Do Neonatal Infections Require a Positive Blood Culture?
Neonatal sepsis is a major cause of worldwide morbidity and mortality. Blood cultures are considered the gold standard for diagnosis, but results are often delayed for 24 to 48 hours, and sensitivity, although improved by modern techniques, such as automated blood cultures, is variable and affected by the bacterial load. For these reasons, empiric antibiotics are frequently administered to avoid potential devastating consequences of untreated sepsis. Unnecessary antibiotic treatment has been associated with increased mortality and other adverse outcomes; therefore, antibiotics should be discontinued as soon as sepsis has been ruled out. Negative cultures pose a challenge to clinicians, who must distinguish between real sepsis and sepsis-like conditions (noninfectious or viral) which do not require antibiotics. Focal infections with negative blood cultures do require antibiotic treatment. Ultra-low bacteremia, primary or secondary to recent antibiotic exposure, is often associated with negative cultures, and some consider a short course of empiric antibiotics sufficient for clearing of bacteremia. Biomarkers and molecular methods based on polymerase chain reaction are important add-ons to clinical signs or symptoms for establishing the diagnosis of sepsis. Other promising future potential adjuvants are metabolomics. Antibiotic stewardship should be implemented to avoid or discontinue unnecessary treatment. Prevention of infection still remains the most important step for dealing with neonatal sepsis.
Blood cultures are the gold standard diagnosis of neonatal sepsis but sometimes may be negative.
Other bacterial, viral, and noninfectious conditions may mimic sepsis, prompting initiation of empiric antibiotic treatments.
Since a definition of neonatal sepsis is lacking, recognizing real septic episodes may be challenging.
Keywordsneonatal sepsis - culture negative neonatal sepsis - biomarkers - bacterial molecular diagnosis - vial sepsis
08 September 2020 (online)
Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.
- 1 Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr 2016; 28 (02) 141-149
- 2 Wynn JL, Polin RA. A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr Res 2019; (e-pub ahead of print) DOI: Doi: 10.1038/ s41390–019–0517–2.
- 3 Vincent JL. Defining sepsis (with or without positive blood cultures). Lancet Child Adolesc Health 2017; 1 (02) 85-86
- 4 Mintz A, Mor M, Klinger G. , et al. Changing epidemiology and resistance patterns of pathogens causing neonatal bacteremia. Eur J Clin Microbiol Infect Dis 2020; (e-pub ahead of print) DOI: Doi: 10.1007/s10096-020-03921-9.
- 5 Fanaroff AA, Korones SB, Wright LL. , et al; The National Institute of Child Health and Human Development Neonatal Research Network. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. Pediatr Infect Dis J 1998; 17 (07) 593-598
- 6 Klingenberg C, Kornelisse RF, Buonocore G, Maier RF, Stocker M. Culture-negative early-onset neonatal sepsis - at the crossroad between efficient sepsis care and antimicrobial stewardship. Front Pediatr 2018; 6: 285
- 7 Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390 (10104): 1770-1780
- 8 Schelonka RL, Chai MK, Yoder BA, Hensley D, Brockett RM, Ascher DP. Volume of blood required to detect common neonatal pathogens. J Pediatr 1996; 129 (02) 275-278
- 9 Yaacobi N, Bar-Meir M, Shchors I, Bromiker R. A prospective controlled trial of the optimal volume for neonatal blood cultures. Pediatr Infect Dis J 2015; 34 (04) 351-354
- 10 Cantey JB, Baird SD. Ending the culture of culture-negative sepsis in the neonatal ICU. Pediatrics 2017; 140 (04) e20170044
- 11 Cordero L, Ayers LW. Duration of empiric antibiotics for suspected early-onset sepsis in extremely low birth weight infants. Infect Control Hosp Epidemiol 2003; 24 (09) 662-666
- 12 Ting JY, Synnes A, Roberts A. , et al; Canadian Neonatal Network Investigators. Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis. JAMA Pediatr 2016; 170 (12) 1181-1187
- 13 Pammi M, Flores A, Versalovic J, Leeflang MMG. Molecular assays for the diagnosis of sepsis in neonates. Cochrane Database Syst Rev 2017; 2 (02) CD011926
- 14 Goldberg O, Amitai N, Chodick G. , et al. Can we improve early identification of neonatal late-onset sepsis? A validated prediction model. J Perinatol 2020; (e-pub ahead of print) DOI: Doi: 10.1038/s41372-020-0649-6.
- 15 Bardanzellu F, Fanos V. How could metabolomics change pediatric health?. Ital J Pediatr 2020; 46 (01) 37