Elham Khatamzas

Background: With a global prevalence of 9.4%, penicillin allergy (PenA) is the most commonly documented drug allergy in hospitalized patients. Since over 90% of these labels cannot be confirmed, structured evaluation is crucial to optimize patient care. Prevalence data are available from several European countries, but data for Germany are lacking. This study provides data on the prevalence of PenA and cephalosporin allergy (CephA) as well as documentation quality from a large German university hospital. Methods: Adult inpatients were screened on 10 days between November 2023 and February 2024, and pediatric inpatients were screened on five days in 2025; 29 adult and seven pediatric wards across various specialties were included. Primary outcome was the average point prevalence of documented PenA or CephA labels across predefined screening days. Secondary outcomes included documentation quality, reported reactions, and beta-lactam use. Results: The mean point prevalence in adults was 8.1% for PenA alone and 8.7% for PenA or CephA (418 allergy labels/4777 screened records). Point prevalence was highest in general internal medicine (12.8%) and lowest in cardiac intensive care units (4.2%). In 65% of cases, no reaction was documented, and 70% of labels were unspecific. In the pediatric cohort, the mean point prevalence was 1.7% (8/477). Conclusion: Our findings demonstrate substantial potential for improved allergy assessment and highlight the relevance of PenA evaluation in German hospitals. Targeting low-risk patients in higher prevalence wards may offer a practical approach, particularly when allocating resources to delabeling programs. Improved clinical awareness and consistent documentation could further support safe and sustainable PenA delabeling strategies.

Background: Penicillin allergy (PenA) is reported in up to 15% of hospitalized patients, although true IgE-mediated hypersensitivity is rare. PenA delabeling is an important antimicrobial stewardship intervention, as mislabeling is associated with adverse clinical outcomes. While structured delabeling interventions are safe and effective, their translation into routine care across different healthcare settings remains unclear. Methods: This prospective implementation study was conducted on four wards of a 2600-bed German tertiary care center. All adult inpatients with reported PenA underwent structured allergy assessment and risk stratification by clinical pharmacists. Low risk patients were delabeled directly, while moderate-risk patients were evaluated for direct oral challenge (DOC). Outcomes included delabeling rate at discharge, ward-specific differences, and implementation barriers and facilitators assessed by staff questionnaires. Sustainability was evaluated by primary care follow-up 32 weeks after discharge. Results: Among 2890 screened patients, 179 (6.2%) reported a PenA. Of 162 eligible patients, 54 (33.3%) were successfully delabeled. DOC was well tolerated, with only one mild skin reaction observed. Ward-specific environments influenced the use of different delabeling strategies. Key barriers included staffing shortages, short hospital stays, and patient-related factors, whereas facilitators included easy integration into pharmacist workflows and interprofessional collaboration. Follow-up showed limited transfer of delabeling outcomes to primary care, reducing long-term sustainability. Conclusion: Pharmacist-led PenA delabeling can be safely integrated and is feasible within existing clinical workflows. However, real-world implementation barriers and incomplete transfer to primary care limited its full potential. Improve standardized documentation and cross-sector communication are important for sustainable and widespread implementation of delabeling strategies.

Background: Most penicillin allergy labels are documented in early childhood and result from events of low risk for allergy. In Germany, evidence-based strategies to evaluate the likelihood of a true penicillin allergy are still lacking. As general practitioner input is indispensable regarding required resources for the implementation of successful delabeling strategies in outpatient care, a mixed-methods study in Baden-Württemberg, Germany explored untapped delabeling potential and conditions for successful initiatives based on their experiences, to support preservation of penicillin as a treatment option and prevent resistance development. Methods: A cross-sectional convergent mixed-methods study was conducted with an online survey and semi-structured interviews. The survey link and invitation to participate in an interview was sent to randomly selected publicly available e-mail addresses. Survey data were analyzed descriptively. Qualitative data were analyzed inductively based on thematic analysis. Results: n = 101 survey questionnaires and n = 15 interviews were analyzed regarding relevance, experiences, framework conditions, and potential approaches to delabeling. All participants with limited recollection of the index reaction. Most participants considered delabeling a highly relevant topic in general practice. Delabeling efforts were discouraged by lack of time, expertise, and remuneration, and uncertainty due to missing guidelines. Taking a sufficient medical history and, if necessary, subsequent testing were seen as one approach to delabeling. For a standardized approach in primary care, patient and care provider education, precise guideline recommendations, and delabeling expert teams were suggested. Conclusions: The findings mirror aspects already identified in international research. A nationwide survey with general practitioners could confirm that addressing necessary resources and systemic adjustments would support effective penicillin allergy delabeling in outpatient care.

Background: Most penicillin allergy labels are documented in early childhood and re-sult from events of low risk for allergy. In Germany, evidence-based strategies to eval-uate likelihood of a true penicillin allergy are still lacking. As general practitioner in-put is indispensable regarding required resources for an implementation of successful delabeling strategies in outpatient care, a mixed-methods study in Ba-den-Württemberg, Germany explored untapped delabeling potential and conditions for successful initiatives based on their experiences. to support preservation of penicil-lin as a treatment option and prevent resistance development. Methods: A cross-sectional convergent mixed-methods study was conducted with an online survey and semi-structured interviews. The survey link and invitation to participate in an in-terview was sent to randomly selected publicly available e-mail addresses. Survey data were analyzed descriptively. Qualitative data were analyzed inductively based on thematic analysis. Results: N=101 survey questionnaires and n=15 interviews were analyzed regarding relevance, experiences, framework conditions, and potential ap-proaches to delabeling. All participants had patients with limited recollection of the index reaction. Most participants considered delabeling a highly relevant topic in gen-eral practice. Delabeling efforts were discouraged by lack of time, expertise, and re-muneration, and uncertainty due to missing guidelines. Taking a sufficient medical history and, if necessary, subsequent testing were seen as one approach to delabeling. For a standardized approach in primary care, patient and care provider education, precise guideline recommendations, and delabeling expert teams were suggested. Conclusion: The findings mirror aspects already identified in international research. A nationwide survey with general practitioners could confirm that addressing necessary resources and systemic adjustments would support effective penicillin allergy delabel-ing in outpatient care.

Background: Penicillin allergy is the most frequently reported allergy in hospitalized patients, although rarely confirmed. Given the negative outcomes associated with incorrect penicillin allergy diagnoses, implementation of programmatic delabeling strategies is important for successful antibiotic stewardship. This systematic review evaluates the effectiveness of different delabeling strategies and highlights elements and settings that facilitate or constrict their implementation. Methods: Following the PRISMA-statement PubMed/MEDLINE, EMBASE, Cochrane Library, and grey literature databases “Worldcat” and “OpenGrey” were searched for studies reporting on interventions to identify, evaluate, or rule out incorrect penicillin allergy in hospitalized adults. Data extraction included settings, intervention types, and their effectiveness, barriers, facilitators, and regulatory factors. Results: This review included 42 studies, involving 6269 patients undergoing penicillin allergy delabeling, with 5017 (80%) successfully delabeled. Effectiveness varied from 32% to 99%. Skin testing had the highest success rate at 87%, followed by a combination of skin testing and oral challenge (84%), and direct oral challenges (77%). Direct delabeling alone had a lower effectiveness (67%), which improved to 80% when paired with oral challenges. Key facilitators included standardized algorithms and involvement of interdisciplinary teams. Barriers included patient refusal, staff resistance, time constraints, and financial limitations, particularly in smaller hospitals. Conclusion: Dependent on financial and staffing resources, oral challenges and direct delabeling after risk stratification may be alternatives to resource-intensive methods, such as skin testing, for successful delabeling. To address barriers to widespread delabeling implementation, patient and provider education must be improved, interprofessional collaboration enhanced, and standardized protocols developed.

Introduction: Up to 15 % of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabeling processes for penicillin allergy is an important part of antibiotic stewardship programs. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabeling interventions and summarizes components and structures that facilitate, support, or constrain structured penicillin allergy delabeling. Methods and analysis: This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The Databases MEDLINE (via PubMed), EMBASE, and Cochrane Library were searched for studies reporting on any intervention to identify, assess, or rule out erroneous penicillin allergy. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting, and associated regulatory factors will be extracted and analyzed. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale. Ethics and dissemination: Because individual patient-related data is not analyzed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal. STRENGHTS AND LIMITATIONS OF THIS STUDY: - The systematic review will adhere to the PRISMA guidelines. - A wide search strategy is used and the search will be conducted on three major databases. - The search is focused on studies reporting on facilitators and barriers for implementation as well as effectiveness of penicillin allergy delabeling interventions. - Data extraction will be performed using an established second look process. - Risk for bias in the individual studies as well as external validity is assessed using an established checklist (Newcastle Ottawa Scale).

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.

BACKGROUND: In this case report the authors present two female patients with intracranial mucormycosis after coronavirus disease 2019 (COVID-19). OBSERVATIONS: The first patient was a 30-year-old woman with no past medical history or allergies who presented with headaches and vomiting. Magnetic resonance imaging (MRI) and computed tomography of the skull showed an endonasal infection, which had already destroyed the frontal skull base and caused a large frontal intracranial abscess. The second patient was a 29-year-old woman with multiple pre-existing conditions, who was initially admitted to the hospital due to a COVID-19 infection and later developed a hemiparesis of the right side. Here, the MRI scan showed an abscess configuration in the left motor cortex. In both cases, rapid therapy was performed by surgical clearance and abscess evacuation followed by antifungal, antidiabetic, and further supportive treatment for several weeks. LESSONS: Both cases are indicative of a possible correlation of mucormycosis in the setting of severe immunosuppression involved with COVID-19, both iatrogenic with the use of steroids and previous medical history. Furthermore, young and supposedly healthy patients can also be affected by this rare disease.