Is it safe to use cephalosporin (antibiotic) in patients with a penicillin (antibiotic) allergy?

From the Guidelines

Cephalosporins can generally be used safely in patients with penicillin allergy, but caution is warranted, especially in patients with a history of severe penicillin allergy. For patients with a history of mild penicillin allergy (e.g., rash), cephalosporins can be administered with a low risk of cross-reactivity, especially third and fourth-generation cephalosporins, as suggested by the 2022 practice parameter update 1. However, for patients with a history of severe penicillin allergy (e.g., anaphylaxis), it's recommended to avoid first-generation cephalosporins and use later generations with caution. The risk of cross-reactivity between penicillins and cephalosporins is due to their similar beta-lactam ring structure, but the side chains differ, especially in later-generation cephalosporins, reducing the likelihood of cross-reactivity, with an estimated cross-reactivity rate of about 1-3% for third and fourth-generation cephalosporins 1. If a cephalosporin is necessary, consider skin testing or graded challenge under medical supervision, as recommended by the Dutch Working Party on Antibiotic Policy (SWAB) guideline 1. Start with a small test dose (e.g., 1/10th of the full dose) and observe the patient for at least 30 minutes before administering the full dose, and monitor closely for any signs of allergic reaction during and after administration. If cephalosporins must be avoided, consider alternative antibiotics such as fluoroquinolones, macrolides, or vancomycin, depending on the infection being treated and local resistance patterns, and always weigh the risks and benefits of antibiotic choice in the context of the individual patient's history and current clinical situation. Additionally, aztreonam may be a suitable alternative for patients with a history of penicillin or cephalosporin allergy, unless there is a history of ceftazidime allergy, as suggested by the 2022 practice parameter update 1.

Some key points to consider:

• Cephalosporins with dissimilar side chains can be used in patients with a suspected immediate-type allergy to a cephalosporin, irrespective of severity and time since the index reaction, as recommended by the SWAB guideline 1.
• Aztreonam can be used in patients with a suspected non-severe, delayed-type allergy to cephalosporins other than ceftazidime or cefiderocol, irrespective of time since the index reaction, as suggested by the SWAB guideline 1.
• Patients with a suspected severe, delayed-type allergy to cephalosporins, monobactams, or carbapenems should avoid all β-lactam antibiotics, unless there is no acceptable alternative antimicrobial treatment, in which case the use of beta-lactam antibiotics should be discussed in a multidisciplinary team, as recommended by the SWAB guideline 1.

Overall, the use of cephalosporins in patients with penicillin allergy requires careful consideration of the individual patient's history and current clinical situation, and alternative antibiotics should be considered when necessary.

From the FDA Drug Label

Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. It is not entirely safe to use cephalosporin (antibiotic) in patients with a penicillin (antibiotic) allergy, as there is a risk of cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2.

From the Research

Safety of Cephalosporin Use in Patients with Penicillin Allergy

• The use of cephalosporins in patients with a penicillin allergy is a topic of ongoing debate, with some studies suggesting a low risk of cross-reactivity 3, 4.
• A literature review published in 2012 found that the overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
• However, another study published in 2010 found that patients with a history of penicillin allergy and a positive penicillin skin test were at increased risk of adverse drug reactions when administered cephalosporin, with a reaction rate of 6% compared to 0.7% in those with a negative skin test 5.
• A study published in 2005 found that 8.4% of patients with a history of penicillin allergy developed a reaction to a cephalosporin, with a higher reaction rate in those who received second-generation cephalosporins or cephalosporins with an amino benzyl ring 6.
• The chemical structure of cephalosporins, particularly the shared side chain, is thought to be the determining factor in immunologic cross-reactivity, rather than the β-lactam ring structure 7.

Factors Influencing Cross-Reactivity

• The generation of cephalosporin used, with first-generation cephalosporins having a higher cross-reactivity rate with penicillins than later generations 3, 6.
• The presence of a similar R1 side chain between the penicillin and cephalosporin, which can increase the risk of cross-reactivity 3.
• The results of penicillin skin testing, which can help identify patients at increased risk of adverse reactions to cephalosporins 5.

Clinical Implications

• The decision to use cephalosporins in patients with a penicillin allergy should be made on a case-by-case basis, taking into account the patient's medical history and the potential benefits and risks of treatment 4, 7.
• Skin testing to the cephalosporin in question may be useful in identifying patients at increased risk of adverse reactions, although standardized diagnostic skin testing is not available for cephalosporins 7.