History Of Penicillin Allergy Research Articles

Carbapenem Appropriateness in a Rural Facility

Objective Inappropriate carbapenem prescribing leads to increased resistance, secondary infections, serious side effects, and wasted resources. A history of penicillin allergy has been identified as a potential trigger for inappropriate carbapenem prescribing. The PEN-FAST score is a validated tool that provides a high negative predictive value for allergic reaction with low scores. The objectives of this study were to determine the proportion of imipenem/cilastatin and meropenem prescriptions deemed appropriate according to published criteria and to evaluate the proportion of penicillin allergies with a low PEN-FAST score. Methods A convenience sample of 100 carbapenem prescriptions (imipenem/cilastatin [n = 50] and meropenem [n = 50]) was evaluated with a retrospective chart review. Objective published criteria were used to assign a score of appropriate, suboptimal, or inappropriate. In patients with a history of penicillin allergy, a PEN-FAST score was retrospectively applied. Indications for use and risk factors for resistant infections were also recorded. Analysis was largely descriptive statistics, with a χ2 used to compare drug cohorts in R Studio. Results Prescribing was considered appropriate (25%), suboptimal (20%), and inappropriate (55%) in the combined cohort. Inappropriate prescribing was more common with imipenem/cilastatin (66% vs. 44%, P = 0.03). In 28 patients with a historical penicillin allergy, the PEN-FAST score was 0 (low risk for reaction) in the majority of cases (93%). Conclusions Inappropriate carbapenem prescribing is common at the study facility and may benefit from directed antimicrobial stewardship measures. Implementing the PEN-FAST scoring method may be beneficial in a multifaceted intervention.

Rupioid psoriasis: A complex, multifactorial presentation

Introduction: Secondary syphilis, also termed the great mimicker due to its vast array of clinical presentations, is associated with skin manifestations including rupioid, macular, psoriasiform, and condylomatous lesions. On clinical examination alone, it can be difficult to differentiate between rupioid syphilis and rupioid psoriasis, especially among cases of human immunodeficiency virus (HIV) and syphilis co-infection; however, histologic examination can aid in their differentiation. Additional testing such as serum rapid plasma reagin (RPR), anti-HIV antibody, rheumatoid factor, and fungal cultures should be performed to exclude other causes of rupioid lesions. Case Report: A 19-year-old HIV-positive male developed numerous hyperkeratotic skin lesions involving the head, trunk, and extremities over a 4-week period. His RPR was positive (1:64), suggesting a diagnosis of rupioid syphilis. The patient was treated with doxycycline, given a reported history of penicillin allergy. Rapid plasma reagin titers decreased to 1:2 following treatment; however, the skin eruption did not improve. A biopsy of a lesion demonstrated psoriasiform acanthosis with confluent hyperkeratosis, clusters of intracorneal neutrophils, and negative spirochete immunostaining. Based on histopathology and clinical presentation, a diagnosis of rupioid psoriasis was favored. The patient was started on targeted anti-psoriatic therapy with apremilast and maintains close follow-up with his dermatologist every three months. Conclusion: Although the patient’s presentation was initially presumed to be secondary to syphilis, his lack of response to treatment prompted further workup to assess the etiology of the patient’s skin findings more accurately. In doing so, a diagnosis of rupioid psoriasis was favored based on the histologic findings observed.

In-Office Amoxicillin to Increase Graded-Dose Challenges at Initial Evaluation for Penicillin Allergy.

More than 90% of pediatric patients labeled with a penicillin allergy can tolerate subsequent treatment courses without reaction. Graded-dose challenges (GDCs) are an important tool to clarify reported penicillin allergy. To increase the use of same-day amoxicillin GDCs among patients with a low-risk penicillin allergy history who presented for outpatient allergy office evaluation from 2% to 15% and sustain for 6 months. New patients evaluated in an academic pediatric allergy clinic with a documented penicillin allergy were included, regardless of reason for referral. The percentage of these patients who were administered a GDC to amoxicillin at the initial evaluation was assessed over time. Multiple interventions were implemented to increase same-day GDC: amoxicillin, previously only available from pharmacy, was made available in clinic, and penicillin-allergic patients were scheduled earlier in the clinic session. The baseline rate of new patients with penicillin allergy who received a GDC increased from 2% to 18% after amoxicillin was stocked in the allergy clinic. GDCs further increased to 34% after penicillin-allergic patients were scheduled at a time conducive to challenge. Amoxicillin availability in the clinic setting increased the percentage of eligible patients who completed same-day GDCs. Scheduling adjustments further increased the ability to conduct GDCs. Proactive penicillin allergy delabeling efforts can be assisted through practical approaches in the outpatient setting.

Pregnant Patients with a Documented History of Penicillin Allergy and Associated Maternal and Neonatal Outcomes at a Tertiary Care Center.

Pregnant individuals are likely to need antibiotics during the peripartum period. For pregnant individuals who report a history of penicillin allergy, non-β-lactam antibiotics are often administered. Compared with first-line β-lactam antibiotics, alternative antibiotics can be less effective, more toxic, and more costly. It remains unclear if being labeled with a penicillin allergy is associated with adverse maternal and neonatal outcomes. We conducted a retrospective cohort study of all pregnant patients who delivered a viable singleton between 24 and 42 weeks of gestation at a large academic hospital from 2013 to 2021. We compared patients who had a documented penicillin allergy history in their electronic medical record versus those who did not and examined whether there were significant differences in maternal outcomes and neonatal outcomes. Bivariable and multivariable analyses were performed. Of 41,943 eligible deliveries included in the analysis, 4,705 (11.2%) patients had a penicillin allergy history documented in their electronic medical record and 37,238 (88.8%) did not. Even after adjusting for potential confounders, patients with a documented penicillin allergy had a higher risk of postpartum endometritis (adjusted odds ratio [aOR]: 1.46; 95% confidence interval [CI]: 1.01-2.11) and a higher risk of their neonates having a postnatal hospital stay lasting more than 72 hours (aOR: 1.10; 95% CI: 1.02-1.18). There were no significant differences seen in the other maternal and neonatal outcomes in both bivariable and multivariable analyses. Pregnant patients who are labeled as having a penicillin allergy are more likely to have postpartum endometritis, and neonates born to mothers who are labeled as having a penicillin allergy are more likely to have a postnatal hospital stay lasting more than 72 hours. There were no other significant differences seen in pregnant patients and their newborns whether they were labeled as having a penicillin allergy history or not. However, pregnant individuals with a penicillin allergy documented in their medical record were significantly more likely to receive alternative non-β lactam antibiotics, and may have benefitted from having more details of their allergy history available as well as proper allergy verification with testing. · It is unclear whether pregnant individuals labeled with penicillin allergies have worse obstetric outcomes.. · These individuals were significantly more likely to have endometritis and their newborns hospitalized for >72 hours.. · They were significantly more likely to receive alternative non-β lactam antibiotics than those without documented allergies..

A pharmacist-led penicillin allergy de-labelling project within a preoperative assessment clinic: the low-hanging fruit is within reach

Having a false penicillin-allergy label is linked to longer hospital stays and to an increased risk of Clostridioides difficile and meticillin-resistant Staphylococcus aureus infection. To assess a penicillin-allergy de-labelling tool designed for use by the non-allergist. Patients attending the surgical preoperative assessment clinic (POAC) at a large UK teaching hospital, who reported a penicillin allergy, were directly de-labelled by nursing or pharmacy staff, where appropriate. A penicillin-allergy de-labelling tool designed for use by the non-allergist was adapted and applied; nursing staff were provided with supporting information and education to enable removal of spurious labels. Antimicrobial pharmacists (AMPs) provided follow-up, cross-checked prophylactic antibiotics administered, interrogated clinical notes, and telephoned patients following their surgery, for details of any adverse reactions suffered. A total of 163 patients reporting a penicillin allergy were identified for intervention. Twenty-nine (17.8%) patients reported a penicillin-allergy history appropriate for direct de-labelling, of whom eight (27.6%) declined to consent. The remaining 21 patients (12.8%) were directly de-labelled, with 12 (7.4%) patients consenting during their POAC appointment; the remaining nine (5.5%) patients were consented and de-labelled after their surgery by an AMP. The POAC was identified as an appropriate location and time-point in the patient pathway to enable the direct removal of spurious penicillin-allergy labels prior to surgery. Results suggest that this could be undertaken by nursing staff, although support from AMPs enabled a greater number of patients to be de-labelled.

Phase 1b/2 dose expansion, open-label study to evaluate safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer.

TPS4618 Background: Bladder cancer is the most common malignancy involving the urinary system, with over 700,000 individuals living with bladder cancer in the US in 2019. In the US, approximately 80,000 new cases and 18,000 deaths occur each year due to bladder cancer. Approximately 70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC). With the current Bacillus Calmette-Guerin (BCG) shortage and limited effective alternate therapies, there continues to be a significant unmet need for treatment options for patients with NMIBC. TARA-002 is being developed for intravesical instillation for the treatment of high-grade (HG) NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. The chemical characteristics of TARA-002 are intended to be comparable to OK-432. Therefore, nonclinical and clinical evidence with OK-432 and TARA-002 support the ADVANCED-1 study (dose escalation Phase 1a [NCT05085977] and dose expansion Phase 1b/2 [NCT05085990]). The dose for the planned Phase 1b/2 study (ADVANCED-1-Ph1b/2) will be based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study. Methods: ADVANCED-1-Ph1b/2 is a Phase 1b/2, dose expansion, open-label study of intravesical instillation of TARA-002 in adults with HG carcinoma in situ (CIS) NMIBC. The purpose of this study is to evaluate the safety and anti-tumor activity of TARA-002 administered intravesically for the treatment of subjects with CIS NMIBC (± Ta/T1) with active disease. The study includes approximately 102 eligible male and female subjects ≥ 18 years of age enrolled in 2 cohorts based on their prior BCG experience. Cohort A includes subjects unable to obtain BCG or subjects who have not received BCG in the last 24 months prior to CIS diagnosis, and Cohort B includes subjects with CIS who are BCG unresponsive after completion of adequate BCG therapy (at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course). Those with current or a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The overall study duration is 6 months/24 weeks per subject for Ph1b/2-Cohort A (includes induction, reinduction [if applicable]), and 24 months/96 weeks per subject for Ph1b/2-Cohort B (includes induction, reinduction [if applicable], maintenance until 18 months). The ADVANCED-1 study started in March 2022. Phase 1a is open for enrollment. Phase 1b/2 is expected to begin enrollment in May 2023. Clinical trial information: NCT05085977 ; NCT05085990 .

Inaccurate penicillin allergy labels: Consequences, solutions, and opportunities for rhinologists.

A patient-reported history of penicillin allergy is a common label with a prevalence of about 10%. However, as many as 95% of patients reporting a penicillin allergy do not have a true immunoglobin-E (IgE)-mediated allergic reaction. Unfortunately, penicillin allergy mislabeling is problematic, leading to inappropriate antibiotic use and negative consequences, such as adverse drug events, suboptimal outcomes, and increased costs. As physicians who treat patients of all ages for common sinonasal pathology in the clinic and operating room in addition to frequently providing testing and management of allergic diseases, rhinologists are well positioned to aid in delabeling patients with inaccurate penicillin allergies. This viewpoint highlights the consequences of inaccurate penicillin allergy designation in the clinic and perioperative period and explores misconceptions regarding cross-reactivity between penicillins and cephalosporins. Opportunities are explored for shared decision-making with colleagues in other specialties, such as anesthesiology, and practical recommendations are provided to aid rhinologists when faced with a patient who holds a questionable history of penicillin allergy. Rhinologists can play an active role in delabeling patients with inaccurate penicillin allergies with the goal of ensuring appropriate antibiotic use for future medical encounters.

MP08-05 PHASE 1a/b STUDY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023MP08-05 PHASE 1a/b STUDY OF INTRAVESICAL INSTILLATION OF TARA-002 IN ADULTS WITH HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER William Tabayoyong, Edward Messing, Sima Porten, Donald Lamm, Jathin Bandari, Jacqueline Zummo, Wei Sun, Khushboo Belani, Andrea DiFiglia, Eppie Brown, McKenna Metcalf, and Nuwan Nanayakkara William TabayoyongWilliam Tabayoyong More articles by this author , Edward MessingEdward Messing More articles by this author , Sima PortenSima Porten More articles by this author , Donald LammDonald Lamm More articles by this author , Jathin BandariJathin Bandari More articles by this author , Jacqueline ZummoJacqueline Zummo More articles by this author , Wei SunWei Sun More articles by this author , Khushboo BelaniKhushboo Belani More articles by this author , Andrea DiFigliaAndrea DiFiglia More articles by this author , Eppie BrownEppie Brown More articles by this author , McKenna MetcalfMcKenna Metcalf More articles by this author , and Nuwan NanayakkaraNuwan Nanayakkara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer is the most common malignancy involving the urinary system, resulting in ∼18,000 US deaths/year; ∼70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC). TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin and is being developed for the treatment of high-grade (HG) NMIBC. TARA-002 is manufactured using the same master cell bank as OK-432 (Picibanil®). OK-432 is approved in Japan and Taiwan for the treatment of several oncology indications. We report on the design and progress of study ADVANCED-1 (NCT05085977; NCT05085990). METHODS: ADVANCED-1 is a P1a/b, dose finding, open-label study of intravesical TARA-002 in adults ≥ 18 yrs with HG NMIBC. The purpose of 1a dose escalation is to establish the maximum tolerated dose (MTD) and recommended P2 dose (RP2D) for the treatment of HGTa or CIS NMIBC (±Ta). The purpose of 1b dose expansion is to evaluate the anti-tumor activity and safety of induction ± re-induction of TARA-002 for the treatment of CIS NMIBC (±Ta/T1) with active disease at the established RP2D. 1a includes up to 18 subjects at 3 doses (10 KE, 20 KE, 40 KE) in a 3+3 design; 1b includes ∼102 subjects enrolled in 2 cohorts based on prior BCG experience: Cohort A includes subjects unable to obtain BCG and BCG-exposed subjects who have not received BCG in the last 24 months; Cohort B includes subjects with BCG unresponsive CIS. Those with a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The duration is 12 weeks per subject for 1a (includes induction), 6 months per subject for 1b-Cohort A (includes induction, reinduction [if applicable]), and 24 months per subject for 1b-Cohort B (includes induction; reinduction [if applicable]; maintenance until 18 months). RESULTS: In the 1a, at the time of writing, 3 subjects (2 female; 1 male) 66-80 yrs have completed treatment with TARA-002 at 10 KE with no dose limiting toxicities (DLT), and enrollment at 20 KE is ongoing. CONCLUSIONS: The 1a will establish the RP2D of TARA-002 and 1b will provide further evidence of anti-tumor activity and safety of TARA-002. Source of Funding: Protara Therapeutics, Inc. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e94 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Tabayoyong More articles by this author Edward Messing More articles by this author Sima Porten More articles by this author Donald Lamm More articles by this author Jathin Bandari More articles by this author Jacqueline Zummo More articles by this author Wei Sun More articles by this author Khushboo Belani More articles by this author Andrea DiFiglia More articles by this author Eppie Brown More articles by this author McKenna Metcalf More articles by this author Nuwan Nanayakkara More articles by this author Expand All Advertisement PDF downloadLoading ...

Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy

BackgroundMeropenem is a widely prescribed beta-lactam for hospitalized patients. There are few data on meropenem allergy assessments in inpatients with a reported history of penicillin allergy who require a treatment with meropenem. This can lead to the use of less effective second-line antibiotics that may increase antibiotic resistances. We aimed to evaluate the clinical outcomes of a meropenem allergy assessment in admitted patients with a reported history of penicillin allergy that required meropenem for the treatment of an acute infection. MethodsA retrospective analysis was performed on 182 inpatients labelled with a penicillin-allergy who received meropenem after an allergy assessment. The allergy study was performed bedside if meropenem was required urgently. The study included skin prick tests (SPTs) followed by an intradermal skin test (IDT) to meropenem, and a meropenem drug challenge test (DCT). If a non-immediate reaction to a beta-lactam was suspected, it was initiated with patch tests. ResultsThe median age of the patients was 59.7 years (range 28–95) and 80 (44%) were women. A total of 196 sets of diagnostic workups were performed, with 189 (96.4%) of them being tolerated. Only two patients had a positive meropenem IV DCT, both presenting a non-severe cutaneous reaction that completely resolved after treatment. ConclusionsThis study evidenced that a bedside meropenem allergy assessment of hospitalized patients labelled with a ‘penicillin allergy’ who require a broad-spectrum antibiotic for empiric coverage is a safe and effective procedure, avoiding the use of second-line antimicrobial agents.

Can clarithromycin be used without testing in patients with penicillin allergy?

BackgroundPenicillin hypersensitivity is a common cause of suspected and proven drug allergy and drug-induced anaphylaxis in medical records and causes social and economic burdens. ObjectiveSince the rate of clarithromycin hypersensitivity is low in the general population, we aimed to investigate whether clarithromycin can be prescribed to patients with penicillin allergy without a provocation test. MethodsThe medical records of 186 patients referred to our clinic between 2015 and 2021 with a history of penicillin allergy were evaluated retrospectively. Patients having a history of at least two immediate-type hypersensitivity reactions with penicillin antibiotics or having a history of immediate-type hypersensitivity with penicillin and diagnosed by positive penicillin V/G specific IgE and/or penicillin skin tests were included in the study. Penicillin skin tests were performed according to the manufacturer's instructions. Concentrations of serum specific IgE against phenoxymethylpenicillin (penV) and benzylpenicillin (pen G) were determined using The Phadia CAP System FEIA method. An oral drug provocation test with clarithromycin was performed in all patients. ResultsThe data of 64 patients diagnosed with penicillin allergy and who underwent clarithromycin oral provocation test were analyzed. Oral provocation test with clarithromycin was positive in only two of these patients (3%). These two patients had a history of multidrug hypersensitivity, and one of them also had food and venom allergies. ConclusionWe suggest that clarithromycin can be given without an oral provocation test when an alternative antibiotic is required in patients with penicillin allergy and without multidrug hypersensitivity.

Implementing Preoperative Penicillin Allergy Testing in Surgical Patients.

Penicillin allergy is the most reported immunoglobulin E (IgE)-mediated reaction. About 10% of the general population and 20% of hospitalized patients have a history of penicillin allergy. Unconfirmed penicillin allergy with subsequent administration of second-line antibiotics has been associated with increased morbidity. However, when penicillin allergy testing is performed, the incidence of IgE-mediated reactions is extremely low; in fact, the negative predictive value of penicillin allergy testing exceeds 99%. This article aims to briefly describe implementing safe penicillin allergy testing as a routine test during the preoperative evaluation of surgical patients.

Surgical antimicrobial prophylaxis : frequent questions in the perioperative setting

Surgical Site Infections account for 15-30% of healthcare-associated infections. Surgical antibiotic prophylaxis is one of well-documented measures to decrease the risk of infections. However, many situations threaten its proper application and thereby its effectiveness: patient already receiving antibiotics or carrying resistant germs, clinicians' misunderstanding about timing and duration of antibiotic prophylaxis or patient history of penicillin allergy. In this article we try to clarify these situations to favour good practice in perioperative antibiotic prophylaxis.

Barriers to paediatric penicillin allergy de-labelling in UK secondary care: a regional survey

BackgroundIncorrect penicillin allergy labels result in the use of inappropriately broad-spectrum antibiotics. De-labelling inaccurate penicillin allergy promotes antimicrobial stewardship and optimises prescribing practices. The objectives were to evaluate paediatric clinicians’...

1663. Risk-benefit assessment of cefazolin use for surgical site infection prevention among patients allergic to penicillins and cephalosporins

Abstract Background Prosthetic joint infection (PJI) is a devastating complication following knee and hip arthroplasty. Perioperative antibiotics are routinely used in an effort to decrease the risk of surgical site infections (SSI), including superficial skin infections and deep PJI. The American Academy of Orthopedic Surgeons recommend cefazolin as standard of care for SSI prophylaxis. However, non-beta-lactams are often used in patients labeled as allergic to penicillins or cephalosporins due to concern of increased hypersensitivity reactions (HSR). Methods This study examined the frequency of SSI and HSR after receipt of perioperative cefazolin compared to clindamycin and/or vancomycin (C/V) within adult patients labeled as allergic to penicillins or cephalosporins. Patients were included if they underwent primary total hip or knee replacement surgery between January 2020 and July 2021 within the University of Colorado Health system. The outcome of SSI was assessed up to 90 days after surgery. The outcome of HSR was assessed up to 60 minutes after the conclusion of surgery. Results The cohort included 1,128 patients (cefazolin, n=809; C/V, n=319). Baseline characteristics were similar between groups except the proportion of patients with a history of immediate allergy symptoms was greater in the C/V group (59.6%) compared to the cefazolin group (35.8%). The frequency of SSI was lower in the cefazolin group compared to the C/V group (0.9% vs. 3.8%, p < .01). The cefazolin group included 7 SSI, consisting of 6 superficial SSI and 1 deep PJI. The C/V group included 12 SSI, consisting of 6 superficial SSI and 6 deep PJI. HSR were not significantly different between patients receiving cefazolin vs. C/V (0.2% vs. 1.3%, p=.06). HSR in the cefazolin group consisted of skin involvement (n=1) and self-reported allergy in post-operative window (n=1). Both patients had a non-descript history of penicillin allergy. HSR in the C/V group consisted of skin involvement (n=2) and hemodynamic instability (n=2). Three of the four patients had a history of immediate cephalosporin allergy. Conclusion Among penicillin or cephalosporin allergic patients, the use of cefazolin was associated with a lower frequency of PJI without an increase in HSR during surgery. Disclosures All Authors: No reported disclosures.

Single-step Direct Drug Provocation Testing is Safe for Delabelling Selected Non−low-risk Penicillin Allergy Labels

To describe the outcome of an oral amoxicillin challenge in patients labeled allergic to penicillin.One hundred forty nine patients from 1 to 98 years of age labeled allergic to penicillin were included in the study.Patients were categorized as low risk (side effects, family history of penicillin allergy, remote [>5 years] history of penicillin allergy without IgE-mediated features, or unknown reaction not requiring hospitalization, n = 64) or nonlow risk (anaphylaxis, urticaria within 2 hours of penicillin administration, or angioedema with or without urticaria, n = 85). The low risk patients underwent challenge with a single dose of oral amoxicillin (125 mg for patients 1 to 11 months of age, 250 mg for 1 to 11 years, and 500 mg for all patients more than 12 years) followed by 2 hours of observation to evaluate for Gell and Coombs type 1/IgE-mediated/immediate-type hypersensitivity reactions. The nonlow risk patients underwent penicillin skin testing and if negative, oral amoxicillin challenge. Excluded patients were those with history of: (1) Gell and Coombs type 2 reactions, for example, hemolytic anemia or thrombocytopenia; (2) type 3 reactions, for example, serum sickness or vasculitis; or (3) severe type 4 or severe cutaneous adverse reactions, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms.All (64 of 64, 100%) of the low risk patients tolerated the amoxicillin challenge without reaction during the observation period, although 3 developed a maculopapular rash subsequently. All (85 of 85, 100%) of the nonlow risk patients had negative penicillin skin testing, and 84 of 85 (99%) tolerated the amoxicillin challenge without reaction during the observation period, whereas 1 patient developed pruritus and rash that resolved with antihistamine treatment, and 2 subsequently developed a maculopapular rash.The authors conclude that a single step oral amoxicillin challenge is safe.Six percent of children are reported to be allergic to penicillin, although only about 5% of that 6% (0.3%) have positive penicillin skin tests. The remainder either never had IgE-mediated allergy or the allergy was lost over time. Being mislabeled as allergic to penicillin is not benign, but rather leads to suboptimal treatment, more side effects (eg, Clostridium difficile), higher costs, and more antibiotic resistance. Thus, there is currently a strong push to “delabel” the vast majority of children who are labeled as allergic to penicillin but are not. Children are typically referred to allergists to undergo oral amoxicillin challenges under observation with or without prior penicillin skin testing, depending on the history. However, this paper suggests that, given the safety of these challenges, consideration can be given to performing them in pediatricians’ offices. If a careful history excludes patients with histories of “nonlow risk” immediate allergic reactions and those with serious nonimmediate reactions, the remainder with low risk histories can undergo a single dose oral amoxicillin challenge, which the vast majority will tolerate and can be successfully “delabeled.”URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.anai. 2021.04.008

UTILIZATION OF A HOSPITALIST DRIVEN PENICILLIN SKIN TESTING PROTOCOL TO PROMOTE ANTIBIOTIC STEWARDSHIP

<h3>Introduction</h3> Antibiotic resistance is an increasing problem throughout the world. Inappropriate labeling of penicillin allergies results in suboptimal antibiotic selection for patients. Penicillin skin testing is a valuable tool for facilitating a switch to beta-lactam antibiotics. <h3>Methods</h3> A retrospective analysis of all patients with a documented history of penicillin allergy were included in the study from March 2017 to May 2019; a total of 128 patients were included. Analysis involved nature of penicillin allergy and results of penicillin skin test. Benzylpenicilloyl polylysine (PRE-PEN®) tested major determinant, and diluted penicillin G tested minor determinant. The primary outcome of the study is the rate of antibiotic deescalation, and secondary outcome is a comparison of the duration of non beta-lactam therapy in appropriately re-labeled versus non re-labeled subjects (student t-test). <h3>Results</h3> 12 of 128 patients (9.4%) had a negative histamine test and were labeled indeterminate. Of the remaining 116 patients, 111 had a negative test (95.7%) and 5 (4.3%) had a positive test to PRE-PEN ® or dilute penicillin G. 78 of the 111 negative (70.3%) were switched to a narrower spectrum-based antibiotic, and subsequently did not experience allergic reaction. There was a significantly decreased use of vancomycin, aztreonam, carbapenem, fluoroquinolone and clindamycin. There was no significant difference in duration of non beta-lactam therapy in appropriately re-labeled versus non re-labeled subjects (3.6 days vs. 4.25 days; p=0.35). <h3>Conclusion</h3> Our protocol has demonstrated that a penicillin skin testing protocol can substantially reduce broad spectrum antibiotic use and increase antibiotic stewardship.

Techniques for Decreasing Bacterial Load for Open Shoulder Surgery.

Benzoyl peroxide (BPO) 5% has been shown to reduce Cutibacterium acnes load on the skin. BPO 5% with miconazole nitrate (MN) 2% may be beneficial, whereas BPO 5% with clindamycin cream 1% to 1.2% does not seem to have additive effects when compared with BPO 5% alone. Chlorhexidine gluconate solutions reduce the total bacterial load on the skin, but do not seem to have a significant effect on C. acnes. ChloraPrep seems to be the best surgical skin preparation to decrease overall positive skin cultures. Preincisional hydrogen peroxide 3% application has been shown to be a cost-effective practice to inhibit growth of C. acnes. Vancomycin powder before deltopectoral interval closure has antimicrobial effects against C. acnes and is a cost-effective practice. Finally, Bactisure surgical lavage is protective against the formation of biofilms. IV cefazolin has been shown to be more effective for shoulder arthroplasty infection prophylaxis than antibiotic alternatives such as vancomycin. Thus, patients with a questionable history of penicillin allergy should undergo additional testing. For shoulder surgery infection prophylaxis, we recommend the use of BPO 5% cream for 5 days preoperatively with chlorhexidine wipes the night before and the morning of surgery. IV cefazolin should be administered perioperatively, and patients with a questionable history of penicillin allergy should be tested. Surgeons should consider preincisional application of hydrogen peroxide 3% for 5 minutes, followed by standard ChloraPrep preparation. Normal saline should be used for preclosure lavage. Finally, application of vancomycin powder deep to the deltopectoral interval closure should be considered.

IS IT A HERXHEIMER REACTION OR ANAPHYLAXIS COMPLICATING USE OF PENICILLIN IN SYPHILIS TREATMENT?

<h3>Introduction</h3> Herxheimer reactions, similar to anaphylaxis, can occur after the first dose of penicillin and can be associated with dyspnea, hypotension, rash, vomiting and tachycardia. Herein we describe a case regarding a complication of syphilis treatment that was thought to be anaphylaxis, but further investigation suggested Herxheimer reaction. <h3>Case Description</h3> A 62-year-old man with a distant history of syphilis infection was seen by an outpatient ophthalmologist for 1.5 months of rapidly worsening vision in his right eye secondary to ocular syphilis. RPR testing was positive and the patient was directly admitted for treatment. The patient reported developing a reaction to penicillin more than thirty years prior which included vomiting, dyspnea, throat tightening, and a rash fitting the description of urticaria that was reflexively diagnosed as anaphylaxis at the time. Due to the 30-year history of penicillin allergy, the Allergy Immunology Service was consulted. The patient passed the indicated penicillin skin testing and challenge. On further evaluation, it was determined that he previously had rigors, fever, and chills, which were more compatible with Herxheimer Reaction. He was then started on penicillin G 4MU IV q4 hours. Fortunately, he did not develop an "ocular" Herxheimer reaction. <h3>Discussion</h3> Distinguishing anaphylaxis from a Herxheimer reaction in this patient is important for several reasons: (1) treatment can cause an ocular Herxheimer reaction, (2) avoidance of penicillin for 30 years may have led to delayed, more expensive, and less effective therapies, and (3) the cost of skin testing, challenge, and if-needed desensitization could have been avoided based on the history.

The Impact of Patient-Reported Penicillin or Cephalosporin Allergy on the Occurrence of the Periprosthetic Joint Infection in Primary Knee and Hip Arthroplasty.

Reducing the risk of periprosthetic joint infections (PJI) requires a multi-pronged strategy including usage of a prophylactic antibiotic. A history of penicillin or cephalosporin allergy often leads to a change in prophylactic antibiotic regimen to avoid serious side effects. The purpose of the present retrospective study was to determine incidence of PJI based on perioperative antibiotic regimen in total hip arthroplasty (THA), total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA). A review of all primary THAs, primary TKAs and primary UKAs, undertaken between 2011 and 2020 in a tertiary referral hospital, was performed. The standard perioperative antibiotic for joint arthroplasty (JA) in the analyzed tertiary hospital is cefuroxime. There were no differences in prophylactic antibiotic regimen over time. In 7.9% (211 of 2666) of knee arthroplasties and in 6.0% (206 of 3419) of total hip arthroplasties, a second-line prophylactic antibiotic was used. There was no statistically significant higher occurrence of PJI between the first-line and second-line prophylactic antibiotic in knee arthroplasties (p = 0.403) as well as in total hip arthroplasties (p = 0.309). No relevant differences in age, American Society of Anesthesiologists (ASA) score and body mass index (BMI) between the groups were observed.

Drug allergy: A 2022 practice parameter update

Drug allergy: A 2022 practice parameter update