zithromax and Death--Sudden--Cardiac

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation.. Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded.. The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc).. Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.

Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antimalarials; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Azithromycin; Bradycardia; Cardiac Pacing, Artificial; COVID-19; COVID-19 Drug Treatment; Death, Sudden, Cardiac; Electric Countershock; Hospitalization; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; SARS-CoV-2; Tachycardia, Ventricular; Torsades de Pointes; Ventricular Fibrillation

Most patients with end-stage renal disease depend on intermittent hemodialysis to maintain levels of serum potassium and other electrolytes within a normal range. However, one of the challenges has been the safety of using a low-potassium dialysate to achieve that goal, given the concern about the effects that rapid and/or large changes in serum potassium concentrations may have on cardiac electrophysiology and arrhythmia. Additionally, in this patient population, there is a high prevalence of structural cardiac changes and ischemic heart disease, making them even more susceptible to acute arrhythmogenic triggers. This concern is highlighted by the knowledge that about two-thirds of all cardiac deaths in dialysis are due to sudden cardiac death and that sudden cardiac death accounts for 25% of the overall death for end-stage renal disease. Developing new approaches and practice standards for potassium removal during dialysis, as well as understanding other modifiable triggers of sudden cardiac death, such as other electrolyte components of the dialysate (magnesium and calcium), rapid ultrafiltration rates, and safety of a number of medications (ie, drugs that prolong the QT interval or use of digoxin), are critical in order to decrease the unacceptably high cardiac mortality experienced by hemodialysis-dependent patients.

Topics: Aged; Arrhythmias, Cardiac; Azithromycin; Bicarbonates; Black or African American; Calcium; Coronary Circulation; Death, Sudden, Cardiac; Drug Interactions; Fatal Outcome; Hemodialysis Solutions; Humans; Hypertension; Hypokalemia; Kidney Failure, Chronic; Long QT Syndrome; Magnesium; Male; Omeprazole; Potassium; Proton Pump Inhibitors; Renal Dialysis; Time Factors; Ultrafiltration

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Death, Sudden, Cardiac; Fluoroquinolones; Humans; Levofloxacin; Renal Dialysis; Renal Insufficiency; United States

Hydroxychloroquine (HQ) has been used for the treatment of novel coronavirus disease (COVID-19) even though there is no clear evidence for its effectiveness yet. In contrary, HQ has major side effects like QTc prolongation and subsequent development of ventricular arrhythmias. Such side effects may possess additional risks on end-stage renal disease (ESRD) patients who have higher cardiovascular risks than general population. We herein present 2 cases of sudden cardiac death in 2 ESRD patients with COVID-19 for whom a treatment regimen including HQ was preferred. Both patients were clinically stable at the time of arrest. Death could not be attributed to worsening of the COVID-19 since the patients' clinical picture and laboratory values were improving. The cardiac events coincided with the end of routine haemodialysis sessions of both patients. Electrocardiography controls upon admission and on the 24 and 48 h of treatment showed normal QTc intervals. Potential risks contributing to sudden cardiac death during HQ treatment of ESRD patients are discussed.

Topics: Aged; Aged, 80 and over; Azithromycin; COVID-19; COVID-19 Drug Treatment; Death, Sudden, Cardiac; Drug Synergism; Drug Therapy, Combination; Fatal Outcome; Female; Heart Conduction System; Heparin; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Kidney Failure, Chronic; Magnesium; Male; Potassium; Renal Dialysis; SARS-CoV-2

Coronavirus disease of 2019 (COVID-19) has rapidly become a worldwide pandemic. Many clinical trials have been initiated to fight the disease. Among those, hydroxychloroquine and azithromycin had initially been suggested to improve clinical outcomes. Despite any demonstrated beneficial effects, they are still in use in some countries but have been reported to prolong the QT interval and induce life-threatening arrhythmia. Since a significant proportion of the world population may be treated with such COVID-19 therapies, evaluation of the arrhythmogenic risk of any candidate drug is needed.. Using the O'Hara-Rudy computer model of human ventricular wedge, we evaluate the arrhythmogenic potential of clinical factors that can further alter repolarization in COVID-19 patients in addition to hydroxychloroquine (HCQ) and azithromycin (AZM) such as tachycardia, hypokalaemia, and subclinical to mild long QT syndrome. Hydroxychloroquine and AZM drugs have little impact on QT duration and do not induce any substrate prone to arrhythmia in COVID-19 patients with normal cardiac repolarization reserve. Nevertheless, in every tested condition in which this reserve is reduced, the model predicts larger electrocardiogram impairments, as with dofetilide. In subclinical conditions, the model suggests that mexiletine limits the deleterious effects of AZM and HCQ.. By studying the HCQ and AZM co-administration case, we show that the easy-to-use O'Hara-Rudy model can be applied to assess the QT-prolongation potential of off-label drugs, beyond HCQ and AZM, in different conditions representative of COVID-19 patients and to evaluate the potential impact of additional drug used to limit the arrhythmogenic risk.

Topics: Azithromycin; COVID-19 Drug Treatment; Death, Sudden, Cardiac; Humans; Hydroxychloroquine; Long QT Syndrome; SARS-CoV-2

Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established.. We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control.. Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability.. Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.

Topics: Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Death, Sudden, Cardiac; Drug Monitoring; Electrocardiography; Female; Hospitalization; Humans; Hydroxychloroquine; Long QT Syndrome; Male; Middle Aged; Outcome and Process Assessment, Health Care; Pandemics; Pneumonia, Viral; SARS-CoV-2

Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.

Topics: Animals; Antiviral Agents; Arrhythmias, Cardiac; Azithromycin; Bradycardia; COVID-19 Drug Treatment; Death, Sudden, Cardiac; Drug Interactions; Heart; Heart Failure; Humans; Hydroxychloroquine; Interferon Type I; Mice; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk; SARS-CoV-2

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Clarithromycin; Coronary Artery Disease; Coronary Disease; Death, Sudden, Cardiac; Erythromycin; Humans; Macrolides; Plaque, Atherosclerotic; Risk Factors; Torsades de Pointes

Topics: Anti-Bacterial Agents; Azithromycin; Death, Sudden, Cardiac; Female; Humans; Long QT Syndrome; Middle Aged; Mitral Valve Prolapse; NAV1.5 Voltage-Gated Sodium Channel; Out-of-Hospital Cardiac Arrest

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Bacterial Infections; Death, Sudden, Cardiac; Heart Rate; Humans

Azithromycin is commonly used in sexual health and respiratory medicine, often when the diagnosis is presumptive. A recent article by Ray et al. reported that 1 out of 20?000 courses of low-dose azithromycin was associated with (sudden) cardiovascular death (including 1 out of 4000 courses in high-risk cardiovascular patients), ascribing these deaths to azithromycin itself. Here, we critique the actual study and examine conflicting data from randomised control trials, animal studies and observational data.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chloramphenicol; Death, Sudden, Cardiac; Humans; Research Design

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Penicillin V

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Penicillin V

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Penicillin V

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Penicillin V

Topics: Adverse Drug Reaction Reporting Systems; Anti-Bacterial Agents; Azithromycin; Death, Sudden, Cardiac; Humans; Practice Guidelines as Topic; Risk Assessment; Risk Factors; United States; United States Food and Drug Administration

Corrected QT-interval (QTc) prolongation with increased risk of fatal arrhythmia is a well-established toxicity of methadone. In this study, a case of sudden cardiac arrest in a patient on chronic methadone therapy is presented. A 47-year-old man presented unresponsive to the emergency department after pulseless arrest at his home. The patient's wife revealed he was taking methadone as part of an ongoing opioid dependency treatment and that he was prescribed azithromycin for an upper respiratory tract infection 3 days before his presentation. A 12-lead electrocardiogram at the time of presentation showed sinus tachycardia and a QTc of 490 milliseconds. It was concluded that the patient experienced a fatal arrhythmia because of QTc prolongation, precipitated by azithromycin in the setting of ongoing methadone use.

Topics: Azithromycin; Death, Sudden, Cardiac; Drug Therapy, Combination; Heart Arrest; Humans; Male; Methadone; Middle Aged

Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.. We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score-matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).. During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.. During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.).

Topics: Adult; Anti-Bacterial Agents; Arrhythmias, Cardiac; Azithromycin; Cardiovascular Diseases; Cohort Studies; Death, Sudden, Cardiac; Female; Humans; Incidence; Male; Medicaid; Middle Aged; Retrospective Studies; Risk; United States

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Patient Education as Topic; Risk Factors

Topics: Anti-Bacterial Agents; Azithromycin; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Male; Patient Education as Topic; Risk Assessment; Risk Factors