Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency

Background: Antibody-deficient patients are at high risk of respiratory tract infections. Many therefore receive antibiotic prophylaxis and have access to antibiotics for self-administration in the event of breakthrough infections, which may increase antimicrobial resistance (AMR). Objectives: To understand AMR in the respiratory tract of patients with antibody deficiency. Methods: Sputum samples were collected from antibody-deficient patients in a cross-sectional and prospective study; bacteriology culture, 16S rRNA profiling and PCR detecting macrolide resistance genes were performed. Bacterial isolates were identified using MALDI-TOF, antimicrobial susceptibility was determined by disc diffusion and WGS of selected isolates was done using Illumina NextSeq with analysis for resistome and potential cross-transmission. Neutrophil elastase was measured by a ProteaseTag immunoassay. Results: < 0.001) were found. Similar relationships were noted for the change in elastase concentration between consecutive samples, increases in elastase associating with reduced α-diversity. Conclusions: Measures to limit antibiotic usage and spread of AMR should be implemented in immunodeficiency clinics. Sputum neutrophil elastase may be a useful marker to guide use of antibiotics for respiratory infection.