The Association between Prolonged Antibiotic Use in Culture Negative Infants and Length of Hospital Stay and Total Hospital Costs

Abstract

Objective This study aimed to determine if prolonged antibiotic use at birth in neonates with a negative blood culture increases the total cost of hospital stay.

Study design This was a retrospective study performed at a 60-bed level IV neonatal intensive care unit. Neonates born <30 weeks of gestation or <1,500 g between 2016 and 2018 who received antibiotics were included. A multivariate linear regression analysis was conducted to determine if clinical factors contributed to increased hospital cost or length of stay.

Results In total, 190 patients met inclusion criteria with 94 infants in the prolonged antibiotic group and 96 in the control group. Prolonged antibiotic use was associated with an increase length of hospital stay of approximately 31.87 days, resulting in a $69,946 increase in total cost of hospitalization.

Conclusion Prolonged antibiotics in neonates with negative blood culture were associated with significantly longer hospital length of stay and increased total cost of hospitalization.

Key Points

• Prolonged antibiotic use at birth is associated with prolonged hospital stay.

• Prolonged antibiotic use at birth is associated with increased cost of hospitalization.

• Prolonged antibiotic use at birth is associated with increased days on total parenteral nutrition.

• Prolonged antibiotic use at birth is associated with increased subsequent courses of antibiotics.

Keywords

prolonged antibiotic use - length of stay - total hospital cost - antibiotic stewardship

Authors' Contributions

W.S. drafted the initial manuscript, completed the data collection, and revised the final paper. V.S. assisted with data collection and reviewed the final paper. M.S. performed the statistical analysis of the data and reviewed the final paper. J.B. conceptualized and designed the study and reviewed the final paper. E.R.L. reviewed and edited the manuscript. D.N. assisted with the study design, reviewed, and edited the manuscript. S.K.J. reviewed and revised the manuscript for important intellectual content in addition to conceptualizing the study. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Publikationsverlauf

Eingereicht: 06. August 2020

Angenommen: 16. März 2021

Artikel online veröffentlicht:
11. Mai 2021

• References

• 1 Stoll BJ, Puopolo KM, Hansen NI. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early-onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategies. JAMA Pediatr 2020; 174 (07) e200593
• 2 Puopolo KM, Benitz WE, Zaoutis TE. Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of neonates born at ≤34 6/7 weeks' gestation with suspected or proven early-onset bacterial sepsis. Pediatrics 2018; 142 (06) e20182896
• 3 Weston EJ, Pondo T, Lewis MM. et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J 2011; 30 (11) 937-941
• 4 Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371 (9606): 75-84
• 5 Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol 1999; 94 (02) 274-278
• 6 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
• 7 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
• 8 Arboleya S, Sánchez B, Milani C. et al. Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. J Pediatr 2015; 166 (03) 538-544
• 9 Fouhy F, Guinane CM, Hussey S. et al. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 2012; 56 (11) 5811-5820
• 10 Fjalstad JW, Esaiassen E, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic therapy in neonates and impact on gut microbiota and antibiotic resistance development: a systematic review. J Antimicrob Chemother 2018; 73 (03) 569-580
• 11 Neu J, Douglas-Escobar M, Lopez M. Microbes and the developing gastrointestinal tract. Nutr Clin Pract 2007; 22 (02) 174-182
• 12 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
• 13 Fajardo C, Alshaikh B, Harabor A. Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures. J Matern Fetal Neonatal Med 2019; 32 (24) 4060-4066
• 14 Cotten CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin Jr DK. National Institute for Child Health and Human Development Neonatal Research Network. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics 2006; 118 (02) 717-722
• 15 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
• 16 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
• 17 Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores. J Pediatr 2001; 138 (01) 92-100
• 18 Parry G, Tucker J, Tarnow-Mordi W. UK Neonatal Staffing Study Collaborative Group. CRIB II: an update of the clinical risk index for babies score. Lancet 2003; 361 (9371): 1789-1791
• 19 Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982; 145 (01) 1-8
• 20 Bell MJ, Ternberg JL, Feigin RD. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (01) 1-7
• 21 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
• 22 International Committee for the Classification of Retinopathy of Prematurity. The International classification of retinopathy of prematurity revisited. Arch Ophthalmol 2005; 123 (07) 991-999
• 23 ACOG Practice Bulletin No. 202. Obstet Gynecol 2019; 133 (01) e1-e25
• 24 Reid S, Bajuk B, Lui K, Sullivan EA. NSW and ACT Neonatal Intensive Care Units Audit Group, PSN. Comparing CRIB-II and SNAPPE-II as mortality predictors for very preterm infants. J Paediatr Child Health 2015; 51 (05) 524-528
• 25 Ting JY, Roberts A, Sherlock R. et al; Canadian Neonatal Network Investigators. Duration of initial empirical antibiotic therapy and outcomes in very low birth weight infants. Pediatrics 2019; 143 (03) e20182286
• 26 Tripathi N, Cotten CM, Smith PB. Antibiotic use and misuse in the neonatal intensive care unit. Clin Perinatol 2012; 39 (01) 61-68
• 27 Mowitz ME, Ayyagari R, Gao W, Zhao J, Mangili A, Sarda SP. Health care burden of bronchopulmonary dysplasia among extremely preterm infants. Front Pediatr 2019; 7: 510
• 28 Novitsky A, Tuttle D, Locke RG, Saiman L, Mackley A, Paul DA. Prolonged early antibiotic use and bronchopulmonary dysplasia in very low birth weight infants. Am J Perinatol 2015; 32 (01) 43-48
• 29 Flannery DD, Dysart K, Cook A, Greenspan J, Aghai ZH, Jensen EA. Association between early antibiotic exposure and bronchopulmonary dysplasia or death. J Perinatol 2018; 38 (09) 1227-1234
• 30 Maier RF, Blondel B, Piedvache A. et al; MOSAIC and EPICE Research Groups. Duration and time trends in hospital stay for very preterm infants differ across european regions. Pediatr Crit Care Med 2018; 19 (12) 1153-1161
• 31 Hintz SR, Bann CM, Ambalavanan N, Cotten CM, Das A, Higgins RD. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Predicting time to hospital discharge for extremely preterm infants. Pediatrics 2010; 125 (01) e146-e154
• 32 El Manouni El Hassani S, Berkhout DJC, Niemarkt HJ. et al. Risk factors for late-onset sepsis in preterm infants: a multicenter case-control study. Neonatology 2019; 116 (01) 42-51
• 33 Assad M, Elliott MJ, Abraham JH. Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet. J Perinatol 2016; 36 (03) 216-220
• 34 Garber S, Dhudasia M, Flannery D, Passarella M, Puopolo K, Mukhopadhyay S. Delivery-based criteria for empiric antibiotic administration among preterm infants. J Perinatol 2020;
• 35 NICU antibiotics and outcomes trial - full text view - ClinicalTrials.gov. Clinicaltrials.gov. Published 2020. Accessed December 8, 2020 at: https://clinicaltrials.gov/ct2/show/NCT03997266
• 36 Antibiotic “dysbiosis” in preterm infants - full text view - ClinicalTrials.gov. Clinicaltrials.gov. Published 2020. Accessed December 8, 2020 at: https://clinicaltrials.gov/ct2/show/NCT02784821