Drug allergy evaluation for betalactam hypersensitivity: Cross-reactivity with cephalosporines, carbapenems and negative predictive value

Al‐Ahmad, Mona; Rodriguez-Bouza, Tito

doi:10.12932/ap0853

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…These individual level barriers originated from lack of confidence in determining the patient’s risk of future reaction, and discomfort managing the consequences to both the patient and healthcare team if adverse reactions developed. This finding is not surprising, as other studies showed that general practitioners were reluctant to prescribe penicillin even after a successful oral challenge [ 26 – 28 ]. Fragmentation of allergy-related documentation in the EMR and having easy access to second-line antibiotics also reinforced this behavior [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 61%

Barriers to penicillin allergy de-labeling in the inpatient and outpatient settings: a qualitative study

Alagoz,

Saucke,

Balasubramanian

et al. 2023

Allergy Asthma Clin Immunol

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Background Penicillin allergy is the most commonly reported drug allergy in the US. Despite evidence demonstrating that up to 90% of labels are incorrect, scalable interventions are not well established. As part of a larger mixed methods investigation, we conducted a qualitative study to describe the barriers to implementing a risk-based penicillin de-labeling protocol within a single site Veteran’s hospital. Methods We conducted individual and group interviews with multidisciplinary inpatient and outpatient healthcare teams. The interview guides were developed using the Theoretical Domains Framework (TDF) to explore workflows and contextual factors influencing identification and evaluation of patients with penicillin allergy. Three researchers iteratively developed the codebook based on TDF domains and coded the data using thematic analysis. Results We interviewed 20 clinicians. Participants included three hospitalists, five inpatient pharmacists, one infectious disease physician, two anti-microbial stewardship pharmacists, four primary care providers, two outpatient pharmacists, two resident physicians, and a nurse case manager for the allergy service. The factors that contributed to barriers to penicillin allergy evaluation and de-labeling were classified under six TDF domains; knowledge, skills, beliefs about capabilities, beliefs about consequences, professional role and identity, and environmental context and resources. Participants from all groups acknowledged the importance of penicillin de-labeling. However, they lacked confidence in their skills to perform the necessary evaluations, such as test dose challenges. The fear of inducing an allergic reaction and adding further complexity to patient care exacerbated their reluctance to de-label patients. The lack of ownership of de-labeling initiative was another significant obstacle in establishing consistent clinical workflows. Additionally, heavy workloads, competing priorities, and ease of access to alternative antibiotics prevented the prioritization of tasks related to de-labeling. Space limitations and nursing staff shortages added to challenges in outpatient settings. Conclusion Our findings demonstrated that barriers to penicillin allergy de-labeling fall under multiple behavioral domains. Better role clarification, opportunities to develop necessary skills, and dedicated resources are needed to overcome these barriers. Future interventions will need to employ a systemic approach that addresses each of the behavioral domains influencing penicillin allergy de-labeling with stakeholder engagement of the inpatient and outpatient health care teams.

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Section: Discussionmentioning

confidence: 61%

Barriers to penicillin allergy de-labeling in the inpatient and outpatient settings: a qualitative study

Alagoz,

Saucke,

Balasubramanian

et al. 2023

Allergy Asthma Clin Immunol

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“…Note that this meta-analysis 12 included studies on at least 10 subjects (children and adults) with a documented penicillin allergy (IgE-or T-cell-mediated). In studies carried out since 1990 on more than 25 subjects with proven IgE-mediated allergy to penicillins, [27][28][29][30][31][32][33][34] the rate of positive cephalosporin STs ranged from 0% 28,30 to 33.3% (Table 1). 31 The highest rate was found in the study of ours, 31 in which participants underwent STs with a panel of 9 cephalosporins, including 3 aminocephalosporins (ie, cephalexin, cefadroxil, and cefaclor) that share similar or identical side-chain determinants with the aminopenicillins that were responsible for HSRs in 96% of the 252 patients assessed.…”

Section: Selecting Cephalosporinsmentioning

confidence: 99%

“…31 The highest rate was found in the study of ours, 31 in which participants underwent STs with a panel of 9 cephalosporins, including 3 aminocephalosporins (ie, cephalexin, cefadroxil, and cefaclor) that share similar or identical side-chain determinants with the aminopenicillins that were responsible for HSRs in 96% of the 252 patients assessed. In the aforesaid studies, [27][28][29][30][31][32][33][34] 821 penicillinallergic subjects negative to cephalosporin STs underwent a total of 1825 graded challenges with the related cephalosporins; only 11 challenges (0.6%) were positive. Specifically, there were 7 positive challenges (1.9%) out of 366 performed with aminocephalosporins, and 4 positive challenges (0.3%) out of 1459 carried out with cephalosporins like cefazolin, cefuroxime, ceftriaxone, and ceftazidime that have side chains different from those of penicillins.…”

Section: Selecting Cephalosporinsmentioning

confidence: 99%

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

Valluzzi¹,

Colantuono²,

Gaeta³

et al. 2021

JAA

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β-Lactams which include penicillins, cephalosporins, carbapenems, and monobactams are the most common antibiotic classes reported to cause allergic reactions to drugs. This review is mainly about published studies assessing the cross-reactivity among β-lactams in penicillin-or cephalosporin-allergic subjects by carrying out diagnostic tests with alternative β-lactams and, if appropriate, graded challenges. Several studies demonstrated that cross-reactivity connected with the β-lactam ring, causing positive responses to allergy tests with all β-lactams, is infrequent in subjects with an IgE-mediated allergy and anecdotal in those with a T-cell-mediated allergy. Identities or similarities of βlactam side-chain structures are mainly responsible for cross-reactivity among these antibiotics. For example, in aminopenicillin-allergic subjects, cross-reactivity with aminocephalosporins could possibly be over 30%. On the other hand, in a few prospective studies of penicillin-allergic individuals, less than 1% of cases show a cross-reactivity between penicillins and both aztreonam and carbapenems. Particular patterns of allergytest positivity observed in some studies that assessed cross-reactivity among β-lactams seem to indicate that prior exposures may be responsible for coexisting sensitivities. Therefore, pre-treatment skin tests with the related β-lactams are suggested before administering them via graded challenges to β-lactam-allergic patients who need alternative β-lactams.

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“…This high rate of cross-reactivity has decreased since the 1980s. In later reports, approximately 1% of patients who were allergic to penicillin reacted to cephalosporins, likely due to the decrease in the use of first-generation cephalosporins, which have structures similar to that of penicillin [16-19]. In practice, although it has been shown to be incorrect, that overestimation has led to the avoidance of all β-lactam antibiotics if there is a history suggestive of penicillin allergy.…”

Section: Introductionmentioning

confidence: 99%

Suspected Reaction with Cephalosporin May Be a Predictive Factor for β-Lactam Allergy in Children

Şimşek

Çöğürlü

Aydoğan³

2018

Int Arch Allergy Immunol

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Background: Most children diagnosed with β-lactam allergy based only on history are not truly allergic, and mislabeling leads to use of less effective and more costly alternative broader-spectrum antibiotics, significantly increasing drug resistance. Objective: To determine the frequency and risk factors of confirmed allergy in patients with β-lactam allergy reported by parents or their doctors and evaluate cross-reactivity between β-lactams in children with confirmed allergy. Method: Sixty-seven children with suspected β-lactam allergy were evaluated via history, sIgE measurements, skin tests, and drug provocation tests over a period of 5 years. Results: β-Lactam allergy was confirmed in 10 (14.9%) patients. Six patients had a positive intradermal test result to one or more of the penicillin skin test materials or ceftriaxone, 4 patients with negative skin test results had positive test results with suspected drugs. Age, gender, time interval between evaluation and the initial reaction, personal history of atopy, parental history of drug allergy, reaction type, and multiple drug allergy history were not significantly different between allergic and tolerant patients. For culprit drugs, there was a significant different between the 2 groups; the rate of confirmed diagnosis was significantly higher for cephalosporins such as ceftriaxone, cefuroxime, and cefprozil (p = 0.03). Three patients with allergy to penicillin tolerated cefuroxime; in 4 patients with selective allergy to ceftriaxone tolerated cephalosporins with a dissimilar side chain (cefadroxil, cefuroxime, cefaclor, and cefdinir). Conclusion: Our study indicates that most patients with a suspected β-lactam allergy tolerated this drug. An appropriate diagnostic allergy workup may prevent the use of less effective and more expensive alternatives.

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Drug allergy evaluation for betalactam hypersensitivity: Cross-reactivity with cephalosporines, carbapenems and negative predictive value

Abstract: Carbapenems and cephalosporines can be safely given to penicillin allergic patients by means of skin testing and if negative, proceeding with a graded challenge. Our calculated NPV for penicillin testing is similar to other studies.

Cited by 7 publications

References 28 publications

Barriers to penicillin allergy de-labeling in the inpatient and outpatient settings: a qualitative study

Barriers to penicillin allergy de-labeling in the inpatient and outpatient settings: a qualitative study

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

Suspected Reaction with Cephalosporin May Be a Predictive Factor for β-Lactam Allergy in Children

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