P250 Minimum inhibitory concentration targeted antibiotic dose optimization in patients with cystic fibrosis

Frequent pulmonary exacerbations of Cystic Fibrosis (CF) reduce survival and quality of life even among patients receiving highly effective modulator therapy suggesting the need for better treatments. Our primary objective was to discern whether antibiotics matched with bacterial culture susceptibilities and meeting minimum inhibitory concentration (MIC)-based target serum levels improve pulmonary exacerbation treatment outcomes. MIC directed antibiotic dose selection and optimization therapy is standard practice at our center. A retrospective chart review was conducted from 2010–2015, with 2 year follow up, evaluating CF patients admitted for a pulmonary exacerbation. We used Kaplan-Meier statistics and Cox proportional hazards modeling to evaluate time to next exacerbation. We randomly selected adult CF inpatients who had pre-admission sputum cultures with MIC data for antibiotics prior to a randomly selected exacerbation admission. Treatment included intravenous (IV) antibiotics with nearly all patients receiving continuous infusion β-lactam and most receiving daily IV aminoglycoside. We dosed based on individual MIC levels and verified dosing decisions with therapeutic drug monitoring (TDM). 99 patients met inclusion and exclusion criteria. Kaplan-Meier plots showed that MIC directed targeting of β-lactam serum and aminoglycoside area under the curve (AUC) values were associated with a lengthened median time to next exacerbation by 80 [HR = 0.55, 95% CI (0.33–0.90)] and 185 days [HR = 0.42, 95% CI (0.24–0.74)] respectively. However, achieving both extended median time to next exacerbation by 414 days [HR = 0.23, 95% CI (0.10–0.53)]. Highly effective modulator therapy did not change our results. Dual antibiotic therapy with successful MIC targeting and TDM prolongs time to next pulmonary exacerbation. This strategy applies to all people with CF regardless of modulator eligibility status or access.