An article in the New York Times yesterday gave a face to a controversial treatment for COVID-19 that’s been the stuff of rumors for weeks https://www.nytimes.com/2020/04/02/technology/doctor-zelenko-coronavirus-drugs.html. Dr. Zev Zelenko, primary care doctor to his community of 35,000 Hadassic Jews in Kiryas Joel, about an hour’s drive from Manhattan, has been treating even mild cases with not only Plaquenil, but adding in zinc supplements and azithromycin (the stuff in your Z-Pac). Now doctors have been giving Z-Pacs to their patients with viral infections for years. Thought leaders in infectious disease warn against the practice, as the drug has no anti-viral activity and indiscriminate antibiotic use can spread drug resistance. Zinc is harmless, competes with viruses in some of the host proteins they try to hijack, and zinc lozenges are a staple in my medicine cabinet to pop in at the first sign of a scratchy throat.
Azithromycin is a popular, well known and well-studied antibiotic. It was derived from erythromycin, another antibiotic in the macrolide class. It prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome and thus does not let bacterial messenger RNA latch on to the ribosmome and tell various amino acids to start hooking together into a new protein. Macrolides have also been shown to have immune-modulating and anti-inflammatory effects. Morbidity and mortality caused by respiratory viral infections is associated more with an overexuberant host response, with the excessive elaboration of cytokines and immunopathologic host inflammatory responses, than with direct effects of the virus. Pre-clinical and clinical studies have shown that macrolides diminish the inflammatory response, attenuating extreme cytokine production and promote the induction of immune protein antibodies which may reduce the complications of respiratory viral infections. Given these properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, fidaxomicin, telithromycin) have been studied for their potential use as targeted therapy for a wide spectrum of viral respiratory infections including influenza. Results from studies in these various diseases have been mixed. There seems to be a positive influence on the course of kids with flu or respiratory syncytial virus (RSV, a common cause of pneumonia in kids), but not on adults with flu.
In the 2012 MERS epidemic in Saudi Arabia, caused by a coronavirus 87% identical to COVID-19, doctors used a lot of azithromycin, but in no consistent manner. In a paper published just last year, 26 authors in service to the Saudi Clinical Trials Group looked back on outcomes of 349 critically ill MERS patients, which included 136 who had received macrolides (azithromycin the most common, used in 72%). The group could find no evidence that antibiotics reduced 90 day mortality or shortened the duration that virus was shed by the patients.
While these results seem to put a damper on any enthusiasm for azithromycin in COVID-19, realize the Saudi patients were critically ill, and that might get a COVID-19 patient high dose steroids or even an interleukin-6 inhibitor, like Actemra. Dr. Zelenko’s patients weren’t nearly as sick, and no doubt were grateful for any shortening of symptoms they thought his treatment was providing. Did he keep some out of the ICU? With the large population of new infected patients, a proper trial comparing Plaquenil alone to Plaquenil plus a Z-Pac, with monitoring of viral shedding as well as symptoms, seems eminently doable, especially with our huge medical research infrastructure. Let’s get to it, Dr. Fauci!
PS. Why not? Here’s the list of azithromycin side effects from one of the articles below: anorexia, dyspepsia, flatulence, dizziness, headache, drowsiness, convulsions, arthralgia, and disturbances in taste and smell; rarely constipation, hepatitis, hepatic failure, syncope, insomnia, agitation, anxiety, asthenia, paraesthesia, hyperactivity, thrombocytopenia, hemolytic anemia, interstitial nephritis, acute renal failure, photosensitivity, tooth and tongue discoloration
Bakheit AH, Al-Hadiya BM, Abd-Elgalil AA.. Azithromycin. Profiles Drug Subst Excip Relat Methodol. 2014;39:1-40. doi: 10.1016/B978-0-12-800173-8.00001-5.
Arabi YM, Deeb AM, Al-Hameed F, Mandourah Y, Almekhlafi GA, Sindi AA, Al-Omari A, Shalhoub S, Mady A, Alraddadi B, Almotairi A, Al Khatib K, Abdulmomen A, Qushmaq I, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Al Harthy A, Kharaba A, Jose J, Dabbagh T, Fowler RA, Balkhy HH, Merson L, Hayden FG; Saudi Critical Care Trials group. Macrolides in critically ill patients with Middle East Respiratory Syndrome. Int J Infect Dis. 2019 Apr;81:184-190. doi: 10.1016/j.ijid.2019.01.041. Epub 2019 Jan 25.