Individualized Duration of Antibiotic Treatment in Early Onset Infection in Newborns.

Individualized Duration of Antibiotic Treatment in Culture Negative Early Onset Infection in Term Born Newborns: A Nationwide Randomized Controlled Non-inferiority Trial.

A nationwide multicenter open label randomized controlled non-inferiority trial, including 18 departments. The study aims to compare an individualized antibiotic treatment duration with standard seven days of antibiotic treatment for culture negative early-onset infection in term newborns.

There is a documented antibiotic overuse in newborns, and a lack of evidence for the optimal duration of antibiotic therapy in culture-negative infection. The study aims to evaluate the effect of individualized treatment duration in early-onset infection.

The study aims to compare an individualized treatment duration with seven days of treatment for culture negative early-onset infection. The investigators hypothesize that the individualized treatment duration, based on structured clinical assessment of symptoms and level of CRP is non-inferior to the standard care being seven days of treatment. In the experimental treatment arm, antibiotics will be stopped when the participant had 24 hours without symptoms and at same time point have decreasing level of CRP, with an absolute threshold of CRP ≤ 30 mg/l. The investigators hypothesize that individualized treatment will shorten the duration of antibiotic therapy in newborns with early onset infection with very little risk of relapse. Newborns who fulfill criteria to stop antibiotics within 48 hours will not be eligible for inclusion.

Inclusion Criteria:

• Gestational age ≥ 35 weeks
• Birth weight ≥ 2000
• Probable or possible infection according to the structured infection risk assessment
• Sufficient size blood culture, preferably 0.5-1 ml, but at least 0.2 ml, drawn after onset of symptoms but before start of antibiotic treatment
• Negative blood culture after 48 hours

Exclusion Criteria:

• Infants with positive blood culture
• Blood culture volume prior to antibiotics of < 0.2 ml
• Site-specific infection as for example, meningitis or osteomyelitis
• Infant fulfill current recommendation to stop antibiotic treatment at 36-48 hours; Low suspicion of sepsis initially including few and vague symptoms, CRP maximum 35-50 mg/l, negative blood culture and no symptoms after 48 hours of treatment