History Of Penicillin Allergy Research Articles

Pediatric Residents Knowledge of Penicillin Allergy.

Penicillin allergy knowledge has not been evaluated specifically in the pediatric resident population. An anonymous electronic survey was distributed to all the pediatric residents in a single residency program to ascertain knowledge of penicillin allergies and allergy history taking skills. Responses among each resident class were compared using the Fisher exact test, 2-tailed. A total of 46 (52%) of 88 pediatric residents completed the survey. Only 63% reported to have had prior penicillin allergy education. All residents incorrectly identified low-risk symptoms as high-risk symptoms. The knowledge of penicillin allergy was poor across all training levels with no improvement over the duration of training. There is large support in the literature for de-labeling penicillin allergy in patients. Pediatric residents evaluate patients in childhood when most of the allergy labeling occurs. We need to consider strategies for incorporating penicillin allergy education in pediatric residency training.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively

Study objectiveTo characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DesignQuasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SettingOutpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. Patients670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. InterventionA paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MeasurementsAntibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 – April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. Main resultsOf 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09–2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42–0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35–0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. ConclusionsA simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

Management of Penicillin Allergy in the Perioperative Setting.

The selection of perioperative antibiotic prophylaxis is challenging in patients with a history of penicillin allergy; as such, we present a literature review exploring current best practices and the associated supporting evidence, as well as areas for future research. Guidelines recommend the use of alternative agents in patients with an IgE-mediated hypersensitivity reaction, but those alternative agents are associated with worse outcomes, including an increased risk of surgical site infection, and higher cost. More recent data suggest that the risk of cross-reactivity between penicillins and cephalosporins, particularly cefazolin, is extremely low, and that cefazolin can be used safely in most penicillin-allergic patients. Studies have therefore explored how best to implement first-line cefazolin use in patients with a penicillin allergy label. A variety of interventions, including preoperative allergy de-labeling with incorporation of penicillin skin testing, use of patient risk-stratification questionnaires, and utilization of clinician algorithms to guide antibiotic selection intraoperatively, have all been shown to significantly increase cefazolin utilization without a corresponding increase in adverse events. Further studies are needed to clarify the most effective interventions and implementation strategies, as well as to evaluate whether patients with severe delayed hypersensitivity reactions to penicillin should continue to be excluded from receipt of other beta-lactams.

Resource utilization and cost assessment of a proactive penicillin allergy de-labeling program for low-risk inpatients.

Resource utilization and costs can impede proactive assessment and de-labeling of penicillin allergy among inpatients. Our pilot intervention was a proactive penicillin allergy de-labeling program for new inpatients with penicillin allergy. Patients deemed appropriate for a challenge with a low-risk penicillin allergy history were administered 250mg amoxicillin and monitored for 1h. We performed an explorative economic evaluation using various healthcare professional wages. Over two separate 2-week periods between April 2021 and March 2022, we screened 126 new inpatients with a penicillin allergy. After exclusions, 55 were appropriate for formal assessment. 19 completed the oral challenge, and 12 were directly de-labeled, resulting in a number needed to screen of 4 and a number needed to assess of 1.8 to effectively de-label one patient. The assessor's median time in the hospital per day de-labeling was 4h08 with a range of (0h05, 6h45). A single-site annual implementation would result in 715 penicillin allergy assessments with 403 patients de-labeled assuming 20,234 annual weekday admissions and an 8.9% penicillin allergy rate. Depending on the assessor used, the annual cost of administration would be between $21,476 ($53.29 per effectively de-labeled patient) for a pharmacy technician and $61,121 ($151.67 per effectively de-labeled patient) for a Nurse Practitioner or Physician Assistant. A proactive approach, including a direct oral challenge for low-risk in-patients with penicillin allergy, appears safe and feasible. Similar programs could be implemented at other institutions across Canada to increase access to allergy assessment.

Assessing the rationale of prescribing carbapenems among hospitalized patients with documented penicillin allergy: implications for stewardship.

A reported history of penicillin allergy frequently leads to the prescription of carbapenems as a substitute for penicillin to avoid allergic reactions. Such self-reported allergies need to be accurately characterized to identify targeted antibiotic stewardship interventions that potentially minimize unnecessary carbapenem use. Retrospective cohort study. The proportion of hospitalized patients with penicillin allergy history receiving carbapenem prescriptions was evaluated between January 1st, 2017 and December 31st, 2018 at the University Hospital Basel, Switzerland. The appropriateness of carbapenem prescription of each patient was evaluated using institutional guidelines based on previously published recommendations. Our analysis revealed that among 212 patients with recorded penicillin allergy, of the 247 carbapenem treatment episodes, 79 (32%) were unjustified. Abdominal and lower respiratory tract infections were most frequently associated with inappropriate carbapenem use (OR 2.64, 95% CI 1.22-5.71, P = .014 and OR 2.26, 95% CI 1.08-4.73, P = .031). The recorded allergy type was not documented or unclear in 153 patients (72%) and penicillin allergy was only confirmed in 2 patients (0.9%). Inconsistencies in allergic symptom documentation and allergy types were found between the institution's two software programs. While a multimodal approach to identify and accurately label penicillin allergies remains essential to reduce inappropriate carbapenem use, our findings highlight the need for comprehensive and easily accessible guidelines for carbapenem utilization and structured history-based allergy assessment as an initial screening tool, embedded in a tailored digital allergy record template.

1196. Determining Risk Criteria for Direct Oral Penicillin Challenge in Hospitalized Adults with a History of Penicillin Allergy

Abstract Background Beta (β)-lactam antibiotics such as penicillin (PCN) and its derivatives are safe and effective for many bacterial infections. PCN allergies are self-reported in approximately 10% of Americans. Concerns for allergy cross-reactivity often causes the use of broad-spectrum antibiotics and second-line agents. This may increase the cost of care, lengthen therapy, increase side effects, contribute to the development of resistance, and worsen patient outcomes. Recent studies have shown direct oral penicillin challenge (DOC) may be safe and effective in patients with low to moderate risk for reaction. Methods This single-site retrospective analysis reviewed hospitalized adult patients with penicillin allergy assessment (PAST) completed by an antimicrobial stewardship team (AST) between May 1, 2017 and September 30, 2022 at a large academic medical center. Our primary aim is to determine risk stratification criteria for a DOC using primary literature and internal data. Secondary aims include cost avoidance analysis, updating PAST guidance, and creating an order set for the administration and monitoring of DOC. Results A total of 256 patients were screened and 200 were included. Most common reasons for exclusion were non-PCN allergies, PAST completed at a different hospital, and PAST not completed before discharge. There were 60 patients (30%) deemed to be high-risk for allergic reaction of which 58 (96.7%) received non-PCN alternative and 2 (3.3%) received no antibiotics. AST recommended oral or IV challenge for 107 patients (53.5%) of which 34 (31.8%) received a challenge, 68 (63.6%) received non-penicillin alternative antibiotics, 3 (2.8%) were directly de-labeled, and 2 (1.9%) received no antibiotics. No anaphylactic reactions occurred in patients that received a challenge. De-labeling based on history was recommended in 33 patients (16.5%) of which 12 (36.4%) were directly de-labeled, 2 (6.1%) received a challenge, and 19 (56.1%) received non-penicillin alternative antibiotics. Conclusion Our study confirms risk stratification for DOC is feasible and safe. Standardization of PCN allergy de-labeling with clinician and patient education may improve patient outcomes. Disclosures All Authors: No reported disclosures

Management of BAME patients with a history of penicillin allergy: barriers to best practice and strategies to overcome these

Management of BAME patients with a history of penicillin allergy: barriers to best practice and strategies to overcome these

APAAACI clinical pathway on direct provocation testing for penicillin allergy delabeling

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a “hub-and-spoke” approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist’s care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Penicillin Allergy Evaluation Should Be Performed Proactively in Patients With a Penicillin Allergy Label

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

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.