Macrolide antibiotics and the risk of cardiac arrhythmias

American Journal of Respiratory and Critical Care Medicine

Volumn 189, Issue 10, 2014, Pages 1173-1180

  Albert, Richard K ^a,b   Schuller, Joseph L ^a,b  

^a DENVER HEALTH AND HOSPITAL AUTHORITY   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

Arrhythmias; Azithromycin; QT prolongation

Indexed keywords

AZITHROMYCIN; CLARITHROMYCIN; ERYTHROMYCIN; MACROLIDE;

CARDIOVASCULAR RISK; DOSE RESPONSE; GENETICS; HEART ARRHYTHMIA; HEART ELECTROPHYSIOLOGY; HUMAN; PRIORITY JOURNAL; REVIEW; RISK FACTOR; RISK REDUCTION;

ANTI-BACTERIAL AGENTS; ARRHYTHMIAS, CARDIAC; AZITHROMYCIN; CYSTIC FIBROSIS; HEART CONDUCTION SYSTEM; HUMANS; MACROLIDES; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS;

EID: 84901011433     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201402-0385CI     Document Type: Review

References (90)

1. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012;366:1881-1890.
2. Shah RR. Pharmacogenetic aspects of drug-induced torsade de pointes: potential tool for improving clinical drug development and prescribing. Drug Saf 2004;27:145-172.
3. Straus SMJM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, Deckers JW, Kingma JH, Sturkenboom MC, Stricker BH, et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol 2006;47:362-367.
4. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013-1022.
5. Stratmann HG, Kennedy HL. Torsades de pointes associated with drugs and toxins: recognition and management. Am Heart J 1987;113:1470-1482.
6. Al-Khatib SM, LaPointe NMA, Kramer JM, Califf RM. What clinicians should know about the QT interval. JAMA 2003;289:2120-2127.
7. Malik M, Camm AJ. Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling. Drug Saf 2001;24: 323-351.
8. Arizona Center for Education and Research in Therapeutics. Drugs that prolong the QT interval and/or induce torsades de pointes [accessed 2013 Aug 19]. Available from: http://www.azcert.org/medical-pros/drug-lists/printable- drug-list.cfm
9. Rubart M, Pressler ML, Pride HP, Zipes DP. Electrophysiological mechanisms in a canine model of erythromycin-associated long QT syndrome. Circulation 1993;88:1832-1844.
10. Daleau P, Lessard E, Groleau MF, Turgeon J. Erythromycin blocks the rapid component of the delayed rectifier potassium current and lengthens repolarization of guinea pig ventricular myocytes. Circulation 1995;91:3010-3016.
11. Antzelevitch C, Sun ZQ, Zhang ZQ, Yan GX. Cellular and ionic mechanisms underlying erythromycin-induced long QT intervals and torsade de pointes. J Am Coll Cardiol 1996;28: 1836-1848.
12. Itoh H, Sakaguchi T, Ding WG, Watanabe E, Watanabe I, Nishio Y, Makiyama T, Ohno S, Akao M, Higashi Y, et al. Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. Circ Arrhythm Electrophysiol 2009;2:511-523.
13. Lazzara R. Amiodarone and torsade de pointes. Ann Intern Med 1989; 111:549-551.
14. Donger C, Denjoy I, Berthet M, Neyroud N, Cruaud C, Bennaceur M, Chivoret G, Schwartz K, Coumel P, Guicheney P. KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome. Circulation 1997;96:2778-2781.
15. Napolitano C, Schwartz PJ, Brown AM, Ronchetti E, Bianchi L, Pinnavaia A, Acquaro G, Priori SG. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol 2000;11:691-696.
16. Paulussen ADC, Gilissen RAHJ, Armstrong M, Doevendans PA, Verhasselt P, Smeets HJM, Schulze-Bahr E, Haverkamp W, Breithardt G, Cohen N, et al. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl) 2004;82:182-188.
17. Lehtonen A, Fodstad H, Laitinen-Forsblom P, Toivonen L, Kontula K, Swan H. Further evidence of inherited long QT syndrome gene mutations in antiarrhythmic drug-associated torsades de pointes. Heart Rhythm 2007;4:603-607.
18. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, Hohnloser SH, Shimizu W, Schwartz PJ, Stanton M, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002;105:1943-1948.
19. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome: clinical impact. Circulation 1999;99:529-533.
20. Viskin S. Long QT syndromes and torsade de pointes. Lancet 1999; 354:1625-1633.
21. Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med 1992;327:846-852.
22. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SAN. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 1999;97: 175-187.
23. Roden DM. Taking the "idio" out of "idiosyncratic": predicting torsades de pointes. Pacing Clin Electrophysiol 1998;21:1029-1034.
24. Jackman WM, Friday KJ, Anderson JL, Aliot EM, Clark M, Lazzara R. The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 1988;31:115-172.
25. Minardo JD, Heger JJ, Miles WM, Zipes DP, Prystowsky EN. Clinical characteristics of patients with ventricular fibrillation during antiarrhythmic drug therapy. N Engl J Med 1988;319:257-262.
26. Ponsonnaille J, Citron B, Richard A, Trolese JF, Chaperon A, Barret B, Gras H. Electrophysiological study of pro-arrhythmogenic effects of erythromycin [in French]. Arch Mal Coeur Vaiss 1988;81:1001-1008.
27. Mishra A, Friedman HS, Sinha AK. The effects of erythromycin on the electrocardiogram. Chest 1999;115:983-986.
28. Kdesh A, McPherson CA, Yaylali Y, Yasick D, Bradley K, Manthous CA. Effect of erythromycin on myocardial repolarization in patients with community-acquired pneumonia. South Med J 1999;92: 1178-1182.
29. Nattel S, Ranger S, Talajic M, Lemery R, Roy D. Erythromycininduced long QT syndrome: concordance with quinidine and underlying cellular electrophysiologic mechanism. Am J Med 1990; 89:235-238.
30. Houin G, Tillement JP, Lhoste F, Rapin M, Soussy CJ, Duval J. Erythromycin pharmacokinetics in man. J Int Med Res 1980;8:9-14.
31. Austin KL, Mather LE, Philpot CR, McDonald PJ. Intersubject and dose-related variability after intravenous administration of erythromycin. Br J Clin Pharmacol 1980;10:273-279.
32. Nilsen OG. Comparative pharmacokinetics of macrolides. J Antimicrob Chemother 1987;20:81-88.
33. Ohtani H, Taninaka C, Hanada E, Kotaki H, Sato H, Sawada Y, Iga T. Comparative pharmacodynamic analysis of Q-T interval prolongation induced by the macrolides clarithromycin, roxithromycin, and azithromycin in rats. Antimicrob Agents Chemother 2000;44: 2630-2637.
34. Milberg P, Eckardt L, Bruns H-J, Biertz J, Ramtin S, Reinsch N, Fleischer D, Kirchhof P, Fabritz L, Breithardt G, et al. Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. J Pharmacol Exp Ther 2002;303:218-225.
35. McComb JM, Campbell NPS, Cleland J. Recurrent ventricular tachycardia associated with QT prolongation after mitral valve replacement and its association with intravenous administration of erythromycin. Am J Cardiol 1984;54:922-923.
36. Gueugniaud PY, Guerin C, Mahul P, Deu C, Robert D. Torsade de pointes induced by the combination lidocaine-erythromycin and hepatic insufficiency [in French]. Presse Med 1985;14:896.
37. Guelon D, Bedock B, Chartier C, Haberer J-P. QT prolongation and recurrent "torsades de pointes" during erythromycin lactobionate infusion. Am J Cardiol 1986;58:666.
38. Freedman RA, Anderson KP, Green LS, Mason JW. Effect of erythromycin on ventricular arrhythmias and ventricular repolarization in idiopathic long QT syndrome. Am J Cardiol 1987;59: 168-169.
39. Kilani F, Marsepoil T. Attack of torsades de pointes induced by an intravenous injection of erythromycin lactobionate [in French]. Ann Fr Anesth Reanim 1988;7:270-271.
40. Hummel JC, Haberer JP. Peroperative circulatory arrest after intravenous injection of erythromycin lactobionate [in French]. Ann Fr Anesth Reanim 1988;7:85-86.
41. Schoenenberger RA, Haefeli WE, Weiss P, Ritz RF. Association of intravenous erythromycin and potentially fatal ventricular tachycardia with Q-T prolongation (torsades de pointes). BMJ 1990;300: 1375-1376.
42. Lindsay J Jr, Smith MA, Light JA. Torsades de pointes associated with antimicrobial therapy for pneumonia. Chest 1990;98:222-223.
43. Benoit A, Bodiou C, Villain E, Bavoux F, Checoury A, Badoual J. QT prolongation and circulatory arrest after an injection of erythromycin in a newborn infant [in French]. Arch Fr Pediatr 1991;48:39-41.
44. de Koning J, van der Hoeven H, Hamer B, Thompson J. Erythromycininduced torsades de pointes and ventricular fibrillation in a patient with Legionella pneumonia. Neth J Med 1994;44:131-135.
45. Rezkalla MA, Pochop C. Erythromycin induced Torsades de Pointes: case report and review of the literature. S D J Med 1994;47: 161-164.
46. Brandriss MW, Richardson WS, Barold SS. Erythromycin-induced QT prolongation and polymorphic ventricular tachycardia (torsades de pointes): case report and review. Clin Infect Dis 1994; 18:995-998.
47. Tschida SJ, Guay DR, Straka RJ, Hoey LL, Johanning R, Vance-Bryan K. QTc-interval prolongation associated with slow intravenous erythromycin lactobionate infusions in critically ill patients: a prospective evaluation and review of the literature. Pharmacotherapy 1996;16:663-674.
48. Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. Am J Med 1989;86: 465-466.
49. Vogt AW, Zollo RA. Long Q-T syndrome associated with oral erythromycin used in preoperative bowel preparation. Anesth Analg 1997;85:1011-1013.
50. Lee KL, Jim M-H, Tang SC, Tai Y-T. QT prolongation and Torsades de Pointes associated with clarithromycin. Am J Med 1998;104: 395-396.
51. Hayashi Y, Ikeda U, Hashimoto T, Watanabe T, Mitsuhashi T, Shimada K. Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia. Pacing Clin Electrophysiol 1999;22:672-674.
52. Wasmer K, Hindricks G, Kottkamp H. Clarithromycin-assoziierte syncope als erstmanifestation eines angeborenen langen QT-syndromes? Intensivmed 1999;36:534-4.
53. Kamochi H, Nii T, Eguchi K, Mori T, Yamamoto A, Shimoda K, Ibaraki K. Clarithromycin associated with torsades de pointes. Jpn Circ J 1999; 63:421-422.
54. Hicks LA, Taylor TH Jr, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med 2013;368:1461-1462.
55. Granowitz EV, Tabor KJ, Kirchhoffer JB. Potentially fatal interaction between azithromycin and disopyramide. Pacing Clin Electrophysiol 2000;23:1433-1435.
56. Arellano-Rodrigo E, Garćia A, Mont L, RoquéM. Torsade de pointes and cardiorespiratory arrest induced by azithromycin in a patient with congenital long QT syndrome [in Spanish]. Med Clin (Barc) 2001;117: 118-119.
57. Samarendra P, Kumari S, Evans SJ, Sacchi TJ, Navarro V. QT prolongation associated with azithromycin/amiodarone combination. Pacing Clin Electrophysiol 2001;24:1572-1574.
58. Matsunaga N, Oki Y, Prigollini A. A case of QT-interval prolongation precipitated by azithromycin. N Z Med J 2003;116:U666.
59. Russo V, Puzio G, Siniscalchi N. Azithromycin-induced QT prolongation in elderly patient. Acta Biomed 2006;77:30-32.
60. Kim MH, Berkowitz C, Trohman RG. Polymorphic ventricular tachycardia with a normal QT interval following azithromycin. Pacing Clin Electrophysiol 2005;28:1221-1222.
61. Kezerashvili A, Khattak H, Barsky A, Nazari R, Fisher JD. Azithromycin as a cause of QT-interval prolongation and torsade de pointes in the absence of other known precipitating factors. J Interv Card Electrophysiol 2007;18:243-246.
62. Raschi E, Poluzzi E, Koci A, Moretti U, Sturkenboom M, De Ponti F. Macrolides and torsadogenic risk: emerging issues from the FDA pharmacovigilance database. J Pharmacovigilance 2013;1:104.
63. Justo D, Zeltser D. Torsades de pointes induced by antibiotics. Eur J Intern Med 2006;17:254-259.
64. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 2004;351:1089-1096.
65. Mosholder AD, Mathew J, Alexander JJ, Smith H, Nambiar S. Cardiovascular risks with azithromycin and other antibacterial drugs. N Engl J Med 2013;368:1665-1668.
66. Owens RC Jr. Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes. Pharmacotherapy 2001;21:301-319.
67. Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993;270:2590-2597.
68. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 1996;94: 1471-1474.
69. Drici MD, Knollmann BC, Wang WX, Woosley RL. Cardiac actions of erythromycin: influence of female sex. JAMA 1998;280:1774-1776.
70. Pham TV, Sosunov EA, Gainullin RZ, Danilo P Jr, Rosen MR. Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I(K)-blocking drugs. Circulation 2001;103:2207-2212.
71. Pham TV, Sosunov EA, Anyukhovsky EP, Danilo P Jr, Rosen MR. Testosterone diminishes the proarrhythmic effects of dofetilide in normal female rabbits. Circulation 2002;106:2132-2136.
72. Wu Y, Anderson ME. Reduced repolarization reserve in ventricular myocytes from female mice. Cardiovasc Res 2002;53:763-769.
73. Rautaharju PM, Zhou SH, Wong S, Calhoun HP, Berenson GS, Prineas R, Davignon A. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol 1992; 8:690-695.
74. Lehmann MH, Hardy S, Archibald D, Quart B, McNeil DJ. Sex difference in risk of torsade de pointes with d,l-sotalol. Circulation 1996;94:2534-2541
75. Svanström H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. N Engl J Med 2013;368:1704-1712.
76. Albert RK. "Lies, damned lies ..." and observational studies in comparative effectiveness research. Am J Respir Crit Care Med 2013;187:1173-1177.
77. Jespersen CM, Als-Nielsen B, Damgaard M, Hansen JF, Hansen S, Helo OH, Hildebrandt P, Hilden J, Hensen GB, Kastrup J, et al.; the CLARICOR Trial Group. Randomized placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ 2006;332:22-27.
78. Schembri S, Williamson PA, Short PM, Singanayagam A, Akram A, Taylor J, Singanayagam A, Hill AT, Chalmers JD. Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies. BMJ 2013;346:f1235.
79. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96:404-407.
80. Anderson JL, Muhlesstein JB, Carlquist J, Allen A, Trehan S, Nielson C, Hall S, Brady J, Egger M, Horne B, Lim T. Randomized secondary prevention trail of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumonia infection: the Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study. Circulation 1999;99:1540-1547.
81. Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B. Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes: the final report of the ROXIS Study. Eur Heart J 1999;20:121-127.
82. Sinisalo J, Mattila K, Valtonen V, Anttonen O, Juvonen J, Melin J, Vuorinen-Markkola H, Nieminen MS for the Clarithromycin in acute coronary syndrome patients in Finland (CLARIFY) Study Group. Effect of 3 months of antimicrobial treatment with clarithromycin in acute non-q-wave coronary syndrome. Circulation 2002;105: 1555-1560.
83. Stone AFM, Mendall MA, Kaski J-C, Edger TM, Risley P, Poloniecki J, Camm AJ, Northfield TC. Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA). Circulation 2002;106:1219-1223.
84. Zahn R, Schneider S, Frilling B, Seidl K, Tebbe U, Weber M, Gottwik M, Altmann E, Seidel F, Rox J, et al.; Working Group of Leading Hospital Cardiologists. Antibiotic therapy after acute myocardial infarction: a prospective randomized study. Circulation 2003;107:1253-1259.
85. Cercek B, Shah PK, Noc M, Zahger D, Zeymer U, Matetzky S, Maurer G, Mahrer PK; AZACS Investigators. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet 2003; 361:809-813.
86. O'Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD; Investigators in the WIZARD Study. Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA 2003;290:1459-1466.
87. Leowattana W, Bhuripanyo K, Singhaviranon L, Akaniroj S, Mahanonda N, Samranthin M, Pokum S. Roxithromycin in prevention of acute coronary syndrome associated with Chlamydia pneumoniae infection: a randomized placebo controlled trial. J Med Assoc Thai 2001;84:S669-S675.
88. Berg HF, Maraha B, Scheffer G-J, Quarles-van Ufford M, Vandenbroucke-Grauls CM, Peeters MF, Kluytmans JA. Treatment with clarithromycin prior to coronary artery bypass graft surgery does not prevent subsequent cardiac events. Clin Infect Dis 2005;40: 358-365.
89. Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, et al.; ACES Investigators. Azithromycin for the secondary prevention of coronary events. N Engl J Med 2005;352:1637-1645.
90. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JAD Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, et al.; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-698.