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.
Franz
Axel R
AR
Department of Pediatrics, Division of Neonatology and Pediatric Critical Care, University of Ulm, Ulm, Germany. axel.franz@ukb.uni-bonn.de
Bauer
Karl
K
Schalk
Andreas
A
Garland
Suzanne M
SM
Bowman
Ellen D
ED
Rex
Kerstin
K
Nyholm
Calle
C
Norman
Mikael
M
Bougatef
Adel
A
Kron
Martina
M
Mihatsch
Walter Andreas
WA
Pohlandt
Frank
F
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D002097:C-Reactive Protein / Q000032:analysis*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000188:drug therapy; D016209:Interleukin-8 / Q000097:blood*; D012680:Sensitivity and Specificity; D019564:Unnecessary Procedures
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D002097:C-Reactive Protein