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Oral Antibiotics

Mechanisms of resistance. The mechanism we are all used to and have thinking about for a couple of decades are the beta-lactamases, but there are actually over 150 beta-lactamases, so when somebody comes in and tells you they’ve got a beta-lactamase stable drug, you’ve got to know to which beta-lactamase. The folic acid pathway enzyme mutations are the ones where the sulfa drugs and trimethoprim have suffered recently and pneumococcus has acquired one of these recently. And that’s made pneumococcus again another level harder to treat. These are kind of cool things. Efflux pumps. For all of you who live in low-lying areas.

Now there’s this thing called porin mutants and porins are those little channels in the cell wall and sometimes in the membrane that the bacteria use to flush things in and out. A way to get nutrients in and bad things out. They are supposed to be a certain size, and the mutants are ones in which those porins have been shrunk down.

We also know that there are no penicillin-resistant group A streptococci. If you find one, let me know, we’ll be famous. Everybody’s looking for one, nobody has found one. But what we know is that if you compare the MIC, the least amount of drug it takes the bug from growing - minimum inhibitory concentration - we know that it now.

Then there is this thing called the eagle effect. The eagle effect is a point in which gram-positives - and particularly staph aureus and group A strep - if they get into a pocket where the pH is low and there is a lot of their own.

Now what about erythromycin? Well erythromycin resistance is not as big a problem in the United States, in fact it’s very very rare. But if you have patients who travel, especially to the Far East or to certain parts of Europe.

The toxin producers. It tends to follow varicella, that’s the flesh-eating bacteria. One of the key things you probably know and have heard, is that if it looks very red and it’s tender out of proportion to what you would expect for what it looks like - I mean, they have this exquisite tenderness - that’s probably a hypertoxin producer and that’s the one you want to worry about developing either shock or necrotizing fasciitis from. They also can occur after trauma, so the car accident where they have tissue damage, or burns and other tissue damage.

Staph aureus. What about what a can of worms. Everywhere you look for it you seem to find it. It’s actually normal to have it in your nose, your throat and in your conjunctiva. You will also carry it on your skin for up to 3 to 5 months after you’ve had a pyoderma. So just finding it there doesn’t mean it’s a pathogen.

Now there’s this VIRSA thing that you probably … there was a little blurb about three or four months ago about the vancomycin intermediately resistant staph aureus because if staph aureus becomes resistant to methicillin and vancomycin, we have not a lot of tools left. This would put us back in the 20’s as far as trying to treat staph aureus and that would be devastating. There have only been four isolates. Most of them have been east of the Mississippi. There have been those ones up around Wisconsin and then a couple on the East Coast. It turns out that these, even though they were intermediately resistant to vancomycin and were resistant to methicillin, were actually susceptible to things like doxycycline and chloramphenicol.

One of the problems with that is that we can’t get rid of this with antibiotics. It’s not like H. flu B or meningococcus. You give them rifampin, you get rid of it. Group A streptococcal carriage, you can eradicate it a lot of times with clindamycin or with dicloxacillin. We can’t do that with this. In fact, the more antibiotics we use the more persistent is the drug resistant pneumococcus in the nasopharynx. The only way to get rid of it is to have them off antibiotics for two to three months. It doesn’t compete well with wild-type pneumococcus so if we knock off normal pneumococcus then this one fills the niche. So what it takes is for us to be helping it along. One of the things that people ask is, "Well, why did we have antibiotics for 30 years, even 40 years, before drug resistant pneumococcus appeared? What happened in the 90’s to make this happen?"

We talked about the penicillin-binding proteins being the alteration and it happens quite frequently. And it’s not just the penicillin’s it affects. It affects the cephalosporins too. You can tell what we are saying here about the ribosomal mutants, efflux pump, folic acid enzyme mutants, all of the above, pneumococcus is acquiring genes rapidly.

What about E. coli? E. coli is normal flora in like everybody. So having it is not a problem, but we know that beta-lactamase production is increasing and it runs around 40% to 50% here in Omaha, 60% nationally. So that’s why amoxicillin is not the drug of choice for UTI’s. The folic acid mutants are up to 20% nationally.

The 0157 strain is still … you know, here in Nebraska where they shut down whole factories and whole towns because of this stuff. So it’s become a big problem around here. Remember the 0157 strain is acquired by a lot more people than get disease and not everybody who gets the disease gets the hemolytic uremic syndrome.

Group A streptococcus, ten times more penicillin to kill it. Non type-able H. flu, is twice as much to that group on there. Pneumococcus, two to four times more penicillin and amoxicillin to kill it. All the p.o. cephalosporins and Bactrim, all the macrolides and now clindamycin is staring to take a hit, which was our ace in the hole until recently.

So that’s the template that we are going on to use the different drugs, and as you can tell, Ceclor is not a medal winner. It has problems. While it tastes good - and I have families who are emotionally attached to this drug - it is not a very effective drug. It’s sort of a drug we used up. It was great in the 70’s, okay in the 80’s and it’s terrible in the 90’s. It’s a drug whose time has passed. It’s a problem also that there’s this little tiny serum sickness-like thing.

If we then look at Keflex, which is next. This is sort of a bronze medal. It’s a low potency. It’s mostly a gram-positive drug. It doesn’t cost very much. It’s got a couple of cousins there; cefadroxil and cephradine, which we know as Duricef and Velosef. You can see it’s a real strong gram-positive one.

What about erythromycin? Another bronze medal winner. Low potency, a little more expensive than Keflex. I like the estolate version which, if you take care of a lot of adults, you know there’s this caveat in all the books.

Bactrim, trimethoprim sulfa, also known as Septra or Cotrim. A bronze medal winner. Low potency. Used to be mid, now it’s low. Very inexpensive though. Remember, no group A streptococcal coverage. Here’s this drug resistant pneumococcal coverage, like nil. And what’s been a problem is that we only now get 70% of drug susceptible pneumococcus. So if Bactrim is starting to fail in your community when you are treating sinusitis, otitis.

Doxycycline, Vibramycin. This is sort of the original azithromycin, if you think about it. Twice a day for the first day and then one a day for five to ten days thereafter. It’s a user-friendly drug. It’s low potency and not very expensive.

What about Pediazole? Well, Pediazole is low to mid potency because you are kind of throwing two drug classes together here. It is a middle-weight as far as both potency and as far as cost, and you can see it’s sort of an up.

Amoxicillin. Amoxicillin is a gold medal winner. Why is it a gold medal winner? It’s a low to mid potency - and you are thinking, mid? How did it get to be mid potency? Well, what makes it mid potency is its activity against drug resistant pneumococcus. It is the most potent oral drug, except for trovafloxacin, against drug resistant.

What about clarithromycin? Clarithromycin is a drug we thought was going to be the home run drug, the gold medal winner of the macrolides and it held up for about six months and then it’s been dropping ever since. As you can see

Azithromycin is the better Biaxin. It tastes better. Less doses, less GI side effects. Basically the same profile except a little better against H. flu. So if you are going to use one of the new macrolides, this is the one I would use. Now

This is cefprozil, in it’s old form, BMY against Augmentin in the red box, in the middle - is the one I want you to focus on - those are the failures at two weeks and we found that there was a lot of failures with it back when we did

Loracarbef, son of Ceclor, is also a bronze medal winner, but for different reasons. This one is a better gram negative than gram positive. You can see the staph aureus, not much activity. Drug resistant pneumococcus, basically none. So this is better for the H. flu’s over there and group A strep and penicillin susceptible pneumococcus. So why would you use this drug? It’s one of the really good-tasting drugs out there. It is once or

If we then go to cefixime or Suprax, this is predominantly a gram negative drug. See how all the big bars are over here on that other side. No drug resistant pneumococcal coverage, no staph aureus coverage, not even great drug susceptible pneumococcal coverage. So if you are thinking gram negatives, this is a good drug. Think of it almost

Ceftibuten, Cedax is Suprax part deux. Same things I just said all over again. Almost exactly. Which ever one is cheapest, use it. Same dose, same side effects, same good effects.

Cefuroxime axetil, Ceftin. What do two names on an antibiotic mean? Well, expensive, that’s true. The other thing it

Cefpodoxime proxetil, two names. Much the same thing. It tastes a little less worse and it had a little better pneumococcal coverage. So if you are going to use one of the bad-tasting twins, this tends to be the one that

Amoxicillin, clavulanic acid, Augmentin, the new 7:1 ratio. The 4:1 ratio has no utility except when you want to use real high dose amoxicillin. There’s this trick of using 0500 amoxicillin clavulanic acid tablet with a 500 regular

Quinolones can be cheap, Cipro expensive, trovafloxacin, mid to high potency, so you’ve got mixed medals up here. The taste can be … it’s really not an issue most of the time because they are almost all in tablet form. The doses are easy most of the time. Not many side effects and when do we use them? The different bars are whether you are in first or second generation ciprofloxacin kind of drugs, with quinolones on the bottom bars. The second bar on top is if you go to the levo or trovafloxacin later generation cephalosporins, you get a lot better gram positive coverage. But they all have very good gram negative coverage and I think that the things we think about, ciprofloxacin is still good for UTI’s, occasionally for the chronic draining otitis that has those gram negatives in it, and for people who come back from Mexico and can’t take Bactrim for their turista, this is a good drug. The ofloxacin, levofloxacin, trovafloxacin, have the same kind of indications but add the fact that they work well against sinusitis and LRI’s because they bring back some of that gram positive pneumococcal coverage you didn’t have.

Ceftriaxone is not only an old drug but has been used a lot in the outpatient arena and the main thing I want you to focus on is the drug resistant pneumococcus, that bar fourth over from the end. And you can see there’s a one and a