Online Canadian Pharmacy Blog

Azlocillin is like piperacillin in its spectrum and its uses. It basically is essentially as good as piperacillin and I would suggest that whichever one you use depends on which one your institution can get the least expensively. You do not need to have both azlocillin and piperacillin in a given hospital.

Penicillin H resistant penicillins are useful for Staph aureus infections. That is essentially the only reason that these should be used because they are significantly more expensive and more toxic for other uses. Therefore, they should be limited to treatment of suspected or proven Staph aureus. These should not be used for methicillin resistant Staph aureus and I might point out that methicillin resistant Staph aureus is a misnomer. These are not only methicillin resistant, they are also beta-lactam resistant, so they are unlikely to be susceptible to any of the penicillins or the cephalosporins.

One other thing that you need to consider when you are prescribing these products is that most of the oral liquids of these products are literally unpalatable. I don’t know if you have ever tasted oxacillin or dicloxacillin liquid but in taste tests with children, we routinely find that these products end up at the very bottom in terms of acceptability. If you have used these over the years and you went back and talked to your patients and they were honest with you, they might have taken one or two doses and refused to take anymore. There are some alternatives that I will be talking about in a minute but I would strongly encourage you wherever possible to stay away from using the oral liquids of these products.
Antibiotics
Methicillin, too, is probably a product that has fallen by the wayside in terms of its use because it is the most nephrotoxic of this group. While it is the least highly protein bound and should achieve the highest blood levels of free drug, it also is the most nephrotoxic. So most institutions that I am aware of no longer have this on their formulary.

Nafcillin is a parenteral product that has some Staph that are susceptible to it that are not to others in this group. So in terms of the most effective of these drugs, this is the most effective. But the IV dosage form is very irritating. Many hospitals have switched to syringe pump administration systems because a syringe costs 50 cents and a piggy back costs a patient $5 and so it is more economical to do it that way. But when we put this drug in a syringe pump and run it in over 20 minutes, it is more concentrated than it would have been in a piggy back and it can lead to major venous irritation, phlebitis and loss of IV sites. Regardless, the oral dosage form should not be used. Oral nafcillin is too unpredictable in terms of its bioavailability so I would strongly encourage you to forget that oral nafcillin even exists.

The alternative to nafcillin IV is oxacillin and many institutions use that. That is the product that we use here as our penicillinase resistant parenteral penicillin because we use a syringe pump system.

Oral oxacillin, cloxacillin and dicloxacillin. In the solid dosage forms, you may be able to get a patient to take it but (1) They need to all be given on an empty stomach. Hopefully the pharmacist will tell them that but it is probably best to prescribe them that way. (2) There is confusion and controversy about which of these is the best one to use. Cloxacillin is better absorbed than oxacillin. It is monochlorinated oxacillin. Dicloxacillin is dechlorinated oxacillin. It’s the best absorbed of the three. I will give you that. But it’s also the most highly protein bound. There is nearly twice as much free drug with oxacillin than there is with dicloxacillin. The bottom line then is that you probably should be using whichever one of these three is the least expensive for your institution to purchase. Dicloxacillin is really not that much better.

Ticarcillin is also a penicillin derivative but its major activity, rather than being Gram positive, is Pseudomonas. That is the principal use of ticarcillin. We give it IV in large doses. It is impractical to give this product IM. It contains about 5 milliequivalents of sodium per gram and we give big doses. So we potentially could be running the equivalent of two-thirds or a full liter of normal saline into our patient with the sodium content of this product. So you can get into sodium overload problems. You can also, in patients who are predisposed to bleeding, run into problems with this because it can interfere with platelet adhesiveness and directly with the coagulation sequence. In most normal patients that is not a concern but if you have someone with a preexisting severe nutritional deficiency or coagulopathy, you probably should be careful about using this particular product.

Carbenicillin indanyl sodium used to be available parenterally. It is no longer available that way. It is only available in an oral tablet that can be useful in urinary tract infections and prostatitis. It is a big pill. It is very bitter. It is very hard to get some people to take it and please don’t ask them to crush it. If you crush it and try to mix it with something, it tastes like rotten eggs. Fortunately, we have other drugs such as the fluoroquinolones that are effective instead of this drug in prostate problems so it’s not as necessary as it once was.

Ticarcillin clavulanate is Timentin. This is a parenteral product that may be useful when Ticar effectiveness is being reduced by beta-lactamase production. However, there are other single entity antibiotics that are equally effective and possibly less expensive. So we haven’t found a lot of use for this particular drug but it is certainly one that is out there that may occasionally be useful.

Also we don’t use mezlocillin a great deal but mezlocillin is better than ticarcillin against Pseudomonas. It’s not quite as good, though, as piperacillin or azlocillin and rather than having a whole number of antibiotics with similar spectrum on our formulary we choose not to have this particular product.

Piperacillin is sort of the top of the line of the anti-Pseudomonal penicillins. It is better than ticarcillin against Pseudomonas but it is significantly more expensive. It doesn’t have the significant bleeding problems. It has less sodium although sometimes it can be enough to get you into trouble. It is also available as Zosyn as a parenteral product combined with Tazobactam. Again, the Tazobactam is useful in preventing beta-lactamase induced destruction. It probably should be restricted to resistant organisms or treatment failures. Please note that the dose of piperacillin contained in this, if you are dosing it properly, is considered inadequate to treat Pseudomonas. So this is not a supercharged anti-Pseudomonal med but rather using Zosyn may extend the spectrum against some other Gram negative organisms which may be beta-lactamase producers.

Penicillin resistant Pneumococcus and other bacterial resistance have become a rapidly increasing problems. So we have to be careful with the way we use antibiotics as we do any other drug. Some resistant mechanisms work by competitive antagonism. The sulfas are folic acid synthesis inhibitors. Those bacteria that are obligate folate synthesizers are inhibited because there are non-utilizable forms of folate that are synthesized when the sulfas are present. Some others are cell wall inhibitors. For example, penicillins and cephalosporins will cause defects in the formation of the cell walls. Essentially it’s like taking the cement out from between the bricks. The cell membrane may, too, be interfered with. The antifungals very often will align themselves between the lipid and protein complexes and interfere with the metabolic functions of the cell membrane in fungi. Some will inhibit protein synthesis. For example, erythromycin, tetracycline and chloramphenicol will basically stop protein synthesis. They are therefore considered bacteriostatic drugs.

Others will cause protein synthesis to be altered. For example, the aminoglycosides like tobramycin or gentamicin cause the formation of non-utilizable proteins. So the bacteria go on trying to grow and yet the proteins which are critical to their structural integrity – enzymes, etc – are no longer there. Lastly, nucleic acid interference includes drugs like ciprofloxacin, which is a DNA gyrase inhibitor.

Penicillins. That is typically where most antibiotic lectures start. A reminder that if someone is truly allergic to one penicillin, they should be considered allergic to all other penicillins. But penicillins in general are fairly low in toxicity other than allergic reactions. You can occasionally get into electrolyte overload with some of the parenteral forms. Most of them contain either potassium or sodium and if you have a patient who has electrolyte disturbances, you might get into trouble with sodium or potassium overload.

Penicillin G is the first drug that we will basically talk about. It is useful in a number of Gram positive infections. It is relatively nontoxic. It is cheap. If you give it IM, though, it is painful and you have to give it frequently. IV, if you order aqueous penicillin G or penicillin G K or crystalline penicillin, the pharmacy will send you the potassium salt. Now, that contains about 1.8 milliequivalents of potassium per million units and if you are giving large doses, for example, in treating SBE, you might very well be giving 30 or 40 milliequivalents of unanticipated potassium each day and you could get into trouble with that. There is also a sodium salt available. If that is the situation you might switch to the sodium salt or in some cases we may even have to alternate the sodium and potassium every other dose.

Phenoxymethyl penicillin is oral penicillin. There is no longer oral penicillin G on the market. That has been taken off the market. Penicillin V would be used when oral penicillin is indicated. Procaine penicillin gets around the problem of pain on IM injection of aqueous penicillin by complexing it with procaine. Obviously the patient history needs to include inquiry about both the history of penicillin allergy and a history of local anesthetic or procaine allergy. If this drug is given IV, it is neurotoxic and will cause hallucinations and delirium. It has a duration of 12-24 hours and may be useful when moderately high blood levels of penicillin are acceptable. You don’t get very high levels with procaine penicillin.

But you get even lower blood levels with benzathine penicillin. This is another IM suspension marketed as Bicillin L-A where the release is extremely slow. You get very low blood levels so we would use this for rheumatic fever prophylaxis or for treatment of very susceptible infections like susceptible Strep throats where we don’t think compliance is going to be very good. The problem with this is that it hurts. Many patients will complain of pain for three days or so after they get a shot of benzathine penicillin.

There is also a Bicillin C-R on the market. That is Bicillin Controlled-Release, if you will. That is a 50/50 mixture of procaine and benzathine penicillin. The procaine gives a moderately high blood level for the first day. After that, the benzathine is there to help eradicate what is left of the infection. The problem with this is that some infectious disease people didn’t think that that was quite enough benzathine penicillin and suggested a different mix – that is, Bicillin C-R 900/300, which contains 75% of the slow release or the benzathine and 25% of the faster release procaine penicillin.

The bottom line, though, regardless of which you choose, Bicillin L-A, the C-R or the C-R 900/300, make sure you are giving enough of the benzathine to eradicate the infection because within 24 hours the procaine component is gone.
Antibiotics. Ampicillin. Amoxicillin.

Ampicillin is a drug that has a fairly broad spectrum. We typically use this for infections where H. flu or E. coli are likely pathogens. Obviously beta-lactamase production is somewhat limiting the utility of this drug in those cases but it still is a useful drug in many cases of infections like that. The problems are diarrhea. When you give it orally, a fair proportion of the patients will develop this – 10 to 20%. Rash is two-fold. You, no doubt, have run into lots of ampicillin rashes in your practice but just to remind you, about 3% of patients will develop a rash within 24 hours which is urticarial or hive-like. When that occurs, that is an allergic reaction to ampicillin and the patient should be considered penicillin allergic.

On the other hand, three to seven days out usually, the patient may develop a rash that is maculopapular or is described as a fine red rash or a measles-like rash. It typically starts on the trunk, spreads peripherally and it doesn’t itch much. That is an ampicillin-type rash. It is not allergic. It probably indicates the concurrent presence of some sort of virus in the system and that is supported by the fact that in 90-95% of patients with infectious mono, which is a viral infection, the drug will cause this sort of measles-like or fine red rash. Therefore, the drug is relatively contraindicated in infectious mono.

Because of the beta lactamase production problems, there is also a product that contains ampicillin sulbactam marketed as Unasyn. It may be useful when you suspect that you have beta-lactamase producing organisms and is particularly useful in gynecologic and abdominal infections. But be aware that it is significantly more expensive than ampicillin and certainly should not be routinely substituted unless there is a strong suspicion of beta-lactamase production.

Amoxicillin is the oral derivative of ampicillin that I would recommend be used in all except one circumstance where you normally would choose to use oral ampicillin. Oral ampicillin has to be given, usually, about every six hours. This can be given three times a day or every eight hours. It is better absorbed and it causes less diarrhea. So this is the preferred drug. The exception would be in Shigella. In Shigella or bacillary dysentery you want a lot of the antibiotic to reach the lower gut and therefore you would prefer to use oral ampicillin if you are using oral therapy. It does still have the same problems of rash, though, that we’ve already gone over.

Amoxicillin is also marketed orally with a beta-lactamase inhibitor that is potassium clavulanate. This particular drug would be useful as Augmentin in the treatment of things like otitis media and other infections where it is likely that resistant organisms are present, including M. cat., GI upset and diarrhea are fairly common. A lot of people don’t like the taste of this product and it is significantly more expensive than amoxicillin alone but often is less expensive, for example, than a cephalosporin, second or third generation would be.