Invasive candidiasis in pediatric intensive care patients: epidemiology, risk factors, management, and outcome.

BACKGROUND: The incidence of candidemia in pediatric patients follows the same pattern of increase as in adults, but the rate of increase is greater. Pediatric patients in critical condition, particularly young infants, are especially vulnerable to invasive Candida infections (ICI), partly because of their age and severe underlying disease and partly because of the invasive procedures used. DISCUSSION: Central venous catheters and arterial lines, parenteral nutrition, mechanical ventilation and extended use of antimicrobials enhance the risk of ICI. C. albicans continues to be the most prevalent isolate. However, an increasing role of non-C. albicans (NAC) spp., some of which are intrinsically or potentially resistant to antifungal agents, has been observed. NAC spp., particularly C. parapsilosis and C. tropicalis, account for almost half of ICI. The increased use of antifungals in immunocompromised patients, mainly prophylactically, is considered the strongest contributory factor to the changes in species distribution, which have subsequently affected the mortality and choice of empirical treatment. CONCLUSIONS: 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.

Fungal colonization in the neonatal intensive care unit: risk factors, drug susceptibility, and association with invasive fungal infections.

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.

Filamentous fungi in a tertiary care hospital: environmental surveillance and susceptibility to antifungal drugs.

OBJECTIVE: To evaluate filamentous fungi with respect to environmental load and potential drug resistance in a tertiary care teaching hospital. DESIGN: Monthly survey in 2 buildings of the hospital during a 12-month period. SETTING: Hippokration Hospital in Thessaloniki, Greece. METHODS: Air, surface, and tap water sampling was performed in 4 departments with high-risk patients. As sampling sites, the solid-organ transplantation department and the hematology department (in the older building) and the pediatric oncology department and the pediatric intensive care unit (in the newer building) were selected. RESULTS: From January to May of 2000, the fungal load in air (FLA) was low, ranging from 0 to 12 colony-forming units (cfu) per m(3) in both buildings. During the summer months, when high temperature and humidity predominate, the FLA increased to 4-56 cfu/m(3). The fungi commonly recovered from culture of air specimens were Aspergillus niger (25.9%), Aspergillus flavus (17.7%), and Aspergillus fumigatus (12.4%). Non-Aspergillus filamentous fungi, such as Zygomycetes and Dematiaceous species, were also recovered. The pediatric intensive care unit had the lowest mean FLA (7.7 cfu/m(3)), compared with the pediatric oncology department (8.7 cfu/m(3)), the solid-organ transplantation department (16.1 cfu/m(3)), and the hematology department (22.6 cfu/m(3)). Environmental surfaces were swabbed, and 62.7% of the swab samples cultured yielded filamentous fungi similar to the fungi recovered from air but with low numbers of colony-forming units. Despite vigorous sampling, culture of tap water yielded no fungi. The increase in FLA observed during the summer coincided with renovation in the building that housed the solid-organ transplantation and hematology departments. All 54 Aspergillus air isolates randomly selected exhibited relatively low minimum inhibitory or effective concentrations for amphotericin B, itraconazole, voriconazole, posaconazole, micafungin, and anidulafungin. CONCLUSION: Air and surface fungal loads may vary in different departments of the same hospital, especially during months when the temperature and humidity are high. Environmental Aspergillus isolates are characterized by lack of resistance to clinically important antifungal agents.

Candida tropicalis in a neonatal intensive care unit: epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen.

From June to July 1998, 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.

Amphotericin B formulations exert additive antifungal activity in combination with pulmonary alveolar macrophages and polymorphonuclear leukocytes against Aspergillus fumigatus.

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.

Trichosporon asahii: an unusual cause of invasive infection in neonates.

Trichosporon asahii causes white piedra, an infection of hair shafts and onychomycosis in immunocompetent patients, as well as various localized or disseminated invasive infections in immunodeficient hosts. We describe a 26-week gestation 890-g vaginally delivered female neonate who had severe respiratory distress syndrome and on the sixth day of life developed Klebsiella pneumoniae sepsis. At the same time two blood cultures were positive for T. asahii. The neonate was also colonized with T. asahii in the pharynx and perineum. The infant was successfully treated with conventional amphotericin B.