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).