Penicillin allergy is the most common drug allergy in the US population. A penicillin allergy label is associated with poor patient outcomes including increased hospital length of stay, increased perioperative infections, and overall increased mortality. A penicillin allergy evaluation accurately identifies approximately 9 of 10 patients who, despite reporting a history of penicillin allergy, can receive penicillins safely. Penicillin allergy evaluations should be offered proactively to healthy patients during routine visits, including children and pregnant women, in advance of antibiotic need.

A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt at a large northeastern US health care system.
To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system.
Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n = 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n = 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n = 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n = 50,840; Surgical-No-PCAAL, n = 29,845; Ob/Gyn-No-PCAAL, n = 6109). χ2 tests were used to compare categorical variables, and analysis of variance was used to compare continuous and interrupted time series analyses (ITSA) to investigate the guideline/OS implementation effect on penicillin/cephalosporin receipt.
In the Medical-PCAAL group, penicillin/cephalosporin receipt increased (58%-68%, P < .001), specifically for cefazolin (8%-11%, P = .02) and third- to fifth-generation cephalosporins (43%-48%, P = .04), and aztreonam use decreased (12 DOT/1000PD, P = .03). In the Medical-No-PCAAL group, penicillin/cephalosporin receipt increased (88%-90%, P = .004), specifically for penicillin (40%-44%, P < .001), without changes in aztreonam use. Significant changes were not observed in these outcomes on surgical or obstetrics/gynecology services. Per ITSA, guideline/OS implementation was associated with increased penicillin/cephalosporin receipt in the Medical-PCAAL group only.
Guideline and OS implementation was associated with improved antibiotic stewardship on inpatient services that also received allergy education.

Antibiotic allergy labels are important barriers to treatment and antimicrobial stewardship, but their prevalence in UK hospitals is poorly described.
To ascertain the prevalence and characteristics of antibiotic allergy labels in a large UK hospital setting and estimate the proportion of penicillin allergy labels for which point-of-care (POC) delabeling assessment would be appropriate.
Electronic health records data were analyzed from all patients treated at Cambridge University Hospitals NHS Foundation Trust in 2019. Validated POC delabeling risk stratification criteria were retrospectively applied to penicillin allergy labels.
Recorded reactions to antibiotics were present in 11.8% of all patients (32,148 of 273,216), 16.3% of inpatients (13,874 of 85,230), and 9.7% of outpatients (18,274 of 187,986). Penicillins were the commonest reaction precipitant described (9.0% of patients; 24,646 of 273,216), followed by sulfonamides/trimethoprim (1.4%; 3869 of 273,216) and macrolides/lincosamides (1.3%; 3644 of 273,216). A total of 3.9% of inpatients had recorded reactions to >1 antibiotic class (3348 of 85,230). Cutaneous manifestations were the most commonly described reaction features (40.7% of labels; 15,821 of 38,902). Of 15,949 labels describing probable or possible penicillin \"allergy\" with sufficient detail to allow for the retrospective assessment of POC delabeling suitability, 1702 were deemed suitable for removal or downgrading of the label to \"intolerance\" without further investigation (10.7%), 11,887 were appropriate for POC assessment using an oral penicillin challenge (OPC) or OPC with prior bedside skin testing (74.5%), and 2360 were identified as unsuitable for any form of POC assessment (14.8%).
Antibiotic allergy labels are highly prevalent in a UK hospital setting. A large proportion of penicillin allergy labels may be suitable for POC delabeling assessment.

Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies.
We hypothesized that a digital decision support tool could improve antibiotic selection and confidence when managing β-lactam allergies.
A digital decision support tool was designed to guide non-allergist providers in managing patients with β-lactam allergy labels. Non-allergists were asked to make decisions in clinical test cases without the tool, and then with it. These decisions were compared using paired t tests. Users also completed surveys assessing their confidence in managing antibiotic allergies.
The tool\'s algorithm was validated by confirming its recommendations aligned with that of five allergists. Non-allergist providers (n = 102) made antibiotic management decisions in test cases, both with and without the tool. Use of the tool increased the proportion of correct decisions from 0.41 to 0.67, a difference of 0.26 (95% CI, 0.22-0.30; P < .001). Users were more likely to give full-dose antibiotics in low-risk situations, give challenge doses in medium-risk situations, and avoid the antibiotic and/or consult allergy departments in high-risk situations. A total of 98 users (96%) said the tool would increase their confidence when choosing antibiotics for patients with allergies.
A point-of-care clinical decision tool provides allergist-designed guidance for non-allergists and is a scalable system for addressing antibiotic allergies, irrespective of allergist availability. This tool encouraged appropriate antibiotic use in low- and medium-risk situations and increased caution in high-risk situations. A digital support tool should be considered in quality improvement and antibiotic stewardship efforts.

BACKGROUND: In Europe, North America, and Australia, 5% to 10% of the population are now classified as penicillin (β-lactam) allergic. Only ~ 10% of these questionable diagnoses, mostly made in childhood, can be confirmed by allergy diagnostics.
METHODS: The aim of this review is to show causes and consequences as well as recommendations for dealing with the often questionable diagnosis of penicillin (β-lactam) allergy (BLA).
RESULTS: An incorrect BLA diagnosis may negatively impact antibiotic treatment needed in the future, by using a less effective antibiotic or using a broad-spectrum antibiotic, for example, further exacerbating the problem of increasing antibiotic resistance. Accordingly, there is growing pressure from antibiotic stewardship programs to critically challenge the BLA diagnosis. Conservatively, a suspected BLA is reviewed by an allergist using medical history, skin testing, laboratory testing, and provocation. This clarification is costly and is not remunerated in the German health care system; that is the reason why this testing is only offered in a few specialized clinics and practically not at all in general practice. In view of thousands of affected patients, additional strategies are needed to treat patients with a low risk of hypersensitivity reaction despite suspected allergy with a β-lactam antibiotic. In recent years, various methods have been proposed to eliminate suspected allergy as promptly as possible and directly before necessary treatment with a β-lactam antibiotic, including standardized history (also in the form of an algorithm), skin test with immediate reading after 15 minutes, or administration of a small test dose. Investigations of small case series and also multi-center studies to date have yielded promising results in terms of feasibility and safety.
CONCLUSIONS: Of the large number of patients with (questionable) BLA, most have never been tested and - if antibiotic treatment becomes necessary - simply receive an alternative antibiotic. The diagnosis of BLA therefore requires new approaches besides classical allergy testing to critically question BLA.

OBJECTIVE: Patients with a reported β-lactam allergy (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSIs), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview service in the preoperative setting.
METHODS: A pharmacist performed BLA clarification telephone interviews before elective procedures from November 2018 to March 2019. On the basis of allergy history and a decision algorithm, first-line preoperative antibiotics, alternative antibiotics, or allergy testing referral was recommended. The pharmacist intervention (PI) group was compared to a standard of care (SOC) group who underwent surgery from November 2017 to March 2018.
RESULTS: Eighty-seven patients were included, with 50 (57%) and 37 (43%) in the SOC and PI groups, respectively. The most common surgeries included orthopedic surgery in 41 patients (47%) and neurosurgery in 17 patients (20%). In the PI group, all BLA labels were updated after interview. Twenty-three patients were referred for allergy testing, 12 of the 23 (52%) completed BLA testing, and penicillin allergies were removed for 9 of the 12 patients. Overall, 28 of the 37 (76%) pharmacy antibiotic recommendations were accepted. Cefazolin use significantly increased from 28% to 65% after the intervention (P = 0.001). SSI occurred in 5 (10%) patients in the SOC group and no patients in the PI group (P = 0.051). All of these SSIs were associated with alternative antibiotics. Incidence of AKI and CDI was similar between the groups. No allergic reactions occurred in either group.
CONCLUSIONS: Implementation of a pharmacy-driven BLA reconciliation significantly increased β-lactam preoperative use without negative safety outcomes.

Use of penicillin skin testing (PST) to rule out penicillin (PCN) allergies is safe and effective in immunocompetent patients; however, data on immunocompromised patients are limited.
We aimed to determine safety, efficacy, and clinical impact of PST in immunocompromised patients with cancer.
A quality improvement process establishing a PST service was implemented at MD Anderson Cancer Center. Adult patients admitted to leukemia and genitourinary medical oncology (GUMO) services with history of possible type I reactions to PCN were eligible for testing.
Between April and October 2017, 218 patients with reported PCN allergies were screened; 100 met inclusion criteria and underwent PST (67 leukemia, 33 GUMO). The most common reported allergy was to PCN (64%), with 61% reporting cutaneous reactions and 79% reporting reactions more than 20 years ago. PST with oral challenge results were overwhelmingly negative (95%); only 4% tested positive, and 1 test result was indeterminate (negative histamine control). After negative PST and oral challenge results, 51% patients were transitioned to PCN-based antibiotics during the same hospitalization. During the follow-up period (median 177 days), 65 of 95 patients were readmitted (185 total readmissions), and 51 patients required antibiotic therapy, with 37 receiving a PCN-based antibiotic (accounting for 336 days of therapy). No patient who received PCN-based antibiotics experienced an immediate-type allergic reaction.
Our findings support PST use in immunocompromised hosts. The widespread use of PST in patients with cancer will allow for optimal use of antimicrobial therapy and stewardship, which are vital in a population at increased risk for infections.

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.
METHODS: 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).
CONCLUSIONS: 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.

β-Lactam drugs (penicillins, amoxicillin, and cephalosporins) account for 42.6% of all severe drug-induced anaphylaxis. In this review, we focus on clinically significant immunologic cross-reactivity in patients with confirmed penicillin allergy to cephalosporins, and the structural involvement of the R1 and R2 chemical side chains of the cephalosporins causing IgE-mediated cross-reactivity with penicillin and other cephalosporins. Skin tests predict IgE-mediated reactions and showed cross-reactivity between penicillins and early generation cephalosporins that shared side chains, but confirmatory challenge data are lacking. Later-generation cephalosporins, which have distinct side chains, do not have any skin test cross-reactivity with penicillin/amoxicillin. There is debate as to the involvement of R2 side chains as the antigenic determinants that cause IgE-mediated hypersensitivity with various cephalosporins. Avoidance of cephalosporins, when they are the drug of choice in a penicillin-allergic individual, results in significant morbidity that outweighs the low risk of anaphylaxis. We conclude that there is ample evidence to allow the safe use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy.

Allergies to β-lactam antibiotics are commonly documented in hospitalized patients; however, true allergy is uncommon. Cross-reactivity rates for advanced generation cephalosporins and carbapenems are low; particularly for patients without a history of symptoms consistent with type 1 hypersensitivity. We observed that providers preferentially prescribed antipseudomonal carbapenems (APC) over advanced generation cephalosporins for patients with β-lactam allergy history, including those with low risk for antimicrobial-resistant infections. Information was inserted into the computerized decision support system (CDSS) to aid clinicians in assessing β-lactam cross-reactivity risk and selecting appropriate therapy. A retrospective evaluation was conducted in a small hospital to assess the impact of the CDSS changes in APC prescribing. Inpatients (n = 68) who received at least one APC dose during hospitalization over a 13 month pre-intervention period were compared to inpatients who received an APC during the 15 month post-intervention period (n = 59) for documented APC indications and β-lactam allergy history. APC initiations were measured and corrected per 1000 patient-days; interrupted time-series analysis was performed to assess changes in use before and after implementation. Aggregate monthly APC initiations decreased from 7.01 to 6.14 per 1000 patient-days after the implementation (p = 0.03). Post-intervention APC initiations for patients with low-risk β-lactam histories decreased from 92% to 83% (p = 0.17). No adverse events were observed in patients with low-risk β-lactam histories. The intervention was associated with a reduction in APC initiations.