Spontaneous clearance and real-world management after first asymptomatic MRSA isolation in pediatric cystic fibrosis

Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly isolated in people with cystic fibrosis (CF) and has been associated with poorer clinical outcomes in CF populations. Although early treatment after first detection is commonly practiced, management of asymptomatic patients varies considerably, and the short-term natural course following initial isolation remains incompletely characterized. This retrospective cohort study included 94 pediatric patients with CF and a first asymptomatic MRSA-positive respiratory culture between 2014 and 2023. Patients were managed with observation ( n = 74) or antibiotic treatment ( n = 20) according to routine clinical practice. Most treated patients received trimethoprim–sulfamethoxazole (TMP-SMX) monotherapy ( n = 17), while three received a combination eradication regimen consisting of TMP-SMX plus rifampicin with intranasal mupirocin and chlorhexidine body cleansing. Outcomes assessed over one year included MRSA clearance, development of chronic colonization, pulmonary exacerbation frequency, FEV₁ changes, and BMI z scores. Overall, 41.5% of patients achieved MRSA clearance within one year. Clearance rates were similar between treated and observed patients (45% vs. 40.5%). Chronic colonization developed in 50% of patients in both groups. No statistically significant differences were observed between management groups in pulmonary exacerbation frequency, FEV₁ trajectory, or BMI z scores during follow-up. All three patients who received the combination eradication regimen achieved clearance. A substantial proportion of children with asymptomatic first MRSA isolation demonstrated subsequent culture negativity during follow-up. In this cohort, no statistically significant differences in short-term microbiological or clinical outcomes were observed between management strategies; however, interpretation is limited by the retrospective non-randomized design, potential confounding by indication, and small treatment group. These findings highlight variability in current clinical practice and support the need for prospective studies evaluating standardized and feasible MRSA management strategies across different clinical settings.