Selective developmental defects of cord blood antigen-presenting cell subsets.

Defective antigen-presenting cell (APC) function has been hypothesized to contribute to increased infection susceptibility in newborns. We used multiparameter flow cytometry to characterize APC subsets in adult peripheral blood (APB) and cord blood (CB). APB had a higher proportion of CD11c+ dendritic cells (DC), whereas CB mainly contained CD123+ DC. APB was enriched in CD16+CD11c+ DC subset, whereas CD34+CD11c-CD123lo cells were prominent in CB. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was dampened in myeloid DC and monocytes from CB, whereas IL-1alpha production was not different. The reduction in TNF-alpha response did not appear to result from reduced surface detection of LPS, because CD14, toll-like receptor (TLR)-4 and TLR-2 levels were not reduced in CB APC compared with APB cells. Also, there was no correlation between TLR-2 or TLR-4 levels and TNF-alpha production in myeloid DC and monocytes. CB monocytes had lower surface HLA-DR immediately ex vivo. Both APB and CB monocytes upregulated HLA-DR after incubation, but an additional LPS-induced increase in HLA-DR was suggested only in APB monocytes. APB monocytes also showed a greater LPS-induced increase in CD40 expression. Together, our data show significant, selective differences in circulating APC between neonates and adults.

Low yield of ancillary diagnostic studies in neonates infected with Candida.

BACKGROUND: Fungal infection can be a significant complication for the critically ill neonate. However, the usefulness of extensive radiologic and ophthalmologic investigations in this population has not been thoroughly elucidated. OBJECTIVE: To report the incidence of organ fungal involvement diagnosed by ancillary testing (echocardiogram, ophthalmologic examination, brain imaging, and renal ultrasound (RUS)) among neonatal intensive care unit (NICU) patients with Candida infection. METHODS: This was a single center review of all NICU patients with Candida-positive cultures of blood, urine, peritoneal fluid, endotracheal tube aspirate, or cerebrospinal fluid from January 1, 1997 to June 1 2002. Data regarding the number of positive cultures, species isolated, and presence of specific risk factors and clinical symptoms were recorded for each case, as well as occurrence, timing and results of ancillary testing. RESULTS: In all, 66 patients had at least one positive culture for Candida. The majority (71%) were <1500 g at birth, and mean gestational age was 29.5+/-5.6 weeks. Echocardiograms were obtained in 54/66 (82%), and ophthalmology examinations were obtained in 36/66 (55%); none of these was consistent with fungal involvement. Brain imaging was performed in 50/66 (76%), only one of which was positive, in a patient with 16 positive blood cultures for Candida albicans. RUS were performed in 58/66 (88%) of patients, with concerning findings for fungal involvement in seven of the studies. RUS findings alone did not appear to consistently influence the length of therapy. CONCLUSIONS: Ancillary evaluations to investigate for fungal dissemination were undertaken frequently, but were of overall low yield. Although ancillary testing may be of limited additional value in centers with a low threshold for suspecting fungal infections and an aggressive approach to therapy, potentially important findings, which could impact management, may occur.

Candida (amphotericin-sensitive) lens abscess associated with decreasing arterial blood flow in a very low birth weight preterm infant.

In this report, we review the case of a candidal lens abscess in a premature infant girl who was 28 weeks' gestational age at birth. The culture obtained from the lens abscess grew Candida albicans sensitive to amphotericin B but resistant to flucytosine. This case is unique in that the infant developed a fungal lens cataract at 34 weeks' postconceptional age during the last week of a 30-day course of amphotericin B. The embryonic hyaloid artery system, which perfuses the developing lens, regresses between 29 and 32 weeks of gestation; thus, the mechanism for an infection of the lens may be inoculation of the lens by Candida before hyaloid artery system regression, followed by developmental loss of this blood supply, which makes the lens inaccessible to antimicrobial penetration. Candidal endophthalmitis with lens abscess is an uncommon morbidity that requires prompt recognition and surgical intervention for effective management.