Are Early-Onset Sepsis Evaluations and Empiric Antibiotics Mandatory for All Neonates Admitted with Respiratory Distress?

Abstract

Objective The objective of this study was to evaluate the success and safety of an antimicrobial stewardship protocol for neonates admitted with respiratory distress at birth.

Study Design A retrospective cohort analysis of all infants admitted to the neonatal intensive care unit (NICU) with respiratory distress from January 2013 to February 2018 was conducted. In April 2016, an antimicrobial stewardship protocol was implemented, dividing neonates into two groups: maternal indications for delivery (no infectious risk factors for early-onset sepsis [EOS]) and fetal indications (risk factors present) for delivery. Neonates with risk factors for EOS were started on empiric antibiotics, those who lacked risk factors were observed. Paired sample t-test and descriptive statistics were used to compare the pre- and postprotocol implementation.

Results There were no missed cases of EOS in our study. Management with empiric antibiotics decreased from 95 to 41% of neonates with respiratory distress after initiation of the protocol. Newborns with a lower mean (±standard errors of the mean [SEM]) gestational age were more likely to receive empiric antibiotics (35.1 ± 0.4 [range: 23–42 weeks] vs. 37.7 ± 0.2 weeks [range: 24–42 weeks]; p < 0.05). Similar findings were seen for neonates with lower mean birth weights (2,627 ± 77 [range: 390–5,440 g] vs. 3,078 ± 51 g [range: 620–6,260 g]; p < 0.05).

Conclusion The antibiotic stewardship protocol safely reduces the administration of empiric antibiotics to symptomatic neonates without missing any cases of sepsis.

Key Points

• Newborns born with respiratory distress often receive broad-spectrum antibiotics upon NICU admission.

• An antibiotic stewardship program was created for this population and considered perinatal risk factors for sepsis when determining whether antibiotics were indicated.

• This antibiotic stewardship program was safe and effective, significantly reducing antibiotic use without missing any cases of sepsis.

Keywords

neonatology - stewardship - antibiotics - sepsis - respiratory distress

Authors' Contribution

I.C. collected the data, performed statistical analysis, drafted the initial manuscript, and reviewed and revised the manuscript. A.H. aided in collecting data. B.V. aided in implementing the antimicrobial stewardship protocol. P.R. critically reviewed and revised the manuscript for important intellectual content. J.B. created the antimicrobial stewardship protocol, aided in its implementation, and critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publication History

Received: 28 January 2020

Accepted: 04 August 2020

Article published online:
18 September 2020

• References

• 1 Schrag SJ, Farley MM, Petit S. et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics 2016; 138 (06) e20162013
• 2 Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev 2014; 27 (01) 21-47
• 3 Stoll BJ, Hansen N, Fanaroff AA. et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1): 285-291
• 4 Stoll BJ, Hansen NI, Higgins RD. et al. National Institute of Child Health and Human Development. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005; 24 (07) 635-639
• 5 Bakhuizen SE, de Haan TR, Teune MJ. et al. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr 2014; 103 (12) 1211-1218
• 6 Schrag SJ, Farley MM, Petit S. et al. Epidemiology of invasive early-onset neonatal sepsis, 2005 to 2014. Pediatrics 2016; 138 (06) e20162013
• 7 Stoll BJ, Hansen NI, Sánchez PJ. et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics 2011; 127 (05) 817-826
• 8 Puopolo KM, Mukhopadhyay S, Hansen NI. et al. NICHD Neonatal Research Network. Identification of extremely premature infants at low risk for early-onset sepsis. Pediatrics 2017; 140 (05) e20170925
• 9 Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Available at: https://cmr.asm.org/content/cmr/27/1/21.full.pdf. Accessed August 19, 2020
• 10 Benitz WE, Gould JB, Druzin ML. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics 1999; 103 (06) e77
• 11 Schrag SJ, Zell ER, Lynfield R. et al. Active Bacterial Core Surveillance Team. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002; 347 (04) 233-239
• 12 Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr 2016; 28 (02) 141-149
• 13 Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr 2011; 159 (05) 720-725
• 14 Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 2011; 159 (03) 392-397
• 15 Cantey JB, Pyle AK, Wozniak PS, Hynan LS, Sánchez PJ. Early antibiotic exposure and adverse outcomes in preterm, very low birth weight infants. J Pediatr 2018; 203: 62-67
• 16 Risnes KR, Belanger K, Murk W, Bracken MB. Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children. Am J Epidemiol 2011; 173 (03) 310-318
• 17 Candon S, Perez-Arroyo A, Marquet C. et al. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes. PLoS One 2015; 10 (05) e0125448
• 18 Cotten CM, Taylor S, Stoll B. et al. NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123 (01) 58-66
• 19 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
• 20 Bin-Nun A, Bromiker R, Wilschanski M. et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 2005; 147 (02) 192-196
• 21 Lin HC, Hsu CH, Chen HL. et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics 2008; 122 (04) 693-700
• 22 La Rosa PS, Warner BB, Zhou Y. et al. Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A 2014; 111 (34) 12522-12527
• 23 Grier A, Qiu X, Bandyopadhyay S. et al. Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth. Microbiome 2017; 5 (01) 158
• 24 Groer MW, Luciano AA, Dishaw LJ, Ashmeade TL, Miller E, Gilbert JA. Development of the preterm infant gut microbiome: a research priority. Microbiome 2014; 2: 38
• 25 Brooks B, Firek BA, Miller CS. et al. Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants. Microbiome 2014; 2 (01) 1
• 26 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 (12) 1304-1309