Abstract Background Cystic fibrosis (CF) pulmonary exacerbations shorten survival. Treatment guidelines omit minimal inhibitory concentration (MIC)–based antibiotic dose selection. We tested whether MIC-guided intravenous antibiotic strategies prolong time between exacerbations. Methods We retrospectively studied randomly chosen intravenous antibiotic–treated pulmonary exacerbations from 2015 to 2018, followed through 2021. Using pre-admission sputum culture–derived MICs to select dosing targets, we estimated measured:target ratios for β-lactam steady-state and aminoglycoside area under the curve pharmacokinetics. We used Kaplan-Meier and Cox proportional hazards methods to test whether measured:target ratios were associated with time to next exacerbation. We evaluated serial laboratory measurements with linear mixed-effects models for adverse events. We tested model sensitivities to concurrent treatments and severe acute respiratory syndrome coronavirus 2 pandemic–related events. Results Compared with measured:target ratios ≤1, β-lactam ratios 1 were associated with a median of 19 more (from 204 to 223) exacerbation-free days (91 exacerbations; hazard ratio HR, 0.60; 95% CI, 0.37–0.99; P = .045); aminoglycoside ratios 1 were associated with a median of 83 more (from 153 to 236) exacerbation-free days (65 exacerbations; HR, 0.54; 95% CI, 0.31–0.93; P = .026); both antibiotic ratios 1 simultaneously were associated with a median of 210 more (from 185 to 396) exacerbation-free days (60 exacerbations; HR, 0.33; 95% CI, 0.15–0.71; P = .004). No toxic antibiotic levels and few adverse laboratory or clinical events occurred. Models were insensitive to other treatments and pandemic events. Conclusions MIC-guided antibiotic dosing prolongs time between pulmonary exacerbations with few adverse events. Reduced exacerbation frequency predicts better survival and may improve quality of life for people with CF.
Jacobs et al. (Sat,) studied this question.