A prospective observational study of invasive candidiasis was conducted in the neonatal intensive care unit of Aristotle University in Hippokration Hospital between 1994 and 2000. During this period, 59 neonates developed invasive candidiasis (58 cases of candidemia and 1 case of peritonitis), resulting in an overall incidence of 1.28% that showed a decreasing trend over the study period. Eleven (18.6%) cases developed within the first week of life and the others within a mean (+/-SEM) of 13.4+/-1.7 days after birth. The three most frequent causative species were Candida albicans (65.5%), Candida parapsilosis (15.5%), and Candida tropicalis (7%). C. albicans was the predominant species between 1994 and 1998, whereas, non-albicans Candida spp., particularly C. parapsilosis, were the most frequent species during the period 1999-2000 (P<0.001). While the overall mortality due to candidemia was 29% (17 of 59 cases), mortality associated with C. albicans and C. parapsilosis was 39.5% and 11.1%, respectively (P=0.032), and that observed in the 1999-2000 period was 0% (P=0.011). Virtually all isolates were susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole, and no increases in minimal inhibitory concentrations were observed during these years. With the exception of a limited cluster of cases due to genotypically identical isolates, no clonal relation of C. albicans isolates was found. Moreover, no clonal persistence of C. albicans and no decrease in antifungal drug susceptibility occurred over the 6-year study period. Non-albicans Candida spp., mostly C. parapsilosis, have emerged as important pathogens in neonatal intensive care units, with infected patients having better outcomes as compared to patients infected with C. albicans.

, two episodes of Candida tropicalis fungemia occurred in the Aristotle University neonatal intensive care unit (ICU). To investigate this uncommon event, a prospective study of fungal colonization and infection was conducted. From December 1998 to December 1999, surveillance cultures of the oral cavities and perinea of the 593 of the 781 neonates admitted to the neonatal ICU who were expected to stay for >7 days were performed. Potential environmental reservoirs and possible risk factors for acquisition of C. tropicalis were searched for. Molecular epidemiologic studies by two methods of restriction fragment length polymorphism analysis and two methods of random amplified polymorphic DNA analysis were performed. Seventy-two neonates were colonized by yeasts (12.1%), of which 30 were colonized by Candida albicans, 17 were colonized by C. tropicalis, and 5 were colonized by Candida parapsilosis. From December 1998 to December 1999, 10 cases of fungemia occurred; 6 were due to C. parapsilosis, 2 were due to C. tropicalis, 1 was due to Candida glabrata, and 1 was due to Trichosporon asahii (12.8/1,000 admissions). Fungemia occurred more frequently in colonized than in noncolonized neonates (P < 0.0001). Genetic analysis of 11 colonization isolates and the two late blood isolates of C. tropicalis demonstrated two genotypes. One blood isolate and nine colonization isolates belonged to a single type. The fungemia/colonization ratio of C. parapsilosis (3/5) was greater than that of C. tropicalis (2/17, P ‫؍‬ 0.05), other non-C. albicans Candida spp. (1/11, P ‫؍‬ 0.02), or C. albicans (0/27, P ‫؍‬ 0.05). Extensive environmental cultures revealed no common source of C. tropicalis or C. parapsilosis. There was neither prophylactic use of azoles nor other risk factors found for acquisition of C. tropicalis except for total parenteral nutrition. A substantial risk of colonization by non-C. albicans Candida spp. in the neonatal ICU may lead to a preponderance of C. tropicalis as a significant cause of neonatal fungemia.Candida spp. are common causes of nosocomial invasive infections in neonatal intensive care units (ICUs). Although Candida albicans has historically been the most frequently isolated species, infections caused by non-C. albicans Candida spp. have been diagnosed with increased frequency in recent years (14,17). In particular, Candida parapsilosis has become the predominant fungal pathogen in many neonatal ICUs (11,14,17). Moreover, recent studies have shown that C. parapsilosis is often a cause of clusters and common-source outbreaks (12, 29).In contrast, little is known about the roles of other non-C. albicans Candida spp. in neonatal ICUs (4). To our knowledge, Candida tropicalis fungemia in neonates has not been adequately described, and the significance of mucocutaneous colonization of neonates by this pathogen remains speculative.Two chronologically related unusual cases of C. tropicalis fungemia that occurred in the Aristotle University neonatal ICU prompted us to initiate a prospective study of fungal co...

A prospective study was conducted to determine risk factors for fungal colonization, drug susceptibility, and association with invasive fungal infections (IFIs) in a neonatal unit. On admission and weekly thereafter, surveillance fungal cultures were taken from mouth, rectum, and trachea of neonates with expected stays of > 1 week. Fungal colonization was detected in 72 (12.1%) of 593 neonates during 12 months. CANDIDA ALBICANS was isolated from 42% of colonized neonates. Although early colonization (age 1.3 +/- 0.2 days) was found in 2.5% of the neonates, late colonization (age 17.6 +/- 1.4 days) was noted in 14.2% of neonates hospitalized for > 5 days. Neonates born vaginally were at higher risk for early colonization than those delivered after cesarean section ( P = 0.01). By multivariate logistic regression, very low birthweight was the only independent risk factor for late colonization. Ten IFIs (nine candidemias) were diagnosed, yielding a rate of 1.1%. These episodes occurred in 6.9% of colonized neonates, compared with 0.76% of noncolonized neonates ( P = 0.002). C. ALBICANS was susceptible to azoles, but some non- ALBICANS CANDIDA spp. exhibited decreased susceptibility to these drugs.

Aiming to define the evolution pattern of 10 acute-phase proteins in early infancy, we measured nephelometrically the serum concentrations of albumin, prealbumin, retinol-binding protein, transferrin, ceruloplasmin, hemopexin, haptoglobin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, and alpha 1-antitrypsin in 395 term and preterm infants (gestational ages 26-41 weeks). Measurements were performed within 24 h after birth and then at the end of 1 (n = 171), 3 (n = 155), and 6 (n = 90) months afterwards. Data obtained from 250 healthy adults were used as adult reference values. All proteins increased progressively with postnatal age, except for alpha 1-antitrypsin, which remained stable from birth to the 6th month. Concentrations of almost all measured proteins were significantly lower in preterm than in term infants in the first 3 months. Compared with adult values, alpha 2-macroglobulin and alpha 1-antitrypsin were higher in infants throughout the 6 months. The other proteins were significantly lower at birth than adult values but after 6 months, only albumin, prealbumin, retinol-binding protein, and alpha 1-acid glycoprotein still remained lower in infants. Thus both gestational and postnatal age should be considered when interpreting concentrations of these proteins in early infancy.

The aim of this study was to evaluate the impact of prematurity, sepsis and stress on the neutrophil respiratory burst activity (NRBA) of neonates. For this purpose 122 healthy neonates (89 term and 33 preterm), 33 preterm stressed neonates, 59 septic neonates (12 term and 47 preterm) and 26 healthy adults were studied. The NRBA was assessed after in vitro stimulation by PMA using a whole blood flow cytometric microassay with dihydrorhodamine 123 (DHR 123). It was found that the percentage of responding neutrophils in term neonates was comparable to that found in adults (medians 83.5 and 89.8%, respectively), whereas it was significantly lower in the healthy preterm neonates (median 70.6%, p < 0.05). The NRBA was further depressed in the stressed (median = 63%) and septic neonates, both term and preterm (medians 60.5 and 54.3%, respectively). No correlation with the levels of G-CSF, TNF-α and IL-1β, which were found to be higher in the stressed and septic neonates, was observed. These findings indicate that prematurity, sepsis and stress significantly depress the respiratory burst activity of neonatal neutrophils.