Diseases information. Disorders. Treatment.

Enoxacin or Penetrex has lots of drug interactions. So probably this may, as it implies, penetrate, but if it’s got lots of drug interactions, this probably isn’t one of the better products to recommend.

Ofloxacin or Floxin is a pretty good drug. It is basically as good for most indications as ciprofloxacin including things like chlamydia and gonorrhea. It should be given between meals. It can be useful in pelvic inflammatory disease.

Sparfloxacin is Zagam. This is given once a day. It is especially good against pneumococci. However, this product has photosensitivity problems. Even with the sunscreen we’re seeing people who develop photosensitivity so I think that probably you’re not going to find a lot of clinicians using this drug, at least for very long.

Levofloxacin is Levaquin, again, given once a day. Again, good against pneumococci. It may be useful in respiratory infections and basically this is just a stereoisomer of ofloxacin.

Grepafloxacin. This is Raxar. Again, given once a day. It may be useful in community acquired pneumonias. It looks like this is going to be a good drug against penicillin resistant pneumococci but there is not a lot of data about this drug at this particular point.

Since I put the handout together, there has been another fluoroquinolone introduced and that is not on your handout. This is trovafloxacin. The trade name is Trovan. It also comes in an IV form. Again, this is given once a day. In fact, from preliminary data it looks as though this drug may be the most effective of all of the fluoroquinolones in terms of in vitro coverage including anaerobes. So here is a drug that we have that has reasonable pneumococcal coverage and also some anaerobic coverage. What I would suggest for the time being is to limit its use to mixed infections where anaerobes are likely to be present.

Its cost is comparable to other oral fluoroquinolones. Dizziness is a problem with this drug in about 10% of patients. They found that giving it at bedtime or with food for some reason cuts down on the dizziness. Unlike sparfloxacin, this drug does not seem to have much of a problem with photosensitivity reactions. So that’s a new one. If you haven’t seen it yet, I’m sure that they will be bringing samples by any day now.

Incidentally I would comment very quickly about samples. Be careful of those things. Those can lead to some dangerous prescribing practices. When they bring them in, ask them how much they are. Ask them how much a 10 day or 5 day or whatever a normal course is or call your pharmacy and find out. If it does not represent a significant advantage over something that you already have that’s cheaper, stick with prescribing the cheaper drug and reserve those samples for the people who really need them.

Unfortunately, many people treat samples like they were not prescription drugs. They’re to be handed out to the neighbors, you take only a few of them and you keep them around forever. You don’t pay any attention to the expiration date and I think we’ve got a lot of unrecognized toxicity out there because of all of the samples of antibiotics that we have floating around. Certainly I think it contributes to the problem of resistance development that we have out there.

Fluoroquinolones. These are DNA gyrase inhibitors. They are derivatives of nalidixic acid basically but they have a greater spectrum against Gram negative aerobes. They do have a number of drug interactions. I would just simply, rather than talking a lot about it, encourage you whichever ones of these products you use, consult the literature so that you are aware of what interactions you have with it. It is suggested that these be given orally two hours before antacids or heavy metals. They are not recommended in people under 18 years of age or in pregnancy or breast feeding because they have caused arthropathy in lab animals but there have also been reports of tendinitis and tendon rupture in patients who have been receiving these drugs.

Major uses are principally for Gram negative infections, chronic otitis media. They have been used in some cystic fibrosis patients because these are about the only drugs that are available that can be given orally that have activity against Pseudomonas. But I would add one caution. We sometimes use ciprofloxacin, for example, in our patients with cystic fibrosis for home therapy. They get resistant to it. I mentioned earlier, you don’t use single entities to treat Pseudomonas. We don’t have anything else that we can treat Pseudomonas with at home orally so we accept the fact that they are going to become resistant to it. We will stop the drug at that point and we will have hopefully knocked it back far enough that the patient will do okay.

Once you’ve stopped the drug and if you come back a month later, that Pseudomonas may be sensitive again and you can use another course. However, this drug should not be used in acute otitis. It should not be used for pneumococcal pneumonia or for anaerobic infections although some of the newer drugs do have coverage of some of those agents.

Norfloxacin is a drug that basically has been used for urinary tract infections. The adverse affects are listed here. I think you probably are fairly familiar with them. I would encourage you to review them if you haven’t recently.

In the interest of time, ciprofloxacin is used parenterally or orally for things like osteomyelitis, pneumonias, skin infections, bacterial diarrhea except for cases of C. diff or pseudomembranous colitis. It can be used in gonorrhea and it is useful in C. jejuni eradication but we really suggest that it be used in multiple antibiotic resistant infections or situations where it represents a significant cost advantage over parenteral therapy. Therein lies the major advantage of these drugs. These drugs can be used orally where you might otherwise have to use IV therapy. So when you can do that, you probably are cost justifiable. To use these as routine drugs for every garden variety infection, I think you are probably incurring increased cost for your patient. There is some activity against Pseudomonas but resistance development is a problem, as I mentioned.

Lomefloxacin and enoxacin are a couple of these products that have been out some years. Lomefloxacin is Maxaquin. It can be useful in UTIs or bronchitis from H. flu and M. cat. It does not interact with theophylline.

Amikacin is the best anti-Pseudomonal aminoglycoside that we have. However, the dose is higher, the recommended blood levels are higher and we usually recommend restricting this to treatment failures with tobramycin or Pseudomonas that is resistant to tobramycin because this may very well cost $20-30 per gram. It is significantly more expensive than the others of this group.
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Neomycin is not given parenterally at all but it can sometimes be used topically. It’s an extremely nephro- and ototoxic drug. We do not suggest that high concentrations be used for extensive wound irrigation. I would add a caution here. Topical drugs are later and I don’t know that we will get a chance to talk about those. Neomycin is a fairly potent contact sensitizing agent. It’s commonly sold over the counter in antibiotic creams and ointments. Neosporin is a classic example. Neomycin polymyxin and, I believe, it’s bacitracin that’s contained in there. The bacitracin is like penicillin. It covers the Gram positives. Polymyxin and neomycin have essentially the same spectrum. There is no reason to need to use both of those drugs together. Neomycin increases the risk of contact allergic reactions.

The suggestion that I have is instead of recommending Neosporin, recommend the product that contains polymyxin and bacitracin which is Polysporin. It should be readily available. Unfortunately, it is a little more expensive than neosporin but it may save you some phone calls in the middle of the night or some hysterical people who have broken out in a rash.

Lastly, streptomycin is an aminoglycoside that may be used in combination therapy for tuberculosis occasionally and I’ve listed some information about the availability of that product.

Clindamycin is Cleocin. This is used primarily for anaerobic infections, principally of GI origin. It can also be used in the treatment of Staph. It’s used a lot in dental work, for example. Its problem is pseudomembranous colitis. This is C. difficile overgrowth. The treatment of choice here is either oral or IV metronidazole or Flagyl or oral vancomycin.

Now, in the past, the practice has been to use vancomycin first orally and then use metronidazole or Flagyl second. I would suggest the opposite. The current thinking is to use metronidazole or Flagyl as your drug of choice and go to vancomycin oral if you get a treatment failure. You probably will have a treatment failure about 10% of the time with either drug. However, a course of Flagyl is about $15 or $20. A course of vancomycin may very well be upwards to $200 or more and that’s the oral drug. It’s extremely expensive and it also tastes terrible.

Be aware too, and notice here, that IV Flagyl can be used for pseudomembranous colitis but IV vancomycin cannot. So if you have a patient that is NPO and develops pseudomembranous colitis, your drug of choice is IV Flagyl.

Vancomycin is a drug that we would use for methicillin resistant Staph aureus or for Staph epidermidis. It can be used orally but that is only for local effect on the gut. When it is used, it needs to be administered over at least an hour to cut down on the so-called “red neck” or “red man” syndrome. This is a syndrome of flushing and very often hypotension and dizziness that occurs when you run in vancomycin too quickly. You will find some people will not even tolerate an hour and you may have to go infuse it over two or three hours.

Used alone, this drug, frankly, is not particularly nephrotoxic although it got a wrap as being nephrotoxic when it was originally brought out some decades ago. However, when you start using other nephrotoxic drugs with it, watch out. If you are using vancomycin and you add gentamicin, watch out. Watch your renal function, watch your blood levels because you are probably going to have to change one or the other drug dosage to accommodate declining renal function. Usually it is reversible.
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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.

Imipenem cilastatin is the next product we will talk about. This is Primaxin. Hopefully you don’t have to use this drug too often but when you do you may find it to be quite useful. Basically imipenem is metabolized by the kidney. Cilastatin cuts down on its metabolism. It’s useful in Gram negative bacilli, anaerobes and Staph resistant to other antibiotics. Seizures can be a problem with this product and it is very expensive. It can induce resistance to all other penicillins and cephalosporins so if you’ve made a choice to put your patient on imipenem cilastatin or Primaxin, you DC any cephalosporins and any penicillins thereon because the patient will become resistant to them.
Meropenem is a newer product that is marketed as Merrem. It is like imipenem but it doesn’t require the cilastatin and it does have an increased incidence of seizure problems. It is used essentially the same as would be imipenem and it is a very expensive product. But in certain circumstances like severe resistant Gram negative infections, you may be backed into a corner and end up having to use something like this.
I use the term monobactams here but there really is only one monobactam currently marketed. This is a single ring from the basic penicillin nucleus. Rather than having two rings it has only one of them so there is some risk for cross allergenicity with penicillins and cephalosporins but it is reasonably low. Again, probably be cautious if they have a rash history and use it with extreme caution if there is an anaphylactoid history of penicillin or cephalosporin allergy.
This is useful strictly in Gram negative aerobes. It has no effect against Gram positive or anaerobes. Aztreonam is the drug that is a monobactam. This may have some synergy with aminoglycosides versus Pseudomonas and may be useful in certain, for example, abdominal uses for prophylaxis or treatment. The problem here, though, is because it does not cover Gram positives, you may suppress the Gram negatives and get Gram positive super infection.
Switching away then from the beta-lactam drugs we now come to the macrolide antibiotics. Erythromycin is the one that we’ve had around forever. It can be used as a substitute for penicillin. However, pneumococcal and streptococcal resistance is a growing problem with this particular drug. You no doubt are aware that it can be used for lots of other things like Campylobacter and mycoplasma. It is a drug that can be used for impetigo although about one-third of patients will get pretty severe GI upset when you are giving oral erythromycin. Many clinicians have switched to using Keflex or cephalexin for systemic treatment of widespread impetigo and that appears from the literature to be equally effective with erythromycin and probably a lot better tolerated. So for widespread impetigo that might be a reasonable choice.
Toxicities with erythromycin. GI upset is a major one. Remember it does stimulate motilin activity in the gut. It causes GI hypermotility. We use erythromycin in some patients to stimulate GI motility but it is that same stimulation that causes a lot of the GI upset. So giving it with food (some people will try it to cut down the GI upset) often does not have much of an effect because you get the same release of motilin. More importantly these drugs can potentially cause hepatotoxicity. The drug that is most often associated with it is erythromycin estolate or Ilosone although erythromycin ethylsuccinate can sometimes cause it. Erythromycin ethylsuccinate is marketed as numerous products but it probably is less likely to cause it and many clinicians suggest that you try E.E.S. If they get significant GI upset and you still want to stay with an erythromycin then try erythromycin estolate or Ilosone. Others will say, “Well, we’re going to use erythromycin estolate first in children because it is the best absorbed and best tolerated but will avoid using it in adults.” That’s probably a wise suggestion. The use of Ilosone should probably be avoid in adults because the risk of hepatotoxicity tends to increase with age.
Erythromycin derivatives do also come IV but the IV is extremely irritating. It’s almost impractical to use this drugarenterally. There is no IM erythromycin product available.

I would point out to you that the Physician’s Desk Reference does explain how to mix this product with a local anesthetic for injection to cut down on the IM pain. So if you have patients who are going to be doing this or if you are administering this in your office, you may want to refer to that if pain has been a problem with the product and it very often is. Be aware that some of the cephalosporins do have those instructions in the PDR now.

Cefoperazone is a product that used to be used for Pseudomonas. It still is available but it causes bleeding and Antabuse-like reactions and so we prefer to use newer products such as ceftazidime.

Ceftazidime is a drug that while it has a very broad Gram negative spectrum, it is principally used in treating Pseudomonas. Remember when we are treating Pseudomonas we would use at least two different agents because Pseudomonas tends to become resistant to any single agent used alone. This says it’s the best cephalosporin in treating Pseudomonas and I would say it is that currently but it is not the most effective.

Cefepime is probably the most effective cephalosporin. This is Maxipime. This was marketed about 18 months ago. It is given twice a day. They consider it fourth generation cephalosporin because it has greater Gram negative coverage. It is more effective against Pseudomonas than is ceftazidime. Yet we would prefer for initial therapy to use ceftazidime and then if they become resistant or fail ceftazidime, switch to cefepime. We’re using a fair amount of cefepime now in some of our older patients who have cystic fibrosis who have become resistant to ceftazidime. Its expense is similar to the IV third generation cephalosporins so it is no more expensive but they all are reasonably expensive.

Cefixime is Suprax. This is given orally as a tablet or suspension. It has increased Gram negative activity and may be useful in gonorrhea but be aware that this product has no coverage of anaerobes, Staph or Pseudomonas and doesn’t have very good pneumococcal coverage either. Diarrhea is common with this product – about 1 in 3 patients will develop loose stools, very often at about the second day. Usually that will spontaneously subside by the fourth day. Dividing it into two doses a day may reduce the GI upset or the diarrhea which suggests that this is more chemical irritation than it is actually an overgrowth. Like all of the third generation agents it is somewhat expensive.

Ceftibuten is the next product we are going to talk about. This is Cedax. It is given once a day. It is good against H. flu and M. cat but it has poor pneumococcal coverage. So if you were considering using this for many common pediatric soft tissue infections, for otitis media, it may not be the best choice.

Cefpodoxime is Vantin. This particular product is just about as good as cefuroxime against common soft tissue infections. It is considered one of the cephalosporins of choice for treating acute otitis media. Again, like cefuroxime, it has a bitter aftertaste and may be problematic in kids over three. But under three, many kids will take this without any objections. Most otitis is seen in kids under three so it may very well be a reasonable drug to try if you want to use a cephalosporin for acute otitis.

Loracarbef is not truly a cephalosporin but it is darn close. Actually what it is is Ceclor that’s had a sulfur taken out of the ring nucleus and substituted with a carbon. It’s called a carbacephem but for all intensive purposes it behaves like a cephalosporin. In doing that, it’s gotten around the high incidence of serum sickness that we see with cefaclor and it may be a reasonable alternative drug to consider if you want to treat soft tissue infections with a cephalosporin type drug.
Antibiotics