Antibiotic Stewardship Challenges in a Referral Neonatal Intensive Care Unit

Abstract

Background Antibiotic overuse in neonates is associated with adverse outcomes. Data are limited to guide antibiotic stewardship in the neonatal intensive care unit (NICU). Our objective was to identify areas for antibiotic stewardship improvement in a referral NICU.

Methods Retrospective review of antibiotic use administered to infants admitted to a referral NICU compared with an inborn NICU. Antibiotic use was quantified by days of therapy (DOT) per 1,000 patient-days (PD).

Results A total of 78% of referral NICU infants received ≥ 1 course of antibiotics. Infants in the referral NICU received more antibiotic DOT/1,000 PD than in the inborn NICU (558.9 vs. 343.2, p < 0.001), with a higher proportion of broad-spectrum therapy. For infants in the referral NICU, 39% of antibiotic courses were started at the transferring hospital; these were broader in spectrum (28 vs. 20%, p < 0.001) and less likely to be de-escalated or discontinued at 48 to 72 hours (58 vs. 87%, p < 0.001) than courses started after transfer.

Conclusions Compared with the inborn NICU, suspected sepsis in the referral NICU accounted for more antibiotic utilization, which was broad-spectrum and less likely to be de-escalated. Stewardship interventions should include reserving broad-spectrum therapy for infants with risk factors and de-escalating promptly once culture results become available.

Keywords

antibiotic - neonate - sepsis - NICU - stewardship

• References

• 1 Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 2006; 117 (6) 1979-1987
• 2 de Man P, Verhoeven BA, Verbrugh HA, Vos MC, van den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet 2000; 355 (9208) 973-978
• 3 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 (2) 717-722
• 4 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 (1) 58-66
• 5 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 (5) 720-725
• 6 Saiman L, Ludington E, Dawson JD , et al; National Epidemiology of Mycoses Study Group. Risk factors for Candida species colonization of neonatal intensive care unit patients. Pediatr Infect Dis J 2001; 20 (12) 1119-1124
• 7 Shah P, Nathan E, Doherty D, Patole S. Prolonged exposure to antibiotics and its associations in extremely preterm neonates—the Western Australian experience. J Matern Fetal Neonatal Med 2013; 26 (17) 1710-1714
• 8 Al Reyami E, Al Zoabi K, Rahmani A, Tamim M, Chedid F. Is isolation of outborn infants required at admission to the neonatal intensive care unit?. Am J Infect Control 2009; 37 (4) 335-337
• 9 Cohen-Wolkowiez M, Moran C, Benjamin DK , et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009; 28 (12) 1052-1056
• 10 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 (3) 267-272
• 11 Cantey JB, Sánchez PJ. Prolonged antibiotic therapy for “culture-negative” sepsis in preterm infants: it's time to stop!. J Pediatr 2011; 159 (5) 707-708
• 12 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 (9) 662-666
• 13 Spitzer AR, Kirkby S, Kornhauser M. Practice variation in suspected neonatal sepsis: a costly problem in neonatal intensive care. J Perinatol 2005; 25 (4) 265-269
• 14 Liem TB, Krediet TG, Fleer A, Egberts TC, Rademaker CM. Variation in antibiotic use in neonatal intensive care units in the Netherlands. J Antimicrob Chemother 2010; 65 (6) 1270-1275
• 15 Isaacs D, Wilkinson AR, Moxon ER. Duration of antibiotic courses for neonates. Arch Dis Child 1987; 62 (7) 727-728
• 16 Rubin LG, Sánchez PJ, Siegel J, Levine G, Saiman L, Jarvis WR ; Pediatric Prevention Network. Evaluation and treatment of neonates with suspected late-onset sepsis: a survey of neonatologists' practices. Pediatrics 2002; 110 (4) e42
• 17 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
• 18 Ibrahim OM, Polk RE. Antimicrobial use metrics and benchmarking to improve stewardship outcomes: methodology, opportunities, and challenges. Infect Dis Clin North Am 2014; 28 (2) 195-214
• 19 Zervou FN, Zacharioudakis IM, Ziakas PD, Mylonakis E. MRSA colonization and risk of infection in the neonatal and pediatric ICU: a meta-analysis. Pediatrics 2014; 133 (4) e1015-e1023
• 20 Hamilton KW, Fishman NO. Antimicrobial stewardship interventions: thinking inside and outside the box. Infect Dis Clin North Am 2014; 28 (2) 301-313
• 21 Kullar R, Goff DA. Transformation of antimicrobial stewardship programs through technology and informatics. Infect Dis Clin North Am 2014; 28 (2) 291-300
• 22 Charani E, Holmes AH. Antimicrobial stewardship programmes: the need for wider engagement. BMJ Qual Saf 2013; 22 (11) 885-887
• 23 Fischer JE, Ramser M, Fanconi S. Use of antibiotics in pediatric intensive care and potential savings. Intensive Care Med 2000; 26 (7) 959-966
• 24 Bekhof J, Reitsma JB, Kok JH, Van Straaten IH. Clinical signs to identify late-onset sepsis in preterm infants. Eur J Pediatr 2013; 172 (4) 501-508
• 25 Shani L, Weitzman D, Melamed R, Zmora E, Marks K. Risk factors for early sepsis in very low birth weight neonates with respiratory distress syndrome. Acta Paediatr 2008; 97 (1) 12-15
• 26 Weintraub AS, Cadet CT, Perez R, DeLorenzo E, Holzman IR, Stroustrup A. Antibiotic use in newborns with transient tachypnea of the newborn. Neonatology 2013; 103 (3) 235-240
• 27 Dempsey EM, Barrington KJ. Diagnostic criteria and therapeutic interventions for the hypotensive very low birth weight infant. J Perinatol 2006; 26 (11) 677-681
• 28 Brady MT, Polin RA. Prevention and management of infants with suspected or proven neonatal sepsis. Pediatrics 2013; 132 (1) 166-168
• 29 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 (2) 275-278