Background: Pseudomonas aeruginosa (PA) respiratory infection in Cystic Fibrosis (CF) can be associated with lung damage and decline in lung function. Current Cystic Fibrosis Foundation guidelines recommend treatment with 28 days of inhaled tobramycin to attempt eradication when PA is identified in routine sputum cultures. Eradication therapy for initial PAinfection has been widely evaluated, but there is limited data investigating optimal time to reculture post eradication therapy. Standard reculture timing of 4 to 6 weeks is currently based on study protocols and has not been assessed for impact on successful rates of eradication and maintenance of PA free cultures in a real-world setting. The objective of this study is to compare the rate of PA positive cultures if reculture is less than 4 weeks post eradication therapycompared to the standard reculture timing of 4 to 6 weeks in pediatric CF patients.
Methods: This single‐center retrospective study included pediatric patients with CF with a first lifetime PA‐positive respiratory culture or first positive after at least 1‐year of PA -free respiratory cultures between January 1st, 2008 and June 30th, 2021 that received 28 days of inhaled tobramycin 300 mg inhaled twice a day for eradication. Patients were excluded if they were chronically colonized with PA, received chronic inhaled tobramycin, aztreonam, or colistin, received a lung transplant, were enrolled in the OPTIMIZE trial, had incomplete documentation, or children with a sibling or parent with CF with a previous PA -positive respiratory culture.
Results: A total of 89 patients were included in this study; 25 patients in the early reculture group and 64 patients in the standard reculture group. Baseline characteristics were similar between early and standard reculture groups: age (3 years [0.92, 10] vs 3.5 [1, 9], p=0.64), sex (40% vs 42% female, p=0.85), and baseline ppFEV1 (98.5 ± 12.3 vs 96 ± 16.6, p=0.61). Reculture timing was significantly different between the early and standard groups (21 days [14, 25.5] vs 41 days [35, 48], p< 0.01). The primary outcome of number of PA -positive OP-swab or sputum cultures at initial reculture was not statistically significant between the early and standard reculture group [5 (20%) vs 14 (21.8%) p = 0.85]. There was no difference in number of positives at 6 months [5 (20.8%) vs 11 (17.7%) p = 0.74] however there was a statistically significant difference at the 12 month reculture [6 (26%) vs 4 (7.7%) p = 0.04]. No significant differences in clinical outcomes were observed: time to next outpatient exacerbation (32 days [3.8, 148] vs 90 days [2.3, 168], p=0.44), time to next inpatient exacerbation (20 days [0, 139] vs 62.5 days [24, 183], p=0.43), change in ppFEV1 from baseline to 1 year post initial PA culture (4.55 ± 6.4 vs 7.19 ± 9.0, p=0.3), change in BMI percentile from baseline to 1 year post initial PA culture (7.3 [0.5, 15.1] vs 7.5 [0, 18.9], p=0.96); number of hospitalizations within 1 year post initial PA culture (0 [0, 1] vs 0 [0, 0], p=0.06).
Conclusions: Early initial reculture timing after completion of inhaled tobramycin did not impact the rate of PA positive cultures in the study. Clinical outcomes were not different between the two groups. Reculture timing did not influence early microbiological outcomes but there was a difference in long term PA eradications rates.
