Bacterial resistance to azithromycin: causes, effects, and the fight against COVID-19

Authors

DOI:

https://doi.org/10.33448/rsd-v11i6.29198

Keywords:

Azithromycin; Antibacterial Drug Resistance; COVID-19; Virology.

Abstract

Introduction: azithromycin was one of the most employed medications during the beginning of the SARS-CoV2 pandemic, despite the lack of scientific basis for its use treatment of COVID-19. Its uncontrolled adoption has risen as a public health problem, as it promotes the appearance of drug-resistant bacterial strains, making it difficult to effectively treat many bacterial infections. Objective: to understand the implications of bacterial resistance to azithromycin in the treatment of infections in the fight against COVID-19. Methods: we surveyed a total of 38 scientific articles. The inclusion criteria were: studies whose central theme was bacterial resistance to azithromycin in the treatment of bacterioses and azithromycin in the fight against COVID-19, published from 2015 to 2022. Results: the widespread use of antibiotics may act in the selection of bacterial strains which had long held genetic traits for drug resistance, but which, not representing adaptative advantages, did not proliferate in the subsequent lineages. This direct proportionality between the widespread use and bacterial resistance to azithromycin is yet more aggravated in COVID-19 times, when part of the medical community and layman population self-medicates with azithromycin, without a scientific basis that justifies choosing this drug. Conclusion: there is a direct relationship between the indiscriminate use of azithromycin and a potential bacterial resistance to this drug. The appearance of resistant bacteria represents a serious public health problem due to the broad use of azithromycin against several bacterial infections.

References

Freires, M. S., & Junior, O. M. R. (2022). Resistência bacteriana pelo uso indiscriminado da azitromicina frente a Covid-19: uma revisão integrativa. Research, Society and Development, 11(1), e31611125035-e31611125035.

Adam, A. M. A., Saad, H. A., Alsuhaibani, A. M., Refat, M. S., & Hegab, M. S. (2021). Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part III: A green protocol for facile synthesis of complexes with TCNQ, DDQ, and TFQ acceptors. Journal of Molecular Liquids, 335, 116250.

Sandman, Z ., & Iqbal, O. A. (2020). Azithromycin.

Freires, M. S., & Junior, O. M. R. (2022). Resistência bacteriana pelo uso indiscriminado da azitromicina frente a Covid-19: uma revisão integrativa. Research, Society and Development, 11(1), e31611125035-e31611125035.

Martinez, M. A., Vuppalanchi, R., Fontana, R. J., Stolz, A., Kleiner, D. E., Hayashi, P. H., ... & Chalasani, N. (2015). Clinical and histologic features of azithromycin-induced liver injury. Clinical gastroenterology and hepatology, 13(2), 369-376.

Firth, A., & Prathapan, P. (2020). Azithromycin: the first broad-spectrum Therapeutic. European journal of medicinal chemistry, 207, 112739.

Imperador, C. H. L., Junior, C. R. E., do Nascimento Antonio, M. V., Chin, C. M., & Bosquesi, P. L. (2020). Cloroquina e hidroxicloroquina associado ao zinco e/ou azitromicina na COVID-19. ULAKES JOURNAL OF MEDICINE, 1.

Merad, M., & Martin, J. C. (2020). Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature reviews immunology, 20(6), 355-362.

Cavalli, G., De Luca, G., Campochiaro, C., Della-Torre, E., Ripa, M., Canetti, D., ... & Dagna, L. (2020). Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. The Lancet Rheumatology, 2(6), e325-e331.

Zimmermann, P., Ziesenitz, V. C., Curtis, N., & Ritz, N. (2018). The immunomodulatory effects of macrolides-a systematic review of the underlying mechanisms. Front Immunol 2018; 9: 302.

Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet, 395(10229), 1033-1034.

Niederman, M. S. (2015). Macrolide-resistant pneumococcus in community-acquired pneumonia. Is there still a role for macrolide therapy?. American journal of respiratory and critical care medicine, 191(11), 1216-1217.

Fiolet, T., Guihur, A., Rebeaud, M. E., Mulot, M., Peiffer-Smadja, N., & Mahamat-Saleh, Y. (2021). Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Clinical microbiology and infection, 27(1), 19-27.

Molina, J. M., Delaugerre, C., Le Goff, J., Mela-Lima, B., Ponscarme, D., Goldwirt, L., & de Castro, N. (2020). No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Medecine et maladies infectieuses, 50(4), 384.

Rosenberg, E. S., Dufort, E. M., Udo, T., Wilberschied, L. A., Kumar, J., Tesoriero, J., ... & Zucker, H. A. (2020). Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. Jama, 323(24), 2493-2502.

Sekhavati, E., Jafari, F., SeyedAlinaghi, S., Jamalimoghadamsiahkali, S., Sadr, S., Tabarestani, M., ... & Ghiasvand, F. (2020). Safety and effectiveness of azithromycin in patients with COVID-19: an open-label randomised trial. International journal of antimicrobial agents, 56(4), 106143.

Nguyen, L. S., Dolladille, C., Drici, M. D., Fenioux, C., Alexandre, J., Mira, J. P., ... & Salem, J. E. (2020). Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: an analysis of the World Health Organization Pharmacovigilance Database. Circulation, 142(3), 303-305.

Sultana, J., Cutroneo, P. M., Crisafulli, S., Puglisi, G., Caramori, G., & Trifirò, G. (2020). Azithromycin in COVID-19 patients: pharmacological mechanism, clinical evidence and prescribing guidelines. Drug safety, 43(8), 691-698.

Abaleke, E., Abbas, M., Abbasi, S., Abbott, A., Abdelaziz, A., Abdelbadiee, S., ... & Allison, K. (2021). Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet, 397(10274), 605-612.

Blair, J., Webber, M. A., Baylay, A. J., Ogbolu, D. O., & Piddock, L. J. (2015). Molecular mechanisms of antibiotic resistance. Nature reviews microbiology, 13(1), 42-51.

Silva Filho, L. V. R. F. D., Pinto, L. A., & Stein, R. T. (2015). Uso de macrolídeos em doenças pulmonares: controvérsias da literatura recente. Jornal de Pediatria, 91, S52-S60.

Ayerbe, L., Risco-Risco, C., Forgnone, I., Pérez-Piñar, M., & Ayis, S. (2022). Azithromycin in patients with COVID-19: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, 77(2), 303-309.

Echeverría-Esnal, D., Martin-Ontiyuelo, C., Navarrete-Rouco, M. E., De-Antonio Cusco, M., Ferrández, O., Horcajada, J. P., & Grau, S. (2021). Azithromycin in the treatment of COVID-19: a review. Expert Review of Anti-infective Therapy, 19(2), 147-163.

Hinks, T. S., Cureton, L., Knight, R., Wang, A., Cane, J. L., Barber, V. S., ... & Richards, D. (2021). Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial. The Lancet Respiratory Medicine, 9(10), 1130-1140.

Sivapalan, P., Ulrik, C. S., Lapperre, T. S., Bojesen, R. D., Eklöf, J., Browatzki, A., ... & Jensen, J. U. S. (2022). Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomised double-blinded placebo-controlled trial. European Respiratory Journal, 59(1).

Furtado, R. H., Berwanger, O., Fonseca, H. A., Corrêa, T. D., Ferraz, L. R., Lapa, M. G., ... & COALITION COVID-19 Brazil II Investigators. (2020). Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. The Lancet, 396(10256), 959-967.

Cavalcanti, A. B., Zampieri, F. G., Rosa, R. G., Azevedo, L. C., Veiga, V. C., Avezum, A., ... & Berwanger, O. (2020). Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. New England Journal of Medicine, 383(21), 2041-2052.

Horby, P. W., Roddick, A., Spata, E., Staplin, N., Emberson, J. R., Pessoa-Amorim, G., ... & Landray, M. J. (2020). Azithromycin in hospitalised patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. MedRxiv.

Gautret, P., Lagier, J. C., Parola, P., Meddeb, L., Mailhe, M., Doudier, B., ... & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents, 56(1), 105949.

Butler, C. C., Dorward, J., Yu, L. M., Gbinigie, O., Hayward, G., Saville, B. R., ... & Hobbs, F. R. (2021). Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. The Lancet, 397(10279), 1063-1074.

Oldenburg, C. E., Pinsky, B. A., Brogdon, J., Chen, C., Ruder, K., Zhong, L., ... & Doan, T. (2021). Effect of oral azithromycin vs placebo on COVID-19 symptoms in outpatients with SARS-CoV-2 infection: a randomized clinical trial. Jama, 326(6), 490-498.

Rodrigues, C., Freitas-Santos, R. S., Levi, J. E., Senerchia, A. A., Lopes, A. T. A., Santos, S. R., ... & Pierrotti, L. C. (2021). Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance. International journal of antimicrobial agents, 58(5), 106428.

Miranda, C., Silva, V., Capita, R., Alonso-Calleja, C., Igrejas, G., & Poeta, P. (2020). Implications of antibiotics use during the COVID-19 pandemic: present and future. Journal of Antimicrobial Chemotherapy, 75(12), 3413-3416.

Vellano, P. O., & de Paiva, M. J. M. (2020). O uso de antimicrobiano na COVID-19 e as infecções: o que sabemos. Research, Society and Development, 9(9), e841997245-e841997245.

WHO. (2020). Preventing the COVID-19 pandemic from causing an antibiotic resistance catastrophe. World Health Organization, Europa. 1(1), 1-1. https://www.euro.who.int/ en/health-topics/disease-prevention/antimicrobial-resistance/news/ news/2020/11/preventing-the-covid-19-pandemic-from-causingan-antibiotic-resistance-catastrophe

Wei, W., Ortwine, J. K., Mang, N. S., Joseph, C., Hall, B. C., & Prokesch, B. C. (2020). Limited role for antibiotics in COVID-19: scarce evidence of bacterial coinfection. Available at SSRN 3622388.

Juurlink, D. N. (2020). Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. Cmaj, 192(17), E450-E453.

Carvalho, W., & Guimarães, Á. S. (2020). Desinformação, Negacionismo e Automedicação: a relação da população com as drogas “milagrosas” em meio à pandemia da COVID-19. InterAmerican Journal of Medicine and Health, 3.

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Published

27/04/2022

How to Cite

SILVA SEGUNDO, R. J. e; RUFINO, J. P.; SOUSA, L. G. V.; RODRIGUES, A. E. L.; FALCÃO, A. L. S.; LIMA, I. C. de M.; CAVALCANTI , L. A. de M. .; DIAS, A. C. S.; OLIVEIRA FILHO, J. W. G. de. Bacterial resistance to azithromycin: causes, effects, and the fight against COVID-19. Research, Society and Development, [S. l.], v. 11, n. 6, p. e27711629198, 2022. DOI: 10.33448/rsd-v11i6.29198. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/29198. Acesso em: 23 dec. 2024.

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Review Article