I think you understand pretty well. Think of a small boat on the ocean. The boat is the bacterial cell and the ocean waves represent the antibiotic. If the waves are throwing water into the boat, you begin to bail. As long as you bail the water out faster than it is coming in, you stay afloat. If on the other hand the water(antibiotic) comes in faster than you can bail, you sink.
Hope that isn't too cheesy.
Honestly, A message Board is the last place I would worry about being popular. I speak what I believe to be the truth. If it popular, great. If it isn't, I'll take that too. Your honesty and integrety arethe few things a man has to standon.
A couple of issues in favor of Zithromax. As much of 70% of all antibiotics are written unnecessarily. Dr's are writing to satisfy patients perceptions. People go to the doctor, they don't feel well, they take off from work, wait an hour after their appointment to get out of the waiting room, spend another hour waiting for the physician and the last thing they want to hear is " You have a virus and an antibiotic won't help." If the physician doesn't write something, they leave and find a doctor who will. In this day and age of managed care, doctors must keep their patients happy. Sad but true.
Secondly, Zithromax is also indicated and written for Clamydia infections. Actually, this is one place where it does work well.
There is also chemical modification of macrolide within cell. I don't know the prevalence of this type of resistance.
The reason that bacteria with macrolide efflux pump remain susceptible in clinical setting may be related, as you state, to large amount of drug outside cell. The passive movement assisted by the binding affinity of the ribosomes may be exceeding the capacity of the pump to expell the drug.
Stop.... I should have added a ;) or something. It's hard to joke on a message board. My typing skills are much worse than yours. I have to look at the keyboard while I'm typing. Unless I reread everything I type, I KNOW it has spelling errors.
And just for the record. I am not a researcher even though I have done reseach. UTHSC in Houston, Southwestern Medical Center in Dallas and University of Louisville Medical School in Louisville, KY. I just try to sound like I know more than I do.
I'm not sure that Zithromax is losing favor with M.D.s. Calhoun obviously knows more about this stuff than I do. But my daughter works in a retail pharmacy and they sell it by the truckload. She said it outsells Biaxin about 20 to 1 when I asked her tonight. Granted, it's a local situation, but I don't think the ABT market share against Zithromax has improved. If it had, Abbott, PPD would be stronger. I know the past couple flu seasons have been mild and that's hurt Biaxin. But I'd like more than a generalization from Calhoun that Zithromax is losing business. I don't hear that and I know some people at Abbott PPD.
Welcome to the board. I think you've been here before. Anyway, I stand corrected on the hospital treatment with quinolones vs Biaxin. A few years back ABT was trying to fight a losing battle with quinolones as second line of defense against susceptible pathogens. They were pushing favorable data for Biaxin vs quinolones. I thought then that the data was in a hospital setting.
I mentioned macrolide accumulation in host cells without getting technical. Macrolides, especially Zithromax, do rapidly accumulate in susceptable bacteria due to the ribosomes to which they bind. Ribosome mediated accumulation rates depend upon binding rates and Zithro is tighter binder for some bacterial ribosomes.
I was aware of the Biaxin metabolite and the fact that Zithromax is not found in interstitial tissue. I was not aware that Zithro was losing favor with MD's. Thanks for the insite.
AS soon as I correct all your spelling mistakes. Besides, it isn't as difficult as you seem to want to make it sound.
There are 2 types of resistance tomacrolides. 1) Efflux, which is a proton pump, which removes an antibiotic out of the cell before it has a chnce to work; and 2)Taarget Site Modification,in which there is an actual physical change in the target site due to a mutation in the genomic sequence.
Resistance studies will show Efflux pump type resistant strains as resistant, even though in a clinical setting Biaxins concentrations are high enough at the site of infection(i.e. ELF, bronchialmucosa, etc...) to overcome it. That becomes what is known as the In Vitro/In Vivo Parodox. In Vitro studies do not always coorelate with In Vivo studies.
It really doesn't require two people trying to actlike theyknow more than they really do.