Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns)
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Multicenter Study, Randomized Controlled Trial
PubMed
28711318
DOI
10.1016/s0140-6736(17)31444-7
PII: S0140-6736(17)31444-7
Knihovny.cz E-resources
- MeSH
- Anti-Bacterial Agents administration & dosage MeSH
- Biomarkers blood MeSH
- Early Diagnosis MeSH
- Time Factors MeSH
- Gestational Age MeSH
- Internationality MeSH
- Calcitonin blood MeSH
- Infant MeSH
- Humans MeSH
- Drug Monitoring methods MeSH
- Infant, Newborn, Diseases blood diagnosis drug therapy MeSH
- Infant, Newborn MeSH
- Decision Making * MeSH
- Sepsis blood diagnosis drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- Biomarkers MeSH
- Calcitonin MeSH
BACKGROUND: Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. METHODS: We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. FINDINGS: Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI -4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (-5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group). INTERPRETATION: Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death. FUNDING: The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
Department of Biostatistics Erasmus MC University Medical Centre Rotterdam Netherlands
Department of Neonatology Albert Schweitzer Hospital Dordrecht Netherlands
Department of Neonatology Atrium Medical Centre Heerlen Netherlands
Department of Neonatology Reinier de Graaf Gasthuis Delft Netherlands
Department of Neonatology Sint Franciscus Gasthuis Rotterdam Netherlands
Department of Neonatology St Josephs Healthcare Hamilton Health Sciences Hamilton ON Canada
Department of Neonatology VU University Medical Centre Amsterdam Netherlands
Department of Paediatrics Bronovo Hospital 's Gravenhage Netherlands
Department of Paediatrics Flevo Hospital Almere Netherlands
Department of Paediatrics Jeroen Bosch Hospital 's Hertogenbosch Netherlands
Department of Paediatrics Kantonsspital Winterthur Winterthur Switzerland
Department of Paediatrics Maxima Medical Centre Veldhoven Netherlands
Department of Paediatrics MC Haaglanden 's Gravenhage Netherlands
Department of Paediatrics Stadtspital Triemli Zürich Switzerland
Julius Training General Practitioner University Medical Centre Utrecht Netherlands
References provided by Crossref.org
Less is more: Antibiotics at the beginning of life
Neonatal sepsis definitions from randomised clinical trials
Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials
Evaluation of presepsin as a diagnostic tool in newborns with risk of early-onset neonatal sepsis
ClinicalTrials.gov
NCT00854932
