Estimated cardiac risk associated with macrolides and fluoroquinolones decrease substantially when adjusted for patient characteristics

18 July, 2018

Researchers at the University of Iowa discovered a decrease in cardiac risk associated with macrolides and fluoroquinolones – when underlying patient characteristics and conditions related to the indication of these antimicrobials were taken into consideration.1


Macrolides and fluoroquinolones are commonly prescribed for respiratory tract infections and community-acquired pneumonia; however, recent studies have raised concerns about negative cardiac outcomes associated with their use. For instance, patients with infections of the ear, nose or throat, and bronchitis, treated with azithromycin had an increased risk of cardiovascular death compared with those treated with amoxicillin.2 In another study, increased cardiac arrhythmia and mortality were observed with macrolides and fluoroquinolones when compared with amoxicillin-clavulanate.3 These findings may be attributable to omitted variable bias ie, failing to account for both the antimicrobial indications and the patients’ characteristics – thus suggesting an association between increased cardiac risk and the antimicrobial agent itself.1


The current study shows a reduced risk of cardiac events associated with the use of macrolides and fluoroquinolones when adjusted for comorbidities and patient demographics. For levofloxacin, the unadjusted odds ratio for any cardiac event or death was 2.18 (p<0.0001) versus the adjusted odds ratio of 0.87 (p<0.0001).1 The adjusted analyses in this study were controlled for a wide range of patient and environmental covariates including the national rate of influenza-like illness due to inappropriate antimicrobial treatment and association with cardiac events; the patient’s total inpatient and outpatient visits which reflect the patient’s health; common indications for antimicrobial, eg pneumonia, urinary tract infection, and chronic obstructive pulmonary disease; patient demographics including age, sex, and race; and, pre-index and at-index comorbidities.1


The adjusted analyses also demonstrated that both macrolides and fluoroquinolones were associated with reduction in the risk of any-cause death – which may be a result of healthier patients being more proactive in pursuing antimicrobial treatment, and so their risk of death is relatively lower than their sicker counterparts.1 Besides, prescriptions of macrolides and fluoroquinolones may be predictive of cardiac events in hospitalised patients with pneumonia.4-6 Antimicrobials are also frequently prescribed inappropriately for acute respiratory tract infections – in particular influenza –7 which is thought to be a risk factor for acute myocardial infarction.8,9


The cohort is composed of acute myocardial infarction patients only – thus the findings of this study may not be generalisable to other populations; nevertheless, the authors concluded that the risk of cardiac events is most likely associated with underlying patient factors and the indications of antimicrobials, rather than because of the direct effects of macrolides and fluoroquinolones.1 The authors also suggest weighing the immediate benefits of the antimicrobials against the potential risks when prescribing.



Estimated cardiac risk associated with macrolides and fluoroquinolones decreases substantially when adjusting for patient characteristics and comorbidities.

PMID: 29680825

DOI: 10.1161/JAHA.117.008074



  1. Polgreen LA, et al. J Am Heart Assoc 2018;7: e008074.
  2. Ray WA, et al. N Engl J Med 2012;366:1881-1890.
  3. Chou HW, et al. Clin Infect Dis 2015;60:566-577.
  4. Musher DM, et al. Clin Infect Dis 2007;45:158-165.
  5. Perry TW, et al. Am J Med 2011;124:244-251.
  6. Aliberti S, et al. ERJ Open Res 2015;1:00020-2015.
  7. Grijalva CG, et al. JAMA 2009;302:758-766.
  8. Foster ED, et al. Epidemiol Infect 2013;141:735-744.
  9. Pearce DC, et al. Environ Res 2017;156:688-696.