Background: Antibiotics sales without medical prescriptions are increasingly recognized as sources of antimicrobial misuse that can exacerbate the global burden of antibiotic resistance. We aimed to determine the percentage of pharmacies who sell antibiotics without medical prescriptions, examining the potential associated risks of such practice in Riyadh, Saudi Arabia, by simulation of different clinical scenarios. Methods: A cross sectional study of a quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who simulated having a relative with a specific clinical illness (sore throat, acute bronchitis, otitis media, acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged women). Results: A total of 327 pharmacies were visited. Antibiotics were dispensed without a medical prescription in 244 (77.6%) of 327, of which 231 (95%) were dispensed without a patient request. Simulated cases of sore throat and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters, followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed (51%) for the other simulated cases. None of the pharmacists asked about antibiotic allergy history or provided information about drug interactions. Only 23% asked about pregnancy status when dispensing antibiotics for UTI-simulated cases. Conclusions: We observed that an antibiotic could be obtained in Riyadh without a medical prescription or an evidence-based indication with associated potential clinical risks. Strict enforcement and adherence to existing regulations are warranted.

Background: Chloroquine (CQ) and hydroxychloroquine (HCQ) show anti-SARS-CoV-2 activity in vitro; however, clinical studies have reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin (AZ) on outcomes of COVID-19 patients. Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, preprints and grey literature up to July 7, 2020. We included studies that assessed COVID-19 patients treated with CQ or HCQ, with or without AZ. We pooled only adjusted effect estimates of mortality using a random effect model. We summarized the effect of CQ or HCQ on viral clearance and ICU admission/ mechanical ventilation. Results: Out of 1463 citations screened for eligibility, five RCTs and 14 cohort studies were included (20,263 hospitalized patients). Thirteen studies (1 RCT and 12 cohorts) with 15,938 patients examined the effect of HCQ on short term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I ² =0 %, p=0.647). Six cohort studies examined the effect of HCQ and AZ combination among 14,016 patients. The pooled adjusted OR was 0.93 (95% CI 0.79-1.11, I ² =59.3%, p=0.003). Two cohort studies and three RCTs found no significant effect of HCQ on viral clearance. One RCT with 48 patients demonstrated improved viral clearance in patients treated with CQ and HCQ. Three cohort studies found that HCQ with or without AZ had no significant effect on mechanical ventilation/ ICU admission. Conclusion: Moderate certainty evidence suggests that HCQ, with or without AZ, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19. Summary: This systematic review and meta-analysis showed that in-hospital treatment of COVID-19 patients with antimalarials medications failed to reduce short-term mortality and morbidity with potential harm if used in combination with azithromycin.

Importance: The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective: To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources: A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection: Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and Synthesis: Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures: Pooled Incidence of: (1) change in QTc value from baseline ≥ 60 ms, (2) QTc ≥ 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. Results: A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I ² =96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I ² =98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms was 7%, 95% CI (3-14), I ² =94% (12 studies of 2008 patients). The pooled incidence of QTc ≥ 500 ms was 6%, 95% CI (2-12), I ² =95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I ² =97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance: Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring. Key Points: Question: What are the risks of different cardiac toxicities in patients receiving chloroquine (CQ) or hydroxychloroquine (HCQ) for COVID-19. Findings: In this systematic review, treatment of COVID-19 patients with CQ or HCQ is associated with a clinically significant risk of drug-induced QT prolongation, and torsades de pointes (TdP) arrhythmia/ventricular tachycardia/cardiac arrest in a relatively higher incidence compared to drugs withdrawn from the market for such adverse effects. Meaning: These agents should be used only in the context of clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.