The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients
Background/aim: Effective therapeutic approaches for SARS-CoV-2 pandemic are urgently needed. Hydroxychloroquine (HCQ) alone or in combination with azithromycin has been used in several countries, without any clear evidence. This study aimed to determine the effectiveness and safety of hydroxychloroquine as compared to hydroxychloroquine and azithromycin combination in patients with COVID-19 pneumonia. Materials and methods: This retrospective study evaluated all patients admitted to two university hospitals between 18 March and 20 May 2020 with the diagnosis of COVID-19 pneumonia. Out of 496 patients, 370 met the eligibility criteria and were included in the final analysis. The primary outcome was in-hospital mortality. Secondary outcomes were time to recovery, presence of severe acute respiratory infection (SARI), the requirement for oxygen therapy, and/or mechanical ventilation, length of hospital stay, and adverse events. Results: A total of 222 patients received hydroxychloroquine and 148 were treated with HCQ and azithromycin combination. The in-hospital mortality rates were similar in the two groups (10.8% vs. 6.8%, respectively, p=0.186). Additionally, the needs for oxygen therapy, invasive mechanic ventilation (IMV) and intensive care unit (ICU) admission were not different. The rate of the requirement of non-invasive mechanic ventilation (NIV) was higher in patients receiving HCQ plus azithromycin (10.1% vs. 4.5%, p=0.035). Time to recovery was 3.5 days in HCQ and 5.0 days in HCQ plus azithromycin group (p<0.001). The median length of hospital stay was longer in patients with the combination therapy (7.0 vs. 5.5 days, p<0.001). Amongst all patients, only 3 patients developed electrocardiographic changes needing discontinuation of therapy. Limitations: Observational design of the study is the main limitation. Conclusions: The present findings suggest that adding azithromycin to HCQ is not associated with any improvement in clinical outcome and mortality in patients with COVID-19 pneumonia and supports the current knowledge not to include azithromycin in the initial treatment of COVID-19.
References
Andreani, Bideau, Duflot, Jardot, Rolland, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb Pathog
Cavalcanti, Zampieri, Rosa, Azevedo, Veiga, Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
Das, Bhowmick, Tiwari, Sen, An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19
Gautret, Lagier, Parola, Hoang, Meddeb, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label nonrandomized clinical trial, International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105949Geleris, Sun, Platt, Zucker, Baldwin, Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med
Gezer, Ergan, Baris, Appak, Sayiner, COVID-19 S: A new proposal for diagnosis and structured reporting of COVID-19 on computed tomography imaging, Diagn Interv Radiol
Gérard, Romani, Fresse, Viard, Parassol, Off-label" use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: A survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers, Therapies,
doi:10.1016/j.therap.2020.05.002Ji, Zhang, Xu, Chen, Yang, Prediction for Progression Risk in Patients With COVID-19 Pneumonia: The CALL Score, Clinical Infectious Diseases,
doi:10.1093/cid/ciaa414Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochemical and Biophysical Research Communications,
doi:10.1016/j.bbrc.2004.08.085Li, Huang, Wang, Wang, Liang, COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of metaanalysis, J Med Virol
Liang, Liang, Ou, Chen, Chen, Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19, JAMA Intern Med,
doi:10.1001/jamainternmed.2020.2033Liu, Cao, Xu, Wang, Zhang, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery,
doi:10.1038/s41421-020-0156-0Magagnoli, Narendran, Pereira, Cummings, Hardin, Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19, Med,
doi:10.1016/j.medj.2020.06.001Mahevas, Tran, Roumier, Chabrol, Paule, No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial,
doi:10.1101/2020.04.10.20060699Mercuro, Yen, Shim, Maher, Mccoy, 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,
doi:10.1001/jamacardio.2020.1834Ramireddy, Chugh, Reinier, Ebinger, Park, Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring, J Am Heart Assoc
Rosenberg, Dufort, Udo, Wilberschied, Kumar, Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19, JAMA,
doi:10.1001/jama.2020.8630Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases, The Lancet Infectious Diseases,
doi:10.1016/s1473-3099(03)00806-5Silverio, Di Maio, Citro, Esposito, Iuliano, Cardiovascular risk factors and mortality in hospitalized patients with COVID-19: systematic review and meta-analysis of 45 studies and 18,300 patients, BMC cardiovascular disorders,
doi:10.1186/s12872-020-01816-3Tang, Cao, Han, Wang, Chen, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ,
doi:10.1136/bmj.m1849Vincent, Bergeron, Benjannet, Erickson, Rollin, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J
Yao, Ye, Zhang, Cui, Huang, Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clinical Infectious Diseases,
doi:10.1093/cid/ciaa237
