Prompt removal of lines and initiation of antifungal treatment are the milestones of management. Conventional amphotericin B remains a commonly used antifungal agent, but its lipid formulations and fluconazole are also used frequently. Novel antifungal agents such as second-generation triazoles and echinocandins exhibit potential as alternative agents in critically ill children with ICI. Although response rates are still far from satisfactory, improved understanding of risk factors, preventive strategies and new treatment options promise a better future outcome.

, 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...

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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.

Deoxycholate amphotericin B (DAMB) and amphotericin B lipid complex (ABLC) additively augmented the fungicidal activity of pulmonary alveolar macrophages against the conidia of Aspergillus fumigatus. DAMB, ABLC, and liposomal amphotericin B similarly displayed additive effects with polymorphonuclear leukocytes in damaging the hyphal elements of A. fumigatus.During the past two decades, invasive pulmonary aspergillosis (IPA) has emerged as an important life-threatening opportunistic fungal infection in immunocompromised hosts (6,9,17,22,24,26). The conidia of Aspergillus fumigatus enter the respiratory tract, swell, germinate, and invade pulmonary tissue as hyphae. The predominant host defenses against A. fumigatus in the lungs are pulmonary alveolar macrophages (PAMs) and peripheral blood polymorphonuclear leukocytes (PMNs). PAMs ingest inhaled Aspergillus conidia and inhibit their intracellular germination (7,16,23). PMNs defend the host against A. fumigatus by mediating damage to invading hyphae through the release of microbicidal metabolites (2,7,16).Conventional deoxycholate amphotericin B (DAMB) and newer lipid formulations of amphotericin B are standard antifungal agents used in the management of IPA. Whether these compounds have a potentially beneficial additive antifungal effect in combination with host phagocytic defenses is not well understood. We therefore investigated the potential additive effects between PAMs or PMNs and conventional or lipid formulations of amphotericin B against A. fumigatus conidia or hyphae.PAMs were obtained by bronchoalveolar lavage from 22 pathogen-free female New Zealand White rabbits (Hazleton, Rockville, Md.), as described previously (3). PAMs were incubated at a concentration of 10 6 /ml in RPMI 1640 containing 10% fetal bovine serum (Gibco), 100 U of penicillin per ml, and 100 g of streptomycin per ml (complete medium) at 37°C in 5% CO 2 for 2 days before the conidiocidal assay was performed (see below).Whole blood was obtained from healthy young adult volunteers. PMNs were isolated by dextran sedimentation and Ficoll centrifugation as reported previously (15).Strain 4215 (MYA-1163; American Type Culture Collection, Manassas, Va.), a well-characterized isolate of A. fumigatus, was stored, cultured, and processed for generation of conidial suspensions (12).The amphotericin B formulations, DAMB (Bristol-Myers Squibb, Paris, France), amphotericin B lipid complex (ABLC; The Liposome Company, Princeton, N.J.), and liposomal amphotericin B (LAMB; Gilead Nextar, San Dimas, Calif.), were used at concentrations of 0.062, 0.125, and 2.5 g/ml, respectively, in combination with PAMs and at concentrations of 0.062, 0.125, and 0.625 g/ml, respectively, in combination with PMNs. The higher concentration of LAMB (2.5 g/ml) was necessary in order to assess conidiocidal activity. These concentrations were selected as the most appropriate, as determined from separate dose-response conidiocidal assays and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide (XTT) experi...