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.

Scedosporium apiospermum and its teleomorph (sexual form) Pseudallescheria boydii are ubiquitous saprophytic fungi, which under specific conditions, such as near-drowning, may cause therapy-refractory and life-threatening infections. We reviewed 22 cases (eight children and 14 adults) of S. apiospermum infection after near-drowning reported in the literature including an additional paediatric case from our institution. Scedosporiosis after near-drowning was associated with high mortality (16/23, 70%) even in immunocompetent hosts. It affected mainly young (mean age 24 years) and immunocompetent (83% with no apparent immune defect) males (male to female ratio 2.5 : 1). Scedosporiosis after near-drowning was a slow progressive disease (mean survival time 87 days) involving virtually all body organs. However, central nervous system (CNS) dissemination predominated (21/23, 91%) presenting mainly as multiple brain abscesses (15/23, 65%). All 23 patients showed preceding clinical and/or radiological evidence of lung disease indicating the mode of invasion. Diagnosis was delayed (median time to diagnosis 28 days) and was made by culture (16/23, 69.5%) or culture and tissue examination (7/23, 30.5%). The majority of the patients (20/23, 87%) received antifungal treatment and underwent neurosurgery. While the optimal treatment remains undefined, the most recent reports indicated voriconazole as a potentially effective option. Better knowledge of scedosporiosis after near-drowning could lead to improved intervention and ultimately to more favourable outcome.

CNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients.

Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency.

QoL and mainly the dimension of physical well-being, may be affected dramatically in children with CKD unrelated to disease stage. In early school years children with CKD seem to feel higher social acceptance than the healthy controls, exhibiting better score in this dimension. Optimal care requires attention not only to medical management, but also to an assessment of QoL factors, that may help promote pediatric patient's health.

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1␤ (IL-1␤), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF-␣), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1␤ (MIP-1␤) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF-␣) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1␤, TNF-␣, MCP-1, and MIP-1␤ (2 to 6 h) and in a late increase of antiinflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1␤ and TNF-␣, whereas ABLC additionally decreased MIP-1␤. In protein measurement studies, DAMB and ABCD up-regulated production of IL-1␤ (P < 0.05), decreased the IL-1ra/IL-1␤ ratio, and up-regulated the production of MCP-1 and MIP-1␤. In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1␤ ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and antiinflammatory cytokines that potentially may explain the differences in infusion-related reactions and dosedependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections.Historically, deoxycholate amphotericin B (DAMB) has been considered the "gold standard" of antifungal therapy, and it remains the drug with the broadest antifungal spectrum (21, 25). However, DAMB causes adverse infusion-related reactions and dose-dependent nephrotoxicity, which are clearly associated with increased morbidity in immunocompromised patients (1,13,19). The lipid-based amphotericin B formulations liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) have been developed with the goal to decrease toxicity and improve drug tolerance and thus efficacy (17, 38). Patients with neutropenia and invasive fungal infections developed infusion-related adverse reactions less frequently with LAMB than with ABLC and ABCD, whereas nephrotoxic tolerability was improved with all three lipid formulations compared to with DAMB (8,17,22,41).In vivo, amphotericin B-related toxicity has been previously correlated with increased levels in plasma of interleukin-1␤ (IL-1␤), tumor necrosis factor alpha (TNF-␣), and IL-1 receptor antagonis...

Chronic granulomatous disease (CGD) is a rare inherited disorder characterised by inability of phagocytes to kill catalase-positive organisms including certain fungi. Aspergillus species are the most frequent fungal pathogens. This study is a systematic review of the reported cases of osteomyelitis due to Aspergillus species in CGD patients. Retrospective analysis of 46 osteomyelitis cases caused by Aspergillus species in 43 CGD patients (three females) published in the English literature (PubMed) was performed. Twenty-three cases were due to Aspergillus fumigatus (50%), 20 to Aspergillus nidulans (43.5%), one to Aspergillus flavus and two to unspecified Aspergillus species. The median age was 8 years (range 1.5-21). Osteomyelitis due to A. nidulans was associated with pulmonary infection and involved 'small bones' more frequently than A. fumigatus osteomyelitis (P = 0.001). Amphotericin B was used in 91.3% and surgical debridement in 67.4% of all cases. The overall mortality of osteomyelitis due to Aspergillus species in CGD patients was 37%; 55% for A. nidulans compared to 13% for A. fumigatus (P = 0.008). Aspergillus fumigatus causes osteomyelitis in CGD patients almost as frequently as A. nidulans and much more frequently than A. flavus. Osteomyelitis due to A. nidulans is associated with higher mortality than A. fumigatus.

Background Candida parapsilosis constitutes a common Candida spp. isolated in children with candidemia. Few data exist on risk factors and outcome of candidemia caused by C. parapsilosis in pediatric patients. Methods We conducted a retrospective analysis of demographic data, clinical features, therapeutic procedures and outcomes associated with Candida bloodstream infections (BSIs) that occurred at the Children’s Hospital of Philadelphia between 1997–2009. Results Among 406 Candida BSIs, Candida albicans accounted for 198 (49%), C. parapsilosis for 99 (24%) and all other species for 109 (27%) episodes. There was no consistent change in proportion of C. parapsilosis BSIs during the study. C. parapsilosis BSI was more frequent than non-parapsilosis Candida spp. at age ≤2 years as compared with older patients [62% vs. 50%; OR=1.24, 95% CI=1.03–1.51, p=0.038]. Patients with C. parapsilosis were more likely to be mechanically ventilated within 48 hours of BSI (OR=1.38, 95% CI=1.01–1.85, p=0.047). Presence of a urinary catheter a week before infection was a protective factor for developing candidemia due to C. parapsilosis spp. (p=0.003). No significant differences were found between the two groups in presence of central intravascular catheters, co-morbidities and clinical or surgical procedures, previous administration of immunosuppressive or antifungal agents and mortality. Conclusions C. parapsilosis is the second most frequent cause of candidemia after C. albicans. While it is more frequent at the age of ≤2 years and is more likely associated with mechanical ventilation than other Candida spp., mortality does not significantly differ between those with and without C. parapsilosis candidemia.