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IMPACT OF LONG-TERM AZITHROMYCIN THERAPY ON CARRIAGE AND ANTIBIOTIC RESISTANCE OF RESPIRATORY BACTERIA AMONG CHILDREN WITH HIV-ASSOCIATED CHRONIC LUNG DISEASE: A RANDOMISED CONTROLLED TRIAL
Selection for antibiotic resistance remains a concern with long-term azithromycin (AZM) use in chronic lung diseases (CLD).
We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD.
Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed post-intervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher's exact test were used to compare carriage and resistance respectively.
Of 347 (174 AZM, 173 placebo) participants (median age 15 years [IQR =13–18], females 49%),NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% vs 41%, p<0.001), HI (7% vs 16%, p=0.01), and MC (4% vs 11%, p=0.02); SP resistance to AZM (62% [18/29] vs 13%[8/63], p<0.0001) or tetracycline (60%[18/29] vs 21%[13/63], p<0.0001) were higher in the AZM arm. Carriage of SA resistant to AZM (91% [31/34] vs 3% [1/31], p<0.0001), tetracycline (35% [12/34] vs 13% [4/31], p= 0.05) and clindamycin (79% [27/34] vs 3% [1/31], p<0.0001) was also significantly higher in the AZM arm and persisted at 72 weeks. Similar findings were observed for sputa.
The risk of drug resistance should be considered during long-term AZM use. The clinical significance of antibiotic resistance needs investigation.