For people whose immune defenses are already weakened, antibiotics can be lifesaving. But this study finds that the bacteria living in their airways may already resist many of those drugs—and may even pass resistance between patients.

People with antibody deficiency are at high risk of respiratory infections. Many therefore receive antibiotic prophylaxis and can self-administer antibiotics when breakthrough infections occur. That protection creates a difficult trade-off: repeated antibiotic use, including preventive and self-administered courses, may increase antimicrobial resistance in the respiratory tract.

The study investigated antibiotic resistance in people with antibody deficiency and looked for possible transmission of genetic elements carrying resistance between patients. It also tested whether changes in a substance released during inflammation could be linked with bacterial infection.

To understand the result, imagine a garden treated repeatedly with weedkiller. The treatment may remove some plants, leaving a few resistant weeds with more room to take over. The researchers found azithromycin resistance was especially widespread, even among people who were not taking macrolide antibiotics as preventive treatment.

The worrying message is that resistance is common even among bacteria from people not taking preventive antibiotics. Across all isolates, azithromycin resistance reached 81.7%, leaving this frequently used treatment with limited reliability. The study then found clues that resistance could travel.

Resistance-carrying genetic material appeared among related bacteria from the same sputum sample, from the same patient at different times, and even from different patients. That pattern may suggest cross-transmission: resistance-carrying plasmids could move between bacteria, including related bacteria found in samples from different patients.

The study also looked for a warning signal in sputum. When the amount of an inflammation-related substance increased, the airway community became less varied and more dominated by a smaller number of bacteria. The same pattern appeared when changes from one sample to the next were compared: increases in this substance predicted a reduction in the variety of bacteria present.

The researchers caution that the groups were relatively small, partly because the underlying conditions are rare. The study has important limitations: its cohorts were relatively small, although this largely reflects the rarity of the underlying conditions.

The main finding is that antibiotic resistance was high in the airway bacteria of people with antibody deficiency, especially resistance to the drugs commonly used for long-term prevention. The study recommends reassessing the long-term usefulness of preventive antibiotics, especially for people already receiving immune replacement treatment.

The study points toward two practical changes: use long-term antibiotics more carefully, and investigate whether a simple signal in sputum can help guide treatment before infection becomes harder to treat.