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PURPOSE Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODSWe studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days.RESULTS During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82).CONCLUSIONS Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period. Ann Fam Med 2014;12:121-127. doi: 10.1370/afm.1601. INTRODUCTIONA zithromycin is a macrolide antibiotic commonly prescribed for outpatient treatment of respiratory infections, urinary tract infections, and sexually transmitted diseases.1 Macrolide antibiotics, primarily erythromycin and clarithromycin, are known to increase cardiac arrhythmogenic risks, including QT interval prolongation, torsades de pointes, and polymorphic ventricular tachycardia.2 Between 2001 and 2007, case reports described arrhythmias among persons receiving azithromycin. [3][4][5][6][7] In 2012, Ray et al 8 reported increased risks of cardiovascular death and all-cause mortality among adult, predominantly female, Medicaid patients in Tennessee who received azithromycin compared with amoxicillin, particularly among those with a high baseline risk for cardiovascular disease. Subsequently, the Food and Drug Administration (FDA) 10 and pharmaceutical manufacturer issued public safety notifications warning of QT prolongation risks with azithromycin. Researchers from Denmark then reported that in comparison with penicillin V, azi...

Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia/eclampsia was significantly associated with greater odds of ASD (OR = 1.85, p < .0001 without controlling for birth weight; OR = 1.69, p = .0005, when controlling for birth weight). We conclude that reduced birth weight partially mediates the association between pre-eclampsia/eclampsia and ASD. Additional research is needed to investigate the potential mechanism(s) by which pre-eclampsia/eclampsia may influence ASD risk.

Maternal GU infection appeared to be associated with increased risk of ADHD, and based on the findings it was concluded that further research is needed to describe the mechanism(s) underlying the association.