Antibiotic Allergy Research Articles

Effects of Sex and Gender in Immediate Beta-Lactam Antibiotic Allergy: A Systematic Review and Meta-analysis

BackgroundBeta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics. ObjectiveThis systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy. MethodsWe performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis. ResultsWe included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I2 =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies. ConclusionsOur findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females.

Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network.

Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point-of-care penicillin allergy assessment and direct oral challenge for low-risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals.

Knowledge, Awareness and Attitude of Pharm.D. Students on Antimicrobial Stewardship: A Report

Antimicrobial Stewardship (AMS) is a strategy to optimize antimicrobials and prevent the emergence of antimicrobial resistance (AMR). Pharm.D. students are future Clinical pharmacists who play a key role in promoting rational use and implementing AMS programs. Only a few studies about their knowledge, awareness and attitude regarding AMS exist. A cross-sectional study was conducted in the middle of December 2023, among Pharm.D. students of different academic years from three Pharmacy colleges and Pharm.D. graduates in South India. The survey was conducted online using a validated questionnaire and Pharm.D. students audited the results under the guidance of an Infectious disease specialist. The survey comprised 17 questions covering demographic information, AMS knowledge, attitude and awareness questionnaires. This study included a total of 190 respondents. However, only 32.11% reported having participated in any AMS activity during their period of pharmacy education. Pharm.D. students have a positive attitude (72.48%) and optimal awareness (65.13%) but they lack sufficient knowledge (45.19%) towards AMS, specifically regarding surgical prophylaxis and antibiotic allergy testing. It serves as a valuable resource for educators, policymakers and stakeholders involved in shaping the curricula of Pharm.D. programs to enhance the training and preparedness of students in AMS practices. In the future, AMS education programs should target not only clinicians but also Pharm.D. students and interns.

Cross-reactivity of triptans and sulfonamide antibiotics - a clinically relevant question?

After repeated inquiries from patients whether sulfonamide antibiotic allergy should be considered in the context of taking a triptan, we present here the pharmaceutical background, the chemical structure of triptans, and the clinical relevance in a narrative review. In fact, evidence-based cross-reactivity referring to the well-known allergic reaction of sulfonamide antibiotics has not been described so far.

The Role of the Basophil Activation Test in the Diagnosis of Drug-Induced Anaphylaxis.

The diagnosis of drug-induced anaphylaxis (DIA) is a serious health problem. The Basophil activation test (BAT) is considered a specific in vitro provocation, and compared to in vivo provocation, it is more convenient, cheaper, and safer for the patient. This study aimed to evaluate the usefulness of the BAT in the diagnosis of DIA. This study included 150 patients referred to a reference allergy clinic with suspected drug allergies. All patients underwent a detailed clinical evaluation supplemented with the BAT. Positive BAT results were obtained in two out of 21 patients who were to receive the COVID-19 vaccine. The sensitivity and specificity of the BAT were 40% and 75% for the COVID-19 vaccine, 67% and 58% for DMG PEG 2000, and 100% and 75% for PEG 4000, respectively. Nine out of 34 patients with suspected antibiotic allergies had positive BAT results with 14 different antibiotics. Positive BAT results were also obtained with NSAIDs in two patients and with local anesthetics in three patients. The confirmation of allergy by the BAT improves the safety profile of the diagnostic work-up as it may defer the need for drug provocation, preventing potential anaphylactic reactions.

Retrospective study on penicillin allergy delabeling and evaluation of an antibiotic allergy assessment tool

BackgroundIt has been reported that 95 % of patients labeled as penicillin-allergic may be mislabeled. However, the process of delabeling has not advanced due to a shortage of allergy specialists capable of conducting accurate assessments. To address this issue, The Antibiotics Allergy Assessment Tool (AAAT) has been proposed as a tool to evaluate patients who can be delabeled by non-specialists. ObjectiveThis study aims to identify patients who can be delabeled and to evaluate patients who are likely to be delabeled using AAAT. MethodsPatients admitted to the hospital between January 1, 2017, and December 31, 2021, with documented penicillin allergy labels were included in the study. Patients who demonstrated tolerance to labeled antibiotics or were labeled without explicit allergy declarations were defined as delabeling. Subsequently, patients who did not meet the criteria for delabeling were evaluated for their potential to be delabeled using the AAAT, retrospectively. Results530 patients were selected, of which 62 (11.7 %) were delabeled. The AAAT evaluation of the remaining patients indicated that at least an additional 137 (25.8 %) patients could potentially be delabeled. ConclusionThe use of AAAT demonstrated the potential to delabel approximately third as many patients without the need for specialist evaluation. To promote broader delabeling efforts in the future, prospective studies should investigate the safety and effectiveness of evaluation tools such as the AAAT.

Drug Allergies in Older Adults: A Major Problem in a Specific Population

Introduction: The use of medications in older adults is increasing due to the prevalence of chronic diseases. Data on the characteristics of drug allergies (DAs) in older adults are limited. This study investigated the prevalence and clinical characteristics of DAs in patients aged 65 years and older. Methods: Patient records were examined retrospectively between January 2018 and December 2022. The study included 200 patients aged ≥18 years who met the criteria for diagnosis of type B drug reactions. The patients were divided into two groups: the adult group (18–64 years) and the older adult group (≥65 years). Results: Advanced age was an independent risk factor for the development of anaphylaxis and immediate and delayed hypersensitivity reactions (odds ratio [OR] = 4.296; 95% confidence interval [CI] = 1.700–10.855; p = 0.002, OR = 3.800; 95% CI = 1.247–11.579; p = 0.019, OR = 3.028; 95% CI = 1.248–7.343; p = 0.014, respectively). Older adults had higher rates of comorbidities and polypharmacy (p < 0.001, p = 0.016, respectively), beta-lactam antibiotic allergy (p < 0.001), and hospitalization and intensive care unit (ICU) admission for DAs (p = 0.024, p = 0.045, respectively). Conclusion: Older age was an independent risk factor for anaphylaxis and both immediate and delayed reactions. Older adults had higher rates of comorbidities, polypharmacy, beta-lactam antibiotic triggers, and hospitalization and ICU admission.

Patient-related factors impact the implementation of inpatient antibiotic allergy delabeling

BackgroundThe clinical consequences of an antibiotic allergy label (AAL) are detrimental impacting health care delivery and patient outcomes. We assessed hospital inpatients with intent to offer free AAL assessment within a randomised controlled trial (RCT). ObjectiveTo determine the feasibility of establishing an adult antibiotic allergy delabeling service in a Western Australian tertiary public hospital. MethodsInpatients (N=1503) with AAL were identified through medical records and screened for eligibility to participate in an RCT. Those recruited were randomised to undergo assessment by skin testing +/- oral challenge, or direct oral challenge. A control group received usual care. ResultsOf the 1503 inpatients with an AAL, 429 (28.5%) were eligible for AAL assessment. The primary excluding factor (1,074, 71.5%) was contraindicated medication use (387, 36.0%), followed by cognitive impairment (298, 27.9%). Thirty-nine patients were randomised, 20 received allergy testing and 19 usual care; all patients were followed up for 5 years. Older patients were less likely to be eligible (10- year increase: OR = 0.82, 95% CI = 0.77-0.88, p<0.0001); whilst surgical patients were more likely to be eligible than medical patients (OR = 2.49, 95% CI = 1.97-3.16, p<0.0001). ConclusionsAntibiotic allergy delabeling in the acute care context is not straightforward. Competing clinical concerns and patient acceptance are some barriers to an inpatient service. Nor is it apparent that inpatient vs outpatient testing is cost saving although select patient groups may benefit. Testing younger people and those with predicted high antibiotic usage will derive maximal individual and health system benefits.

Patient-related factors drive high rates of reported antibiotic allergies: A qualitative study

BackgroundUnnecessary antibiotic avoidance due to allergy fears has adverse cost and health implications however, the problem is difficult to resolve because patient and provider-related factors leading to avoidance are multifactorial. We use qualitative research methods to explore patient perspectives of antibiotic allergy and testing to reach the heart of the problem. ObjectiveTo reveal factors leading patients to report antibiotic allergy, and determine what education is required to prevent the cycle of erroneous allergy reporting. MethodsThe 29 patients were a sample of convenience recruited from a tertiary public hospital in Western Australia between March 2020 until August 2020; 18 were inpatients and 11 outpatients, with a median age of 64.2 years, and 15 (55%) were female. Semi-structured interviews assessed patients’ understanding and knowledge of three topics: (1) antibiotic allergy, (2) antibiotic allergy testing, and (3) outcomes of testing. Interview transcripts underwent thematic analysis by two researchers, independently. ResultsThree main, overlapping themes emerged as influential across topics: (1) Severity of the Index Reaction, (2) Trust in family and health care providers, and (3) Health literacy. Patients were largely unaware of the benefits of confirmatory testing, and the detrimental health consequences of unnecessary avoidance. Patients displayed trust in health care providers’ expertise and assumed that medical records were accurate to prevent prescribing errors. ConclusionsThe findings provide evidence for an effective patient education strategy and highlight failures among hospital and primary health providers to recognise the potential harm of unverified antibiotic allergy. Healthcare professionals are influential at multiple steps of a patient's healthcare journey and addressing unconfirmed antibiotic allergy should be taken at each opportunity.

Validation of a digital self-assessment to identify low-risk penicillin and sulfa antibiotic allergies in adults (SELF-FAST)

Validation of a digital self-assessment to identify low-risk penicillin and sulfa antibiotic allergies in adults (SELF-FAST)

Comparing Skin and Serum Testing to Direct Challenge Outcomes in Children With β-Lactam Allergies

BackgroundThere is a scarcity of prospective studies investigating the relative roles of skin prick and intradermal testing, serum-specific Immunoglobulin E, and extended oral challenges in diagnosing children with reported beta-lactam allergies. ObjectiveTo determine the sensitivity and specificity of skin testing and serum-specific Immunoglobulin E in children with beta-lactam allergies, with immediate and non-immediate historic reactions. MethodsFour hundred children with parent-reported beta-lactam allergies were recruited into an open-label prospective study. Detailed allergy histories were collected. Those with medically observed and documented histories of anaphylaxis, requiring epinephrine, or SCARs were excluded. In total, 380 children underwent all testing modalities and a direct provocation test. Each child was followed up for a minimum of three years. ResultsTrue allergy in children was uncommon, 8·3% reacted to the direct provocation challenge or the 5-day extended oral provocation challenge. Children reporting cephalosporin allergy or a reaction within one year were more likely to react to direct provocation testing. The sensitivity, specificity, and positive predictive value of skin testing was 12·5%, 98·8% and 20·0% for direct challenge outcomes, 4·76%, 99·0% and 25·0% for extended challenge outcomes, and 6·9%, 99·0% and 40·0% for both challenges combined. Follow-up investigations revealed that 5·7% of children had a mild repeat reaction and 2·7% continued to avoid the culprit despite successful delabeling. The relabeling rate for children readmitted to hospital was 15% with the relabeing being unfounded. ConclusionGenuine beta-lactam allergies were rare, with over 90% of children effectively delabeled. Skin and serum-specific Immunoglobulin E testing did not aid the diagnosis of beta-lactam antibiotic allergy in children, regardless of medical history. Extended oral challenges proved valuable in confirming allergies and boosted parental confidence.

Effectiveness of direct delabelling of allergy labels in type A adverse drug reactions to penicillin: a multicentre hospitalwide prospective cohort study.

Patient-reported penicillin allergy labels (PALs) are associated with adverse patient outcomes and inappropriate antibiotic prescribing. Removal of PALs via direct oral challenge (DOC) is associated with increased penicillin utilization post removal. To assess the impact of direct delabelling (allergy label removal via medical reconciliation alone) of type A adverse drug reaction (ADR) PALs on inpatient prescribing. From January 2019 to December 2022 at two tertiary hospitals in Melbourne, patients aged ≥18 years with type A ADR PALs, as defined by the validated Antibiotic Allergy Assessment Tool, were offered direct delabelling or single-dose DOC. The primary endpoint was antibiotic use pre- and post-assessment (during index admission and 90 days post assessment). The secondary endpoint was the proportion of patients delabelled in the direct delabelling and DOC cohorts in the electronic medical record at 90 days post assessment. Allergy labels (n = 4108) were assessed for 488 participants, with 490 individual type A ADR PAL assessments included. Three hundred and thirty-seven patients were directly delabelled, 69 underwent DOC and 84 were not delabelled. There was increased use of any penicillin following direct delabelling (OR 19.19, 95% CI 2.48-148.36) and DOC (OR 56.98, 95% CI 6.82-476.19) during the index admission, higher in the DOC group compared with direct delabelling (OR 2.97, 95% CI 1.39-6.37). Relabelling at 90 days was low with no statistically significant difference between direct delabelling (5/337; 1.5%) and DOC (0/69; 0%). Both direct delabelling and DOC of type A ADR PALs increased penicillin usage; however, the impact was greatest with DOC. Most patients remain delabelled at 90 days.

Antibiotic Allergies in Children: Clinical Impact and Emerging Strategies in Management.

Antibiotic Allergies in Children: Clinical Impact and Emerging Strategies in Management.

First-line treatment with ceftriaxone for Neisseria gonorrhoeae infection less likely to be prescribed to patients with a penicillin allergy label: a retrospective audit of medical records.

Background Gonorrhoea notifications have increased substantially in Australia over the past decade. Neisseria gonorrhoeae is already highly resistant to several antibiotics and so, alternatives to first-line treatment are generally strongly discouraged. The penicillin allergy label (AL) on patient medical records has previously been shown to influence prescribing practices, to the detriment of best-practice management and antimicrobial stewardship. This study aimed to understand how the penicillin AL influences antibiotic selection for gonorrhoea treatment at Canberra Sexual Health Centre. Methods A retrospective chart audit of gonorrhoea cases treated at Canberra Sexual Health Centre between January 2020 and October 2023 (n =619 patients, n =728 cases). Antibiotic selection was assessed according to penicillin AL status. Ceftriaxone selection was assessed according to penicillin allergy severity reported in the medical records and as determined using a validated antibiotic allergy assessment tool. Results Cases with a penicillin AL were more likely to receive antibiotics other than ceftriaxone (n =7/41, 17.1%) than cases without the label (n =8/687, 1.2%, P n =28/41, 68.3%) to apply the assessment tool. Those reported as low-severity in the records were more likely to receive ceftriaxone (n =21/22, 95.5%) than those reported as moderate-high (n =7/11, 63.6%) or unreported (n =6/8, 0.75%). Conclusions Treatment of gonorrhoea in outpatient settings requires an understanding of penicillin allergy, and the ability to quickly and accurately identify penicillin-AL patients who can safely tolerate ceftriaxone. Institutionally endorsed penicillin allergy de-labelling protocols and access to easy-to-navigate prescribing advice within national sexually transmitted infection management guidelines would support this.

The appropriateness of penicillin allergy de-labelling by non-allergist clinical ward teams

ObjectivesWe aimed to assess the appropriateness of penicillin allergy (PenA) assessment conducted by clinical teams and to review the safety of subsequent exposure of these patients to penicillin. MethodsOpportunistic, prospective observational study of usual clinical care, between 16 May 2023 and 14 August 2023, of inpatients with a PenA and requiring antibiotics, in a 750-bed hospital in England. To assess the appropriateness of management, PenA patients prescribed penicillins were grouped into risk categories using a validated antibiotic allergy assessment tool: eligible for de-label on history alone (direct de-label; DDL), eligible for direct oral challenge (DOC), high risk or unable to obtain history. ResultsOf the 123 patients admitted with a PenA (or sensitivity record) and exposed to a penicillin, data were collected for 50. Their PenA records were grouped follows: eligible for DDL 34 (68%), eligible for DOC 11 (22%), high risk 4 (8%) and unable to obtain history 1 (2%). In 14/50 (28%) patients there was no evidence of a current PenA assessment in the medical notes. ConclusionsUsing the allergy risk tool, most patients with PenA records were exposed to penicillin appropriately. However, patients meeting high-risk criteria were also exposed to penicillin when the tool excluded them. PenA assessment needs to be carried out with appropriate training and governance structures in place.

Penicillin allergy-Truth or duty?

The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show anegative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play acentral role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and arisk stratification for the identification of patients with apenicillin allergy. This overview article presents apossible delabelling algorithm within the framework of the clarification of abeta-lactam antibiotic allergy. The focus is on astructured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score.

Antibiotic allergy prevalence and documentation quality in Massachusetts long-term care facilities: A cross-sectional survey

BackgroundAntimicrobial resistance poses a significant global health challenge, particularly affecting older adults who are more susceptible to infections and their complications. Accurate diagnosis and documentation of antibiotic allergies are essential for effective antimicrobial stewardship. Despite the recognized overdiagnosis of antibiotic allergies, comprehensive studies on this subject in long-term care (LTC) settings are limited. ObjectiveTo determine the point prevalence of antibiotic allergies and documentation quality in Massachusetts LTC facilities. MethodsWe conducted a cross-sectional, 1-day point prevalence survey from July 1, 2023, to March 31, 2024, across 20 participating LTC facilities in Massachusetts in partnership with the Massachusetts Department of Public Health. The survey assessed the prevalence and documentation of antibiotic allergies among 2345 residents. Multivariable logistic regression was used to explore associations between documented penicillin allergy and demographic factors, including non-penicillin antibiotic allergies. ResultsThe overall point prevalence of documented antibiotic allergies was 39.1%, with the most frequently reported classes being penicillins at 23.1%, sulfonamides at 15.4%, and cephalosporins at 5.2%. Significant documentation gaps were identified, with up to 92.8% of the allergy records found to be incomplete. Factors associated with documented penicillin allergies included female sex (adjusted odds ratio [aOR], 1.50; 95% CI, 1.16-1.94), White race (aOR, 1.92; 95% CI, 1.25-2.94), having allergies to non-penicillin antibiotics (aOR, 2.89; 95% CI, 2.33-3.59), and receipt of antibiotic (aOR, 2.13; 95% CI, 1.68-2.71). ConclusionThe high prevalence of documented antibiotic allergies and the notable deficiencies in their documentation underscore the urgent need for enhanced antibiotic evaluation, documentation practices, and penicillin delabeling in LTC facilities.

Impact of Sulfonamide Allergy Label on Clinical Outcomes in Patients with Pneumocystis jirovecii Pneumonia.

The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP). In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30days after the occurrence of the index event. While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls. The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.

Beta-lactam allergy risk stratification in a maternity population in Australia: Scope for allergy de-labelling.

Unconfirmed beta-lactam allergy in pregnant people has been associated with higher morbidity, unnecessary exposure to broad-spectrum antibiotics and prolonged hospitalisation. There are no published data on beta-lactam allergies in pregnant people in Australia. The aim was to describe patient-reported beta-lactam allergies and appropriateness for antibiotic allergy de-labelling in a maternity cohort in Australia. Maternity patients aged ≥18 years admitted to our institution between March 2021 and June 2021 with a beta-lactam allergy documented in their electronic medical record were interviewed for details of their allergy. The documented allergies were compared to the allergy history obtained from the interview. Severity of the allergy was rated, and appropriateness for allergy de-labelling was assessed using the Victorian Therapeutics Advisory Group beta-lactam antibiotic allergy assessment tool. One hundred and fifty-three beta-lactam allergies (182 reactions) were reported by 145 patients. Penicillin class antibiotics were the most frequently implicated, including unspecified penicillins (95/153, 62%), amoxicillin (19/153, 13%) and amoxicillin-clavulanate (8/153, 5%). Allergy documentation required amending in 52 of 145 patients (36%); 85 of 153 (56%) of the beta-lactam allergies were considered low risk and potentially appropriate for direct oral re-challenge. Beta-lactam allergies were inaccurately documented in more than one third of the maternity patients included in our study. As such, education of maternity care providers about the importance of accurate allergy history taking remains an urgent unmet need. Furthermore, allergy assessment and de-labelling during pregnancy should be considered in maternity patients to optimise antibiotic prescribing and to improve maternal and neonatal health outcomes.

The Role of Medical History and Allergic Tests in the Analysis of Antibiotic Allergy in the Pediatric Population

The Role of Medical History and Allergic Tests in the Analysis of Antibiotic Allergy in the Pediatric Population