Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial

Objective. Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement. Methods. Term and preterm infants who were < 72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center ( standard group) or to receive antibiotic therapy when IL-8 was > 70 pg/mL and/or CRP was > 10 mg/ L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation. Results. In the IL-8 group, fewer infants received antibiotic therapy than in the standard group ( 36.1% [ 237 of 656] vs 49.6% [ 315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group. Conclusions. The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.