Allergy to antibiotics / penecillin and cephalosporine

Question

Hello,
I want to ask a question about an allergy to the group of penecillin antibiotics and cephalosporine antibiotics. 3 years ago I took piperacillin plus tazobactam and after 5 days I got an allergy of the skin (it started itching). One month ago I got Cefepim and after the first dose after 3-5 minutes my hands got red and itched. The doctor stated an allergy of the skin. Blood has been taken from me, but in the laboratory no allergy to penecillin and cephalosporine antibiotics had been found (the specific IgE was negative).
I want to ask if it is inevitable that I have an allergy against the whole group of penecillin antibiotics and cephalosporine antibiotics or can it be, that I have only an allergy to the 2 concrete antibiotic drugs. Is it not possible that I have an allergy to the additives?
Is there an investigation which can find that out? How can we find it out because it is a really broad scale of antibiotics, which I will need certainly. Many thanks.

Answer

Hello,
in general, penecillins are very few poisonous. Only with extrelmey high doses in patients with an impaired kidney function, epileptic seizures and meningitis sometimes disturbances of the nerves can be observed. The far most important side-effect of the penecillins is the appearance of an allergy. Here it can come very seldom to a lethal shock. One has also be cautious giving other beta-lactam antibiotics such as cephalosporines, carbapenems and the aztreonam, in which it could come to a reaction due to a cross-allergy.
Piperacillin is a beta-lactam antibiotic, which belongs to the group of acylaminopenecillins. This drug has the broadest spectrum of effect of all penecillins (including Pseudomonas and Enterobacteria). Due to the combination of the beta-lactamase unstable piperacillin with a beta-lactamase inhibitor, like e.g. tazobactam, the resistance of the bacteria against the beta-lactamase instable penecillins can be overcome.
Due to the risk of an anaphylactic shock, piperacillin is not allowed to be used in patients with a diagnosed penecillin allergy. A cross-allergy with other beta-lactam antibiotics can be present. In patients with an allergic illness in the history, like asthma, allergic rhinitis, urticaria, the risk of heavier allergic reactions at injection- respectively infusion-therapy is increased, because of that piperacillin should be used in such cases after a strict indication with special caution.
In your case you report about skin reactions after the use of piperacillin plus tazobactam and cefepim. Skin reactions however are per se not a proof for the presence of a classic drug allergy, so that a standardized allergic investigation should take place:
In case of allergic immediate reactions the detection of IgE antibodies in the blood (RAST) is at this timepoint only for penecillins to some degree reliably practicable. One problem is to search for the right antibody. In many cases the origin substance is namely not responsible for the allergic reaction but the decomposition products of the drug, which emergy only in the body.
In case the IgE antibodies against certain antibiotics are negative, like in your case, the next step of diagnosing an allergy would be a skin test (pricktest) which is usually done with several substances of the penicillin and cephalosporine group. It can also be done with the concrete drug preparation you reacted to, e.g. piperacillin plus tazobactam, in order to reveal a potential allergy against tazobactam or other additives in the mixed drug preparation. If this test shows a positive, immediate reaction, the allergy is proven and no further tests are needed and the respective drugs are not allowed to be given anymore. In case it is negative, another skin test, called intracutaneous test, which brings the substance even deeper into the skin than the pricktest does, is done. In case this test is still negative, an oral or i.v. exposition of the patient with the drug under suspicion in the hospital is done. Hereby, first of all some substances of the penicillin or cephalosporine group are tested which are not primary under suspicion. If these substances are tolerated well, one has an alternative in case the antibiogram should not allow another therapy. The substance under suspicion is tested at the end of the testing row to see if any reactions occur. The testing has to be in hospital under clinical control, as immediate allergic reactions (which occur in the first 20 minutes after exposure) bear the risk of worsening into an allergic shock. Therefore, if any of the skin test showed a positive immediate reaction, an exposition testing is obsolete.
This flowchart of an allergic diagnostics comprises very tricky investigations, which have to be under standardized conditions in order to make a reliable prediction about an allergy or not. E.g. the skin test and exposition test have not just to be done with the substance itself, but with a row of standardized dilutions. This can only be guaranteed if this tests are performed in an allergy center, in Germany we would strongly recommend to do this diagnostics at a center which belongs to the IVDK (Informationsverbund Dermatologischer Kliniken = informational network of dermatologic hospitals), those centers are for example found in the dermatologic divisions of university hospitals. If you search the web for IVDK, you find a list of participating hospitals.
In summary, it cannot be excluded that you may only react to the two concrete antibiotic drugs or to certain additives, however, the “classical allergy” to certain penecillins or cephalosporines is much more likely. In any case, you should go on and have an extended allergy testing at the above mentioned centers in order to find it out in detail and to get an allergy pass if neccessary.

I hope to have helped you further with this answer.
Yours sincerely,
Dr. med. Wolfgang Gleiber

18.06.2009