BACKGROUNDS: The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. METHODS: Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. RESULTS: In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category 'infection unlikely' and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic. CONCLUSIONS: Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category 'infection unlikely,' and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.

Department of Neonatology Albert Schweitzer Hospital Dordrecht The Netherlands

Department of Neonatology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Neonatology Reinier de Graaf Gasthuis Delft The Netherlands

Department of Neonatology Sint Franciscus Gasthuis Rotterdam The Netherlands

Department of Neonatology St Josephs Healthcare Hamilton Health Sciences Hamilton ON Canada

Department of Neonatology Zuyderland Medical Centre Heerlen The Netherlands

Department of Paediatrics Bern University Hospital Inselspital University of Bern Bern Switzerland

Department of Paediatrics Haaglanden Medical Center 's Gravenhage The Netherlands

Department of Paediatrics Jeroen Bosch Hospital 's Hertogenbosch The Netherlands

Department of Paediatrics Kantonsspital Winterthur Winterthur Switzerland

Department of Paediatrics Maxima Medical Centre Veldhoven The Netherlands

Department of Paediatrics Neonatal and Paediatric Intensive Care Unit Children's Hospital Lucerne Lucerne Switzerland

Department of Paediatrics Stadtspital Triemli Zürich Switzerland

Department of Public Health Erasmus MC University Medical Center Rotterdam P O Box 2040 3000 CA Rotterdam The Netherlands

Division of Neonatology Erasmus MC University Medical Centre Sophia Children's Hospital Rotterdam The Netherlands

Division of Neonatology McMaster University Children's Hospital Hamilton Health Sciences Hamilton ON Canada

Division of Paediatric Infectious Diseases and Immunology Department of Paediatrics Erasmus MC University Medical Centre Sophia Children's Hospital Rotterdam The Netherlands

Institute of Pathological Physiology 1st Medical Faculty Charles University Prague Czech Republic

Julius Training General Practitioner University Medical Centre Utrecht Utrecht The Netherlands

Neonatal Intensive Care Unit Isala Women and Children's Centre Isala Hospital Zwolle The Netherlands

Neonatal Unit Department of Obstetrics and Gynaecology Motol University Hospital 2nd Medical Faculty Charles University Prague Czech Republic

Paediatric Critical Care Research Group Mater Research Institute University of Queensland Brisbane QLD Australia

Paediatric Intensive Care Unit Lady Cilento Children's Hospital Brisbane QLD Australia

See more in PubMed

Vergnano S, Menson E, Kennea N, Embleton N, Russell AB, Watts T, et al. Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed. 2011;96(1):F9–F14. doi: 10.1136/adc.2009.178798. PubMed DOI

Zimmermann P, Curtis N. Effect of intrapartum antibiotics on the intestinal microbiota of infants: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2020;105(2):201–208. doi: 10.1136/archdischild-2018-316659. PubMed DOI

Afroza S. Neonatal sepsis—a global problem: an overview. Mymensingh Med J. 2006;15(1):108–114. PubMed

Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341(8844):515–518. doi: 10.1016/0140-6736(93)90277-N. PubMed DOI PMC

van Rossum AM, Wulkan RW, Oudesluys-Murphy AM. Procalcitonin as an early marker of infection in neonates and children. Lancet Infect Dis. 2004;4(10):620–630. doi: 10.1016/S1473-3099(04)01146-6. PubMed DOI

Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med. 2011;37(5):747–762. doi: 10.1007/s00134-011-2174-8. PubMed DOI

Stocker M, van Herk W, El Helou S, Dutta S, Fontana MS, Schuerman F, et al. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns) Lancet. 2017;390(10097):871–881. doi: 10.1016/S0140-6736(17)31444-7. PubMed DOI

Balk RA, Kadri SS, Cao Z, Robinson SB, Lipkin C, Bozzette SA. Effect of procalcitonin testing on health-care utilization and costs in critically Ill patients in the United States. Chest. 2017;151(1):23–33. doi: 10.1016/j.chest.2016.06.046. PubMed DOI PMC

Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, et al. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg. 2009;394(2):221–226. doi: 10.1007/s00423-008-0432-1. PubMed DOI

Kip MMA, van Oers JA, Shajiei A, Beishuizen A, Berghuis AMS, Girbes AR, et al. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands. Crit Care. 2018;22(1):293. doi: 10.1186/s13054-018-2234-3. PubMed DOI PMC

Mewes JC, Pulia MS, Mansour MK, Broyles MR, Nguyen HB, Steuten LM. The cost impact of PCT-guided antibiotic stewardship versus usual care for hospitalised patients with suspected sepsis or lower respiratory tract infections in the US: A health economic model analysis. PLoS One. 2019;14(4):e0214222. PubMed PMC

Voermans AM, Mewes JC, Broyles MR, Steuten LMG. Cost-Effectiveness Analysis of a Procalcitonin-Guided Decision Algorithm for Antibiotic Stewardship Using Real-World U.S. Hospital Data. OMICS. 2019;23(10):508–15. PubMed PMC

Stocker M, Hop WC, van Rossum AM. Neonatal Procalcitonin Intervention Study (NeoPInS): effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: a multi-centre randomized superiority and non-inferiority Intervention Study. BMC Pediatr. 2010;10:89. doi: 10.1186/1471-2431-10-89. PubMed DOI PMC

Hakkaart-van Roijen L, van der Linden N, Bouwmans C, Kanters T, Swan Tan S. Kostenhandleiding: Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. Rotterdam: Institute for Medical Technology Assessment; Erasmus Universiteit Rotterdam; 2015.

Zorginstituut Nederland. Farmacotherapeutisch Kompas 2020 [Available from: http://www.farmacotherapeutischkompas.nl.

van Herk W, el Helou S, Janota J, Hagmann C, Klingenberg C, Staub E, et al. Variation in current management of term and late-preterm neonates at risk for early-onset sepsis: an international survey and review of guidelines. Pediatr Infect Dis J. 2016;35(5):494–500. doi: 10.1097/INF.0000000000001063. PubMed DOI

Esposito S, Tagliabue C, Picciolli I, Semino M, Sabatini C, Consolo S, et al. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir Med. 2011;105(12):1939–1945. doi: 10.1016/j.rmed.2011.09.003. PubMed DOI

Baer G, Baumann P, Buettcher M, Heininger U, Berthet G, Schafer J, et al. Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): a randomized controlled trial. PLoS ONE. 2013;8(8):e68419. doi: 10.1371/journal.pone.0068419. PubMed DOI PMC