Antibiotic Side Effect, Early-Onset Neonatal Sepsis
Conditions
Keywords
neonatal, early-onset, infection, antibiotic
Brief summary
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.
Detailed description
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.
Interventions
OTHERIndividualized treatment duration strategy
As listed under arm description.
Sponsors
Innovation Fund Denmark
University of Copenhagen
Ulrikka Nygaard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study is a nationwide multicenter open label non-inferiority pragmatic randomized controlled trial. Patients will be randomized 1:1 to experimental treatment duration or standard care. Patients will be stratified based on if maximum CRP level is above or below 90 mg/l.
Eligibility
Sex/Gender
ALL
Age
1 Hours to 72 Hours
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Readmission due to infection. | From 1-21 days after end of first course of antibiotic treatment. | Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment \> 72 hours |
| Total use of antibiotics | From initiation of antibiotics and the next 28 days. | Use of antibiotics (in hours) |
| Death | From 1-21 days after end of first course of antibiotic treatment. | Death of any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive protein (CRP) | CRP measured at follow-up 2 days after initial antibiotic treatment ended | CRP (mg/l) levels at follow-up |
| Readmission due to infection within 3 months | From 1-100 days after first course of antibiotics ended. | Readmission due to infection, defined as symptoms, affected biomarkers and antibiotic treatment \> 72 hours |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hospital stay | From initiation of antibiotics and the next 28 days. | Length of hospital stay within 28 days after initial antibiotic treatment started |
| Positive blood cultures | From 1-21 days after end of first course of antibiotic treatment. | Numbers of culture positive infections |
| Total use of antibiotics | From initiation of antibiotics and the next 100 days. | Use of antibiotics (in hours) |
| Serious adverse events (SAE) | From initiation of antibiotics and the next 100 days. | Any serious adverse events related to the study intervention |
| Breastfeeding | At 2 day and 21 day follow up, after end of initial antibiotic treatment. | Exclusive and partial breastfeeding rates |
Countries
Denmark
Outcome results
None listed