Treatment of mycobacterium abscessus complex pulmonary disease in pediatric cystic fibrosis may improve clinical outcomes

Abstract

RATIONALE Mycobacterium abscessus complex pulmonary disease (MABSC PD) in cystic fibrosis (CF) is challenging to treat. The current guideline suggests therapeutic regimens that are not evidence-based involving an intensive phase of intravenous antibiotics followed by a consolidation phase of inhaled and oral antibiotics. Previous studies in CF have focused on epidemiology and risk factors. The clinical course has not been evaluated in children. This study's objectives were to characterize clinical outcomes and clearance of MABSC from respiratory cultures in children with CF MABSC PD. METHODS This retrospective longitudinal cohort analysis evaluated first course treatment for MABSC PD in 33 children in Queensland, Australia between 2001-2015. Spirometry and nutritional outcomes two years prior and two years post-treatment in children who had and had not completed an intensive plus consolidation treatment regimen were compared for MABSC clearance. MABSC clearance was defined as two negative respiratory cultures post-treatment (acid-fast-bacilli smear negative and culture negative) collected at least one month apart. MABSC infection was defined as either cleared, persistent if clearance was not achieved or recurrent if clearance was achieved and MABSC was cultured again following clearance. Treatment completion was defined as having completed at least two-weeks of intensive phase of intravenous imipenem or cefoxitin plus intravenous amikacin and oral clarithromycin or azithromycin followed by one year of inhaled intravenous formulation of amikacin and at least one oral agent active against MABSC. RESULTS 9/18 children who completed therapy, cleared infection. 3/7 children who completed only intensive phase therapy cleared sputum versus 0/8 children who did not. Patients with sputum clearance had a change in their percentage of the predicted values for forced expiratory volume in one second trajectory of 9.6%/year (95% CI (5.99, 13.23), p<0.0001) for the two-year post treatment period relative to the two year pre-treatment. Patients with persistent/recurrent positive sputum had no significant change in trajectories (1.45, 95% CI (-1.61, 4.51), p=0.35). The change being greater in patients with clear sputum versus patients with persistent/recurrent infection (difference = 8.16 (95% CI 3.42, 12.90, p=0.0008). Percentage of the predicted values for forced vital capacity and age standardized body mass index demonstrate same patterns. CONCLUSION The trajectory of spirometry values and age standardized BMI significantly improved posttreatment in those that cleared sputum (p<0.0001). This suggest that current treatment recommendations for MABSC PD are associated with some success in clearing infection in children with CF. Clinical trials are required to determine best treatment approaches.L6229706332018-07-16 <br />