A Pediatric Antimicrobial Stewardship Program Intervention Leads to Decreased Inappropriate Use of Piperacillin-tazobactam in the Neonatal Intensive Care Unit at an Academic Institution

Abstract Corresponding author: Patricia Pichilingue-Reto, MD, 1501 King Hwy, Shreveport, LA 71130, 347-827-6668, [email protected], [email protected] Alternate corresponding author: Maria Gabriela Dominguez Garcia, MD, 1501 King Hwy, Shreveport, LA 71130, 318-675-6076, [email protected] No conflicts of interest Background Antimicrobial stewardship programs (ASP) were created to improve antimicrobial use without compromising patient outcomes. Nationwide, Pediatric ASPs have shown a very rapid growth during the past decade. Inpatient stewardship can present some challenges, particularly with special patient populations like newborns and premature infants. Methods A new Pediatric Antimicrobial Stewardship committee was established in April 2022 at LSU Health Shreveport- St. Mary’s Medical Center. The first process measurement was a medication usage evaluation (MUE) report of piperacillin-tazobactam from April 1st,2021 to March 31st, 2022, in the Neonatal Intensive Care Unit (NICU) for inappropriate indications including early onset sepsis (EOS), late onset sepsis (LOS) and culture negative sepsis. Neonatologists received education from the ASP committee about the first line agents for these indications, being cefepime the most appropriate choice for suspected severe LOS. The ASP committee obtained a report one year later and compared the use of piperacillin tazobactam and cefepime one year prior to the intervention (April 1st, 2021- March 31st, 2022) and one year after the intervention (April 1st, 2022 - March 31st, 2023). Slicer dicer, a data extraction tool from EPIC Electronic Health Record (EHR) system was used to determine how many NICU patients received piperacillin-tazobactam and cefepime. Results From April 1st, 2021, to March 31st, 2023, the charts of 83 neonatal patients admitted to St. Mary’s Medical Center NICU, who were prescribed piperacillin-tazobactam and cefepime, were reviewed. A total of 49 courses of piperacillin tazobactam were administered during the pre-intervention year and this decreased to 17 courses during the post-intervention year (Figure 1). This represents a 65% decrease in utilization. Among the 49 courses of piperacillin tazobactam, the clinical indications were: Rule/out LOS in 23 courses (47%), culture negative sepsis in 18 (37%) and necrotizing enterocolitis (NEC) in only 6 courses (12%), as shown on Table 1. During the year post-intervention, among the 17 courses of piperacillin tazobactam, 11 (65%) were administered for rule/out LOS, 3 for NEC (18%) and there were no courses administered for culture negative sepsis. Consequentially, there was an increased use of cefepime after the intervention. During the year prior to the intervention, only 23 courses of cefepime were administered, while 68 were prescribed during the year after the intervention (Table 2). Prior to the intervention, 9 courses were administered for rule/out LOS, versus 32 administered post-intervention. There was a four-fold increase in the use of cefepime for culture negative sepsis (3 courses during the pre-intervention year versus 12 courses post-intervention). Conclusion Neonates and premature infants can represent a challenging patient population for Pediatric ASPs’ interventions. Before the introduction of this ASP committee, there was no tracking of the use of broad-spectrum antibiotics. We reported a possible overuse of piperacillin tazobactam for suspected LOS and culture negative sepsis prior to the intervention, which then led to an increase in the use of cefepime for these indications. Our interventions caused a dramatic reduction in the administration of this broad-spectrum antibiotic in the NICU. The future direction of this study implies to determine if there are any differences on the renal function profiles among the neonates treated with antimicrobials before and after the intervention. Figure 1: Piperacillin-tazobactam (blue line) and cefepime (red line) usage in newborns admitted to the Neonatal intensive care unit (NICU). A total of 49 courses of piperacillin tazobactam were administered during the pre-intervention year and this decreased to 17 courses during the post-intervention year. Consequently, there was an increase in cefepime use, with 23 courses administered before and 68 courses prescribed during the year following the intervention. Table 1: Piperacillin-tazobactam courses pre- and post-intervention according to clinical indication Table 2: Cefepime courses pre- and post-intervention according to clinical indication