More serious infectious morbidity and mortality associated with simultaneous candidemia and coagulase-negative staphylococcal bacteremia in neonates and in vitro adherence studies between Candida albicans and Staphylococcus epidermidis.

BACKGROUND: Candida species and coagulase-negative staphylococci (CoNS) are common etiologies of hospital acquired bloodstream infection in the neonatal intensive care unit (NICU). Sepsis with either organism may result in serious infectious sequelae and along with other staphylococci are the most common causes of abscess formation in preterm infants. This increased incidence of abscess formation may be in part due to adherence factors of both pathogens. METHODS: All cases of concurrent positive blood cultures for both Candida species and CoNS were identified from the microbiology database in NICU patients from January 1998 to December 2000 and analyzed for risk factors and outcomes. In vitro co-aggregation studies between Candida albicans and Staphylococcus epidermidis were also performed. RESULTS: Six premature infants were identified as having concurrent Candida and CoNS bloodstream infections during this time period. Four of the six patients developed end-organ dissemination with abscess or infected thrombus formation. Three of the six patients expired during or after their infection. In vitro, co-aggregation studies did not demonstrate reproducible direct adherence between C. albicans and S. epidermidis. CONCLUSIONS: Simultaneous bloodstream infection with Candida and CoNS, compared to either one alone, is more likely to predispose to abscess formation, septic thrombophlebitis and mortality. Further studies are needed to examine the pathogenesis of these complex infections.

Fluconazole prophylaxis in extremely low birth weight infants and neurodevelopmental outcomes and quality of life at 8 to 10 years of age.

OBJECTIVE: To examine the long-term effects of fluconazole prophylaxis in extremely low birth weight infants. STUDY DESIGN: Neurodevelopmental status and quality of life of survivors from a randomized, placebo-controlled trial of fluconazole prophylaxis were evaluated at 8 to 10 years of life using the Vineland Adaptive Behavior Scales-II (VABS-II) and the Child Health Questionnaire Parent-Completed Form 28 (CHQ-PF28), respectively. RESULTS: VABS-II Domain Scores for the fluconazole-treated (n = 21; 9.1 ± 0.7 years) compared with the placebo group (n = 17; 9.3 ± 0.8 years) were similar for communication [94.6 (±14.8) versus 92.6 (±12.6), P = .65], daily living skills [87.9 (±10.6) versus 87.4 (±9.3), P = .89], socialization [97.2 (±9.2) versus 94.4 (±7.9), P = .31], and motor skills [92.1 (±17.8) versus 95.1 (±14.6), P = .57]. Internalizing and externalizing behaviors and maladaptive behavior index were also similar. The CHQ-PF28 revealed no differences between the two groups regarding quality of life. Survivors were also happy or satisfied with school (90% versus 100%, P = .49), friendships (90% versus 88%, P = 1.00), and life (95% versus 100%, P = 1.00). Self esteem scores were 87.3 ± 15.7 versus 89.7 ± 10.4 (P = .59). There were also no differences between groups regarding emotional difficulties or behavior problems. CONCLUSIONS: Fluconazole prophylaxis for the prevention of invasive Candida infections is safe in extremely low birth weight infants and does not appear to be associated with any long-term adverse effects on neurodevelopment and quality of life at 8 to 10 years of life.

Patterns of fungal colonization in preterm infants weighing less than 1000 grams at birth.

BACKGROUND: Colonization with Candida spp. is an important risk factor for systemic infection in very low birth weight (VLBW; <1500 g) and extremely low birth weight (ELBW, <1000 g) infants. ELBW infants are at a higher risk than VLBW infants for fungal sepsis and its associated mortality, but few studies have examined fungal colonization exclusively in ELBW infants. METHODS: Fungal colonization data were analyzed retrospectively in 50 high risk ELBW infants. Weekly surveillance fungal cultures of the skin, gastrointestinal tract, respiratory tract and umbilicus had been performed from birth through the first 6 weeks of life. Colonization was analyzed for time of initial colonization, site, species and spread of Candida from one site to another. RESULTS: Candida was isolated from surveillance cultures in 31 of 50 (62%) infants. Colonization was inversely proportional to gestational age. Initial week of both the fungal colonization of the skin [1 (0-6) week, median (range)] and gastrointestinal tract [2 (0-6)] preceded colonization of the respiratory tract [3 (1-6)] (P = 0.0001). Among infants colonized by only 1 of the species, colonization at 2 or more sites occurred similarly with Candida albicans (77%) and Candida parapsilosis (85%), whereas colonization at 3 or more sites occurred more frequently with C. albicans (69%) compared with C. parapsilosis (23%) (P = 0.047). CONCLUSIONS: Fungal colonization occurs on the skin and gastrointestinal tract before the respiratory tract. In addition, C. albicans is more likely than C. parapsilosis to colonize multiple sites.

Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.

OBJECTIVES: We tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants. STUDY DESIGN: We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients. RESULTS: Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented. CONCLUSIONS: Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance.