A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.

OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, /=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

Development of a vaccine tracking system to improve the rate of age-appropriate primary immunization in children of lower socioeconomic status.

We conducted a randomized, controlled trial to determine the effectiveness of an immunization tracking system designed to increase the number of infants of lower socioeconomic status who receive their primary series of vaccinations at age-appropriate times. By 7 months of age, 91% (274/301) of the infants in the intervention group were up-to-date on their primary series of vaccinations versus 72% (214/296) of the infants in the control group (p < 0.0001). The estimated cost of follow-up for each infant in the intervention group was $18.05.

Hyperimmune human IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats.

Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis.

Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit.

An outbreak of candidemia involving five infants receiving total parenteral nutrition in the neonatal intensive care unit was investigated. Cultures of the intravenous fluids demonstrated that the retrograde medication syringe fluids were significantly more likely to be contaminated with Candida than were other fluids being administered to the infants (p less than 0.001). Candidemia was significantly associated with total parenteral nutrition (p = 0.04) and retrograde medication administration (p = 0.02). A survey of nursing practice found that reuse of the retrograde syringes was the most likely cause of contamination. Molecular typing showed that the strains of Candida albicans that were isolated from the bloodstream were also found in the retrograde syringes and that at least three strains of C. albicans and one strain each of Candida tropicalis and Candida parapsilosis were involved. In vitro growth curves demonstrated that Candida species had a selective growth advantage versus bacteria in the total parenteral nutrition fluid. An in vitro simulation of the retrograde medication administration system suggested that the outbreak probably developed after the frequency of changing intravenous tubing was decreased from every 24 hours to every 72 hours. The outbreak was terminated by using syringes only once and resuming intravenous tubing changes every 24 hours. Retrograde medication administration in association with total parenteral nutrition may increase the risk of Candida line infection.

Apparent increase in the incidence of invasive group A beta-hemolytic streptococcal disease in children.

Recently, among adults, an increase in the incidence of invasive disease caused by group A beta-hemolytic streptococci (GABS) has been noted, as has the appearance of a severe illness called "toxic shock-like syndrome," also caused by GABS. We now report an apparent increase beginning in 1987 in the incidence of invasive disease caused by GABS in children. Among these patients the manifestations were varied. One child had signs and symptoms compatible with the streptococcal toxic shock-like syndrome. Among the GABS isolates from our patients, 8 (80%) of 10 evaluated for M-protein antigens were nontypeable. Further studies will be necessary to determine the relationship between serotypes and virulence of GABS. Physicians should be aware of the possibility of an increasing incidence of invasive GABS disease in children, as well as its manifestations, which may include toxic shock-like syndrome.