Impact of mass administration of azithromycin as a preventive treatment on the prevalence and resistance of nasopharyngeal carriage of Staphylococcus aureus

Soumeya Hema-Ouangraoua, Juliette Tranchot-Diallo, Issaka Zongo, Nongodo Firmin Kabore, Frédéric Nikièma, Rakiswende Serge Yerbanga, Halidou Tinto, Daniel Chandramohan, Georges-Anicet Ouedraogo, Brian Greenwood, Jean-Bosco Ouedraogo, Soumeya Hema-Ouangraoua, Juliette Tranchot-Diallo, Issaka Zongo, Nongodo Firmin Kabore, Frédéric Nikièma, Rakiswende Serge Yerbanga, Halidou Tinto, Daniel Chandramohan, Georges-Anicet Ouedraogo, Brian Greenwood, Jean-Bosco Ouedraogo

Abstract

Staphylococcus aureus is a major cause of serious illness and death in children, indicating the need to monitor prevalent strains, particularly in the vulnerable pediatric population. Nasal carriage of S. aureus is important as carriers have an increased risk of serious illness due to systemic invasion by this pathogen and can transmit the infection. Recent studies have demonstrated the effectiveness of azithromycin in reducing the prevalence of nasopharyngeal carrying of pneumococci, which are often implicated in respiratory infections in children. However, very few studies of the impact of azithromycin on staphylococci have been undertaken. During a clinical trial under taken in 2016, nasal swabs were collected from 778 children aged 3 to 59 months including 385 children who were swabbed before administration of azithromycin or placebo and 393 after administration of azithromycin or placebo. Azithromycin was given in a dose of 100 mg for three days, together with the antimalarials sulfadoxine-pyrimethamine and amodiaquine, on four occasions at monthly intervals during the malaria transmission season. These samples were cultured for S. aureus as well as for the pneumococcus. The S. aureus isolates were tested for their susceptibility to azithromycin (15 g), penicillin (10 IU), and cefoxitine (30 g) (Oxoid Ltd). S. aureus was isolated from 13.77% (53/385) swabs before administration of azithromycin and from 20.10% (79/393) six months after administration (PR = 1.46 [1.06; 2.01], p = 0.020). Azithromycin resistance found in isolates of S. aureus did not differ significantly before and after intervention (26.42% [14/53] vs 16.46% [13/79], (PR = 0.62 [0.32; 1.23], p = 0.172). Penicillin resistance was very pronounced, 88.68% and 96.20% in pre-intervention and in post-intervention isolates respectively, but very little Methicillin Resistance (MRSA) was detected (2 cases before and 2 cases after intervention). Monitoring antibiotic resistance in S. aureus and other bacteria is especially important in Burkina Faso due to unregulated consumption of antibiotics putting children and others at risk.

Trial registration: ClinicalTrials.gov NCT02211729.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Screening, randomization, and follow-up.
Fig 1. Screening, randomization, and follow-up.
Fig 2
Fig 2
Prevalence of S. aureus resistance to antibiotic: a) Resistance to azithromycin by arm before and after intervention; b) resistance to penicillin and cefoxitin before and after administration of azithromycin.

References

    1. Levels and Trends in Child Mortality Estimation. 2019: New York.
    1. Porco TC, Gebre T, Ayele B, et al.. Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA. 2009;302(9):962–968. doi: 10.1001/jama.2009.1266
    1. Keenan JD, Ayele B, Gebre T, et al.. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011;52(7): 883–888. doi: 10.1093/cid/cir069
    1. Chandramohan D, Dicko A, Zongo I, et al.. Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention. N Engl J Med. 2019;380(23):2197–2206. doi: 10.1056/NEJMoa1811400
    1. Batt SL, Charalambous BM, Solomon AW, et al.. Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother. 2003;47(9):2765–2769. doi: 10.1128/AAC.47.9.2765-2769.2003
    1. Gaynor BD, Holbrook KA, Whitcher JP, 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(2):147–148. doi: 10.1136/bjo.87.2.147
    1. Burr SE, Milne S, Jafali J, et al.. Mass administration of azithromycin and Streptococcus pneumoniae carriage: cross-sectional surveys in the Gambia. Bull World Health Organ. 2014;92(7):490–498. doi: 10.2471/BLT.13.133462
    1. Leach AJ, Shelby-James TM, Mayo M, et al.. A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis. 1997;24(3):356–362. doi: 10.1093/clinids/24.3.356
    1. Coles CL, Mabula K, Seidman JC, et al.. Mass distribution of azithromycin for trachoma control is associated with increased risk of azithromycin-resistant Streptococcus pneumoniae carriage in young children 6 months after treatment. Clin Infect Dis. 2013;56(11):1519–1526. doi: 10.1093/cid/cit137
    1. Hema-Ouangraoua S, Aziz Maiga A, Cairns M, et al.. Impact of the addition of azithromycin to antimalarials used for seasonal malaria chemoprevention on antimicrobial resistance of Streptococcus pneumoniae. Trop Med Int Health. 2019;24(12):1442–1454. doi: 10.1111/tmi.13321
    1. Doan T, Arzika AM, Hinterwirth A, Maliki R, Abdou A et al..(2019).Gut and Nasopharyngeal Macrolide Resistance in the MORDOR Study: A Cluster-Randomized Trial in Niger. N EnglJ Med. 380(23):2271–2273.
    1. Doan T, Worden L, Hinterwirth A et al.. (2020). Macrolide and Non macrolide Resistance with Mass Azithromycin Distribution. N Engl J Med 2020; 383:1941–1950. doi: 10.1056/NEJMoa2002606
    1. Oluwalana C, Howie SR, Secka O, et al.. Incidence of Haemophilus influenzae type b disease in The Gambia 14 years after introduction of routine Haemophilus influenzae type b conjugate vaccine immunization. J Pediatr. 2013;163(1 Suppl):S4–S7. doi: 10.1016/j.jpeds.2013.03.023
    1. Kaboré NF, Poda GE, Barro M, et al.. Impact de la vaccination sur la méningite à H. influenzae b de 2004 à 2008, à Bobo Dioulasso (Burkina Faso) [Impact of vaccination on admissions for Haemophilus influenzae b meningitis from 2004 to 2008 in Bobo Dioulasso, Burkina Faso]. Med Sante Trop. 2012;22(4):425–429. doi: 10.1684/mst.2012.0122
    1. Mackenzie GA, Hill PC, Jeffries DJ, et al.. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis. 2016;16(6):703–711. doi: 10.1016/S1473-3099(16)00054-2
    1. Mulholland EK, Ogunlesi OO, Adegbola RA, et al.. Etiology of serious infections in young Gambian infants. Pediatr Infect Dis J. 1999;18(10 Suppl): S35–S41. doi: 10.1097/00006454-199910001-00007
    1. Uzodimma C C, Njokanma F, Ojo O, Falase M, Ojo T. Bacterial Isolates from Blood Cultures of Children with Suspected Sepsis in An Urban Hospital in Lagos: A Prospective Study Using BACTEC Blood Culture System. The Internet Journal of Pediatrics and Neonatology. 2013. Volume 16 Number 1.
    1. Clinical and Laboratory Standards Institut: Performance standards for antimicrobial disk susceptibility tests; aprouved standard, 26 th ed. M100S. 2014.
    1. Reta A., Wubie M. & Mekuria G. Nasal colonization and antimicrobial susceptibility pattern of Staphylococcus aureus among pre-school children in Ethiopia. BMC Res Notes 2017. >; 10, 746. doi: 10.1186/s13104-017-3079-6
    1. Kateete DP., Asiimwe B.B., Mayanja R. et al. Nasopharyngeal carriage, spa types and antibiotic susceptibility profiles of Staphylococcus aureus from healthy children less than 5 years in Eastern Uganda. BMC Infect Dis 2019; 19, 1023. doi: 10.1186/s12879-019-4652-5
    1. Eibach D, Nagel M, Hogan B, et al.. Nasal Carriage of Staphylococcus aureus among Children in the Ashanti Region of Ghana. PLoS One. 2017;12(1): e0170320. Published 2017 Jan 20. doi: 10.1371/journal.pone.0170320
    1. Walter S., Böck R., Antibiotic Resistance Trends of Nasal Staphylococcal Isolates from Namibian School Children. Journal of Biosciences and Medicines, 2020. 8: p. 18–27.
    1. Odutola A, C.Bottomley C., ZamanS A, et al., Staphylococcus aureus Bacteremia in Children of Rural Areas of The Gambia, 2008–2015. Emerging Infectious Diseases, 2019. 25(4). doi: 10.3201/eid2504.180935

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