Are there sever side effect to this? If not, what is there to lose in dosing up with this if it can get that sepsis or that storm.
Yes, there are severe side effects especially from a hydrochloraquine/Azithromycin combination.
The difficulties here is that these studies that are not controlled and blinded, show increased clearance of the virus. However this does not necessarily mean the prognosis will improve.
The problem is the cytokine storm that we see in severe insults. This seems to be a patient idiosyncratic response. Given equivalent insults some patients react in this way and some do not. It is an uncontrolled response. Once unleashed it seems to have to run its course. So once there is widespread capillary damage and protein leaks out in to the instersitium and especially the alveolar air sacks it drags fluid with it, which attracts further fluid.
So if you get a patient going into sepsis your best hope is administering antibiotics early, before this process gets a full head of steam.
So my question would be how early in infections with Covid 19 do you have to administer these drugs? I would bet more likely than not you would have to get in early.
Now Plaquenil, which is hydrochloroquine, is an anti malarial. It is also used as a remitive agent in RA, Lupus and some other autoimmune diseases.
Now the drug is usually administrated orally. The creates a problem in a critically ill patient because of unreliable adsorption. There is an IV version for malarial crises, but I would bet that is in extremely limited supply and hard to ramp up quickly. The other problem is that this drug has a long half life. So if you get into trouble it will be with you for a while. After IV injection the half life is 40 hours. It takes five and a half half lives for a drug to clear. So that is 220 hours! The major side effect in chronic use is macular damage in the eye. It does however have a nasty side effect that we don't like, especially in the ICU. It prolongs the QT interval. This means it slows cardiac repolarization. This can produce a multifocal ventricular tachycardia known as Torsades de Pointes. This quickly degenerates into ventricular fibrillation which is cardiac arrest. The drug can also lead to prolonged PR interval leading to heart block and the need for emergency pacing.
Now Azithromycin is a macrolide antibiotic. I would not really call it broad spectrum. It does have activity against a great many gram positive organisms and is not active against gram negative organisms. Its main use is against atypicals, especially mycoplasma, Legionnaires disease and some atypical mycobacteria .
Now if it should prove to be synergistic to treat Covid 19 with hydrochloroquine, then there is a problem, as the biggest problem with azithromycin is prolonged QT interval. Having two drugs on board that prolong the QT interval is highly problematic.
So this would not be a combination to use in a sick patient unless you had pretty good evidence of efficacy. It is definitely not a case of you might as well use it as it won't do any harm. It could actually do a lot of harm and increase mortality. So even in these desperate situations I fear we have to tread with a degree of caution.
Lastly open label unblinded trials have a history of being misleading. So some form of blinded trial should show efficacy before this is widely recommended. If it is really any good it will not require many cases under rigid trial conditions to show efficacy in improved outcomes. The more marginally effective it is the more cases will be required to show significant benefit. Unless the benefit is really and practically significant, then this combination of drugs will likely not justify the toxicity.
Lastly just showing increased viral clearance does not mean that has to translate to improved outcome. In order to recommend this be used we need to demonstrate reduced ventilator requirement and improved survival.
