Background: Pseudomonas aeruginosa (PA) can infect the respiratory tract of patients with cystic fibrosis (CF) and is associated with worse lung function and increased mortality. A 28-day course of inhaled tobramycin solution (TIS) 300 mg inhaled twice a day is recommended for treatment of initial or new growth of PA from an airway culture. There are no studies primarily analyzing the safety of TIS at this dose in infants with CF. This lack of evidence regarding efficacy and safety makes the selection of treatment strategies more challenging. The objective of this study was to compare the incidence of adverse drug events (ADE) of TIS when used for PA eradication in CF patients less than 1 year of age to CF patients ages one year to 18 years of age.
Methods: This was an IRB approved, retrospective analysis evaluating the incidence of ADEs in infants and children with CF with cultures positive for PA treated with TIS for 28 days. Patients were included if they were ages 14 days to 18 years and received at least one dose of TIS between 01/01/2008 to 07/31/2021. Patients less than 1 year of age (infant group) were matched based on genotype in a 1:3 ratio with a patient at least a year old (children group). Patients were excluded if they received intravenous or inhaled antibiotics with activity against PA in the previous 6 months or prior to completion of 28-day treatment.
Results: A total of 48 patients were included with 12 patients in the infant group and 36 in the children group. The median age was 0.48 years (IQR:0.2-0.7) and 4.7 years (IQR:2.3-10) for the infants and children respectively (p<0.05). The median weight was 6.9 kg (IQR:5.3-8.3) and 18.6 kg (IQR:12.8-28.9) for the infants and children respectively (p<0.05). The two groups did not differ significantly with respect to gender, use of CFTR modulator therapy or concomitant oral azithromycin or ciprofloxacin. There were 5 (42%) ADE in the infant group and 3 (8.3%) in the children group (p=0.016). The most common ADE in both groups was cough but no patient required cessation of therapy because of ADE. When cough was removed as an ADE there was no significant difference between the two groups [2 (16.7%) vs 1 (2.7%), p=0.15]. There was no statistical difference in treatment failure between the two groups, [6 (50%) vs 9 (25%), p=0.1] and cultures remained negative for PA similarly between the two groups at 6 months post treatment [7 (58%) vs 29 (81%), p=0.14]. Fewer in the infant group continued to have negative cultures for PA at 12 [3 (25%) vs 22 (61%), p=0.04] and 18 months [2 (16.7%) vs 22 (61%), p=0.02]. The median number of days to next hospitalization was 336 (IQR:40-1799) and 664 (IQR:150-945) for the infant and children respectively (p=1). The median number of days to next PO antibiotic for CF exacerbation was 46 (IQR:29-264) and 84 (IQR:48-299) for the infant and children respectively (p=0.31). There was no significant difference between the infant and children’s groups with respect to PA colonization [2 (16.7%) vs 5 (14%), p=1] or incidence of multidrug resistant PA [0 (0%) vs 5 (14%), p=0.31].
Conclusions: This study found a higher incidence of ADE in infants treated with TIS compared to children. However, when cough was removed as an ADE as this is a common symptom of PA respiratory infection in CF, there was no significant difference. These results show a low risk of ADE outside of cough indicating that TIS may be safely used in this age group.
