title: Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.
abstract: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm).
  
  
  
  In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (AzmR) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (AzmR7.3% vs. 1.6%, p = 0.010; iMLSB5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes.
  
  
  
  Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of AzmRand iMLSBS. aureus.
  
  
  
  This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia, Fajara, Banjul, The Gambia.
authors.forename: Ebrima
authors.initials: E
authors.lastname: Bojang
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia, Fajara, Banjul, The Gambia.
authors.forename: James
authors.initials: J
authors.lastname: Jafali
authors.affiliation: Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, CH-3012, Bern, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Perreten
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Harding-Esch
authors.affiliation: National Eye Health Programe, Ministry of Health and Social Welfare, Kanifing, The Gambia.
authors.forename: Ansumana
authors.initials: A
authors.lastname: Sillah
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: David C W
authors.initials: DC
authors.lastname: Mabey
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Holland
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bailey
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia, Fajara, Banjul, The Gambia.|Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Roca
authors.affiliation: Disease Control and Elimination Theme, Medical Research Council Unit, The Gambia, Fajara, Banjul, The Gambia. Sarah.Burr@lshtm.ac.uk.|Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. Sarah.Burr@lshtm.ac.uk.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Burr
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000008:administration & dosage* / Q000627:therapeutic use*; D002353:Carrier State / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D003430:Cross-Sectional Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D017589:Immunization Programs; D018942:Macrolides / Q000627:therapeutic use*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests; D009304:Nasopharyngitis / Q000188:drug therapy / Q000382:microbiology; D009305:Nasopharynx / Q000382:microbiology*; D015995:Prevalence; D012307:Risk Factors; D013048:Specimen Handling / Q000379:methods; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D013296:Streptococcus pneumoniae / Q000187:drug effects; D014141:Trachoma / Q000150:complications / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017963:Azithromycin
keywords: Azithromycin; Macrolide resistance; Mass drug administration; Staphylococcus aureus carriage; The Gambia; Trachoma; West Africa; iMLSB