APE occurrence per patients
Our results show that each subsequent APE significantly decreases the probability of achieving a positive outcome by 24% in individual patients. Such decrease may be the result of bacterial resistance. The prevalence of P. aeruginosa among CF patients increases with age. Approximately 20% of patients < 6 years of age are infected, compared to 70% of those who are 35 to 44 years of age (32). The incidence and complexity of P. aeruginosa resistance has been increasing over time (33), which can impact the effectiveness of tobramycin on subsequent APEs.
Our results support previous observations that intravenous antibiotic treated APEs are associated with subsequent decline in ppFEV1 (34), effectively decreasing the probability of return to baseline. Furthermore, it was shown that 1-2 exacerbations/year increases the risk of death 3-fold, and ≥ 3 exacerbations/year increases the risk of death 4.5-fold (4). Subsequent APEs are also associated with lower long-term health-related quality of life (35).
Limiting the number of APEs per patient is paramount in achieving positive clinical outcomes. Antimicrobial prophylaxis has been shown to be effective in young children (36, 37), however its use in adults remains controversial. Optimizing dosing strategies may result in faster and more effective eradication of causative organisms, which may, in turn, decrease early recurrences of APE (38).