First generation cephalosporins versus all cephalosporins: Side chain similarities

Legend:
Italics	Not available in the US
	Estimated rate of cross-reactivity between two intersecting cephalosporins is <2%
	Parenteral forms of cephalosporins available in the US
	Identical drugs that intersect on the X and Y axes
X	Drugs that have identical or very similar R1 side groups (highest risk of cross-reactivity)
R2	Drugs that have identical or very similar R2 side groups (lower risk of cross-reactivity)
		1^st generation cephalosporins
		Cefadroxil	*Cefatrizine*	Cephalexin	Cefazolin	*Ceftezole*	*Cephalothin*	*Cephapirin*
1^st	Cefadroxil^oral		X	X
	Cefatrizine	X		X
	Cephalexin^oral	X	X
	Cefazolin^par					X
	Ceftezole				X
	Cephalothin							R2
	Cephapirin						R2
2^nd	Cefoxitin^par						X
	Cefuroxime^{oral, par}
	Cefotetan^par
	Cefprozil^oral	X	X	X
	Cefaclor^oral	X	X	X
	Cefonicid
	Cefamandole
3^rd	Cefoperazone
	Ceftibuten^oral
	Cefdinir^oral
	Cefixime^oral
	Ceftriaxone^par
	Cefditoren^oral
	Cefodizime
	Cefotaxime^par						R2	R2
	Cefpodoxime^oral
	Ceftazidime^par
4^th	Cefepime^par
4^th	Cefpirome
5^th	Ceftaroline fosamil^par
	Ceftolozane^par
	Cefiderocol
Monobactam	Aztreonam^par

This grid is intended to help select a cephalosporin that is less likely to be cross-reactive in patients who have already experienced a possible immediate-type allergic reaction to a cephalosporin. Note that the selected drugs must be evaluated with skin testing and/or challenge in all cases, and this is especially important if the patient's initial reaction was severe. Empty boxes indicate that the estimated rate of cross-reactivity between the two intersecting cephalosporins is <2%.
The drug to which the patient reacted in the past should be located on the X axis, and then one or more drugs can be selected from the Y axis for further evaluation. Drugs shown in italics are not available in the United States (US). Also, in the US, only parenteral forms of cephalosporins are used for skin testing due to regulatory restrictions (shaded in gray if available in the US), although this is not the case in other countries. Black boxes mark where the identical drugs on the X and Y axes intersect. Red boxes marked with an X indicate drugs that have identical or very similar R1 side groups. Red boxes marked with R2 have identical or very similar R2 side groups. Cephalosporins with a shared R1 group are thought to display higher cross-reactivity than those with a shared R2. Yellow boxes marked with an * indicate drugs that have less similar side chain groups, but cross-reactivity is assumed to be possible.
The level of risk is based upon similarities in structures, in vitro or skin test-based patterns of cross reactivity, and challenge results, where available. Where data are based on skin testing or in vitro testing, the level of risk can only be estimated, because patterns of sensitivities vary around the world and cross-reactivity based on in vitro or skin test results does not always translate into clinical cross-reactivity upon challenge, and patterns of sensitivities vary around the world. Among cephalosporins, cross-reactivity most commonly arises from identical or very similar R1 side groups.

Original figure modified for this publication. From: Zagursky RJ, Pichichero ME. Cross-reactivity in Beta-Lactam Allergy. J Allergy Clin Immunol Pract 2018; 6:72. Table used with the permission of Elsevier Inc. All rights reserved.

Graphic 122928 Version 2.0

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First generation cephalosporins versus all cephalosporins: Side chain similarities