Optimal Timing and Dosing Intervals of Palivizumab in Premature Neonates: Still Some Work to Do: In Reply

Abstract

In Reply.—We appreciate the comments of Manzoni et al regarding our article related to palivizumab use in very premature infants in the neonatal intensive care unit.1 Manzoni et al report respiratory syncytial virus (RSV)-related hospitalizations in 2.3% of high-risk infants treated with palivizumab in Italy despite rigorous adherence to the current American Academy of Pediatrics guidelines for palivizumab use. Their findings are comparable with reports of RSV-related hospitalizations in high-risk infants treated with palivizumab in the United States and other countries.2–5It is interesting that Manzoni et al observed that all RSV-related hospitalizations in their high-risk infants occurred only after the 19th day of palivizumab administration. Based on the findings of our study, we suspect that RSV infection in some of these infants might have been associated with suboptimal palivizumab concentrations. Although 71% of very premature infants (born at <30 weeks' gestation) in our study attained optimal palivizumab concentrations (midpoint concentrations of >40 μg/ml) 2 weeks after the first dose, only 23% were able to sustain optimal concentrations until the second dose or 4 weeks after the first dose (trough concentrations). However, these premature infants were able to attain sustained optimal protective serum concentrations after the second dose of palivizumab. Furthermore, serum concentrations rose with repeated dosing in our study infants; midpoint and trough palivizumab concentrations before the third dose were significantly higher than those before the second dose. Saez-Llorens et al6 have reported that the percentage of infants with trough concentrations of >40 μg/mL increased after each of 5 monthly injections (66%, 86%, 91%, and 95%, respectively).Although the overall rates of RSV-related hospitalization are low, we agree with Manzoni et al that RSV prophylaxis in high-risk infants should be addressed further to prevent failures in this vulnerable group. For instance, we suspect that a majority of very premature infants, who receive the first dose of palivizumab just before discharge from the hospital (as is the common practice), probably remain susceptible to infection in the weeks after discharge and preceding the next injection. We suggest that early initiation of prophylaxis in the NICU to accommodate a second dose before discharge in all such infants may ensure better RSV protection at discharge. The optimal age of initiation of RSV prophylaxis for very premature infants in the NICU during the RSV season and the interval between doses in this most vulnerable population should be closely reviewed.