Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial.
BACKGROUND
Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success.


OBJECTIVE
To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis.


METHODS
This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children's Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age >or=34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48-72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values.


RESULTS
121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics >or=72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12-0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events.


CONCLUSIONS
Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.
Stocker
Martin
M
Neonatal and Pediatric Intensive Care Unit, Children's Hospital of Lucerne, Switzerland. stockermartin@mail.com
Fontana
Matteo
M
El Helou
Salhab
S
Wegscheider
Karl
K
Berger
Thomas M
TM
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D003657:Decision Making; D016903:Drug Monitoring / Q000379:methods*; D042241:Early Diagnosis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide