Antibiotics 3.

Dirithromycin was marketed a year or so ago as Dynabac. The advantage here is that it can be given once a day. It has uses in adverse reactions like erythromycin but it is more expensive. So if once a day dosing is that advantageous, this product might be useful.

The other macrolide antibiotics include azithromycin or Zithromax and clarithromycin or Biaxin. We will first talk about azithromycin. This comes both orally and parenterally. It is used once a day. It does have greater Gram negative coverage than erythromycin. It can be useful especially in things like chlamydia and Mycoplasma where erythromycin can’t be used. In many community acquired pneumonias and in weekly HIV MAC prophylaxis. Be aware that food does inhibit absorption of Zithromax and it probably should be prescribed between meals.

Clarithromycin or Biaxin probably got a jump on erythromycin in terms of its clinical acceptance. Compared with Zithromax or azithromycin, though, it’s given twice a day versus once a day. It can be given with food, though, so you don’t have that caution. It may be useful in some skin and soft tissue infections and in some other infections like M. avium and for eradication of H. pylori combined with several other drugs.

Be aware, though, that the suspension of this product first of all should not be refrigerated. The common mental set that we have is that if you have a liquid antibiotic it should be kept in the refrigerator. There are two problems with that with Biaxin. It destabilizes the drug and it makes it taste worse. It tastes bad. It has a grainy consistency and despite attempts by the manufacturer, it still doesn’t taste very good. I would encourage you to get a sample of this stuff and taste it before you prescribe an awful lot of it.

Chloramphenicol is a drug that hopefully you don’t prescribe very much unless you’re practicing outside the United States. It is a drug that occasionally may be useful. For example, it’s an alternative drug for treating meningitis. In the rare case where you would have a cephalosporin treatment failure, it is a good drug in that even with oral dosage forms you can get fairly high levels in almost every tissue space. It does have a reasonably broad spectrum of activity and this is a drug that you might be able to use in situations where you don’t have venous access. For example, if you were doing missionary work or something like that in the back country and don’t have venous access readily available, here is one that you can give orally and get some pretty profound effects. Be aware though that it can cause an idiosyncratic aplastic anemia with the first dose. There is also dose related bone marrow suppression so it should not be used long term.

Tetracyclines similarly have been around forever. The uses are numerous. They can be useful in Gram negative bacillary infections, for Rickettsial infections. For Lyme disease, doxycycline is the drug of choice in that case for Gram positives resistant to penicillin and in acne. It is also used in combination treatment of ulcers and doxycycline can be an alternate choice for the treatment of syphilis. I would caution though that these drugs should be avoided in pregnancy or in children under eight years of age. There is a progressive accumulation in the teeth and discoloration of the teeth with repeated courses of this drug and it may cause growth inhibition.

Superinfection is a problem. Photosensitivity is a problem with some of these derivatives. Antacids and food may inhibit absorption although it is less of a problem with doxycycline or minocycline. Doxycycline is also the least nephrotoxic and has the fewest effects on teeth so probably it’s the product that would be most widely used. Certainly plain tetracycline is the cheapest of this group and I would comment that some of the brand name products may be significantly more expensive than the generics. While there is controversy in using generics in some areas, the controversy is minimal in using antibiotics because frankly most antibiotics are made by only one or two manufacturers in this country and are jobbed out to other places. So they are all coming from the same vats basically. There is not much concern in terms of generic inequivalence in terms of these products.

Aminoglycoside antibiotics have several toxicities. Ototoxicity is related to high peak concentrations. We know that that is the case. Nephrotoxicity we think is probably related to high predose or trough concentrations although that has not been conclusively proven. Neuromuscular blockade can occur, particularly when other neuromuscular blockers are on board, for example. In an immediate post op period you might want to be careful about giving gentamicin or tobramycin for fear that some of the neuromusculars that may still be around in the system may cause them to stop breathing. Similarly, in myasthenia this may cause increased weakening. They are all excreted unchanged in the urine. We would change the dose in renal impairment.

I want to comment here before I go on and talk about the specific drugs and about the use of these drugs once a day. This has become an increasing trend in the use of aminoglycosides. The reason that you can use aminoglycosides once a day is that these drugs are selectively taken up in white cells or leukocytes and are carried to the site of infection. So long after we have detectable blood levels of these drugs, the drugs are still active at the site of infection. This is a so-called postantibiotic effect. This is not true of the penicillins or the cephalosporins. Once it’s out of the bloodstream, you can assume that it’s largely been removed from the site of infection as well. But that is why we see somewhat larger doses being given once a day with these products.

Now, the thought here is, “Well, if we’re giving such a large dose, don’t we get a peak that exceeds the recommended peaks for ototoxicity?” The answer is yes, we probably do. However, our experience has shown that the ototoxicity problem is no greater with once a day than it was with carefully monitored multiple dose therapy during the day and, on the other hand, the incidence of nephrotoxicity is much less. You probably recognize that the major problem that you have if you have an adverse effect from most of the aminoglycosides is deteriorating kidney function, particularly in older patients.

So this may be a major advantage in the future in treating, particularly our older patients, with aminoglycosides. It also reduces the need to monitor blood levels as closely and, in fact, it may totally circumvent the need to do it or limit it to one or two levels.

Gentamicin. Some hospitals have taken gentamicin all together off their formulary but it still is a good drug against Gram negative infections including Pseudomonas. It does have some Staph activity. In penicillin resistant Staph, sometimes you will see Infectious Disease recommending things like gentamicin be used.

Tobramycin is a little better than gentamicin but it is basically used for the same uses. In fact, its dosage and its blood levels are essentially the same as would be used for gentamicin. Both of these are cheap drugs. Gentamicin is less than $1 a vial. Tobramycin is usually several dollars for a vial so these are not expensive drugs to use. The cost with these drugs in the past has been the cost of drug therapy monitoring and also the cost of whatever toxicity ensues because of nephrotoxicity.

Netilmicin is used like gentamicin. It is better than tobramycin. Some hospitals use this. Others don’t. We have not used netilmicin. Again, like mezlocillin we decided that there are only so many of these we want to have around.

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