%0 Journal Article %A Regina E. Abotsi %A Mark P. Nicol %A Grace McHugh %A Victoria Simms %A Andrea M. Rehman %A Charmaine Barthus %A Lucky G. Ngwira %A Brenda Kwambana-Adams %A Robert S Heyderman %A Jon Ø. Odland %A Rashida A. Ferrand %A Felix S. Dube %A , %T The impact of long-term azithromycin on antibiotic resistance in HIV-associated chronic lung disease %D 2021 %R 10.1183/23120541.00491-2021 %J ERJ Open Research %P 00491-2021 %X Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of 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% versus 41%, p<0.001), HI (7% versus 16%, p=0.01), and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% [18/29] versus 13%[8/63], p<0.0001) or tetracycline (60%[18/29] versus 21%[13/63], p<0.0001) were higher in the AZM arm. Carriage of SA resistant to AZM (91% [31/34] versus 3% [1/31], p<0.0001), tetracycline (35% [12/34] versus 13% [4/31], p=0.05) and clindamycin (79% [27/34] versus 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 persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Regina E. Abotsi has nothing to disclose.Conflict of interest: Mark Nicol reports grants from Australian National Health and Medical Research Council, and Medical Research Council of Norway, paid to the institution, outside the submitted work.Conflict of interest: Grace McHugh has nothing to disclose.Conflict of interest: Victoria Simms has nothing to disclose.Conflict of interest: Andrea M Rehman reports support for the present manuscript from Norwegian Research Council, payment to institution. Grants of contracts received from UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union, and Bill and Melinda Gates Foundation, payments to institution, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from External examiner for Middlesex University MSc in Public Health, outside the submitted work. Unpaid Participant on DSMB for INTE-AFRICA study. Unpaid Chair of the Royal Statistical Society International Development Section Committee.Conflict of interest: Charmaine Barthus has nothing to disclose.Conflict of interest: Lucky G. Ngwira has nothing to disclose.Conflict of interest: Brenda Kwambana-Adams has nothing to disclose.Conflict of interest: Robert S Heyderman has nothing to disclose.Conflict of interest: Jon Ø Odland has nothing to disclose.Conflict of interest: Rashida Ferrand reports support for the present manuscript from the BREATHE Trial was funded by GLOBVAC initiation of the Norwegian Research Council, payment to institution. Grants or contracts from the Wellcome Trust through a Senior Fellowship in Clinical Science, paid to institution, outside the submitted work.Conflict of interest: Felix S. Dube has nothing to disclose. %U https://openres.ersjournals.com/content/erjor/early/2021/11/11/23120541.00491-2021.full.pdf