Cephalosporins OK in Penicillin Allergic

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.

Recent guidelines for the treatment of acute bacterial sinusitis and otitis media advise physicians to do something that most of us were taught never to do: Use a cephalosporin in a penicillin-allergic patient. Unfortunately, those documents neglected to explain why this once-taboo practice is now the standard of care.

The American Academy of Pediatrics' clinical practice guidelines for the management of sinusitis endorse the use of cefuroxime, cefpodoxime, ceftriaxone, and cefdinir for penicillin-allergic patients in whom the previous penicillin reaction was not severe (Pediatrics 2001;108:798-808), while the guidelines for the diagnosis and management of acute otitis media support the use of the same three oral cephalosporins in patients with “non-type-1 allergy” and ceftriaxone for type 1 allergy (Pediatrics 2004;113:1451-65).

Although the two documents are evidence based and have been endorsed by several other professional groups including the American Academy of Family Physicians, many clinicians have not embraced the recommendation because of the often-cited yet inaccurate statistic that there is a 10% rate of cross-sensitivity to cephalosporins among penicillin-allergic patients.

In fact, the risk that a patient with a history of penicillin allergy will experience a reaction to a first-generation cephalosporin is not more than 0.5%, to a second-generation cephalosporin, not more than 0.2%, and to a third-generation cephalosporin, practically nil. In at least 25 studies, cephalosporins were actually given to penicillin-allergic patients with reaction rates not greater than in non-allergic patients. I have reviewed this literature in the April issue of Pediatrics (2005;115:1048-57).

The misconception arose out of the belief that the cross-reactivity is to the shared β-lactam ring.

Now, however, we know that the β-lactam ring of cephalosporins—unlike that of penicillin and ampicillin—becomes rapidly degraded, so that antibodies are instead targeted to side chain structures. Therefore, cross-reactivity is only possible with the cephalosporins that share penicillin side chains. (See chart.) And even then, the likelihood of a reaction is still far less than 10%.

Many of the older studies suggesting greater rates of cross-reactivity were conducted with penicillin and/or amoxicillin that had been made with Cephalosporium mold, which of course would have caused cross-contamination. Yet, the caution remains in the package label for most cephalosporins.

Patients and physicians alike tend to use the term “allergy” very loosely. But unless the patient experienced a generalized pruritic skin reaction, hives, or anaphylaxis, it was not an IgE-mediated (type 1) reaction.

For patients who do report a true allergic history—or who have had a positive skin test—it would be prudent to avoid the four cephalosporins with side chains similar to amoxicillin—namely cefaclor, cefprozil, cephalexin, and cefadroxil. All other cephalosporins are acceptable, including the four endorsed in the sinusitis/otitis guidelines.

Consider that a major reason for the new guidelines is the increasing rates of macrolide-resistant Streptococcus pneumoniae. The rate was 35% in 2002, and it has been rising since. Therefore, the old paradigm of simply putting a penicillin-allergic patient on azithromycin or clarithromycin is no longer good medicine—in doing so, you are substantially compromising the anticipated efficacy of the drug.

There has never been a case of fatal anaphylaxis with a cephalosporin reported in a child. From a medicolegal standpoint, if the AAP/AAFP guideline says you can use a cephalosporin in a penicillin-allergic patient—as does my evidence-based peer reviewed article in AAP's journal, Pediatrics—rest assured you can do it.

Cross-Reactivity Between Penicillins and Cephalosporins

Contrary to long-held belief, the risk of cross-reactivity between penicillins and cephalosporins is based on the similarities of their side-chain structures, not of the b-lactam ring they all share. The three lists below are grouped by side-chain similarity (or lack thereof in the third group). However, even within groups with related side chains, the risk that a patient with a history of sensitivity to one drug will have a reaction to another is still no more than 0.5%.