Penicillin-Cephalosporin Cross-Sensitivity

Background

The rate of penicillin-cephalosporin cross-sensitivity is overestimated in the literature and is likely dependent on the presence of a shared side chain with the penicillin rather than the core beta-lactam ring of the drug’s molecular structure. A higher risk of allergic reaction is expected with cephalosporins that share a similar side chain as a beta- lactam to which a patient is allergic (see cross-sensitivity chart below).

To help determine if a patient can safely be given a penicillin or cephalosporin and if performing penicillin skin testing is appropriate:

Penicillins

Amoxicillin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Ampicillin
🔴 Cloxicillin
🔴 Penicillin
🔴 Piperacillin
🔴 Cefadroxil
🔴 Cephalexin
🔴 Cefaclor
🔴 Cefprozil

No risk for cross-sensitivity:

⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Ampicillin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Cloxicillin
🔴 Penicillin
🔴 Piperacillin
🔴 Cefadroxil
🔴 Cephalexin
🔴 Cefaclor
🔴 Cefprozil

No risk for cross-sensitivity:

⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cloxicillin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Penicillin
🔴 Piperacillin

No risk for cross-sensitivity:

⚪️ Cefadroxil
⚪️ Cephalexin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Penicillin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cloxicillin
🔴 Piperacillin
🔴 Cephalothin
🔴 Cefoxitin

No risk for cross-sensitivity:

⚪️ Cefadroxil
⚪️ Cephalexin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefazolin
⚪️ Cefotetan
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Piperacillin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cloxicillin
🔴 Penicillin

No risk for cross-sensitivity:

⚪️ Cefadroxil
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefoxitin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefazolin
⚪️ Cefotetan
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

1st Generation Cephalosporin

Cefadroxil

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cephalexin
🔴 Cefaclor
🔴 Cefprozil

No risk for cross-sensitivity:

⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefoxitin
⚪️ Cefotetan
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefazolin

Cefazolin shares no side chain and is safe to use in patients with a penicillin allergy history

Cephalexin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cefadroxil
🔴 Cefaclor
🔴 Cefprozil

No risk for cross-sensitivity:

⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cephalothin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Penicillin
🔴 Cefoxitin
🔴 Cefotaxime

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

2nd Generation Cephalosporin

Cefaclor

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cefadroxil
🔴 Cephalexin
🔴 Cefprozil

No risk for cross-sensitivity:

⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefprozil

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Amoxicillin
🔴 Ampicillin
🔴 Cefadroxil
🔴 Cephalexin
🔴 Cefaclor

No risk for cross-sensitivity:

⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefazolin
⚪️ Cephalothin
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefotetan

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 None

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefoxitin

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Penicillin
🔴 Cephalothin
🔴 Cefuroxime

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefuroxime

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Cefoxitin

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

3rd Generation Cephalosporin

Cefixime

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 None

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Cefotaxime

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Cephalothin
🔴 Ceftriaxone
🔴 Cefepime

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Ceftazidime

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 None

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Ceftriaxone

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Cefotaxime
🔴 Cefepime

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

4th Generation Cephalosporin

Cefepime

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Cefotaxime
🔴 Ceftriaxone

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ertapenem
⚪️ Imipenem
⚪️ Meropenem

Carbapenems

Ertapenem

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Imipenem
🔴 Meropenem

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime

Imipenem

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Ertapenem
🔴 Meropenem

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime

Merepenem

Antibiotics that have a similar side chain or structure and a higher risk for cross-sensitivity:

🔴 Imipenem
🔴 Ertapenem

No risk for cross-sensitivity:

⚪️ Amoxicillin
⚪️ Ampicillin
⚪️ Cloxicillin
⚪️ Penicillin
⚪️ Piperacillin
⚪️ Cefadroxil
⚪️ Cefazolin
⚪️ Cephalexin
⚪️ Cephalothin
⚪️ Cefaclor
⚪️ Cefprozil
⚪️ Cefotetan
⚪️ Cefoxitin
⚪️ Cefuroxime
⚪️ Cefotaxime
⚪️ Cefixime
⚪️ Ceftazidime
⚪️ Ceftriaxone
⚪️ Cefepime