Cephalosporins

Cephalosporins

Background

NoteWhat percent of the total US population reports a cephalopsorin allergy?

In the US, 1.3% to 1.7% of the total population reports a cephalosporin allergy whereas 0.5% of pediatric patients report a cephalosporin allergy^{chow2024?,khan2019?}

NoteWhat is the most common drug allergy phenotype associated with cephalosporins?

Most reactions to cephalosporins are immediate (74.7%)–characterized by urticaria and/or angioedema–as opposed to delayed–typically non-severe maculopapular exanthem (25.3%).

NoteWhat is the chemical structure of cephalosporins?

The chemical structure of cephalosporins is a four membered ring fused with a six membered dihydrothiazine ring with R1 and R2 side chains.

NoteWhat is the major structural component responsible for cross-reactivity between penicillins and cephalopsorins?

The R1 side chain is the major component responsible for the cross-reactivity with penicillins and cephalosporins. Tolerance to cephalosporins can usually but always be predicted on the basis of similarities or differences in R1 side chains.

R2 side is less studied but may have a role. There is some evidence that suggests that the opening of the cephalosporin beta-lactam ring destroys the R2 side chain.

NoteWhat penicillins share the same R1 side chain as cefazolin?

Trick question! None!

NoteAztreonam (a monobactam and beta-lactam) can be given without any concerns for cross-reactivity to patients with a cephalosporin allergy except which R1 side chain sharing cephalosporin?

Ceftazadime.

NoteWhat cephalosporin is the main culprit for serum sickness-like reactions?

Cefaclor accounts for up to 80% of serum sickness-like reactions.

Skin Testing

Lack of commercial products and metabolites for skin testing.

Immediate Index agents: cephalexin (55.5%), ceftriaxone (24.9%), and cefazolin (17.5%)

8.9% of pateints had positive skin tests (cefazolin 50% positives)

Time since index reaction, OR 0.71 (95% CI 0.57 - 0.90) for positive skin test.^stone2021?

Oral Challenge

100% NPV if reaction > 5 years, isolated urticaria, benign MPE, isolated GI symptoms or other non-allergic and orally administere vs 98.5% NPV (95% CI 95.8%-99.7%) if include IV and PO administered.^stone2021?

Cephalexin 250 mg oral challenge with 1.5 hour observation.^koo2022?