Abstract 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.

Vascular surgery patients are often multimorbid, older and therefore predisposed to polypharmacy, which can increase the risk of drug-related problems. Meticulous medication analysis is particularly crucial in older patients in order to avoid overtreatment while ensuring treatment that improves the prognosis. In addition, organ function can be impaired by additional factors in the perioperative setting. These can necessitate dose adjustments or increase the risk of interactions due to indicated new drugs. Structured medication management, supported by validated screening tools, helps to identify and adjust potentially inappropriate medications. This article aims to provide practical recommendations for optimizing treatment and guidance on how to make medication in vascular surgery safe and effective.

Penicillin allergy (PenA) is reported in up to 15

Gefäßchirurgische Patienten sind häufig multimorbide, älter und daher prädisponiert für Polypharmazie, die das Risiko für arzneimittelbezogene Probleme erhöhen kann. Eine sorgfältige Medikationsanalyse ist besonders bei älteren Patienten entscheidend, um Übertherapie zu vermeiden und gleichzeitig prognoseverbessernde Therapien zu gewährleisten. Darüber hinaus kann im perioperativen Setting die Organfunktion durch zusätzliche Faktoren beeinträchtigt sein. Diese können sowohl Dosisanpassungen erforderlich machen oder aufgrund indizierter neuer Arzneimittel das Risiko für Interaktionen erhöhen. Ein strukturiertes Medikationsmanagement, unterstützt durch validierte Screening-Tools, hilft, potenziell inadäquate Medikamente zu identifizieren und anzupassen. Der Artikel soll praxisorientierte Empfehlungen zur Therapieoptimierung liefern und eine Orientierungshilfe geben, um die Medikation in der gefäßchirurgischen Versorgung sicher und effektiv zu gestalten.

Over the past years, an increasing number of advanced therapy medicinal products (ATMPs) have received marketing authorization, including gene therapy, somatic cell therapy, and tissue-engineered medicines, fostering development in this field. ATMPs utilise delivery methods effectively introducing recombinant nucleic acids into target cells and tissues to treat a patient’s disease or condition by transferring genetic sequences. In therapeutic settings, it utilizes non-immunogenic vectors with cell- and tissue-specificity that can provide adequate transgene expression to achieve the desired effect. In addition, autologous cells, such as T cells, can be modified ex vivo to target epitope-expressing tissues, e.g. in cancer and rheumatoid arthritis therapy. Overexpression of specific genes or inhibitory molecules can effectively influence cellular regulation. Systemic gene therapy often results in lower specificity, as it can affect unintended tissues and cells, leading to off-target effects and potential side effects such as hepatotoxicity. Additionally, systemic approaches regularly require higher doses to achieve efficacy in the desired tissue or organ, increasing the likelihood of adverse reactions. In contrast, local cell and gene therapy might allow precise delivery to the target area, minimizing risks and improving therapeutic outcomes. This review summarises current knowledge of different delivery methods for ATMPs and the materials used to implement them, as the choice of application method depends on the disease, the target tissue, and the properties of the substance. It discusses the advantages and disadvantages of various delivery possibilities across multiple therapy applications. Finally, current clinical studies and perspectives on localized therapy approaches will be summarised.

To analyze dalbavancin’s potential for long-term suppressive therapy in patients with infected ventricular assist devices (VAD), the VAD register of Heidelberg University Hospital was searched for patients who received dalbavancin for long-term suppression therapy. Clinical data, laboratory, and microbiological results were extracted. Healthcare utilization was analyzed by number of hospitalizations before and during dalbavancin therapy with a generalized linear mixed model. Drug safety was investigated with regard to liver and renal function, and thrombocyte count. Thirteen patients were included in the study; receiving a regimen of 1500 mg dalbavancin at day 1 and day 8 with repetition of the cycle at day 42. The mean follow-up time was 254 days (IQR 252). Eight patients were treated for driveline infection and five patients for driveline and blood stream infection, all of them caused by Staphylococcus aureus. The majority of patients (n = 11/13) underwent surgical wound debridement and intravenous antibiotic therapy before start of dalbavancin. Under dalbavancin therapy, no blood stream infection was observed and significantly fewer hospitalizations occurred with an odds ratio of 0.27 (p < 0.001). In four patients, elevations of liver transaminases were detected and led to discontinuation of dalbavancin therapy in one patient.

Background: Ampicillin/sulbactam, a combination of a β-lactam and β-lactamase inhibitor, is widely used in clinical settings. However, therapeutic drug monitoring (TDM) of ampicillin is not commonly performed, particularly in intensive care units (ICUs). The purpose of this study was to develop and validate a rapid and cost-effective high-performance liquid chromatography (HPLC)–ultraviolet spectrometry method to quantify ampicillin in human serum and evaluate its clinical application in ICU patients. Methods: Sample cleanup included a protein precipitation protocol, followed by chromatographic separation on a C18 reverse-phase HPLC column within 12.5 minutes using gradient elution of the mobile phase. The assay was validated according to the German Society of Toxicology and Forensic Chemistry criteria. Clinical applications involved the retrospective analysis of TDM data from ICU patients receiving continuous infusion of ampicillin/sulbactam, including the attainment of target ranges and individual predicted and observed pharmacokinetics. Results: The method was robust, with linear relations between the peak area responses and drug concentrations in the range of 2–128 mg/L. The coefficient of variation for precision and the bias for accuracy (both interday and intraday) were less than 10%. Clinical application revealed variable pharmacokinetics of ampicillin in ICU patients (clearance of 0.5–31.2 L/h). TDM-guided dose adjustments achieved good therapeutic drug exposure, with 92.9% of the samples being within the optimal (16–32 mg/L) or quasioptimal (8–48 mg/L) range. Conclusions: This method provides a practical solution for the routine TDM of ampicillin, facilitating individualized dosing strategies to ensure adequate therapeutic drug exposure. Given its simplicity, cost-effectiveness, and clinical relevance, HPLC–ultraviolet spectrometry holds promise for broad implementation in hospital pharmacies and clinical laboratories.

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.

Medication history taking at hospital admission is still prone to errors. Despite numerous quality improvement initiatives, new strategies to improve medication history taking are still sought and evaluated. Unfortunately, the gold standard research methodology for evaluation is resource-intensive, as it requires each patient to complete two medication history interviews. Therefore, a new study design and quality parameter were developed. We aimed to pilot our newly developed study design and quality parameter in a study on medication history taking by telephone. In this prospective interventional study, patients with scheduled admissions had their medication histories taken either by telephone before admission (intervention) by a pharmacist or in-person by physicians or medical interns upon admission (control). Following the newly developed design, we compared a patients’ new medication histories to the respective pre-visit medication lists available in the medical records to calculate the new endpoint: the difference in the number of updates per patient. Further, we surveyed patients and staff on their satisfaction. We enrolled 76 intervention and 75 control patients. In the intervention group, a mean of 4.93 (± 4.45, 0–18) updates were found vs. 3.40 (± 3.75, 0–21) in the control group. Accordingly, the incident rate of number of updates per patient was 1.34 times higher in the intervention group (p = 0.044). The distribution of the types of updates was similar with the most common type of update being newly initiated medicines in both groups. Medication history taking by telephone took 15.7 ± 9.8 min (mean ± SD), including preparation, interview, and documentation. Survey results showed that intervention patients felt positive about the telephone interviews. Both groups were open to other digital approaches, e.g., online platforms. The new study design proved feasible to evaluate medication history taking by telephone with comprehensible results. The telephone approach delivered more updates compared to standard care, however, the proposed endpoint needs to be validated against the gold standard before widespread application Patient acceptance for this and other digital approaches was high in both groups.

To investigate the effect of amiodarone on apixaban pharmacokinetics in cardiac surgery patients with postoperative atrial fibrillation. Apixaban concentrations of postoperative cardiac surgery patients with or without amiodarone therapy were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in clinical routine. A population pharmacokinetic model was built using nonlinear mixed effects modeling in NONMEM® 7.5 using first-order conditional estimation with interaction. The impact of amiodarone and creatinine clearance (CrCL) on apixaban exposure under various dosing regimens was analyzed using Simulx® (Lixoft). A total of 33 patients with 76 apixaban concentrations were included. A one-compartment model best described the pharmacokinetics of apixaban with a clearance (CL/F) of 3.05 L/h, apparent volume of distribution (Vd/F) of 23.7 L, and an absorption rate constant (ka) of 0.652/h. Interindividual variability (IIV) was observed in CL/F but not in Vd/F and ka. The covariates amiodarone and CrCL were independently associated with apixaban CL/F. Under concomitant amiodarone therapy, simulations predicted an increase of 44–49

Increasing evidence suggests that dalbavancin is an effective long-term treatment for ventricular assist device (VAD) infections, with various prolonged dosing regimens currently in use. This retrospective study aimed to assess dalbavancin pharmacokinetics in VAD patients and identify optimal, feasible dosing regimens for long-term suppressive outpatient therapy. Data from Heidelberg University Hospital’s VAD register were analyzed using non-linear mixed-effects modeling for pharmacokinetic analysis and dosing simulations (Lixoft®). The probability of target attainment (PTA) and cumulative fraction of response (CFR) were calculated for different protein-binding scenarios considering the minimum inhibitory concentration (MIC) distribution of Staphylococcus aureus. Using data from 13 patients with 38 blood samples, a two-compartment model best described the dalbavancin pharmacokinetics, with a typical value for clearance of 0.050 L/h, central volume of distribution of 6.5 L, and peripheral volume of 15.4 L. No covariates significantly improved the model fit. The observed protein binding varied between 96 and 98%. Dosing simulations demonstrated that 1500 mg every 3 weeks ensured the target attainment for stasis at MIC values of 0.125 mg/L (PTA ≥ 90%) up to a protein binding of 99%. Considering the CRF, longer dosing intervals up to 5 weeks might be possible. Depending on individual MICs and protein binding, a dalbavancin regimen of 1500 mg every 3 to 5 weeks therefore appears to be a valuable option for outpatient therapy of VAD infections. Therapeutic drug monitoring should be considered to manage inter-individual variability and to support clinicians in long-term treatments of subacute and chronic infections.

Hintergrund Die Entlassung aus dem Krankenhaus ist ein Risiko für die Kontinuität der Arzneimitteltherapie. In Deutschland macht der Rahmenvertrag Entlassmanagement seit 2017 Vorgaben, um Versorgungslücken zu vermeiden, und beschreibt auch Mindestanforderungen an die Dokumentation der Medikation in Entlassbriefen. Auch sechs Jahre nach Einführung fehlen systematische Daten, die beurteilen, wie diese in der Routineversorgung umgesetzt werden. Methode Im Rahmen einer explorativen retrospektiven Beobachtungsstudie wurde die Umsetzung des Rahmenvertrags in einer Stichprobe von Entlassbriefen des Universitätsklinikums Heidelberg evaluiert. Hierfür wurden die im Rahmenvertrag formulierten Mindestanforderungen an die Dokumentation der Medikation zunächst operationalisiert und dann auf die in den Entlassbriefen dokumentierte Medikation angewendet. Als vergleichender Qualitätsstandard wurden die Empfehlungen zur „Gute[n] Verordnungspraxis in der Arzneimitteltherapie“ des Aktionsbündnisses Patientensicherheit e. V. eingesetzt. Ausgewählte Kontextfaktoren wie z. B. Mitarbeit von Stationsapotheker*innen oder der Einsatz spezifischer Software wurden als potenzielle Einflussfaktoren auf die Umsetzung untersucht. Ergebnisse Insgesamt wurden aus dem Rahmenvertrag 11 Qualitätskriterien abgeleitet. Gemäß den Einschlusskriterien (z. B. mindestens drei Arzneimittel in der Entlassmedikation) wurden letztlich 352 Briefe (42 Stationen; Mai–Juli 2021) mit insgesamt 3.051 als Entlassmedikation dokumentierten Arzneimitteln eingeschlossen. Es zeigten sich in Abhängigkeit von einzelnen Kriterien, aber auch in Abhängigkeit von spezifischen Kontextfaktoren erhebliche Unterschiede in der Umsetzung. Der Wirkstoffname, die Wirkstärke und die Dosierung bei Entlassung wurden zusammen für 82,8 % der Arzneimittel dokumentiert, während andere Qualitätskriterien selten oder nie erfüllt wurden (z. B. „Erläuterung bei besonderen Darreichungsformen“). Als potenzielle Förderfaktoren zeigten sich die Mitarbeit von Stationsapotheker*innen und die Verwendung einer Software, während Bedarfsmedikationen (im Vergleich zu Dauermedikationen) und Neuverordnungen (im Vergleich zu Weiterverordnungen und geänderten Arzneimitteln) tendenziell schlechter dokumentiert waren. Zudem scheint die Dokumentationsqualität von der Fachrichtung und dem Wochentag der Entlassung abzuhängen. Schlussfolgerung Bislang lässt der Rahmenvertrag in seinen Formulierungen einen gewissen Interpretationsspielraum offen, ohne jedoch die klinische Situation und die tatsächlich verordnete Medikation zu berücksichtigen. Bei einer Präzisierung der Anforderungen sollte daher die klinische Implikation der Formulierung berücksichtigt werden.

Introduction: Discharge from hospital is a risk to drug continuity and medication safety. In Germany, new legal requirements concerning the management of patient discharge from the hospital came into force in 2017. They set minimum requirements for the documentation of medications in patient discharge summaries, which are the primary means of communication at transitions of care. Six years later, data on their practical implementation in routine care are lacking. Methods: Within the scope of an explorative retrospective observational study, the minimum requirements were operationalized and a second set of assessment criteria was derived from the recommendation "Good Prescribing Practice in Drug Therapy" published by the Aktionsb & uuml;ndnis Patientensicherheit e.V. as a comparative quality standard. A sample of discharge summaries was drawn from routine care at the University Hospital Heidelberg and assessed according to their fulfilment of the criteria sets. In addition, the potential influence of certain context factors (e. g., involvement of clinical pharmacists or software usage) was evaluated. Results: In total, 11 quality criteria were derived from the minimum requirements. According to the eligibility criteria (i. e., three or more discharge medications) 352 discharge summaries (42 wards; issued in May-July 2021), containing in total 3,051 medications, were included. The practical implementation of the minimum requirements for documenting medications in patient discharge summaries differed considerably depending on the criterion and defined context factors. Core elements (i. e., drug name, strength, and dosage at discharge) were fulfilled in 82.8 %, while further minimum requirements were rarely met or completely lacking (e. g., explanations for special pharmaceutical forms). Involvement of clinical pharmacists and usage of software were shown to be a facilitator of documentation quality, while on-demand medication (compared to long-term medication) as well as newly prescribed medication (compared to home medication or medication changed during hospitalisation) showed poorer documentation quality. In addition, the documentation quality seemed to depend on the department and the day of discharge. Conclusion: To date, the wording of the German legal requirements allows for different interpretations without considering the respective clinical setting and the medication actually prescribed. For future clarification of the requirements, implications of the wording for the clinical setting should be considered.

ObjectivesTo investigate the performance and risk associated with the usage of Chat Generative Pre-trained Transformer (ChatGPT) to answer drug-related questions. MethodsA sample of 50 drug-related questions were consecutively collected and entered in the artificial intelligence software application ChatGPT. Answers were documented and rated in a standardised consensus process by six senior hospital pharmacists in the domains content (correct, incomplete, false), patient management (possible, insufficient, not possible) and risk (no risk, low risk, high risk). As reference, answers were researched in adherence to the German guideline of drug information and stratified in four categories according to the sources used. In addition, the reproducibility of ChatGPT's answers was analysed by entering three questions at different timepoints repeatedly (day 1, day 2, week 2, week 3). ResultsOverall, only 13 of 50 answers provided correct content and had enough information to initiate management with no risk of patient harm. The majority of answers were either false (38%, n=19) or had partly correct content (36%, n=18) and no references were provided. A high risk of patient harm was likely in 26% (n=13) of the cases and risk was judged low for 28% (n=14) of the cases. In all high-risk cases, actions could have been initiated based on the provided information. The answers of ChatGPT varied over time when entered repeatedly and only three out of 12 answers were identical, showing no reproducibility to low reproducibility. ConclusionIn a real-world sample of 50 drug-related questions, ChatGPT answered the majority of questions wrong or partly wrong. The use of artificial intelligence applications in drug information is not possible as long as barriers like wrong content, missing references and reproducibility remain.

Purpose A comprehensive medication history can contribute to safe therapy. Many approaches aiming to improve medication history taking require significant human resources. To design an efficient process that delivers high-quality medication histories, the individual requirements and resources of a given setting need to be considered. We aimed to provide an overview of existing approaches to medication history taking and their performance in different settings to potentially support the selection of an appropriate procedure. Methods We searched 3 literature databases (PubMed/MEDLINE, CINAHL, PsycINFO) for publications on approaches to medication history taking and analyzed them with regard to their key components as well as the setting, patient population, assessed outcomes, and efficacy. Results In total, 65 publications were included and analyzed. The majority of the reported approaches relied on involvement of dedicated staff (n = 43), followed by process-oriented interventions (eg, checklists; n = 15) and information technology (IT)-guided interventions (n = 11). A mean (SD) of 6 (2.9) outcomes were described in each study. Medication discrepancies were reported in 89% of all studies, yet about 75 different descriptions of this outcome were used, making it difficult to compare study results. Only 11 studies applied a sample size calculation and statistical tests. Of those, 10 reported a positive effect of their respective intervention on the quality of medication histories. Conclusion Most approaches focused on pharmacy staff, which are associated with considerable cost and resources. Therefore, IT-based approaches and patient engagement should be investigated as cost-effective alternatives and tested for superiority in the same setting. Reporting guidelines and standardized methodology are needed to improve the comparability of such studies.

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 delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.Methods and analysis This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. 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 are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal.