What is Dr. Green’s rationale for Z-pak/azithromycin over other antibiotics? Seems dangerous!

As title. Does anyone happen to know? Z-pak is a P-gp/ABCB1 Inhibitor which doesn’t really make sense to me and elevated sirolimus concentration (apparently takes 20 mg sometimes, which may increase ~4.2 fold) with a need for the ED to hold nirmatrelvir/ritonavir in case of COVID-19 with superimposed bacterial pneumonia doesn’t make sense.

Closest human data I am seeing:
“Erythromycin: Erythromycin is a substrate and inhibitor of CYP3A4 and P-gp;
co-administration of sirolimus oral solution or tablets and erythromycin is not recommended
[see Warnings and Precautions (5.17), Drug Interactions (7.2)]. The simultaneous oral
administration of 2 mg daily of sirolimus oral solution and 800 mg q 8h of erythromycin as
erythromycin ethylsuccinate tablets at steady state to 24 healthy volunteers significantly
affected the bioavailability of sirolimus and erythromycin. Sirolimus Cmax and AUC were
increased 4.4- and 4.2-fold respectively and tmax was increased by 0.4 hr. Erythromycin Cmax
and AUC were increased 1.6- and 1.7-fold, respectively, and tmax was increased by 0.3 hr.”

Rapa and Z-pak both may QT prolong which may lead to deadly torsades

Personally, I use a potential anti-tumor Doxy cocktail of my own right now in case of bacterial infections, but so far haven’t used it yet for years. It’s also the empiric antibiotic of choice in my geographical area for respiratory pneumonia for my situation that doesn’t look viral, and also accounting for the experimental vaccines I took.

Note that empiric antibiotics require a physician to determine because they are often highly situation-specific (i.e. likely UTIs in canagliflozin in T2D require very different things than sepsis in different geographical areas) and antibiotic stewardship is necessary. This is not medical advice.

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I agree. Doesn’t make alot of sense to me either especially for skin infections. I also prefer either doxycycline or cephalexin.


Wow, this seems quite the contraindication use.

Can you suggest something mainstream to use instead? Do we wait for swab lab results re bacteria type, and then consider choice?

You have to remember that a prolonged QT doesn’t mean that you’ll get a serious arrhythmia. It’s just a risk factor.

It’s usually not practical to wait for culture results, though sometimes it is, but there’s numerous options . Personally, I almost never take them.

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I normally don’t either, but I’m asking in the context of high dose rapamycin and suppressed (theoretical) immuno? Especially maybe older folks?

That’s true.

I would also add it is possible people are taking things like grapefruit which further increases high drug doses and direct inhibition of IKr channels. Or because of a positive COVID test they may be taking HCQ/CQ. Hypokalemia and hypomagnesemia can be secondary to infection and dehydration. (COVID has hyper activated RAAS on top of that.)

As for some people here, they often have FHx of heart disease or already heart disease on diuretics. Older folks also have higher susceptibility generally.

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I have a few guesses.

Dr. Green may be old school.

As a pathologist he understands things way beyond my lane of medicine - but pathologist do not usually practice in a clinical setting.

Z-pack in general are a decent choice for travel and have broad coverage when a possible atypical infection is involved, but have become an overused go-to antibiotic for years.

All of Dr Tongs points are valid, but most medications have some type of interactions - so clarifying the degree of interaction is helpful otherwise we would never Rx anything:)

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Yes, agree. Skin is usually staph or strep and both of your suggestions or PCN’s should cover and not interact. Z-pack does seem an odd choice. @tongMD


I use topical mupirocin bid 5 days personally in skin things like limited impetigo/MRSA nares based on my geography and individual situation. I also nose breathe, mask, and some other maneuvers to keep any possible bacteria infection at bay without a bias toward interventionism. I’m quite surprised there is so little quality information on immunology/infectious disease out there despite a literal COVID-19 pandemic for 2 years.

No need to go systemic in many scenarios if you include experimental vaccines (mostly viral stuff but also somewhat uncommon stuff like GBS bacteremia that already show potential efficacy) and take care of possible sites of entry and identify any possibilities quickly.

I’d also clarify that it’s not just a minor drug-drug interaction as per the FDA label - it warrants therapy modification in most scenarios not just monitoring therapy, especially with Dr. G’s older age patient group prone to QTC prolongation. I want to give Dr. G the benefit of the doubt with proper due diligence first, but I couldn’t find his reasoning. I found it rather alarming that nobody mentioned these risks ever by sitting down and breaking down the entire claim and intervention risks, despite Dr. G stating bacterial infection is the biggest risk. Any rational risk manager would start with that evaluating that risk first.