(119) Pulmonary Exacerbation Antibiotic Treatment for Children with Cystic Fibrosis and Polymicrobial Infection

Background: Substantial variability exists in pulmonary exacerbation (PEx) management. CF Foundation PEx guidelines do not inform antibiotic selection among people with CF (PwCF) who culture multiple respiratory microorganisms. This study aimed to 1) describe the number of in-hospital treated PEx among PwCF who culture >1 CF-related bacteria, 2) describe the proportion of these in-hospital treated PEx that included antibiotics on admission with predicted antibacterial activity against all bacteria cultured (complete antibiotic coverage), and 3) assess if certain demographic and clinical factors are associated with complete antibiotic coverage. We hypothesized that the majority of PEx among PwCF who cultured >1 CF-related bacteria would be treated with complete antibiotic coverage.

Methods: Retrospective cohort study utilizing the CF Foundation Patient Registry-Pediatric Health Information System (CFFPR-PHIS) dataset. Children with CF age 1-21 years with an in-hospital treated PEx between 2006-2019 were included. Exclusion criteria included length of stay < 4 or >35 days, history of solid organ transplant or malignancy, history of non-tuberculous mycobacteria in the prior 12 months, and ICU stay during the PEx. 2021 Antibacterial activity for each antibiotic was defined according to the Sanford Spectra of Activity Guide. The presence of traditional bacteria (Pseudomonas aeruginosa (Pa), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), A. xylosxidans, S. maltophilia, H. influenzae, and Burkholderia cepacia complex) was defined as any positive respiratory culture for that species in the 12 months prior to a study PEx.

Results: After applying eligibility criteria, 4,034 children with CF cultured >1 CF-related bacteria and contributed 20,214 PEx for analysis. Those who cultured ≤1 CF-related bacteria had mean baseline percent predicted forced expiratory volume in one second (ppFEV₁) of 78% (60-93), compared with 74% (IQR 56-89) in those who cultured >1 bacteria. Complete antibiotic coverage as defined was prescribed at admission in 68% of PEx in those who cultured >1 bacteria. The most common polymicrobial combinations were Pa + MRSA (N=2,852 PEx), Pa + MSSA (N=2,749), and Pa + MRSA + MSSA (N=1,465). Complete antibiotic coverage was prescribed in 82%, 81%, and 75% of PEx where Pa + MRSA, Pa + MSSA, and Pa + MRSA + MSSA were present, respectively. Among those who cultured Pa + MRSA and were prescribed complete antibiotic coverage on a prior admission for PEx, 93% had complete antibiotic coverage for PEx. This was significantly lower (51% with complete coverage) in the group with incomplete antibiotic coverage on previous admission, p< 0.001).

Conclusions: Two-thirds of children with CF hospitalized for PEx treatment who cultured >1 CF-related bacteria in the previous 12 months were prescribed antibiotics with complete antibiotic coverage. In children with CF who culture Pa + MRSA, a prior PEx treated with complete antibiotic coverage was associated with complete coverage at a future PEx. Ongoing work is comparing outcomes of PEx treated with partial versus complete antibiotic coverage, which may help guide antibiotic selection to maximize clinical outcomes and minimize potentially unnecessary use.

Acknowledgements:

References: