A Retrospective Analysis of Clinical Outcomes with Continuous Versus Intermittent Nafcillin Infusions in Children

Introduction: The efficacy of nafcillin therapy is associated with the percentage of time that the free drug concentration remains above the minimum inhibitory concentration (fT>MIC) of the infecting organism. Traditional intermittent doses are administered every 4 to 6 hours, but continuous infusions may allow for more steady drug concentrations and therefore increased fT>MIC, and may decrease pharmacy and nursing time. Minimal experience with continuous infusion anti-staphylococcal beta-lactams has been published. The primary objective of this study was to compare the efficacy and safety outcomes of continuous versus intermittent nafcillin infusions.

Methods: This was a retrospective cohort study performed at a freestanding, tertiary care children’s hospital. Subjects were included if they were at least 30 days old and received more than one dose of nafcillin dosed by intermittent infusion (II; 30 min infusion every 4 or 6 hrs) or continuous infusion (CI) from January 1, 2009 to December 31, 2012. Clinical and microbiological data were extracted from the medical record. Documented nafcillin-associated adverse reactions were recorded. Treatment success was defined by any one of the following without the presence of conflicting data: microbiologic cure, prescriber documented treatment success, or normalization of abnormal clinical or laboratory parameters.

Results: 177 subjects (40 in the CI and 137 in the II group) with median (IQR) ages of 9 yrs (2.3-12) in the CI and 2 years (0.75-9.5) in the II groups were included. Overall treatment success was observed in 92.5% vs. 93.4% of CI vs. II patients, respectively (p=0.735). Similar rates of microbiologic cure (CI: 91.3%; II: 94.4%; p=0.63) and median [IQR] length of stay (days) were observed (CI: 7 [5 – 21.75]; II: 11 [5 – 24.5]; p=0.696). Extended lengths of stay were less common in CI vs. II patients, with 37.5% vs. 56.2% of patients admitted to the hospital for ≥10 days (p=0.037). Adverse reactions were documented in 42.5% vs. 41.6% of CI and II subjects, respectively (p=0.92) with no statistical difference in specific reactions. Patients receiving CI tended to have a higher likelihood of bone marrow suppression/ neutropenia than II patients (88.2% vs. 63.2%; p=0.073).

Conclusions: In this pediatric cohort, overall treatment success and microbiologic cure were similar between CI and II recipients. Patients receiving CI nafcillin may be less likely to experience extended hospital stays as compared to patients receiving II nafcillin. Continuous infusion nafcillin appears to be an acceptable alternative to II nafcillin in children.