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Guidelines
Oral Antibiotics with Similar Side-Chains

Oral Antibiotics with Similar Side-Chains

Oral Antibiotics with Similar Side-Chains

  • The overall cross-reactivity between penicillins and cephalosporins rate is < 1-2% when using structurally dissimilar antibiotics
  • The use of 3rd of 4th gen-cephalosporins or cephalosporins with dissimilar side chains from the penicillin has negligible risk for cross-reactivity

A reported penicillin allergy has been associated with 

  • 23% increased odds of Clostridium difficile
  • 14% increased odds of MRSA colonization or infection
  • 30% increased odds of VRE colonization or infection
  • 50% increased odds of surgical site infection when receiving second line perioperative antibiotics

Antibiotic Side Chain Similarity

Potential for Cross-Sensitivity

  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Amoxicillin (includes Amox/Clav (Augmentin))

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam
  • Cephalexin
  • Cefuroxime
  • Cefdinir

Potential for Cross-Sensitivity

  • Penicillin
  • Ampicillin
  • Cephalexin

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Cefuroxime
  • Cefdinir

Potential for Cross-Sensitivity

  • Ampicillin
  • Penicillin
  • Piperacillin + Tazobactam

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Potential for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Piperacillin + Tazobactam
  • Amoxicillin (includes Amox/Clav (Augmentin))

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam
  • Cephalexin
  • Cefuroxime
  • Cefdinir

Potential for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Potential for Cross-Sensitivity

  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Aztreonam

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Aztreonam

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Ceftolozane + Tazobactam
  • Ceftaroline

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Unknown Risk (structural similarities noted)

  • Aztreonam

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftaroline

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)

Potential for Cross-Sensitivity

  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)
  • Aztreonam

Potential for Cross-Sensitivity

  • Amoxicillin (includes Amox/Clav (Augmentin))

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Penicillin
  • Ampicillin
  • Cefuroxime
  • Cefdinir

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Penicillin
  • Amoxicillin (includes Amox/Clav (Augmentin))
  • Ampicillin
  • Cephalexin
  • Cefdinir

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Penicillin
  • Amoxicillin (includes Amox/Clav (Augmentin))
  • Ampicillin
  • Cephalexin
  • Cefuroxime

Potential for Cross-Sensitivity

  • Meropenem (includes Mero-Vaborbactam)

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Aztreonam

Potential for Cross-Sensitivity

  • Ertapenem

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Cefazolin
  • Ceftazidime (includes Ceftaz-Avibactam)
  • Ceftriaxone
  • Cefiderocol
  • Cefepime
  • Ceftolozane + Tazobactam
  • Ceftaroline
  • Aztreonam

Unknown Risk (structural similarities noted)

  • Ceftolozane + Tazobactam

Potential for Cross-Sensitivity

  • Ceftazidime (includes Ceftaz-Avibactam)
  • Cefiderocol

No Increased Risk (<1-2%) for Cross-Sensitivity

  • Ampicillin
  • Nafcillin/Oxacillin
  • Penicillin
  • Piperacillin + Tazobactam
  • Cefazolin
  • Ceftriaxone
  • Cefepime
  • Ceftaroline
  • Ertapenem
  • Meropenem (includes Mero-Vaborbactam)

Additional Information

  • Chaudhry SB, Veve MP, Wagner JL. Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity. Pharmacy (Basel). 2019 Jul 29;7(3):103. doi: 10.3390/pharmacy7030103. PMID: 31362351; PMCID: PMC6789778.
  • Campagna JD, Bond MC, Schabelman E, Hayes BD. The use of cephalosporins in penicillin-allergic patients: a literature review. J Emerg Med. 2012 May;42(5):612-20. doi: 10.1016/j.jemermed.2011.05.035. Epub 2011 Jul 13. PMID: 21742459.
  • Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol 2014; 133:790–6.