Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention TrialStocker M.a · Fontana M.a · el Helou S.a · Wegscheider K.b · Berger T.M.a
aNeonatal and Pediatric Intensive Care Unit, Children’s Hospital of Lucerne, Switzerland, and bDepartment of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
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 ≧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 ≧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. Conclusion: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.
© 2009 S. Karger AG, Basel
- Polin RA: The ‘ins and outs’ of neonatal sepsis. J Pediatr 2003;143:3–4.
- Escobar GJ: The neonatal ‘sepsis work-up’: personal reflections on the development of an evidence-based approach toward newborn infections in a managed care organization. Pediatrics 1999;103:e360–e373.
- Gendrel D, Bohuon C: Procalcitonin as a marker of bacterial infection. Pediatr Infect Dis J 2000;19:679–688.
- Marchini G, Berggren V, Djilali-Merzoug R, Hansson LO: The birth process initiates an acute phase reaction in the fetus-newborn infant. Acta Pediatr 2000;89:1082–1086.
- Chiesa C, Panero A, Rossi N, Stegagno M, DeGiusti M, Osborn JF, Pacifico L: Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26:664–672.
Assuma M, Signore F, Pacifico L, Rossi N, Osbron JF, Chiesa C: Serum procalcitonin concentrations in term delivering mothers and their healthy offsprings: A longitudinal study. Clin Chem 2000;46:1583–1587.
- Guibourdenche J, Bedu A, Petzold L, Marchand M, Mariani-Kurdjian P, Hurtaud-Roux M, Aujard Y, Porquet D: Biochemical markers of neonatal sepsis: value of procalcitonin in the emergency setting. Ann Clin Biochem 2002;39:130–135.
- Monneret G, Labaune JM, Isaac C, Beinvenu F, Puter G, Bienvenu J: Procalcitonin and C-reactive protein levels in neonatal infections. Acta Pediatr 1997;86:209–212.
- Sachse C, Dressler F, Henkel E: Increased serum procalcitonin in newborn infants without infection. Clin Chem 1998;44:1343–1344.
- Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS: Procalcitonin in preterm infants during the first few days of life: introducing an age-related nomogram. Arch Dis Child Fetal Neonatal Ed 2006;91:F283–F286.
- Ballot DE, Perovic O, Galpin J, Cooper PA: Serum procalcitonin as an early marker of neonatal sepsis. S Afr Med J 2004;94:851–854.
- Blommendahl J, Janas M, Laine S, Miettinen A, Ashorn P: Comparison of procalcitonin with CRP and differential white blood cell count for diagnosis of culture-proven neonatal sepsis. Scand J Infect Dis 2002;34:620–622.
- Distefano G, Curreri R, Betta P, Romeo MG, Amato M: Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm infants. Acta Paediatr 2004;93:216–219.
- Enguix A, Rey C, Concha A, Medina A, Coto D, Dieguez MA: Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children. Int Care Med 2001;27:211–215.
- Franz AR, Kron M, Pohlandt F, Steinbach G: Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants. Pediatr Infect Dis J 1999;18:666–671.
- Gendrel D, Assicot M, Raymond J, Moulin F, Francouai C, Badoual J, Bohuon C: Procalcitonin as a marker for the early diagnosis of neonatal infection. J Pediatr 1996;128:570–573.
- Joram N, Boscher C, Denizot S, Loubersac V, Winer N, Roze JC, Gras-Le Guen C: Umbilical cord blood procalcitonin and C-reactive protein concentrations as markers for early diagnosis of very early onset neonatal infection. Arch Dis Child Fetal Neonatal Ed 2006;91:F65–F66.
- Kordek A, Giedrys-Kalemba S, Pawlus B, Podraza W, Czajka R: Umbilical cord blood serum procalcitonin concentration in the diagnosis of early neonatal infection. J Perinatol 2003;23:148–153.
- Resch B, Gusenleitner W, Müller WD: Procalcitonin and interleukin-6 in the diagnosis of early-onset sepsis of the neonate. Acta Paediatr 2003;92:243–245.
- Meisner M: Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2002;323:17–29.
- Connell TG, Rele M, Cowley D, Buttery JP, Curtis N: How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children’s hospital. Pediatrics 2007;119:891–896.
- Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J: Use of procalcitonin to shorten antibiotic treatment duration in septic patients. Am J Respir Crit Care Med 2008;177:498–505.
- Philip AG, Mills PC: Use of C-reactive protein in minimizing antibiotic exposure: experience with infants initially admitted to a well-baby nursery. Pediatrics 2000;106:e4.
- Ehl S, Gering B, Bartmann P, Högel J, Pohlandt F: C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection. Pediatrics 1997;99:216–221.
- Benitz WE, Han MY, Madan A, Ramachandra P: Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998;102:e41.
- Engle WD, Jackson GL, Sendelbach DM, Stehel EK, Ford DM, McHugh KM, Norris MR, Vedro DA, Velaphi S, Michelow IC, Olsen KD: Pneumonia in term neonates: laboratory studies and duration of antibiotic therapy. J Perinatol 2003;23:372–377.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.