Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Neonatal cutaneous disseminated aspergillosis in a preterm extremely-low-birth-weight infant with favourable outcome at 3-year follow-up: a case report.

Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

Liposomal amphotericin B does not induce nephrotoxicity or renal function impairment in premature neonates.

BACKGROUND: Liposomal amphotericin B (LAMB) is frequently administered in NICU to preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal infections (SFI). Concerns exist on safety and tolerability of such drug in patients who are at risk for renal function impairment due to their prematurity. AIM: To assess the occurrence of renal function impairment related to LAMB in a 10-year cohort of VLBW neonates treated with this drug. METHODS: Through database search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in the years 1998-2007 and undergoing treatment with LAMB were identified. The occurrence of LAMB-attributable renal toxicity was investigated; infants withdrawn from treatment for development of adverse effects or toxicity were identified. RESULTS: In the study period, 71 of 792 admitted VLBW neonates (8.9%) underwent antifungal treatment with LAMB administered at the recommended dosages (3-to-5 mg/kg/day). Mean duration of treatment was 14 (±9) days, mean cumulative dose given was 58 (±25) mg/kg per infant. Renal compromise, defined as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine output, occurred in 2 of 71 (2.8%) treated patients, by 5 (±3) mean days after treatment initiation. In both patients LAMB was withdrawn; renal function impairment was only mild and transient, and normal renal function was restored at discharge. No other significant adverse effects were recorded in any treated neonate. CONCLUSIONS: LAMB is generally safe and well tolerated in VLBW neonates. The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and transient.

Neonatal fungal infections: the state of the art.

Candida spp is the 3rd most frequent cause of sepsis in preterm infants, with high attributable mortality and poor outcome. Neonatal fugal infections include bloodstream, urine, cerebrospinal and peritoneal infections. Preterm infants display specific, often unavoidable, risk factors for SFI, with fungal colonization being the most significant one. Prompt treatment does not prevent poor long-term neurodevelopmental outcomes. Thus, prevention is the milestone, and should mainly rely on the administration of targeted prophylactic fluconazole to high-risk infants, as recently demonstrated by a large Italian multicenter study. As prevention is key in pediatrics, finally we can deliver this to this vulnerable population.

[G-CSF, neutropenia and candidiasis in VLBW patients]. / G-CSF, neutropenia e candidiasi nel VLBW.

OBJECTIVES: Relationships among Early Onset Neutropenia (EON), i.e. neutropenia in the first week of life, treated with Filgrastim, and subsequent colonization by Candida spp. with eventual systemic fungal infection in ELBW patients are not clear. We tried to analyze these features in a retrospective study on a selected population of a large tertiary NICU. METHODS: By a database search, we identified a group of VLBW patients who were diagnosed a systemic fungal infection (SFI) during their stay in NICU (n=52), and divided them in two subgroups: those who had presented Early Onset Neutropenia (EON) and thus had been treated with a 3-day course of Filgrastim (n=14)(group A), and those who had not presented EON and thus had not undergone Filgrastim therapy (n=38) (group B). We investigated in both subgroups the following variables: neutrophil count monitoring during the first 2 weeks of life, colonization by Candida spp, day of onset of SFI, outcome. Statistical analysis was performed by Chi-square test, ANOVA and T-test using SPSS 8.0 for Windows. RESULTS: Absolute neutrophil number was obviously lower in group A at recruitment (354/mmc vs 2910\mmc, Chi-square = 9.776, p <0.005), but became normal at the end of G-CSF treatment, thus detecting no significant differences between the two groups at day 8 (p<0.12) and 14 (p<0.34). The onset of SFI occurred significantly earlier ( 9.6 dol vs 14.6 dol., p<0.004) in group A neonates. Fungal Colonization rate in the 2nd week of life was significantly higher in previously neutropenic patients (71% vs. 37%, p< 0.005), who had also a significantly higher number of sites involved (p<0.003). CONCLUSIONS: Neutropenia in the first days of life in VLBW neonates, even if adequately and succesfully treated, heavily influences rates and severity of colonization by fungal spp., and is associated with an earlier onset of a SFI.

[Drugs administered to the mother during labor and neonatal jaundice]. / Farmaci somministrati alla madre durante il travaglio di parto ed ittero neonatale.

The authors investigated the relationship between neonatal hyperbilirubinaemia and the administering of drugs to mothers during labor and delivery in 756 A.G.A. regular pregnancy born. Findings point out a statistically significant relationship (P less than 0,05) between all drugs administered to mothers, general anesthesia included, and the presence of jaundice in newborn. Authors recommend administration of drugs to women in labor and in delivery only if strictly necessary.