Infection indication and severity

To the editor:

We read with great interest a recent study that investigated the association between the use of azithromycin and the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure.¹ Based on the findings of 2 cohort studies, azithromycin versus amoxicillin-based antibiotic (amoxicillin, amoxicillin/clavulanic acid) was associated with a higher risk of sudden cardiac death but azithromycin versus levofloxacin was associated with a lower risk of sudden cardiac death. Although many confounding factors have been adjusted in this study, we have a serious concern about the confounding effect of infection indication and severity.

First, although these 3 comparators—azithromycin, amoxicillin-based antibiotic, and levofloxacin—are commonly used in the treatment of lower respiratory tract infection and pneumonia, they have many other infection indications. In addition to respiratory tract infection, azithromycin can be indicated in skin infections, ear infections, eye infections, and sexually transmitted diseases. Similarly, amoxicillin is also indicated in the bacterial infection involving the ear, nose, throat, genitourinary tract, skin, and skin structure. However, the risk of sudden cardiac death could be different according to the site of infections. Therefore, the role of infection indication should be clarified.

Second, the severity of infection is an important factor for clinicians to select the appropriate antibiotics. For example, the severity of infection of patients receiving amoxicillin and clavulanic acid would be more complicated than those receiving amoxicillin. Similarly, the infection severity and complexity can be different between azithromycin and levofloxacin users. A further randomized controlled trial is warranted to clarify these issues.