β-Lactam Allergy and Cross-Reactivity: A Clinician’s Guide to Selecting an Alternative Antibiotic

Figures & data

Figure 1 Chemical structures of penicillins, with the amino group of ampicillin and amoxicillin, as well as that of cephalosporins of group B (ie, aminocephalosporins) highlighted in gray.

Figure 2 Continued.

Figure 2 (A and B) Chemical structures of cephalosporins other than aminocephalosporins, with the methoxyimino group of cephalosporins of group A highlighted in gray and the alkoxyimino group of ceftazidime and N-methyltetrazole-thiol group of cefamandole and cefoperazone circled in black.

Figure 3 Chemical structures of carbapenems and aztreonam.

Table 1 Rate of Cephalosporin Positive Skin Tests in Patients with Confirmed IgE-Mediated Hypersensitivity to Penicillins and Rate of Cephalosporin Positive Graded Challenges in Those with Negative Skin Tests to the Cephalosporin Concerned

Study (Reference)	Patients, n	Skin Testing				Challenge
		Penicillin Reagents	Tested Cephalosporin(s)	Positive Patients,* n (%)	Positive Cephalosporins,^¶ (n Positivities)	Administered Cephalosporin(s)	Administration Route	Reactions, n/Challenges, (%)
Audicana et al^Citation27	34	PPL, MDM, AM, AX	Cephalexin, ceftazidime	5 (14.7)	Cephalexin (5)	Cephalexin, ceftazidime	Oral, intravenous	0/29 0/30
Novalbos et al^Citation28	41	PPL, MDM, BP, AX	Cefazolin, cefuroxime, ceftriaxone	0	None	Cefazolin, cefuroxime, ceftriaxone	Intramuscular, intramuscular, intramuscular	0/41 0/41 0/41
Romano et al^Citation29	128	PPL, MDM, BP, AM, AX	Cephalothin, cefamandole, cefuroxime, ceftazidime, ceftriaxone, cefotaxime	14 (10.9)	Cefamandole (9), cephalothin (8), ceftriaxone (3), cefuroxime (2), ceftazidime (2), cefotaxime (2)	Cefuroxime axetil, ceftriaxone	Oral, intramuscular	0/101 0/101
Caimmi et al^Citation30	69	PPL, MDM, BP, AX	Cefuroxime	0	None	Cefuroxime axetil	Oral	2/69 (2.9)
Romano et al^Citation31	252	PPL/BP-OL, MDM/MD, BP, AM, AX, PP	Cephalexin, cefadroxil, cefaclor, cefamandole, cefuroxime, ceftazidime, ceftriaxone, cefotaxime, cefepime	84 (33.3)	Cefadroxil, (62) cefaclor (38), cephalexin (33), cefamandole (11), ceftriaxone (6), cefotaxime (3), cefuroxime (2)	Cefaclor, cefadroxil cefuroxime axetil, ceftriaxone	Oral, oral, oral, intramuscular	3/170 (1.8) 4/167 (2.4) 0/244 0/244
Rodriguez-Bouza^Citation32	29	PPL/BP-OL, MDM/MD, BP, AM, AX	Cefuroxime	1 (3.4)	Cefuroxime (1)	Cefuroxime	Intramuscular	2/28 (7.1)
Romano et al^Citation33	131	BP-OL, MD, BP, AM, AX, PP	Cefazolin, ceftibuten	1 (0.7)	Cefazolin (1), ceftibuten (1)	Cefazolin, ceftibuten	Intramuscular, oral	0/129 0/129
Sánchez de Vicente et al^Citation34	137	PPL, MDM, AX	Cefuroxime, ceftriaxone	2^‡ (1.5)	Cefuroxime (1), ceftriaxone (1)	Cefuroxime, ceftriaxone	Oral, intravenous	0/136 0/125
Total	821			107 (13)				11/1825 (0.6)

Notes: *Patients with positive skin tests to at least one cephalosporin. ^¶Cephalosporins found positive to skin tests. ^‡One subject had experienced immediate reactions to both amoxicillin and cefuroxime.

Abbreviations: AM, ampicillin; AX, amoxicillin; BP, benzylpenicillin; BP-OL, benzylpenicilloyl-octa-L-lysine; MD, minor determinant; MDM, minor determinant mixture; PP, piperacillin; PPL, benzylpenicilloyl-poly-L-lysine.

Table 2 Rate of Cephalosporin Positive Patch Tests and/or Skin Tests in Patients with Confirmed T-Cell-Mediated Hypersensitivity to Penicillins and Rate of Cephalosporin Positive Graded Challenges in Those with Negative Allergy Tests to the Cephalosporin Concerned

					Cephalosporin Challenges
Study (Reference)	Patients, n	Responsible Penicillins	Tested Cephalosporin(s) (Methods)	Positive Patients,* n (%)	Administered Cephalosporin(s)	Administration Route	Reactions, n/Challenges, (%)
Phillips et al^Citation40	16	Aminopenicillin	Cephalexin (patch tests)	5 (31.2)	Cephalexin	Oral	0/6
Trcka et al^Citation23	71	Aminopenicillins	Cefpodoxime, cefixime (patch tests)	0	Cefpodoxime, cefixime	Oral, oral	1/71 (1.4) 1/71 (1.4)
Romano et al^Citation41	214	Aminopenicillins, benzylpenicillin, piperacillin	Cephalexin, cefaclor, cefadroxil (skin tests and patch tests) Cefuroxime, ceftriaxone (skin tests)	40 (18.7%) [16 to cephalexin and cefaclor, 15 to cephalexin, cefaclor, and cefadroxil, 7 to cefaclor, 1 to cefaclor and cefadroxil, and 1 to cefadroxil]	Ceftriaxone, cefuroxime axetil, cephalexin, cefaclor, cefadroxil	Intramuscular, oral, oral, oral, oral, oral	0/213 0/213 0/170 1/170 (0.6) 0/169
Total	301			45 (15)			3/1083

Note: *Patients with positive patch tests and/or skin tests to at least one cephalosporin.

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