Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control

Ebrima Bojang, James Jafali, Vincent Perreten, John Hart, Emma M Harding-Esch, Ansumana Sillah, David C W Mabey, Martin J Holland, Robin L Bailey, Anna Roca, Sarah E Burr, Ebrima Bojang, James Jafali, Vincent Perreten, John Hart, Emma M Harding-Esch, Ansumana Sillah, David C W Mabey, Martin J Holland, Robin L Bailey, Anna Roca, Sarah E Burr

Abstract

Background: 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).

Results: 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 (AzmR 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes.

Conclusions: 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 AzmR and iMLSB S. aureus.

Trial registration: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.

Keywords: Azithromycin; Macrolide resistance; Mass drug administration; Staphylococcus aureus carriage; The Gambia; Trachoma; West Africa; iMLSB.

Figures

Fig. 1
Fig. 1
Time-line of treatment and sample collection. MDA with azithromycin is depicted by black arrows; NPS sample collection is depicted by red arrows
Fig. 2
Fig. 2
Study profile

References

    1. World Health Organization . Report of the first meeting of the WHO alliance for the Global Elimination of Trachoma, WHO/PBL/GET/97.1. 1997.
    1. World Health Organization . Report of the third meeting of the WHO Alliance for the Global Elimination of Trachoma, WHO/PBD/GET/99.3. 1998.
    1. Porco TC, Gebre T, Ayele B, House J, Keenan J, Zhou Z, et al. Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA. 2009;302:962–8. doi: 10.1001/jama.2009.1266.
    1. Keenan JD, Ayele B, Gebre T, Zerihun M, Zhou Z, House JI, et al. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011;52:883–8. doi: 10.1093/cid/cir069.
    1. Matheson AI, Manhart LE, Pavlincan PB, Means AR, Akullian A, Levine GA, et al. Prioritizing countries for interventions to reduce child mortality: tools for maximizing the impact of mass drug administration of azithromycin. PLoS One. 2014;9:e96658. doi: 10.1371/journal.pone.0096658.
    1. . . Accessed 2 Mar 2015.
    1. Solomon AW, Mohammed Z, Massae PA, Shao JF, Foster A, Maclean IW, et al. Impact of mass distribution of azithromycin on the antibiotic susceptibilities of ocular Chlamydia trachomatis. Antimicrob Agents Chemother. 2005;49:4804–6. doi: 10.1128/AAC.49.11.4804-4806.2005.
    1. Hong KC, Schachter J, Moncada J, Zhou Z, House J, Lietman TM. Lack of macrolide resistance in Chlamydia trachomatis after mass azithromycin distributions for trachoma. Emerg Infect Dis. 2009;15:1088–90. doi: 10.3201/eid1507.081563.
    1. West SK, Moncada J, Munoz B, Mkocha H, Storey P, Hardick J, et al. Is there evidence for resistance of ocular Chlamydia trachomatis to azithromycin after mass treatment for trachoma control? J Infect Dis. 2014;210:65–71. doi: 10.1093/infdis/jiu046.
    1. Batt SL, Charalambous BM, Solomon AW, Knirsch C, Massae PA, Safari S, et al. Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother. 2003;47:2765–9. doi: 10.1128/AAC.47.9.2765-2769.2003.
    1. Gaynor BD, Holbrook KA, Whitcher JP, Holm SO, Jha HC, Chaudhary JSP, et al. Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year. Br J Ophthalmol. 2003;87:174–8. doi: 10.1136/bjo.87.2.147.
    1. Burr SE, Milne S, Jafali J, Bojang E, Rajasekhar M, Hart J, et al. Mass administration of azithromycin and Streptococcus pneumoniae carriage: cross-sectional surveys in the Gambia. Bull World Health Organ. 2014;92:490–8. doi: 10.2471/BLT.13.133462.
    1. Fry AM, Jha HC, Lietman TM, Chaudhary JSP, Bhatta RC, Elliott J, et al. Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal. Clin Infect Dis. 2002;35:395–402. doi: 10.1086/341414.
    1. Leach AJ, Shelby-James TM, Mayo M, Gratten M, Laming AC, Currie BJ, et al. A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumonia. Clin Infect Dis. 1997;24:356–62. doi: 10.1093/clinids/24.3.356.
    1. Coles CL, Mabula K, Seidman JC, Levens J, Mkocha H, Munoz B, et al. Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistance S. pneumoniae carriage in young children 6 months after treatment. Clin Infect Dis. 2013;56:1519–26. doi: 10.1093/cid/cit137.
    1. Skalet AH, Cevallos V, Ayele B, Gebre T, Zhou Z, Jorgensen JH, et al. Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial. PLoS Med. 2010;7:e1000377. doi: 10.1371/journal.pmed.1000377.
    1. Haug S, Lakew T, Habtemariam G, Alemayehu W, Cevallos V, Zhou Z, et al. The decline of pneumococcal resistance after cessation of mass antibiotic distributions for trachoma. Clin Infect Dis. 2010;51:571–4. doi: 10.1086/655697.
    1. Waters D, Jawad I, Ahmad A, Lukšić I, Nair H, Zgaga L, et al. Aetiology of community-acquired neonatal sepsis in low and middle-income countries. J Glob Health. 2011;2:154–70.
    1. Marshall C, McBryde E. The role of Staphylococcus aureus carriage in the pathogenesis of bloodstream infection. BMC Res Notes. 2014;7:428. doi: 10.1186/1756-0500-7-428.
    1. Levy PY, Ollivier M, Drancourt M, Raoult D, Argenson JN. Relation between nasal carriage of Staphylococcus aureus and surgical site infection in orthopedic surgery: the role of nasal contamination. A systematic literature review and meta-analysis. Orthop Traumatol Surg Res. 2013;99:645–51. doi: 10.1016/j.otsr.2013.03.030.
    1. Rojo P, Barrios M, Palacios A, Gomez C, Chaves F. Community-associated Staphylococcus aureus infections in children. Expert Rev Anti Infect Ther. 2010;8:541–5. doi: 10.1586/eri.10.34.
    1. Uhlemann AC, Otto M, Lowy FD, DeLeo FR. Evolution of community- and healthcare-associated methicillin-resistance Staphylococcus aureus. Infect Genet Evol. 2014;21:563–74. doi: 10.1016/j.meegid.2013.04.030.
    1. Isendahl J, Manjuba C, Rodrigues A, Xu W, Henriques-Normark B, Giske CG, et al. Prevalence of community-acquired bacteremia in Guinea-Bissau: an observational study. BMC Infect Dis. 2014;14:3859. doi: 10.1186/s12879-014-0715-9.
    1. Falade AG, Lagunju IA, Bakare RA, Odekanmi AA, Adegbola RA. Invasive pneumococcal disease in children aged <5 years admitted to 3 urban hospital in Ibadan, Nigeria. Clin Infect Dis. 2009;48(Suppl 2):S190–6. doi: 10.1086/596500.
    1. Stare D, Harding-Esch E, Munoz B, Bailey R, Mabey D, Holland MJ, et al. Design and baseline data of a randomized trial to evaluate coverage and frequency of mass treatment with azithromycin: the Partnership for Rapid Elimination of Trachoma (PRET) in Tanzania and The Gambia. Ophthalmic Epidemiol. 2011;18:20–9. doi: 10.3109/09286586.2010.545500.
    1. Harding-Esch EM, Sillah A, Edwards T, Burr SE, Hart JD, Joof H, et al. Mass treatment with azithromycin for trachoma: When is one round enough? Results from the PRET Trial in The Gambia. PLoS Negl Trop Dis. 2013;7:e2115. doi: 10.1371/journal.pntd.0002115.
    1. Roca A, Hill PC, Townend J, Egere U, Antonio M, Bojang A, et al. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial. PLoS Med. 2011;8(10):e1001107. doi: 10.1371/journal.pmed.1001107.
    1. Hare KM, Smith-Vaughan HC, Leech AJ. Viability of respiratory pathogens cultured from nasopharyngeal swabs stored for up to 12 years at −70 degrees in skim milk tryptone glucose glycerol broth. J Microbiol Methods. 2011;86:364–7. doi: 10.1016/j.mimet.2011.06.016.
    1. Clinical and Laboratory Standards Institute . Performance standards for antimicrobial susceptibility testing; Twenty third informational supplement. CLSI M100-S23. Wayne: Clinical and Laboratory Standards Institute; 2013.
    1. Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and Coagulase-Negative Staphylococci. J Clin Microbiol. 2003;41:4740–4. doi: 10.1128/JCM.41.10.4740-4744.2003.
    1. Strauss C, Endimiani A, Perreten V. A novel universal DNA labeling and amplification system for rapid microarray-based detection of 117 antibiotic resistance genes in Gram-positive bacteria. J Microbiol Methods. 2015;108:25–30. doi: 10.1016/j.mimet.2014.11.006.
    1. Andersson DI, Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol. 2010;8:260–71.
    1. Maher MC, Alemayehu A, Lakew T, Gaynor BD, Haug S, Cevallos V, et al. The fitness cost of antibiotic resistance in Streptococcus pneumoniae: insight from the field. PLoS One. 2012;7:e29407. doi: 10.1371/journal.pone.0029407.
    1. Smith TC, Forshey BM, Hanson BM, Wardyn SE, Moritz ED. Molecular and epidemiological predictors of Staphylococcus aureus colonization site in a population with limited nosocomial exposure. Am J Infect Control. 2012;40:992–6. doi: 10.1016/j.ajic.2011.11.017.
    1. Leekha S, Diekema DJ, Perencevich EN. Seasonality of staphylococcal infections. Clin Microbiol Infect. 2012;18:927–33. doi: 10.1111/j.1469-0691.2012.03955.x.
    1. The Gambia standard drug treatment guidelines. 2001. . Accessed 27 Mar 2017.
    1. DiPersio LP, DiPersio JR, Beach JA, Loudon AM, Fuchs AM. Identification and characterization of plasmid-borne erm(T) macrolide resistance in group B and group A Streptococcus. Diagn Microbiol Infect Dis. 2011;71:217–23. doi: 10.1016/j.diagmicrobio.2011.07.010.
    1. Woodbury RL, Klammer KA, Xiong Y, Bailiff T, Glennen A, Bartkus JM, Active Bacterial Core Surveillance Team et al. Plasmid-borne erm(T) from invasive, macrolide-resistant Streptococcus pyogenes strains. Antimicrob Agents Chemother. 2008;52:1140–3. doi: 10.1128/AAC.01352-07.
    1. Dipersio LP, Dipersio JR. Identification of an erm(T) gene in strains of inducibly clindamycin-resistance group B Streptococcus. Diagn Microbiol Infect Dis. 2007;57:189–93. doi: 10.1016/j.diagmicrobio.2006.07.013.
    1. Uhlemann AC, Porcella SF, Trivedi S, Sullivan SB, Hafer C, Kennedy AD, et al. Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties. MBio. 2012;3:e00027–12. doi: 10.1128/mBio.00027-12.
    1. Vandendriessche S, Kadlec K, Schwarz S, Denis O. Methicillin-susceptible Staphylococcus aureus ST398-t571 harbouring the macrolide-lincosamide-streptogramin B resistance gene erm(T) in Belgian hospitals. J Antimicrob Chemother. 2011;66:2455–9. doi: 10.1093/jac/dkr348.
    1. Nurjadi D, Olalekan AO, Layer F, Shittu AO, Alabi A, Ghebremedhin B, et al. Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe. J Antimicrob Chemother. 2014;69:2361–8. doi: 10.1093/jac/dku174.
    1. Papenburg J, Fontela P, Raynal L, Jetté L, Ismail J, Bekal S, et al. Panton-Valentine leukocidin in pediatric community-acquired Staphylococcus aureus infections. Clin Invest Med. 2009;32:e352–9.
    1. Shallcross LJ, Fragaszy E, Johnson AM, Hayward AC. The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:43–54. doi: 10.1016/S1473-3099(12)70238-4.
    1. Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rümke HC, et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet. 2004;363:1871–2. doi: 10.1016/S0140-6736(04)16357-5.
    1. Van Gils EJ, Hak E, Veenhoven RH, Rodenburg GD, Bogaert D, Bruin JP, et al. Effect of seven-valent pneumococcal conjugate vaccine on Staphylococcus aureus colonisation in a randomised controlled trial. PLoS One. 2011;6:e20229. doi: 10.1371/journal.pone.0020229.
    1. Regev-Yochay G, Lipsitch M, Basset A, Rubinstein E, Dagan R, Raz M, et al. The pneumococcal pilus predicts the absence of Staphylococcus aureus co-colonization in pneumococcal carriers. Clin Infect Dis. 2009;48:760–3. doi: 10.1086/597040.
    1. Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M. Interference between Streptococcus pneumonia and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae. J Bacteriol. 2006;188:4996–5001. doi: 10.1128/JB.00317-06.
    1. Hill PC, Akisanya A, Sankareh K, Cheung YB, Saaka M, Lahai G, et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis. 2006;43:673–9. doi: 10.1086/506941.
    1. Ebruke C, Dione MM, Walter B, Worwui A, Adegbola A, Roca A, et al. High genetic diversity of Staphylococcus aureus strains colonising the nasopharynx of Gambian villagers before widespread use of pneumococcal conjugate vaccines. BMC Microbiol. 2016;16:38. doi: 10.1186/s12866-016-0661-3.
    1. Ndip RN, Ntiege EA, Ndip LM, Nkwelang G, Akoachere JF, Akenji TN. Antimicrobial resistance of bacterial agents of the upper respiratory tract of school children in Buea, Cameroon. J Health Popul Nutr. 2008;26:97–404.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever