(118) Antibiotic Regimen Changes During Pediatric Pulmonary Exacerbation Treatment

Background: Antibiotic selection for in-hospital treated pulmonary exacerbations (PEx) is typically guided by previous respiratory culture results or by past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in an attempt to find a particular regimen that alleviates symptoms and restores lung function. However, the clinical benefits of changing antibiotics in clinical practice are unknown. This study aimed to describe the frequency and patterns of antibiotic regimen changes among children with CF hospitalized for a PEx, to identify risk factors associated with an antibiotic change, and to determine if changing antibiotics is associated with improved clinical outcomes.

Methods: Retrospective cohort study that utilized the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS) dataset [1]. Children with CF age 1-21 years who had an in-hospital treated PEx between Jan 1^st, 2006 through Dec 31^st, 2018 were eligible for inclusion. Exclusion criteria included length of stay < 7 or >21 days, history of solid organ transplant or malignancy, and history of ICU stay during the PEx. An antibiotic change was defined as any addition or subtraction of an IV antibiotic between hospital day 6 and the day prior to hospital discharge. Inverse probability of treatment weighting was used to address concerns related to disease severity and indication bias that might influence the decision to change antibiotics.

Results: After applying inclusion and exclusion criteria, 6,953 children with CF contributed 32, 853 PEx for analysis. Among these, IV antibiotics were either added or subtracted after day 6 in 13,690 (41.7%) PEx. Children with CF who identified as either Black or Hispanic were less likely to have an IV antibiotic change during PEx treatment. In addition, children with CF who had an IV antibiotic change had a lower baseline percent predicted forced expiratory volume in one second (ppFEV₁), 73.9% [IQR 55-90] versus 76.3% [IQR 58-91], were more likely to have CF-related diabetes (34% vs 29%), and more likely to be colonized with Pseudomonas aeruginosa (46% vs 40%). After applying inverse probability of treatment weighting, a statistically significantly smaller pre- to post-PEx ppFEV₁ change was seen (9.43 [95% CI 9.08, 9.79] versus 10.67 [95% CI 10.37, 10.96]) between PEx with an IV antibiotic change compared to PEx without an IV antibiotic change, respectively. In addition, an IV antibiotic change during PEx treatment was associated with a lower odds of returning to ≥90% of baseline ppFEV₁. There was no statistically significant difference in hazard of future PEx requiring IV antibiotics seen when comparing PEx with versus without an IV antibiotic change.

Conclusions: Our results suggest that changing antibiotic treatment during the course of an inpatient PEx is unlikely to affect clinical outcomes. In the current CFTR modulator era where children with CF are living longer, studies that focus on antibiotic selection for PEx treatment are needed to both improve clinical outcomes and to minimize unnecessary antibiotic exposure that can lead to antibiotic toxicities and the emergence of antibiotic resistance.

Acknowledgements:

References: [1] Cogen JD, Hall M, Loeffler DR, Gove N, Onchiri F, Sawicki GS, Fink AK. Linkage of the Cystic Fibrosis Foundation Patient Registry with the Pediatric Health Information System Database. Pediatr Pulmonol 2019; 54(6): 721-728.