Cephalosporin graded challenges approach in community–acquired pneumonia patient with a history of penicillin allergy

Community-Acquired Pneumonia (CAP) is an acute pulmonary parenchyma infection that acquired in the community. Diagnosis based on clinical manifestations, chest X-ray (CXR) and microbiological diagnosis test (lung aspirates culture). Recently there was advance in antimicrobial treatments of CAP and a microbiological diagnostic test is essential to ensure antimicrobial treatments. In the other hand microbiological diagnostic test does not achieve all of the pneumonic cases. Therefore, antimicrobial treatment should be empirically performed to avoid the delay in establishing appropriate treatment related with the mortality. By administering combination antimicrobial will achieve a better outcome than a mono-therapy. For patients with history of penicillin allergy, though the risk of cephalosporin allergic cross-reactivity is low, a greater awareness is still needed, so a graded challenge approach could be considered. Herein we present a case report of a female, 20-year-old, hospitalized due to CAP, and also had a history of penicillin allergy. She was treated by levofloxacin 750 mg IV q 24 hour and cephalosporin (ceftriaxone) 1 g IV q 12 hour with a Graded challenge approach. Although it does not a novelty, we hope it would remind the health care that a Graded challenge could be considered as an approach of administering cephalosporin in patient who has an experiece of penicillin allergy.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Use of a Beta-Lactam Graded Challenge Process at an Academic Medical Center

Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.Funding: NoneDisclosures: Scott Bergman reports a research grant from Merck.

177. Implementation of Pharmacist-Driven Penicillin Allergy Evaluation and Testing with a Focus on Bypassing Penicillin Skin Testing at an Academic Medical Center

Background Penicillin allergies are reported by approximately 10% of the US population; however, studies reveal that >90% of those patients can tolerate penicillins. Penicillin allergies are associated with negative health outcomes, both clinical and financial, due to reduced efficacy and increased adverse effects of alternative antibiotics. Patient interview, penicillin skin testing (PST) and/or an oral graded challenge can be used to evaluate penicillin allergies. Different facilities use various algorithms for testing. The objective of this project was to determine whether a pharmacist-driven penicillin allergy evaluation and testing protocol which largely bypasses PST could safely de-label patients. Methods Adult patients (≥18 years) admitted with a penicillin allergy were evaluated for eligibility between September 2019 and June 2020. Pregnant patients, critically-ill patients, and patients receiving test-invalidating medication were excluded. Patients were evaluated and tested using institutional protocols, which allowed for the majority of patients to be challenged without PST. Allergies were removed with standardized documentation, and patients were given a pamphlet and counseled to discourage relabeling. Data collected included but were not limited to, the number of patients challenged and de-labeled, number of patients who were relabeled, and number of patients whose change in allergy status resulted in change of therapy. Results Forty-eight patients were interviewed and evaluated. One patient was evaluated by PST and oral graded challenge while 27 patients underwent an oral graded challenge only. Twenty patients were de-labeled as a result of patient interview. One patient failed oral challenge with minor itching that did not require any treatment, while 27 patients passed. Forty-seven allergies were removed or modified. Two patients who were de-labeled were relabeled with no record of a new reaction. Of de-labeled patients, 50% received a penicillin following removal of the allergy. Conclusion Penicillin allergies can be evaluated and removed using a pharmacy-driven algorithm that prioritizes direct challenges when appropriate. Risks of a reaction are low, and removal leads to change in treatment in a significant portion of patients. Disclosures All Authors: No reported disclosures

353. Starry Night, Starry Bright, A Lil’ Doxy Will Help You See the Light

Background Bartonella henselae neuroretinitis (BHNR) is a rare complication of cat scratch disease (CSD) occurring in 1–2% of cases. BHNR requires prompt diagnosis and treatment to prevent potential vision loss. Doxycycline, in combination with rifampin, is consider the treatment of choice. Empiric therapy is often started based on clinical suspicion prior to serologic confirmation. We present a case of BHNR requiring doxycycline graded challenge. Methods We report a case of a 45-year-old female with a past history of multiple sclerosis treated with natalizumab presenting with acute right-sided vision loss. She reported suffering a cat scratch 6 weeks prior and had noteworthy tick exposure. She was admitted to our hospital for progressively worsening vision loss. MRI brain demonstrated right-sided enhancement consistent with retinitis. Ophthalmology exam suggestive of infectious papillitis, neuroretinitis, and granulomatous inflammation. Results Infectious diseases (ID) was consulted with concern for BHNR and a history of a severe tetracycline allergy, throat swelling age 17. Given declining vision and a differential including both Lyme disease and BHNR, the decision was made to empirically treat with doxycycline while awaiting serologic studies. She successfully underwent doxycycline graded challenge (10mg administered IV followed by 100mg administered IV one hour later) and ultimately completed a 6-week course of doxycycline in combination with 2 weeks of rifampin followed by 4 weeks of azithromycin. Bartonella serologies returned positive 1:256 and her Lyme screen was negative. At her 6-week follow up, her vision had significantly improved but not yet returned to baseline. Retina images Visual field testing Conclusion Doxycycline serves as a treatment of choice for BHNR; however, our patient reported a severe, likely IgE-mediated reaction to tetracycline 28 years prior. She subsequently tolerated the first doxycycline graded challenge at our institution. Unlike B-lactam allergies, there is a paucity of literature exploring the cross-reaction potentials of various tetracyclines. Limited evidence has suggested that cross-reactions are not absolute. Tetracycline allergies present an opportunity for antimicrobial stewardship. Disclosures All Authors: No reported disclosures

2543. Implementation of a Fellow-Driven Β-Lactam Allergy De-Labeling Initiative on an Inpatient ID Consult Service

Background Approximately 10% of patients in the US report a penicillin (PCN) allergy, but more than 90% can safely receive β-lactam (BL) antibiotics. Having a reported BL allergy (BLA) is associated with increased length of stay, cost of care, adverse events, and mortality. As part of our institutional quality improvement incentive program for graduate medical trainees, the Infectious Diseases (ID) and Allergy/Immunology (AI) fellows implemented a protocol-driven approach to BLA evaluation. We sought to evaluate the success of this implementation. Methods This is a pre–post investigation of our BLA protocol. As an initial pilot phase prior to house-wide deployment, the ID and AI services implemented a BLA guideline incorporating thorough history-taking, graded challenge, and focused penicillin skin testing for patients on the ID consult service. All patients seen by the ID consult service from July 1, 2018 through June 30, 2019 with a documented BLA were included (baseline period April 1, 2018 through June 30, 2018). The primary endpoint was the proportion of patients meeting any one of the following: receipt of a BL, inpatient or outpatient referral to AI, or removal of BLA from the medical record by the time of discharge. Data were tracked quarterly and fed back to ID and AI fellows electronically. The Chi-square test was used to compare pre-post outcomes. Results Over the first three quarters, 258 patients with BLA were evaluated by the ID consult service. Our baseline compliance was 65%, which increased to an average of 81% over the subsequent three quarters (P = 0.003). Among patients with BLA seen by the ID consult service during the intervention, 177 (69%) received a BL, 37 (14%) underwent inpatient AI evaluation, 11 (4%) received discharge referrals to AI, and 126 (49%) had their BLA removed. Several patients met more than one primary endpoint. Conclusion Implementation of a protocol-driven BLA guideline by ID and AI fellows was feasible and led to an increase in the number of patients either receiving BLs in the hospital or undergoing timely evaluation or removal of BLA. In conclusion, the implementation of a β-lactam allergy de-labeling initiative is an effective way to empower trainees to incorporate BLA de-labeling into their practice. Disclosures All authors: No reported disclosures.

Graded Dalbavancin Challenge in a Patient With Severe Vancomycin Hypersensitivity Reaction

Cross-reactivity should be considered when treating patients with a previous hypersensitivity reaction within the same class of antibiotics that share similar chemical structures. This case report describes a patient with severe hypersensitivity reaction to vancomycin who successfully tolerated a dalbavancin graded challenge.

Rush Immunotherapy Using Ifn-Gamma for Cefazoline Allergy

Cefazolin is a first generation cephalosporin widely used for preoperative antibiotic prophylaxis. Although cefazolin hypersensitivity constitutes a potential life-threatening condition with serious consequences, correct diagnosis of cefazolin hypersensitivity is not straightforward for various reasons. A graded challenge is perhaps the most reliable in vivo test for the diagnosis of cefazolin allergy. Desensitization is performed by the cautious administration of incremental doses of the drug to the patient. In the case of intravenous drug, the challenge and desensitization has been regarded as extremely dangerous. IFN-gamma has allergen-specific tolerogenic effects, together with the administration of allergens. Moreover, IFN-gamma was introduced for desensitization for aspirin and cefaclor. In this case report, two cases were described concerning challenge test and desensitization for anaphylactic drug allergy for intravenous cefazolin using IFN-gamma.

The Eyes Have It: Eyelid Swelling and Rash in a 79-year-old Woman With Macular Degeneration

Introduction A 79-year-old woman with macular degeneration was referred to the Allergy/Immunology clinic for the evaluation of a potential allergy to anti-vascular endothelial growth factor (anti-VEGF) treatments. The patient developed urticaria and eyelid swelling immediately following a retinal injection of aflibercept, which she had previously tolerated. She previously had allergic reactions following ranibizumab and bevacizumab injections. Injections of anti-VEGF treatments were discontinued given concern for allergy with progression of the patient’s disease. Objective To assess the culprit medication(s) responsible for hypersensitivity reactions following anti-VEGF injections for macular degeneration. Methods Medication records were reviewed for each retinal injection. All medications used in each procedure, including the anti-VEGF therapy (aflibercept), topical anesthetics (tetracaine and proparacaine hydrochloride), and antiseptic (povidine), were evaluated with skin testing. She was additionally tested for alternative anti-VEGF therapies (ranibizumab and bevacizumab) as she was thought to have allergies to these agents by prior history. A test dose challenge was completed for aflibercept, ranibizumab, and bevacizumab. Results Skin prick and intradermal testing were negative to aflibercept, ranibizumab, bevacizumab, and povidine. Intradermal testing was positive to tetracaine and proparacaine hydrochloride. The patient passed test dose challenges to aflibercept, ranibizumab, and bevacizumab. Due to her positive hypersensitivity testing to 2 ester anesthetics, the patient underwent skin prick and intradermal testing to the amide anesthetic, lidocaine. This was negative and the patient tolerated a graded challenge to lidocaine. She was deemed to have an immunoglobulin E (IgE)-mediated hypersensitivity to ester-type local anesthetics. She successfully resumed anti-VEGF therapy with an amide local anesthetic. Conclusions The reason for this consult was the concern for hypersensitivity to a biologic anti-VEGF medication. The culprit allergen, the local anesthetic, could have been overlooked without an assessment of all medications used during the procedure. This case highlights the importance of a thorough allergy evaluation of all medications used during procedures to determine the causative agent. Chief Complaint: Eyelid swelling and rash after ophthalmic procedures for macular degeneration.

A Case of Serious Adverse Reaction Following Rabies Vaccination

Introduction. Rabies is one of the most deadly infectious disease. We present a challenging case of an adverse reaction following rabies vaccine in a child. Case Summary. A 10-year-old girl was bitten by a stray dog in Bali and was prescribed rabies post-exposure prophylaxis. She developed breathlessness, abdominal cramps, and lips and eyes swelling 30 minutes after the second dose of rabies vaccine. The subsequent vaccine was successfully administered as a graded challenge with premedication. The final dose was administered in entirety under close observation. She developed transient hypotension 30 minutes later, which spontaneously resolved. Conclusion. There were multiple challenges in the care of this pediatric patient who was potentially exposed to rabies and experienced systemic adverse events during the course of post-exposure prophylaxis. A thorough clinical assessment should be made to weigh benefits versus risks of proceeding with rabies vaccination, bearing in mind that the disease is deadly.