This retrospective cohort study involved children admitted to Mattel Children’s Hospital in Los Angeles, California, during an 11-year period from January 1991 to December 2001. Information obtained on all positive fungal cultures from all body sites included date and site of culture, demographics, and fungal etiology. Additionally, data regarding underlying illness, hospital course, outcome, and antimicrobial treatment were considered.
Study results demonstrated a significant increase in diagnosed fungemia in children. There was a 15% increase in overall pediatric admissions in the study period, and a 23% increase in positive fungal cultures in the same period. Of 272 blood cultures, 97 were positive for fungus. Although this is a relatively small number of total infections, data demonstrated a 91% increase in fungemia during the study period. Candida species were the organisms most frequently isolated from any body site with 85% of the total isolates. Of the total positive isolates, it appeared that approximately 78% reflected colonization as opposed to infection.
Outcomes for fungal infections improved only marginally in the study period. Fifty percent of patients with fungemia died between 1991 and 1996, and 45% died between 1997 and 2001. The mortality rate for immunocompromised conditions was 57%. The cost effectiveness of fungal screening cultures was also evaluated, which demonstrated that fungal cultures identified 14 patients independent of bacterial blood cultures at a cost of $560,000, which resulted in a cost of $40,000 per identified patient.
The study reaches several significant conclusions. First there has been a significant increase in fungal infections that exceeds the increase in overall pediatric hospital admissions. However, it is important to recognize the increase in immunocompromised conditions during the study period, which may account for the higher incidence of fungemia.
Second the addition of fungal blood cultures to bacterial blood cultures as part of a routine workup for febrile patients appeared to yield limited clinical information at a very high cost. Third this study highlights the serious threat fungal infections pose to immunocompromised hosts who have a significantly higher incidence of infection, as well as higher morbidity and mortality. Fourth the use of broad spectrum antibiotics may be increasing fungal colonization in patients and consequently increasing the risk for pathologic fungal infection. Finally morbidity and mortality rates for fungal infections did not greatly improve, despite significant improvements in supportive care made during the study period
This study demonstrates a need for better diagnostic markers for fungal infections, especially those that might provide earlier detection and diagnosis at less cost. The importance of judicious use of antibiotics is underscored while the need for a broader base of therapeutic agents is highlighted. These issues may be key ingredients needed to reduce adverse outcomes from fungal infections, especially in the immunocompromised host.
Rotavirus Vaccine Revisited
Salinas B, Perez Schael I, Linhares AC, et al. Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414. Ped Infect Dis J. 2005;24(9):807-816.
Rotavirus is the leading cause of severe gastroenteritis among children worldwide. In the United States, rotavirus is responsible for approximately 5%-10% of all diarrhea among children older than five and accounts for approximately 50,000 hospitalizations each year. An estimated one in 200,000 children with rotavirus diarrhea dies from complications of infection. The immunizing effect of rotavirus infection stimulated the development of live attenuated vaccines. In 1998, a three-dose regimen of a tetravalent rhesus-human reassortant vaccine (RotaShield: Wyeth Laboratories,) was licensed for infant immunization in the United States. Within the first year of use, it was withdrawn due to an observed risk of intussusception. The current study was designed to evaluate immunogenicity and efficacy of a live attenuated monovalent human rotavirus vaccine, RIX4414.