@PFIZE®baba
Pathophysiological Basis and Rationale for Early
Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection
Peter A.McCulloughMD,
MPHabc
Ronan
J.KellyMDaGaetanoRuoccoMDdEdgarLermaMDeJamesTumlinMDfKevin
R.WheelanMDabcNevinKatzMDgNorman
E.LeporMDhKrisVijayMDiHarveyCarterMDjBhupinderSinghMDkSean
P.McCulloughBSlBrijesh
K.BhambiMDmAlbertoPalazzuoliMD,
PhDnGaetano
M.De FerrariMD, PhDoGregory
P.MilliganMD, MPHaTaimurSafderMD,
MPHaKristen
M.TecsonPhDb…Harvey A.RischMD, PhDq
The American Journal of Medicine
Volume 134, Issue 1, January 2021, Pages 16-22
Azithromycin
Azithromycin is a commonly used macrolide
antibiotic that has antiviral properties mainly attributed to reduced endosomal
transfer of virions as well as established anti-inflammatory effects.27 It has been commonly used in
COVID-19 studies initially based on French reports demonstrating markedly
reduced durations of viral shedding, fewer hospitalizations, and reduced
mortality combination with HCQ as compared to those untreated.28,29 In the large inpatient study
(n = 2451) discussed previously, those who received azithromycin
alone had an adjusted HR for mortality of 1.05, 95% CI 0.68-1.62, and P = 0.83.23 The combination of HCQ and
azithromycin has been used as standard of care in other contexts as a standard
of care in more than 300,000 older adults with multiple comorbidities.30 This agent is
well-tolerated and like HCQ can prolong the QTc in <1% of patients. The same
safety precautions for HCQ listed previously could be extended to azithromycin
with or without HCQ. Azithromycin
provides additional coverage of bacterial upper respiratory pathogens that
could potentially play a role in concurrent or secondary infection. Thus, this
agent can serve as a safety net for patients with COVID-19 against clinical
failure of the bacterial component of community-acquired pneumonia.31,32 The same
safety precautions for HCQ could be extended to azithromycin with or without
HCQ. Because both HCQ and azithromycin have small but potentially additive
risks of QTc prolongation, patients with known or suspected arrhythmias or
taking contraindicated medications or should have more thorough workup (eg,
review of baseline electrocardiogram, imaging studies, etc.) before receiving
these 2 together. One of many dosing schemes is 250 mg po bid for 5 days and
may extend to 30 days for persistent symptoms or evidence of bacterial
superinfection.