Cefazolin Hypersensitivity: Toward Optimized Diagnosis

Uyttebroek, Astrid P.; Decuyper, Ine I.; Bridts, Chris H.; Romano, Antonino; Hagendorens, Margo M.; Ebo, Didier G.; Sabato, Vito

doi:10.1016/j.jaip.2016.05.011

Cited by 62 publications

(34 citation statements)

References 22 publications

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“…Our study is in line with previously published data reporting cefazolin as the most common cause of perioperative hypersensitivity reactions [8, 9, 19]. In a study performed by Kuhlen et al [19], including patients referred due to perioperative hypersensitivity reactions, the culprit drug was identified in 36% (9 of 25) patients, cefazolin being the most common drug used (6 of 9).…”

Section: Discussionsupporting

confidence: 91%

“…If found negative, then we increased concentration to 2.5 mg/mL, and followed the same procedure till a value of 10 mg/mL was reached. We emphasize that concentrations of 2–20 mg/mL in IDT with cefazolin have been used as non-irritating in previous studies [5, 6, 8, 15]. First readings were taken after 15 and 20 min for SPT and IDT respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Studies regarding perioperative anaphylaxis have shown that beta-lactam antibiotics are a leading cause of IgE-mediated hypersensitivity reactions, being cefazolin responsible for most of the reactions [8, 9]. Afterwards, patients are labelled as penicillin allergic, resulting in unnecessary antibiotic avoidance with economic and epidemiologic consequences [10, 11].…”

Section: Introductionmentioning

confidence: 99%

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Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy

Mota

Gáspár

Morais‐Almeida³

2018

Int Arch Allergy Immunol

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Background: Perioperative use of cefazolin has been associated with severe allergic reactions, and patients are usually labelled as allergic to penicillin afterwards. The aim of our study was to describe a group of patients with immediate reactions to cefazolin, with proven selective hypersensitivity reactions. Methods: Systematic review of all patients followed at our drug centre with cefazolin-related reactions, between January 2012 and December 2016. All patients were investigated according to the European Network for Drug Allergy (ENDA) recommendations through skin testing (major and minor penicillin determinants, penicillin, amoxicillin, cefazolin, cefuroxime and ceftriaxone) and oral challenges tests. Results: We included 7 patients (median age 40 years) with perioperative anaphylactic reactions immediately after cefazolin injection, 4 with hypotension and 1 with Kounis syndrome (KS) type I. The presence of a selective IgE-mediated hypersensitivity through positive skin tests to cefazoline has been proven in all patients. Two patients experienced systemic reactions during skin testing. All patients were successfully challenged with amoxicillin, and they tolerated cefuroxime. Conclusions: Cefazolin can be responsible for immediate severe allergic reactions in perioperative setting, including KS. Allergological workup is essential for an accurate diagnosis and to explore cross-reactivity between cefazolin and other beta-lactams. Our experience confirmed that patients with IgE-mediated hypersensitivity reactions to cefazolin can tolerate other beta-lactams. This selective pattern of clinical reactivity may be explained by its particular chemical structure, whose R1 side-chain is different from other beta-lactams.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy

Mota

Gáspár

Morais‐Almeida³

2018

Int Arch Allergy Immunol

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“…30 Further with its unique R1 side chain, cephazolin may result in a selective hypersensitivity not a class hypersensitivity as reactions can occur to it without cross-reactivity with penicillins, cephalosporins, or other betalactams. 31 In our audit, there was only one patient who received a drug (fentanyl) to which they self-reported an allergy, with no reaction throughout the perioperative period. In fact, all patients with a selfreported opioid allergy received fentanyl and two patients reporting ibuprofen allergy received parecoxib (though not the two with a swelling history) without incident.…”

Section: Discussionmentioning

confidence: 95%

“…In the wider healthcare setting, the risk of anaphylaxis appears similar to nonpenicillin allergy patients . Further with its unique R1 side chain, cephazolin may result in a selective hypersensitivity not a class hypersensitivity as reactions can occur to it without cross‐reactivity with penicillins, cephalosporins, or other beta‐lactams …”

Section: Discussionmentioning

confidence: 99%

Allergy alerts — The incidence of parentally reported allergies in children presenting for general anesthesia

Sommerfield

Schilling

et al. 2018

Pediatric Anesthesia

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Summary Background and aim Pediatric patients increasingly report allergies, including allergies to food and medications. We sought to determine the incidence and, nature of parent‐reported allergies in children presenting for surgery and its significance for anesthetists. Methods We prospectively collected data on admissions through our surgical admission unit over a 2‐month period at a pediatric tertiary care teaching hospital. Data collected included patient demographics, history of atopy, with more comprehensive information collected if an allergy was reported. A clinical immunologist and an anesthetist reviewed the documentation of all patients reporting an allergy. Results We reviewed 1001 pediatric patients, 158 (15.8%) patients with parent‐reported allergies; to medications/drugs (n = 73), food (n = 66), environmental allergens (dust/grasses, n = 35), tapes/dressings (n = 27), latex (n = 4), and venom (eg, bee, wasp, n = 9). Forty‐one patients reported antibiotic allergies, with Beta‐lactam antibiotics being the most common, with the majority presenting with rash alone (57%). Ten patients reported allergies to nonsteroidal anti‐inflammatory drugs and eight to opioids. Twenty‐four patients reported egg and/or peanut allergy. Only 3/1001 (0.3%) patients were deemed to have evidence of likely IgE‐mediated drug allergy. Of the reported allergies, only 60 (38.2%) had been investigated prior, most likely to be followed up were food (53%) and environmental allergies (44.4%). Only 4/73 (5.5%) reported medication allergies had further follow‐up. Just four patients (0.4% of the entire cohort) had drug sensitivities/allergies that were likely to majorly alter anesthesia practice. Conclusion Only the minority of parent‐reported allergies in pediatric surgical patients were specialist confirmed and likely to be clinically relevant. Self‐reported food allergy is commonly specialist verified whereas reactions to medications were generally not. Over‐reporting of allergies is increasingly common and limits clinician choice of medications. Better education of patients and their families and more timely verification or dismissal of parent‐reported reactions is urgently needed.

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Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin

et al. 2021

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IMPORTANCE Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections.OBJECTIVE To examine the incidence of dual allergy to cefazolin and natural penicillins.DATA SOURCES MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020.STUDY SELECTION In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion.DATA EXTRACTION AND SYNTHESIS Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions. MAIN OUTCOMES AND MEASURESDual allergy to cefazolin and a natural penicillin. RESULTSSeventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I 2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I 2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I 2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I 2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I 2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I 2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I 2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin.CONCLUSIONS AND RELEVANCE These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.

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Cefazolin Hypersensitivity: Toward Optimized Diagnosis

Abstract: Increasing cefazolin concentration for skin tests up to 20 mg/mL benefits the sensitivity of diagnosis. Furthermore, our data confirm that cefazolin hypersensitivity seems to be a selective allergy with good tolerance to other β-lactam antibiotics.

Cited by 62 publications

References 22 publications

Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy

Perioperative Anaphylaxis Including Kounis Syndrome due to Selective Cefazolin Allergy

Allergy alerts — The incidence of parentally reported allergies in children presenting for general anesthesia

Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin

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