Management of Patients with Suspected or Confirmed Antibiotic Allergy: Executive Summary of Guidelines from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Allergy and Clinical Immunology (SEAIC), the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Intensive Medicine and Coronary Care Units (SEMICYUC).

Suspected or confirmed antibiotic allergy is a frequent clinical circumstance that influences antimicrobial prescription and often leads to the avoidable use of less efficacious and/or more toxic or costly drugs than first-line antimicrobials. Optimizing antimicrobial therapy in patients with antibiotic allergy labels has become one of the priorities of antimicrobial stewardship programs in several countries. These guidelines aim to make recommendations for the systematic approach to patients with suspected or confirmed antibiotic allergy based on current evidence. An expert panel (11 members of various scientific societies) formulated questions about the management of patients with suspected or confirmed antibiotic allergy. A systematic literature review was performed by a medical librarian. The questions were distributed among panel members who selected the most relevant references, summarized the evidence, and formulated graded recommendations when possible. The answers to all the questions were finally reviewed by all panel members. A systematic approach to patients with suspected or confirmed antibiotic allergy was recommended to improve antibiotic selection and, consequently, clinical outcomes. A clinically oriented, 3-category risk-stratification strategy was recommended for patients with suspected antibiotic allergy. Complementary assessments should consider both clinical risk category and preferred antibiotic agent. Empirical therapy recommendations for the most relevant clinical syndromes in patients with suspected or confirmed ß-lactam allergy were formulated, as were recommendations on the implementation and monitoring of the impact of the guidelines. Antimicrobial stewardship programs and allergists should design and implement activities that facilitate the most appropriate use of antibiotics in these patients.

The impact of a drug allergy label in an internal medicine ward.

Summary: Background. Drug hypersensitivity reactions are presumably immune-mediated reactions that cause reproducible signs and/or symptoms. Overdiagnosis of drug allergy, frequently self-reported, is common and carries significant limitations. We intended to analyze the frequency and impact of drug allergy in hospitalized patients. Methods. A retrospective study was conducted in an Internal Medicine ward at a tertiary hospital in Portugal. All patients with a drug allergy report admitted within a 3-year period were included. Data were collected from their electronic medical records. Results. We found that 15.4% of patients had a report of drug allergy, with antibiotics being the most common (56.4%), followed by non-steroidal anti-inflammatory drugs (21.7%) and radiocontrast media (7.0%). The allergy report affected the clinical approach of 14.5% of patients by motivating the use of second-line agents, or the eviction of necessary procedures. The usage of alternative antibiotics entailed a cost increase of 2.4 times. There were 14.7% of patients to whom the suspected drug was administered: 87.0% tolerated and 13.0% developed a reaction. Only 1.9% were referred to our Allergy and Clinical Immunology department and proceeded in their allergy study. Conclusions. In this study, a considerable number of patients had a drug allergy label on their records. This label contributed to an increase in the cost of treatment, or the avoidance of necessary exams. However, disregarding an allergy record may lead to potentially life-threatening reactions that proper risk assessment could avoid. Further investigation should always be part of the follow-up routine of these patients, and better articulation between departments should be encouraged.

Safety and value of pretransplant antibiotic allergy delabeling in a quaternary transplant center.

BACKGROUND: Self-reported antibiotic allergies, also known as antibiotic allergy labels, are common and may lead to worse patient outcomes. Within immunocompromized patients, antibiotic allergy labels can lead to inappropriate use of antimicrobials and may limit options for prophylactic and therapeutic options in the posttransplant period. While antibiotic allergy delabeling is considered an important aspect of antibiotic stewardship protocols, evidence and awareness of its application in transplant recipients is limited. METHODS: We describe our experience with an antibiotic allergy delabeling intervention in the pretransplant evaluation period and its impact on posttransplant antimicrobial utilization. This was a retrospective analysis of patients with an antibiotic allergy label who underwent evaluation for solid organ or stem cell transplantation between 2015 and 2020. Patients included in this analysis were those who completed pretransplant antibiotic allergy delabeling through our Drug Allergy Clinic and were retained in care for 6 months after transplant. RESULTS: Twenty-six of 27 patients underwent pretransplant antibiotic allergy delabeling and safely received the delabeled antibiotic posttransplant. There were no reported side effects to the delabeled antibiotic within 6 months posttransplant. Specific examination of sulfonamide (sulfa)-antibiotic delabeling showed cost savings of $254 to $2910 per patient in the posttransplant period compared to the use of alternative antibiotics for prophylaxis protocol. CONCLUSION: Antibiotic allergy delabeling prior to transplant is safe, is of high value, and should be considered in the pretransplant evaluation period. More resources are needed for the development of delabeling guidelines and support for broad implementation of pretransplant antibiotic allergy delabeling programs.

Antibiotic allergy labels in immunocompromised populations.

Antibiotic allergy labels (AALs) are commonly reported, with well-defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high-antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta-lactam (penicillin) allergy and sulfa-antibiotic (antimicrobial sulfurs) allergy labels.

Beta-lactam allergies, surgical site infections, and prophylaxis in solid organ transplant recipients at a single center: A retrospective cohort study.

BACKGROUND: Beta-lactam allergies (BLAs) are common in hospitalized patients, including transplant recipients. BLA is associated with decreased use of preferred surgical site infection (SSI) prophylaxis and increased SSIs, but this has not been studied in the transplant population. METHODS: We reviewed adult heart, kidney, and liver transplant recipients between January 1, 2016 and December 31, 2019 to characterize reported BLA and collect SSI prophylaxis regimens at time of transplant. We compared the use of preferred SSI prophylaxis and SSI incidence based on reported BLA status. Post hoc we collected antibiotic days of therapy (DOT) (excluding pneumocystis prophylaxis) in the 30-day period posttransplant for patients without SSI. We utilized descriptive statistics for comparisons. RESULTS: Of 691 patients included (116 heart, 400 kidney, and 175 liver transplant recipients), 118 (17%) reported BLA. Rash and hives were the two most reported BLA reactions (36% and 24%), categorized as potential T-cell mediated and IgE mediated, respectively. Preferred SSI prophylaxis was prescribed in 13 (11%) patients with BLA and 573 (92%) without BLA (p < .001). No difference could be detected in SSI incidence between BLA and non-BLA patients (4.2 vs. 4.3%, p = 1.0). Of 659 without SSI, 169 (25.6%) received antibiotics within 30 days of transplant; mean antibiotic DOT for BLA and non-BLA patients were 3.5 ± 8.0 versus 2.3 ± 5.8, p = .12. CONCLUSION: BLA transplant recipients received nonpreferred SSI prophylaxis more frequently than non-BLA recipients, but there was no difference in 30-day SSIs between the groups. One-fourth of solid organ transplant recipients received systemic antibiotics within 30 days of transplant.

Antibiotic allergy labels and optimal antimicrobial stewardship.

BACKGROUND: Although common, antimicrobial allergy labels (AAL) rarely reflect immunologically-mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use. AIMS: To quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission and rates of multidrug-resistant infections. METHODS: We conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) through an electronic referral system (eReferrals) over a 12-month period in 2015. Outcome data were collected for a period of 36 months following the initial review. RESULTS: Of the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to ß-lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline-recommended antimicrobial therapy (50% vs 64%, P = 0.0311); however, there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug-resistant infections. CONCLUSIONS: Our cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, de-labelling, challenge and referral into these rounds.

Assessment of the validity of the beta-lactam antibiotic allergy assessment tool for use in the rural context, QLD.

OBJECTIVE(S): The objective of the study was to validate a clinical aid to guide the assessment and management of a patient's listed beta-lactam antibiotic allergy for use in rural areas of Australia. DESIGN: Rural generalists, pharmacists and junior doctors completed an online assessment of eight patient case studies using the tool. SETTING: The study was conducted in the Southern Downs, QLD. PARTICIPANTS: Twenty-seven rural generalists, nine pharmacists and eight junior doctors. MAIN OUTCOME MEASURES: The sensitivity of the selected allergy phenotype and management option for each case study was calculated by profession and overall. Hazardous responses were reported by management category and profession. RESULTS: The sensitivity overall for phenotype selection was 82.4% (95% CI, 78.0-86.2) and for management 88.1% (95% CI, 84.2-91.2). The sensitivity for phenotype selection was lower for junior doctors than other professions 73.4% (95% CI, 60.9-83.7), but did not reach statistical significance (p = 0.08). A total of 10/308 responses for management recommended the least restrictive option of direct delabelling or oral challenge, where the correct answer was skin prick testing or referral to an allergist. CONCLUSION(S): With further education the tool could be a key component of increased antimicrobial stewardship in rural areas in Australia.

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

BACKGROUND: Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients. METHODS: Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days). RESULTS: Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39-20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45-3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27-.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09-23.31]) and ß-lactam/ß-lactamase inhibitors (OR, 6.68 [95% CI, 3.94-11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36-.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26-.72]) in the delabeled group compared with the group who retained their allergy label. CONCLUSIONS: This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.

Matched Case-Control Study of the Long-Term Impact of Beta-Lactam Antibiotic Allergy Testing.

Whereas the short-term impacts of antibiotic allergy testing on delabeling and antibiotic usage have been demonstrated, the long-term impacts have been less well defined. In a single-center matched case-control study from Melbourne, Australia, we demonstrate that a beta-lactam antibiotic allergy testing program has a significant impact on antibiotic usage and infection-related outcomes. This study supports implementation of an antibiotic allergy testing program as a standard of care of antimicrobial stewardship programs.

Inappropriate Antibiotic Allergy Documentation in Health Records: A Qualitative Study on Family Physicians' and Pharmacists' Experiences.

PURPOSE: It is hypothesized that 90% of antibiotic allergies documented in patients' health records are not actual, potentially life threatening, type I allergies mediated by IgE. This distinction is important because such documentation increases antibiotic resistance, as more second-choice and broad-spectrum antibiotics are then used. Evidence is lacking regarding causes of this inappropriate documentation. To develop interventions aimed at improving documentation, we explored experiences of family physicians and pharmacists in this area. METHODS: We conducted a qualitative study among family physicians and pharmacists using focus group discussions, based on purposeful sampling and a naturalistic approach. Discussions were audio-recorded, transcribed verbatim, and analyzed in duplicate by means of constant comparative technique. RESULTS: We conducted 4 focus group discussions among 34 family physicians and 10 pharmacists, from which 3 main themes emerged: (1) magnitude and awareness of the problem of inappropriate antibiotic allergy documentation, (2) origin of the problem, and (3) approaches for addressing the problem. Participants noted that the magnitude of contamination of medical files with inappropriate documentation leads to skepticism about current documentation. Major hindering factors are electronic health record systems and electronic communication. In addition, family physicians and pharmacists believed they had insufficient knowledge about antibiotic allergies and called for tools to rectify inappropriate allergy documentation and facilitate proper documentation going forward. CONCLUSIONS: Family physicians and pharmacists perceive that few documented antibiotic allergies are in fact correct. Electronic health record barriers and communication barriers, as well as a lack of knowledge and facilitating tools, are main causes for numerous inappropriately documented antibiotic allergies and therefore targets for improving documentation in the future.

The use of in vivo and in vitro tests in children with beta lactam allergy.

BACKGROUND: Drug allergies are reactions within the context of drug hypersensitivity reactions, which are caused by immunological mechanisms due to a previously sensitising drug. Beta-lactam antibiotics (BLA) are the leading agents causing drug hypersensitivity reactions in children. The aim of this study is to evaluate the diagnostic importance of in vivo and in vitro diagnostic tests in children with suspected immediate-type BLA hypersensitivity and to investigate the frequency of their use for the final diagnosis. METHODS: Patients admitted to the Outpatient Clinic of Division of Paediatric Allergy and Immunology with suspicion of immediate-type BLA hypersensitivity between December 2014 and December 2018 were investigated. Patients with a history of immediate reactions to BLA were examined by performing drug specific IgE, skin prick tests, intradermal tests and drug provocation tests (DPT). RESULTS: During the study period, 148 patients were admitted to our clinic with suspected immediate-type BLA hypersensitivity. Forty-eight patients completed all assessment steps and were enrolled in the study. It has been shown that 27 patients did not have drug allergy. BLA hypersensitivity was proven in 21 patients by using in vivo test algorithm. More than half of the patients were diagnosed via skin tests with culprit drug. CONCLUSION: Allergy work-up should be performed in patients with immediate reactions to BLA. A skin test can demonstrate BLA hypersensitivity in most patients. Thus, skin tests should be performed prior to the drug provocation test.

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy, affecting future treatment choices. Variations in HLA class I in particular have been associated with serious T cell-mediated adverse drug reactions, which has led to preventive screening strategies for some drugs. OBJECTIVE: We sought to determine whether variation in the HLA region is associated with vancomycin-induced DRESS. METHODS: Probable vancomycin-induced DRESS cases were matched 1:2 with tolerant control subjects based on sex, race, and age by using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by means of conditional logistic regression. An extended sample set from BioVU was used to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. RESULTS: Twenty-three subjects met the inclusion criteria for vancomycin-associated DRESS. Nineteen (82.6%) of 23 cases carried HLA-A*32:01 compared with 0 (0%) of 46 of the matched vancomycin-tolerant control subjects (P = 1 × 10-8) and 6.3% of the BioVU population (n = 54,249, P = 2 × 10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01-positive group indicated that 19.2% had DRESS and did so within 4 weeks. CONCLUSIONS: HLA-A*32:01 is strongly associated with vancomycin-induced DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug, and preserve future treatment options with coadministered antibiotics.

Antibiotic Allergy in Children: More than Just a Label.

Within the broad category of adverse drug reactions in children, there has been a recent focus specifically on the evaluation of children with antibiotic allergy, in particular, beta-lactam allergy. The potential consequences of being labeled beta-lactam allergy are increasingly recognized. Appropriate evaluation of children with suspected reactions to antibiotics is essential as it is increasingly being recognized that the label of "penicillin allergy" is associated with adverse health and economic outcomes. This review will focus on the 3 main classes of antibiotics reported to cause allergic reactions in children: beta lactams (penicillin derivatives and cephalosporins), macrolides, and sulfonamides. This article is a narrative review of the prevalence, diagnosis, and management of different types of antibiotic allergies in children. Our review reveals that antibiotic allergy is often overreported and not appropriately diagnosed in the pediatric age groups. There is a recent shift in the diagnostic paradigm from the use of skin tests and if negative challenges to the use of challenge only in the pediatric age group. Larger studies to establish the usefulness and safety of this new approach as well as updated guidelines are needed.

Beyond Penicillin: Rapid Desensitization for Specific Flucloxacillin Hypersensitivity.

Beta-lactam therapy for severe staphylococcal infections is associated with superior outcomes, compared to non-beta-lactam therapy. For patients with immediate hypersensitivity to beta-lactams, desensitization has been widely employed to allow beta-lactam therapy, but published protocols for antistaphylococcal beta-lactams such as flucloxacillin are lacking. Here, we report a case and describe the desensitization protocol successfully used for a patient with isolated flucloxacillin immediate hypersensitivity, for whom a penicillin desensitization protocol would likely have resulted in an adverse drug reaction.

Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation.

Background: Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing. Methods: AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre-AAT-AMS) and 3 months following testing (post-AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre- and post-AAT-AMS, and antibiotic appropriateness (using standard definitions). Results: From the 118 antibiotic allergy-tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients-56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45-5.42), as was narrow-spectrum ß-lactams (aOR, 3.54; 95% CI, 1.98-6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00-30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, .09-.29), after adjusting for indication, Charlson comorbidity index, and care setting. Conclusions: An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.

Return to sender: the need to re-address patient antibiotic allergy labels in Australia and New Zealand.

BACKGROUND/AIM: Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand. METHODS: An online multi-choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Australasian Society of Infectious Diseases (ASID). The 37-item survey was distributed in April 2015 to members of ASCIA, ASID, the Society of Hospital Pharmacists of Australia and the Royal Australasian College of Physicians. RESULTS: Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic-allergic. Forty-two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79, 69 and 61% respectively). Patients with the histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76 vs 41%, P = 0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was a preferred AAT model (53%). Knowledge gaps were identified, with the majority overestimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross-reactivity. CONCLUSIONS: A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital-based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving infectious diseases physicians, pharmacists and allergists/immunologists is required.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.