrospectively identified as C. glabrata, and the antifungal susceptibility profiles and, especially, the fluconazole MICs obtained for these strains were the same as those obtained for the infant’s isolates. The reported incidence of vaginal fungal colonization during pregnancy is between 25 and 46% [1]. C. albicans is isolated in 85–90% of cases and C. glabrata in 5–15% [2]. Chorioamnionitis complicates 1–2% of pregnancies overall and up to 25% of preterm deliveries. Candida chorioamnionitis is rare, and usually of ascending origin [1, 3, 4]. A. M. Freydiere (*) . J. M. Andre Laboratoire de Microbiologie, Hopital Debrousse, Hospices Civils de Lyon, 29 Rue Sœur Bouvier, 69322 Lyon cedex 5, France e-mail: anne-marie.freydiere@chu-lyon.fr Tel.: +33-4-72385816 Fax: +33-4-72385535