Culture-Negative Early-Onset Neonatal Sepsis — At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship

Shane, 2017, Neonatal sepsis, Lancet, 390, 1770, 10.1016/S0140-6736(17)31002-4

Wynn, 2018, Progress in the management of neonatal sepsis: the importance of a consensus definition, Pediatr Res., 83, 13, 10.1038/pr.2017.224

Singer, 2016, The third international consensus definitions for sepsis and septic shock (Sepsis-3), JAMA, 315, 801, 10.1001/jama.2016.0287

Schlapbach, 2018, Defining pediatric sepsis, JAMA Pediatr., 172, 312, 10.1001/jamapediatrics.2017.5208

Schlapbach, 2017, Time for sepsis-3 in children?, Pediatr Crit Care Med., 18, 805, 10.1097/PCC.0000000000001203

Haque, 2005, Definitions of bloodstream infection in the newborn, Pediatr Crit Care Med., 6, S45, 10.1097/01.PCC.0000161946.73305.0A

Wynn, 2014, Time for a neonatal-specific consensus definition for sepsis, Pediatr Crit Care Med., 15, 523, 10.1097/PCC.0000000000000157

2012, Antibiotics for Early-onset Neonatal Infection: Antibiotics for the Prevention and Treatment of Early-Onset Neonatal Infection

Cantey, 2017, Ending the culture of culture-negative sepsis in the neonatal ICU, Pediatrics, 10.1542/peds.2017-0044

Fjalstad, 2016, Early-onset sepsis and antibiotic exposure in term infants: a nationwide population-based study in Norway, Pediatr Infect Dis J., 35, 1, 10.1097/INF.0000000000000906

Cantey, 2016, Reducing unnecessary antibiotic use in the neonatal intensive care unit (SCOUT): a prospective interrupted time-series study, Lancet Infect Dis., 16, 1178, 10.1016/S1473-3099(16)30205-5

Schulman, 2015, Neonatal intensive care unit antibiotic use, Pediatrics, 135, 826, 10.1542/peds.2014-3409

Esaiassen, 2017, Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis, J Antimicrob Chemother., 72, 1858, 10.1093/jac/dkx088

Mitre, 2018, Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood, JAMA Pediatr., 172, e180315, 10.1001/jamapediatrics.2018.2513

Rasmussen, 2018, Antibiotic exposure in early life and childhood overweight and obesity: a systematic review and meta-analysis, Diabetes Obes Metab., 20, 1508, 10.1111/dom.13230

Cordery, 2008, Evaluation of risk factors for the acquisition of bloodstream infections with extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in the intensive care unit; antibiotic management and clinical outcome, J Hosp Infect., 68, 108, 10.1016/j.jhin.2007.10.011

Cantey, 2011, Prolonged antibiotic therapy for “culture-negative” sepsis in preterm infants: it's time to stop!, J Pediatr., 159, 707, 10.1016/j.jpeds.2011.07.032

Stoll, 2011, Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues, Pediatrics, 127, 817, 10.1542/peds.2010-2217

Singh, 2018, Early-onset neonatal infections in Australia and New Zealand, 2002-2012, Arch Dis Child Fetal Neonatal Ed., 10.1136/archdischild-2017-314671

Schrag, 2016, Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014, Pediatrics, 10.1542/peds.2016-2013

Bekker, 2014, Incidence of invasive group B streptococcal disease and pathogen genotype distribution in newborn babies in the Netherlands over 25 years: a nationwide surveillance study, Lancet Infect Dis., 14, 1083, 10.1016/S1473-3099(14)70919-3

Cailes, 2017, Epidemiology of UK neonatal infections: the neonIN infection surveillance network, Arch Dis Child Fetal Neonatal Ed., 10.1136/archdischild-2017-313203

Drageset, 2017, Management of early-onset neonatal sepsis differs in the north and south of Scandinavia, Acta Paediatr., 106, 375, 10.1111/apa.13698

Hofer, 2012, Neonates presenting with temperature symptoms: role in the diagnosis of early onset sepsis, Pediatr Int., 54, 486, 10.1111/j.1442-200X.2012.03570.x

Lacaze-Masmonteil, 2014, Value of a single C-reactive protein measurement at 18 h of age, Arch Dis Child Fetal Neonatal Ed., 99, F76, 10.1136/archdischild-2013-303984

Stocker, 2017, Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomized controlled trial (NeoPIns), Lancet, 390, 871, 10.1016/S0140-6736(17)31444-7

Duvoisin, 2014, Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment, Swiss Med Wkly., 10.4414/smw.2014.13981

Bakhuizen, 2014, Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications, Acta Paediatr., 103, 1211, 10.1111/apa.12764

Schlapbach, 2011, Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants, Pediatrics, 128, e348, 10.1542/peds.2010-3338

Weiss, 2014, Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis, Crit Care Med., 42, 2409, 10.1097/CCM.0000000000000509

Polin, 2012, Management of neonates with suspected or proven early-onset bacterial sepsis, Pediatrics, 129, 1006, 10.1542/peds.2012-0541

Jefferies, 2017, Management of term infants at increased risk for early-onset bacterial sepsis, Paediatr Child Health, 22, 223, 10.1093/pch/pxx023

Trijbels-Smeulders, 2007, Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention, Arch Dis Child Fetal Neonatal Ed., 92, F271, 10.1136/adc.2005.088799

Schrag, 2002, A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates, N Engl J Med., 347, 233, 10.1056/NEJMoa020205

Kuzniewicz, 2017, A quantitative, risk-based approach to the management of neonatal early-onset sepsis, JAMA Pediatr., 171, 365, 10.1001/jamapediatrics.2016.4678

van Herk, 2016, 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., 35, 494, 10.1097/INF.0000000000001063

Puopolo, 2011, Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors, Pediatrics, 128, e1155, 10.1542/peds.2010-3464

Goldstein, 2005, International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics, Pediatr Crit Care Med., 6, 2, 10.1097/00130478-200501000-00049

Oeser, 2013, Clinical trials in neonatal sepsis, J Antimicrob Chemother., 68, 2733, 10.1093/jac/dkt297

Hakansson, 2017, Reduced incidence of neonatal early-onset group B streptococcal infection after promulgation of guidelines for risk-based intrapartum antibiotic prophylaxis in Sweden: analysis of a national population-based cohort, Acta Obstet Gynecol Scand., 96, 1475, 10.1111/aogs.13211

Tveiten, 2016, Respiratory rate during the first 24 hours of life in healthy term infants, Pediatrics, 10.1542/peds.2015-2326

Doan, 2014, The timing of elective caesarean deliveries and early neonatal outcomes in singleton infants born 37-41 weeks' gestation, Aust N Z J Obstet Gynaecol., 54, 340, 10.1111/ajo.12220

Koch, 2015, Managing neonatal severe sepsis in Germany: a preliminary survey of current practices, Klin Padiatr., 227, 23, 10.1055/s-0034-1389975

Raju, 1999, Capillary refill time in the hands and feet of normal newborn infants, Clin Pediatr., 38, 139, 10.1177/000992289903800303

Strozik, 1997, Capillary refilling time in newborn babies: normal values, Arch Dis Child Fetal Neonatal Ed., 76, F193, 10.1136/fn.76.3.F193

Puopolo, 2017, Identification of extremely premature infants at low risk for early-onset sepsis, Pediatrics, 10.1542/peds.2017-0925

Ng, 2015, The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis, Arch Dis Child Fetal Neonatal Ed., 100, F448, 10.1136/archdischild-2014-307656

Ng, 2018, Precision medicine for neonatal sepsis, Front Mol Biosci., 10.3389/fmolb.2018.00070

Hornik, 2012, Use of the complete blood cell count in early-onset neonatal sepsis, Pediatr Infect Dis J., 31, 799, 10.1097/INF.0b013e318256905c

Newman, 2010, Interpreting complete blood counts soon after birth in newborns at risk for sepsis, Pediatrics, 126, 903, 10.1542/peds.2010-0935

van der Meer, 2006, Does the band cell survive the 21st century?, Eur J Haematol., 76, 251, 10.1111/j.1600-0609.2005.00597.x

Del Vecchio, 2014, Evaluation and management of thrombocytopenic neonates in the intensive care unit, Early Hum Dev., 90, S51, 10.1016/S0378-3782(14)50014-X

Spector, 1981, Study of the usefulness of clinical and hematologic findings in the diagnosis of neonatal bacterial infections, Clin Pediatr., 20, 385, 10.1177/000992288102000602

Hofer, 2012, An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks, Neonatology, 102, 25, 10.1159/000336629

Perrone, 2018, C reactive protein in healthy term newborns during the first 48 hours of life, Arch Dis Child Fetal Neonatal Ed., 103, F163, 10.1136/archdischild-2016-312506

Turner, 2004, Gestational age and the C reactive protein response, Arch Dis Child Fetal Neonatal Ed., 89, F272, 10.1136/adc.2002.011288

Chiesa, 2011, C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period, Clin Chim Acta, 412, 1053, 10.1016/j.cca.2011.02.020

Chiesa, 2001, 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., 47, 1016, 10.1093/clinchem/47.6.1016

Ishibashi, 2002, C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination, Clin Chem., 48, 1103, 10.1093/clinchem/48.7.1103

Hofer, 2011, Non-infectious conditions and gestational age influence C-reactive protein values in newborns during the first 3 days of life, Clin Chem Lab Med., 49, 297, 10.1515/CCLM.2011.048

Robinson, 2018, How to use, Arch Dis Child Educ Pract Ed., 103, 257, 10.1136/archdischild-2017-313699

Dandona, 1994, Procalcitonin increase after endotoxin injection in normal subjects, J Clin Endocrinol Metab., 79, 1605

Chiesa, 2015, Early-onset neonatal sepsis: still room for improvement in procalcitonin diagnostic accuracy studies, Medicine, 94, e1230, 10.1097/MD.0000000000001230

Chiesa, 2003, C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity, risk status, antenatal and perinatal complications, and infection, Clin Chem., 49, 60, 10.1373/49.1.60

Stocker, 2010, Use of procalcitonin-guided decision-making to shorten antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial, Neonatology, 97, 165, 10.1159/000241296

Chiesa, 1998, Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates, Clin Infect Dis., 26, 664, 10.1086/514576

Franz, 1999, Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections, Pediatrics, 104, 447, 10.1542/peds.104.3.447

Franz, 2001, Interleukin-8: a valuable tool to restrict antibiotic therapy in newborn infants, Acta Paediatr., 90, 1025, 10.1111/j.1651-2227.2001.tb01359.x

Fjalstad, 2017, Antibiotic therapy in neonates and impact on gut microbiota and antibiotic resistance development: a systematic review, J Antimicrob Chemother., 73, 569, 10.1093/jac/dkx426

Rohatgi, 2017, Seven versus 10 days antibiotic therapy for culture-proven neonatal sepsis: a randomized controlled trial, J Paediatr Child Health, 53, 556, 10.1111/jpc.13518

Ting, 2016, Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis, JAMA Pediatr., 170, 1181, 10.1001/jamapediatrics.2016.2132

Mukhopadhyay, 2016, Antibiotic use and mortality among premature infants without confirmed infection-perpetrator or innocent bystander?, JAMA Pediatr., 170, 1144, 10.1001/jamapediatrics.2016.2836

Laxminarayan, 2013, Antibiotic resistance-the need for global solutions, Lancet Infect Dis., 13, 1057, 10.1016/S1473-3099(13)70318-9

Blaser, 2016, Antibiotic use and its consequences for the normal microbiome, Science, 352, 544, 10.1126/science.aad9358

Gensollen, 2016, How colonization by microbiota in early life shapes the immune system, Science, 352, 539, 10.1126/science.aad9378

Gohir, 2015, Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk, Pediatr Res., 77, 196, 10.1038/pr.2014.169

Schulfer, 2015, Risks of antibiotic exposures early in life on the developing microbiome, PLoS Pathog., 11, e1004903, 10.1371/journal.ppat.1004903

Goff, 2017, Eight habits of highly effective antimicrobial stewardship programs to meet the joint commission standards for hospitals, Clin Infect Dis., 64, 1134, 10.1093/cid/cix065

Nzegwu, 2017, Implementation of an antimicrobial stewardship program in a neonatal intensive care unit, Infect Control Hosp Epidemiol., 38, 1137, 10.1017/ice.2017.151

Ting, 2018, Reduction of inappropriate antimicrobial prescriptions in a tertiary neonatal intensive care unit following antimicrobial stewardship care bundle implementation, Pediatr Infect Dis J., 10.1097/INF.0000000000002039

Blackburn, 2012, Neonatal sepsis–many blood samples, few positive cultures: implications for improving antibiotic prescribing, Arch Dis Child Fetal Neonatal Ed., 97, F487, 10.1136/archdischild-2012-302261

Brown, 1995, Bacterial concentration and blood volume required for a positive blood culture, J Perinatol., 15, 157

Buttery, 2002, Blood cultures in newborns and children: optimizing an everyday test, Arch Dis Child Fetal Neonatal Ed., 87, F25, 10.1136/fn.87.1.F25

Paul, 2018, Barriers to implementing the NICE guidelines for early-onset neonatal infection: cross-sectional survey of neonatal blood culture reporting by laboratories in the UK, J Hosp Infect., 98, 425, 10.1016/j.jhin.2017.12.015

Garcia-Prats, 2000, Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system, Pediatrics, 105, 523, 10.1542/peds.105.3.523

Jardine, 2006, Incubation time required for neonatal blood cultures to become positive, J Paediatr Child Health, 42, 797, 10.1111/j.1440-1754.2006.00980.x

Jardine, 2003, Reducing antibiotic use on the neonatal unit by improving communication of blood culture results: a completed audit cycle, Arch Dis Child Fetal Neonatal Ed., 88, F255, 10.1136/fn.88.3.F255-a

Vamsi, 2014, Time to positivity of blood cultures in neonates, Pediatr Infect Dis J., 33, 212, 10.1097/INF.0000000000000018

Giannoni, 2018, Neonatal sepsis of early onset, and hospital-acquired and community-acquired late onset: a prospective population-based cohort study, J Pediatr., 201, 106, 10.1016/j.jpeds.2018.05.048

Sarkar, 2015, Does maternal intrapartum antibiotic treatment prolong the incubation time required for blood cultures to become positive for infants with early-onset sepsis?, Am J Perinatol., 32, 357, 10.1055/s-0034-1387933

Jardine, 2009, Neonatal blood cultures: effect of delayed entry into the blood culture machine and bacterial concentration on the time to positive growth in a simulated model, J Paediatr Child Health, 45, 210, 10.1111/j.1440-1754.2008.01455.x

Pammi, 2011, Molecular assays in the diagnosis of neonatal sepsis: a systematic review and meta-analysis, Pediatrics, 128, e973, 10.1542/peds.2011-1208

Pammi, 2017, Molecular assays for the diagnosis of sepsis in neonates, Cochrane Database Syst Rev., 2, CD011926, 10.1002/14651858.CD011926.pub2

van den Brand, 2018, Evaluation of a real-time PCR assay for detection and quantification of bacterial DNA directly in blood of preterm neonates with suspected late-onset sepsis, Crit Care, 22, 105, 10.1186/s13054-018-2010-4

van Rossum, 2004, Procalcitonin as an early marker of infection in neonates and children, Lancet Infect Dis., 4, 620, 10.1016/S1473-3099(04)01146-6

Vouloumanou, 2011, Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis, Intensive Care Med., 37, 747, 10.1007/s00134-011-2174-8

Ehl, 1997, C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection, Pediatrics, 99, 216, 10.1542/peds.99.2.216

Mukherjee, 2015, NICE neonatal early onset sepsis guidance: greater consistency, but more investigations, and greater length of stay, Arch Dis Child Fetal Neonatal Ed., 100, F248, 10.1136/archdischild-2014-306349

Achten, 2018, Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis, Eur J Pediatr., 177, 741, 10.1007/s00431-018-3113-2

Strunk, 2018, Implementation of the neonatal sepsis calculator in an Australian tertiary perinatal center, Neonatology, 113, 379, 10.1159/000487298