Since some patients with history of penicillin allergy do not recall the type of penicillin they had in the past, and since some are allergic to amoxacillin or ampicillin but not to Pen G, and since amoxacillin and ampicillin cross-react with a list of certain specific cephalosporins (see ref below) but not necessarily to Pen G an other cephalosporins similar to Pen G according to side chains, shouldn't we automatically also test for amoxacillin as well as with Pre-pen & Pen G when the type of penicllin reacted to is not known? If so, what testing protocol do you recommend? What about augmentin sensitivity, is this covered by amoxacillin testing alone? Of course, minor determinant would be nice to have as well. See Table 6 in article below.

Pediatrics 2005;115;1048-1057

Michael E. Pichichero

Penicillin-Allergic Patients

Recommendation for Prescribing Cephalosporin Antibiotics for

A Review of Evidence Supporting the American Academy of Pediatrics

http://www.pediatrics.org/cgi/content/full/115/4/1048

Thank you for your recent inquiry.

I am taking the liberty of asking Dr. Roland Solensky for his opinion regarding whether or not he would recommend automatically skin testing for amoxicillin as well as with Pre-Pen and Pen G when the type of penicillin responsible for the reaction is not known. Normally, if we must administer penicillin, and its administration cannot be avoided (our first choice in this situation), we would test with all three preparations. However, this may not be the conclusion of the newest Parameters on drug allergy. Dr. Solensky is a major co-editor of this publication, and is a nationally known expert on antibiotic allergy. I am therefore asking him to comment in this regard.

In the meantime, I am sending you three references in regards to the other components of your question. These will give you a protocol for skin testing to a number of antibiotics including amoxicillin. In addition, there is one recent reference which states that clavulanic acid can be the responsible component for an anaphylactic reaction to Augmentin. In this case, of course, amoxicillin testing alone would not be sufficient.

When I hear from Dr. Solensky, I will of course get back with you. Thank you again for your inquiry and we hope this response is helpful to you.

Reference:

Empedrad R, et al. Nonirritating intradermal skin test concentrations for commonly prescribed antibiotics. J Allergy Clin Immunol 2003; 112(3):629-630. 

Torres MJ, et al. Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. J Allergy Clin Immunol, February 2010; Volume 125, Issue 2, Pages 502-505. e2.

Romano A. Immediate allergic reaction to cephalosporins: cross-reactivity and selective responses. J Allergy Clin Immunol 2000; 106(6):1177-1183.

Sincerely,

Phil Lieberman, M.D.

Below is the response from Dr. Roland Solensky. Thank you for your question.

Sincerely,

Phil Lieberman, M.D.

In general, if patients do not recall which penicillin they had a reaction to, I would recommend skin testing with Pre-Pen, pcn G and ampicillin, and if one has access to, MDM and amoxicillin (these latter 2 reagents are not commercially available and would need to be produced). I still often see patients with very distant reactions going back to the 1940's, 50's, 60's and 70's, and in those cases I leave out skin testing with amox/amp because those meds weren't in use yet.  

In part of Europe, particularly Spain, inclusion of amoxicillin or ampicillin seems to be important, as there appears to be a large population of patients who are selectively allergic to these semi-synthetic penicillins (and tolerant to penicillin itself). In other words, skin testing these patients with just Pre-Pen, pcn G, and MDM (without amox/amp) would miss identifying them as allergic. In the US, on the other hand, the situation is quite a bit different in that selective IgE-mediated allergy to amoxicillin or ampicillin is rare.  Kaiser San Diego, Mayo and Louis Mendelson's practice (CT Asthma and Allergy) have the largest groups of patients who have undergo pcn skin testing. In published studies (and via personal communication), they have shown that only 7/5,006 (CT), 5/1,429 (Kaiser SD) and 2/1,759 (Mayo) patients were skin test-positive ONLY to amox/amp. The denominator in these fractions is the total # of patients who underwent skin testing. The skin test positive rate ranged between 5-10% or so, meaning that the vast majority of skin test-positive patients were positive to Pre-Pen, pcn G or MDM.   

In terms of allergy to clavulanic acid, this has been felt to be rare, but the recent report in JACI (referenced by Dr. Lieberman) suggests it might be more common than we thougt. However, this report is also from Europe so it remains to be seen how it translates to patients in the US. Lastly, a word of caution regarding tables categorizing beta-lactams in Pichichero's articles, such as Table 6 mentioned below. These are grouping based on similar, not identical, R-group side chains. No one has ever demonstrated that there is increased allergic cross-reactivity due to similar R-group side chains. There are 3 published reports (challenge-proven, not just based on positive testing) showing increased rate of allergic cross-reactivity between a penicillin and cephalosporin that share identical side chains - amoxicillin/cefadroxil (2 reports) and ampicillin/cephalexin (1 report). Also, there are a couple of case reports of patients with selective allergy to ceftazadime/aztreonam (which share an identical R-group side chain) and tolerance to other beta-lactams. Hope that is helpful.

Roland Solensky