Sepsis calculator to support antibiotic stewardship in early-onset neonatal sepsis: a meta-analysis
Abstract
Background Establishing a diagnosis of neonatal sepsis is difficult. As such, appropriate timing of antibiotic therapy remains the biggest challenge. As a consequence of non-definitive diagnoses, inappropriate antibiotic administration is common. Recently, a sepsis calculator to estimate risk of early-onset sepsis (EOS) based on both maternal risk factors and infants' clinical presentation was established.
Objective To determine the impact of the sepsis calculator in daily clinical settings, especially with regards to antibiotic usage.
Methods A literature search of Pubmed, EBSCO, Embase, and Scopus database from January 2011 (after sepsis calculator was established) to June 2018 was performed. We included observational studies that compared the sepsis calculator to recent neonatal sepsis guidelines in terms of antibiotic administration, blood culture, and admission to the neonatal intensive care unit (NICU). The literature search, validation study, and assessment risk of bias were done independently by our four authors, while the first author did the statistical analysis.
Results Of the 35 studies identified, 5 cohort studies met the criteria, with a total sample size of 18,352 infants from various countries. We developed a fixed-effect meta analysis of the data. The use of the sepsis calculator significantly reduced inappropriate use of antibiotics [RR 0.46; 95%CI 0.41 to 0.51; z=13.57; P<0.001], blood culture sampling [RR 0.46; 95%CI 0.40 to 0.52; z=12.11; P<0.001), and higher neonatal care level admissions [RR 0.68; 95%CI 0.59 to 0.78); z=5.47; P<0.001). No safety issues were reported from studies using the sepsis calculator.
Conclusion The new EOS risk estimation using a neonatal sepsis calculator is an easy, effective, and safe tool to improve appropriate antibiotic use and outcomes. This calculator is ready to be implemented in all levels of neonatal care units.
References
Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770–80. https://doi.org/10.1016/S0140-6736(17)31002-4
Cantey JB, Wozniak PS, Sanchez PJ. Prospective surveillance of antibiotic use in the neonatal intensive care unit: results from the SCOUT study. Pediatr Infect Dis J. 2015;34:267–72. https://doi.org/10.1097/INF.0000000000000542 PMid:25191849
Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010;59:1–36. PMid:21088663
Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatric Infect Dis Soc. 2014;3:234–5. https://doi.org/10.1093/jpids/piu063 PMid:26625387
Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med. 2003;31:60–8. https://doi.org/10.1515/JPM.2003.009 PMid:12661146
Cohen-Wolkowiez M, Moran C, Benjamin DK, Cotton CM, Clark RH, Benjamin DK Jr, et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J. 2009;28:1052–6. https://doi.org/10.1097/INF.0b013e3181acf6bd PMid:19953725 PMCid:PMC2798577
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;37:747-62. https://doi.org/10.1007/s00134-011-2174-8 PMid:21380522
Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale: 1928–2003. Pediatrics. 2005;116:595–602. https://doi.org/10.1542/peds.2005-0552 PMid:16140698
Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292:2357–65 https://doi.org/10.1001/jama.292.19.2357 PMid:15547163
Chan GJ, Lee AC, Baqui AH, Tan J, Black RE. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis. PLoS Med. 2013;10:e1001502. https://doi.org/10.1371/journal.pmed.1001502 PMid:23976885 PMCid:PMC3747995
Kerste M, Corver J, Sonnevelt MC, van Brakel M, van der Linden PD, Braams-Lisman BAM, et al. Application of sepsis calculator in newborns with suspected infection. J Matern Fetal Neonatal Med. 2016;29:3860–5. https://doi.org/10.3109/14767058.2016.1149563 PMid:26948457
Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005–2008. Pediatr Infect Dis J. 2011;30:937–41. https://doi.org/10.1097/INF.0b013e318223bad2 PMid:21654548 PMCid:PMC3193564
Puopolo KM, Draper D, Wi S, Newman TB, Zupancic J, Lieberman E, et al. Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics. 2011;128:e1155-63. https://doi.org/10.1542/peds.2010-3464 PMid:22025590 PMCid:PMC3208962
Turhan EE, Gürsoy T, Ovali F. Factors which affect mortality in neonatal sepsis. Turk Pediatri Ars. 2015;50:170-5. https://doi.org/10.5152/TurkPediatriArs.2015.2627 PMid:26568693 PMCid:PMC4629925
Mukhopadhyay S, Eichenwald EC, Puopolo KM. Neonatal early-onset sepsis evaluations among well-appearing infants: projected impact of changes in CDC GBS guidelines. J Perinatol. 2013;33:198-205. https://doi.org/10.1038/jp.2012.96 PMid:22814941 PMCid:PMC3782314
Benitz WE, Wynn JL, Polin RA. Reappraisal of guidelines for management of neonates with suspected early-onset sepsis. J Pediatr. 2015;166:1070-4. https://doi.org/10.1016/j.jpeds.2014.12.023 PMid:25641240 PMCid:PMC4767008
Money N, Newman J, Demissie S, Roth P, Blau J. Anti-microbial stewardship: antibiotic use in well-appearing term neonates born to mothers with chorioamnionitis. J Perinatol. 2017;37:1304-9. https://doi.org/10.1038/jp.2017.137 PMid:28981079
Flidel-Rimon O, Galstyan S, Juster-Reicher A, Rozin I, Shinwell ES. Limitations of the risk factor based approach in early neonatal sepsis evaluations. Acta Paediatr. 2012;101:e540-4. https://doi.org/10.1111/apa.12013 PMid:22937988
Kuzniewicz MW, Walsh EM, Li S, Fischer A, Escobar GJ. Development and implementation of an early-onset sepsis calculator to guide antibiotic management in late preterm and term neonates. Jt Comm J Qual Patient Saf. 2016;42:232–9. https://doi.org/10.1016/S1553-7250(16)42030-1
Dellit TH, Owens RC, McGowan JE, Gerding DN, Weinstein RA, Burke JP, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44:159–77. https://doi.org/10.1086/510393 PMid:17173212
Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, et al. Stratification of risk of early-onset sepsis in newborns > 34 weeks' gestation. Pediatrics. 2014;133:30-6. https://doi.org/10.1542/peds.2013-1689 PMid:24366992 PMCid:PMC4079292
Polin RA; Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129:1006–15. https://doi.org/10.1542/peds.2012-0541 PMid:22547779
Trijbels-Smeulders M, de Jonge GA, Pasker-de Jong PC, Gerards LJ, Adriaanse AH, van Lingen RA, et al. Epidemiology of neonatal group B streptococcal disease in The Netherlands before and after introduction of guidelines for prevention. Arch Dis Child Fetal Neonatal Ed. 2007;92:F271–6. https://doi.org/10.1136/adc.2005.088799 PMid:17227807 PMCid:PMC2675425
Taylor JA, Opel DJ. Choriophobia: a 1-act play. Pediatrics. 2012;130:342–6. https://doi.org/10.1542/peds.2012-0106 PMid:22778303
Braun D, Bromberger P, Ho NJ, Getahun D. Low rate of perinatal sepsis in term infants of mothers with chorioamnionitis. Am J Perinatol. 2016;33:143–50. https://doi.org/10.1055/s-0035-1560045 PMid:26352681
Puopolo KM, Escobar GJ. Early-onset sepsis: a predictive model based on maternal risk factors. Curr Opin Pediatr 2013;25:161–6. https://doi.org/10.1097/MOP.0b013e32835e1f96 PMid:23407183
Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, et al. Stratification of risk of early-onset sepsis in newborns >34 weeks' gestation. Pediatrics. 2014;133:30–6. https://doi.org/10.1542/peds.2013-1689 PMid:24366992 PMCid:PMC4079292
Kaiser Permanente Division of Research. Probability of neonatal early-onset infection based on maternal risk factors and the infant's clinical presentation. 2015 [cited 2018 June 27]. Available from: http://newbornsepsiscalculator.org/calculator.
Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, et al. A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr. 2017;171:365–71. https://doi.org/10.1001/jamapediatrics.2016.4678 PMid:28241253
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. https://doi.org/10.1371/journal.pmed.1000097 PMid:19621072 PMCid:PMC2707599
Newcastle-Ottawa Quality Assessment Scale Cohort Studies. 2014. [cited 2018 June]; Available from: http://www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf.
Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64:380–2. https://doi.org/10.1016/j.jclinepi.2010.09.011 PMid:21185693
Strunk T, Buchiboyina A, Sharp M, Nathan E, Doherty D, Patole S. Implementation of the neonatal sepsis calculator in an Australian tertiary perinatal centre. Neonatology. 2018;113:379–82. https://doi.org/10.1159/000487298 PMid:29514161
Beavers JB, Bai S, Perry J, Simpson J, Peeples S. Implementation and evaluation of the early-onset sepsis risk calculator in a high-risk university nursery. Clin Pediatr (Phila). 2018;57:1080–5. https://doi.org/10.1177/0009922817751337 PMid:29284278
Warren S, Garcia M, Hankins C. Impact of neonatal early-onset sepsis calculator on antibiotic use within two tertiary healthcare centers. J Perinatol. 2017;37:394–7. https://doi.org/10.1038/jp.2016.236 PMid:28005063
Dhudasia MB, Mukhopadhyay S, Puopolo KM. Implementation of the sepsis risk calculator at an academic birth hospital. Hosp Pediatr. 2018;8:243–50. https://doi.org/10.1542/hpeds.2017-0180 PMid:29666161
Achten NB, Dorigo-Zetsma JW, van der Linden PD, van Brakel M, Plötz FB. Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis. Eur J Pediatr. 2018;177:741-6. https://doi.org/10.1007/s00431-018-3113-2 PMid:29455368
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;35:494–500. https://doi.org/10.1097/INF.0000000000001063 PMid:26766143
Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Curr Opin Pediatr. 2012;24:753–9. https://doi.org/10.1097/MOP.0b013e32835a1ac8 PMid:23111681 PMCid:PMC3914299
Madan JC, Salari RC, Saxena D, Davidson L, O'Toole GA, Moore JH, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F456–62. https://doi.org/10.1136/fetalneonatal-2011-301373 PMid:22562869 PMCid:PMC3724360
Mukhopadhyay S, Lieberman ES, Puopolo KM, Riley LE, Johnson LC. Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term neonates. Hosp Pediatr. 2015;5:203–10. https://doi.org/10.1542/hpeds.2014-0126 PMid:25832975
Alm B, Erdes L, Möllborg P, Pettersson R, Norvenius SG, Aberg N, et al. Neonatal antibiotic treatment is a risk factor for early wheezing. Pediatrics. 2008;121:697-702. https://doi.org/10.1542/peds.2007-1232 PMid:18381533
Hviid A, Svanström H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut. 2011;60:49–54. https://doi.org/10.1136/gut.2010.219683 PMid:20966024
Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014;168:1063–9. https://doi.org/10.1001/jamapediatrics.2014.1539 PMid:25265089
Mukhopadhyay S, Taylor JA, Von Kohorn I, Flaherman V, Burgos AE, Phillipi CA, et al. Variation in sepsis evaluation across a national network of nurseries. Pediatrics. 2017;139:e20162845. https://doi.org/10.1542/peds.2016-2845 PMid:28179485
Hofer N, Zacharias E, Muller W, Resch B. An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology. 2012;102:25–36. https://doi.org/10.1159/000336629 PMid:22507868
Mussap M. Laboratory medicine in neonatal sepsis and inflammation. J Matern Fetal Neonatal Med. 2012;25 Suppl 4:32–4. https://doi.org/10.3109/14767058.2012.715000 PMid:22958009
Chiesa C, Signore F, Assumma M, Buffone E, Tramontozzi P, Osborn JF, et al. Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders. Clin Chem. 2001;47:1016–22. PMid:11375286
Chiesa C, Natale F, Pascone R, Osborn JF, Pacifico L, Bonci E, et al. C-reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta. 2011;412:1053–9. https://doi.org/10.1016/j.cca.2011.02.020 PMid:21338596
Berardi A, Fornaciari S, Rossi C, Patianna V, Bacchi Reggiani ML, Ferrari F, et al. Safety of physical examination alone for managing well-appearing neonates >35 weeks' gestation at risk for early-onset neonatal sepsis. J Matern Fetal Neonatal Med. 2015;28:1123–7. https://doi.org/10.3109/14767058.2014.946499 PMid:25034325
Copyright (c) 2018 Rinawati Rohsiswatmo, Hardya Gustada Hikmahrachim, Dinarda Ulf Nadobudskaya, Sonia Miyajima Anjani, Albert You
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Accepted 2018-12-10
Published 2018-12-13
