Tolerability of Cefazolin after Immune-Mediated Hypersensitivity Reactions to Nafcillin in the Outpatient Setting

Abstract

fThe objective of the present study was to assess the safety and tolerability of cefazolin therapy among patients with methicillinsensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to cefazolin during their prescribed course. Of the 60 patients who transitioned to cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash (n ‫؍‬ 10), immune-mediated nephritis (n ‫؍‬ 3), isolated eosinophilia (n ‫؍‬ 2), immune-mediated hepatitis (n ‫؍‬ 1), and a serum sickness-like reaction (n ‫؍‬ 1). All but one patient (94.1%) who switched to cefazolin tolerated the drug with resolution of the HSR and completed their therapy with cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.

Comparative Evaluation of the Tolerability of Cefazolin and Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections in the Outpatient Setting

“…Indeed, in our study population, 65% of patients with PAD were switched to vancomycin, most likely driven by providers' fear of cross-reactivity between β-lactams. This practice might change in the future, as recently published data suggest that patients with non-IgE-mediated reactions to nafcillin can safely be transitioned to cefazolin [19].…”

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

“…In patients with mild/moderate nonimmediate reactions to penicillins who require a cephalosporin, if there’s no time to wait for the delayed reading of pre-treatment STs, giving a full dose of a structurally non-related cephalosporin under close surveillance can be considered, as the increased risk does not concern an immediate reaction, such as anaphylaxis, but that of an exanthema recurrence. In a study by Blumenthal et al, 43 17 patients treated with nafcillin were switched to cefazolin because of non-IgE-mediated HSRs, which included MPE (n = 10), immune-mediated nephritis (n = 3), isolated eosinophilia (n = 2), immune-mediated hepatitis (n = 1), and a serum sickness-like reaction (n = 1). All but one patient (94.1%) who switched to cefazolin tolerated a therapeutic course with it.…”

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Identified in the Electronic Health Record Allergy Module

“…We adapted organ injury criteria from prior studies, including RegiSCAR, and defined liver injury as alanine aminotransferase (ALT) ≥100U/L and kidney injury as at least 0.5mg/dL or 50% increase above baseline creatinine. 21,22,23 Because patients did not have a RegiSCAR 23 score calculated at the time of the HSR, and retrospective EHR data contained unknown RegiSCAR fields, we used a modified RegiSCAR score that excluded "resolution in greater than 15 days." A modified RegiSCAR score ≥2, and a clinical presentation diagnosed as DRESS syndrome by the patients' clinicians, was also required to meet the DRESS syndrome case definition in this study.…”