Tinjauan Azitromisin Pada Penyakit Virus Korona 2019 (COVID-19)

Yosefien Christania Donsu(1*), Didik Hasmono(2)

(1) Airlangga University
(2) Airlangga University
(*) Corresponding Author

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. The World Health Organization has declared this disease a pandemic, where the scale of the spread of the disease occurs globally throughout the world. Currently, there is no validated pharmacological treatment for COVID-19 disease, and is still in the clinical trial stage. Azithromycin in conjunction with hydroxychloroquine or chloroquine has been proposed as a treatment that can improve the prognosis of COVID-19. This review aims to describe the mechanism of action and effectiveness of azithromycin in the treatment of COVID-19 patients. The review of the article literature was carried out through internet searches by accessing the database from google scholar, PubMed, and science direct sites. The inclusion criteria in this review are articles using azithromycin in clinical trials and COVID-19 therapy which were published from December 2019 to October 2020. Azithromycin is a macrolide antibacterial and is based on studies having antiviral and immunomodulatory effects. The use of azithromycin can lower viral load when added to hydroxychloroquine in COVID-19 patients based on small-scale clinical studies. Azithromycin used with hydroxychloroquine or chloroquine has shown good results, although it raises concerns about the risk of increased side effects of prolonged QT interval so that monitoring of the heart is needed and proven in a larger number of COVID-19 patients. The decision to use azithromycin must take into account the potential benefits and risks, evaluating the possibility of the drug being more effective than the risks to the patient.

Keywords

COVID-19; SARS-CoV-2; Azithromycin, Mechanism action, Effectiveness

Full Text:

PDF

References

ASHP - American Society of Health-System Pharmacists, 2020. Assessment of Evidence for COVID-19-Related Treatments: Updated 10/15/2020. https://www.ashp.org. Diakses: 15 Oktober 2020.

Bacharier, L.B., Guilbert, T.W., Mauger, D.T., Boehmer, S., Beigelman, A., Fitzpatrick, A.M., Jackson, D.J., Baxi, S.N., Benson, M., Burnham, C.A.D., Cabana, M., Castro, M., Chmiel, J.F., Covar, R., Daines, M., Gaffin, J.M., Gentile, D.A., Holguin, F., Israel, E., William Kelly, H., Lazarus, S.C., Lemanske, R.F., Ly, N., Meade, K., Morgan, W., Moy, J., Olin, T., Peters, S.P., Phipatanakul, W., Pongracic, J.A., Raissy, H.H., Ross, K., Sheehan, W.J., Sorkness, C., Szefler, S.J., Gerald Teague, W., Thyne, S., Martinez, F.D., 2015. Early Administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses a randomized clinical trial. JAMA - J. Am. Med. Assoc. 314, 2034–2044.

Bernardini, A., Ciconte, G., Negro, G., Rondine, R., Mecarocci, V., Viva, T., Santini, F., de Innocentiis, C., Giannelli, L., Witkowska, E., Locati, E.T., Castelvecchio, S., Marrocco-Trischitta, M.M., Vicedomini, G., Menicanti, L., Pappone, C., 2020. Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen. Int. J. Cardiol. 1–7, doi: 10.1016/j.ijcard.2020.09.038.

Bogoch, I.I., Watts, A., Thomas-Bachli, A., Huber, C., Kraemer, M.U.G., Khan, K., 2020. Pneumonia of unknown aetiology in Wuhan, China: Potential for international spread via commercial air travel. J. Travel Med. 27, 1–3.

Bosseboeuf, E., Aubry, M., Nhan, T., de Pina, J.J., Rolain, J.M., Raoult, D., Musso, D., 2018. Azithromycin Inhibits the Replication of Zika Virus. J Antivir Antiretrovir, 10(1) 6-11

Burhan, E., Susanto, A.D., Nasution, S.A., Ginanjar, E., Pitoyo, C.W., Susilo, A., Firdaus, I., Santoso, A., Juzar, D.A., Arif, S.K., Wulung, N.G.. L., Adityaningsih, D., Syam, A.F., Rasmin, M., Rengganis, I., Sukrisman, L., Damayanti, T., Wiyono, W.H., Prasenohadi, Isbaniah, F., Elhidsi, M., Aniwidyaningsih, W., 2020. Pedoman Tatalaksana COVID-19 Edisi 2 (pp. 11-20) Jakarta: PDPI, PERKI, PAPDI, PERDATIN dan IDAI.

CDC - Centers for Disease Control and Prevention, 2020. Symptoms of Coronavirus (COVID-19). https://www.cdc.gov/coronavirus. Diakses: 1 Oktober 2020

Chorin, E., Wadhwani, L., Magnani, S., Dai, M., Shulman, E., Nadeau-Routhier, C., Knotts, R., Bar-Cohen, R., Kogan, E., Barbhaiya, C., Aizer, A., Holmes, D., Bernstein, S., Spinelli, M., Park, D.S., Stefano, C., Chinitz, L.A., Jankelson, L., 2020. QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin. Hear. Rhythm 17, 1425–1433.

ClinicalTrials.gov. U.S. National Library of Medicine, 2020. http://www.clinicaltrials.gov. Diakses: 15 Oktober

Delang, L., Neyts, J., 2020. Medical treatment options for COVID-19. European Heart Journal: Acute Cardiovascular Care 2020, Vol. 9(3) 209–214.

Eljaaly, K., Alshehri, S., Aljabri, A., Abraham, I., Al Mohajer, M., Kalil, A.C., Nix, D.E., 2017. Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: A systematic review and meta-analysis. BMC Infect. Dis. 17, 1–7.

Furtado, R.H.M., Berwanger, O., Fonseca, H.A., Corrêa, T.D., Ferraz, L.R., Lapa, M.G., Zampieri, F.G., Veiga, V.C., Azevedo, L.C.P., Rosa, R.G., Lopes, R.D., Avezum, A., Manoel, A.L.O., Piza, F.M.T., Martins, P.A., Lisboa, T.C., Pereira, A.J., Olivato, G.B., Dantas, V.C.S., Milan, E.P., Gebara, O.C.E., Amazonas, R.B., Oliveira, M.B., Soares, R.V.P., Moia, D.D.F., Piano, L.P.A., Castilho, K., Momesso, R.G.R.A.P., Schettino, G.P.P., Rizzo, L.V., Neto, A.S., Machado, F.R., Cavalcanti, A.B., 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. Lancet 396, 959–967.

Gautret, P., Lagier, J.C., Parola, P., Hoang, V.T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V.E., Tissot Dupont, H., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J.M., Brouqui, P., Raoult, D., 2020a. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents 56, 105949, 1-6.

Gautret, P., Lagier, J.C., Parola, P., Hoang, V.T., Meddeb, L., Sevestre, J., Mailhe, M., Doudier, B., Aubry, C., Amrane, S., Seng, P., Hocquart, M., Eldin, C., Finance, J., Vieira, V.E., Tissot-Dupont, H.T., Honoré, S., Stein, A., Million, M., Colson, P., La Scola, B., Veit, V., Jacquier, A., Deharo, J.C., Drancourt, M., Fournier, P.E., Rolain, J.M., Brouqui, P., Raoult, D., 2020b. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med. Infect. Dis. 34, 101663, 1-7.

Gielen, V., Johnston, S.L., Edwards, M.R., 2010. Azithromycin induces anti-viral responses in bronchial epithelial cells. Eur. Respir. J. 36, 646–654.

Gorbalenya, A.E., Baker, S.C., Baric, R.S., de Groot, R.J., Drosten, C., Gulyaeva, A.A., Haagmans, B.L., Lauber, C., Leontovich, A.M., Neuman, B.W., Penzar, D., Perlman, S., Poon, L.L.M., Samborskiy, D. V., Sidorov, I.A., Sola, I., Ziebuhr, J., 2020. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544.

Grayson, M.L., Cosgrove, S.E., Crowe, S.M., Hope, W., McCarthy, J.S., Mills, J., Mouton, J.W., Paterson, D.L., 2017. Kucers the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition (pp. 1122-1149). US: CRC Press.

Katzung, B.G., 2018. Basic & Clinical Pharmacology, Fourteenth Edition, Basic and Clinical Pharmacology (pp. 818-820). US: McGraw-Hill Education.

Kawamura, K., Ichikado, K., Takaki, M., Eguchi, Y., Anan, K., Suga, M., 2018. Adjunctive therapy with azithromycin for moderate and severe acute respiratory distress syndrome: a retrospective, propensity score-matching analysis of prospectively collected data at a single center. Int. J. Antimicrob. Agents 51, 918–924.

Li, G., Clercq, E., 2020. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov. 19, 149–150.

Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K.S.M., Lau, E.H.Y., Wong, J.Y., Xing, X., Xiang, N., Wu, Y., Li, C., Chen, Q., Li, D., Liu, T., Zhao, J., Liu, M., Tu, W., Chen, C., Jin, L., Yang, R., Wang, Q., Zhou, S., Wang, R., Liu, H., Luo, Y., Liu, Y., Shao, G., Li, H., Tao, Z., Yang, Y., Deng, Z., Liu, B., Ma, Z., Zhang, Y., Shi, G., Lam, T.T.Y., Wu, J.T., Gao, G.F., Cowling, B.J., Yang, B., Leung, G.M., Feng, Z., 2020a. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 382, 1199–1207.

Li, X., Geng, M., Peng, Y., Meng, L., Lu, S., 2020b. Molecular immune pathogenesis and diagnosis of COVID-19. J. Pharm. Anal. 10, 102–108.

Malik, S., Gupta, A., Zhong, X., Rasmussen, T.P., Manautou, J.E., Bahal, R., 2020. Emerging therapeutic modalities against covid-19. Pharmaceuticals 13, 1–32.

Mercuro, N.J., Yen, C.F., Shim, D.J., Maher, T.R., McCoy, C.M., Zimetbaum, P.J., Gold, H.S., 2020. Risk of QT Interval Prolongation Associated with Use of Hydroxychloroquine with or without Concomitant Azithromycin among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 1–6, doi:10.1001/jamacardio.2020.1834.

Metlay, J., Waterer G., 2020. Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic. Annals of Internal Medicine, 1-3, doi: 10.7326/M20-2189

Million, M., Lagier, J.C., Gautret, P., Colson, P., Fournier, P.E., Amrane, S., Hocquart, M., Mailhe, M., Esteves-Vieira, V., Doudier, B., Aubry, C., Correard, F., Giraud-Gatineau, A., Roussel, Y., Berenger, C., Cassir, N., Seng, P., Zandotti, C., Dhiver, C., Ravaux, I., Tomei, C., Eldin, C., Tissot-Dupont, H., Honoré, S., Stein, A., Jacquier, A., Deharo, J.C., Chabrière, E., Levasseur, A., Fenollar, F., Rolain, J.M., Obadia, Y., Brouqui, P., Drancourt, M., La Scola, B., Parola, P., Raoult, D., 2020. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Med. Infect. Dis. 35, 101738.

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. Med. Mal. Infect. 50, 384.

Nguyen, L.S., Dolladille, C., Drici, M.D., Fenioux, C., Alexandre, J., Mira, J.P., Moslehi, J.J., Roden, D.M., Funck-Brentano, C., Salem, J.E., 2020. Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: An analysis of the world health organization pharmacovigilance database. Circulation 142, 303–305.

NIH - National Institutes of Health, 2020. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Disponible en: https://covid19treatmentguidelines.nih.gov/. Diakses: 29 September 2020.

Oliver, M.E., Hinks, T.S.C., 2020. Azithromycin in viral infections. Rev. Med. Virol. 1–13, doi: 10.1002/rmv.2163

PERKI - Perhimpunan Dokter Spesialis Kardiovaskular Indonesia, 2020. Panduan Diagnostik dan Tatalaksana Penyakit Kardiovaskular Pada Pandemi COVID-19 Edisi Pertama (pp. 72-80). Jakarta.

Ramireddy, A., Chugh, H., Reinier, K., Ebinger, J., Park, E., Thompson, M., Cingolani, E., Cheng, S., Marban, E., Albert, C.M., Chugh, S.S., 2020. Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. J. Am. Heart Assoc. 9, e017144, doi: 10.1161/JAHA.120.017144.

Reijnders, T.D.Y., Saris, A., Schultz, M.J., van der Poll, T., 2020. Immunomodulation by macrolides: therapeutic potential for critical care. Lancet Respir. Med. 8, 619–630.

Risch, H.A., 2020. Opinion: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis. Am. J. Epidemiol. 00, 1–9.

Rosenberg, E.S., Dufort, E.M., Udo, T., Wilberschied, L.A., Kumar, J., Tesoriero, J., Weinberg, P., Kirkwood, J., Muse, A., Dehovitz, J., Blog, D.S., Hutton, B., Holtgrave, D.R., 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 - J. Am. Med. Assoc. 323, 2493–2502.

Rothan, H.A., Byrareddy, S.N., 2020. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 109, 102433.

Tran, D.H., Sugamata, R., Hirose, T., Suzuki, S., Noguchi, Y., Sugawara, A., Ito, F., Yamamoto, T., Kawachi, S., Akagawa, K.S., Ōmura, S., Sunazuka, T., Ito, N., Mimaki, M., Suzuki, K., 2019. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1) pdm09 virus infection by interfering with virus internalization process. J. Antibiot. (Tokyo). 72, 759–768.

Ulrich, H., Pillat, M.M., 2020. CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement. Stem Cell Rev. Reports 16, 434–440.

Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., Zhao, Y., Li, Y., Wang, X., Peng, Z., 2020. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA - J. Am. Med. Assoc. 323, 1061–1069.

WHO, 2020a. Novel Coronavirus (2019-nCoV) Situation Report 22. https://www.who.int. Diakses: 25 September 2020.

WHO, 2020b. Coronavirus Disease 2019 (COVID-19) Situation Report 51. https://www.who.int. Diakses: 25 September 2020.

WHO, 2020c. Coronavirus disease 2019 (COVID-19) Situation Report 73. https://www.who.int. Diakses: 25 September 2020.

Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., Zhou, Q., 2020. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448.

Ye, Q., Wang, B., Mao, J., 2020. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company’s public news and information. J. Infect.

Zhang, Y., Dai, J., Jian, H., Lin, J., 2019. Effects of macrolides on airway microbiome and cytokine of children with bronchiolitis: A systematic review and meta-analysis of randomized controlled trials. Microbiol. Immunol. 63, 343–349.

Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G.F., Tan, W., 2020. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727–733.

Zimmermann, P., Ziesenitz, V.C., Curtis, N., Ritz, N., 2018. The immunomodulatory effects of macrolides-A systematic review of the underlying mechanisms. Front. Immunol. 9:302, 1-14.

DOI: 10.23917/pharmacon.v17i2.12359

Article Metrics

Abstract view(s): 1801 time(s)
PDF: 11322 time(s)

Refbacks

  • There are currently no refbacks.