Effect and sustainability of a stepwise implemented multidisciplinary antimicrobial stewardship programme in a university hospital emergency department.

Objectives: To explore effectiveness and sustainability of guideline adherence and antibiotic consumption after establishing treatment guidelines and initiating antimicrobial stewardship (AMS) ward rounds in a university hospital emergency department (ED). Methods: Data were gathered retrospectively from 2017 to 2021 in the LMU University Hospital in Munich, Germany. Four time periods were compared: P1 (pre-intervention period); P2 (distribution of guideline pocket cards); P3 (reassessment after 3 years); and P4 (refresher of guideline pocket cards and additional daily AMS ward rounds for different medical disciplines). Primary outcome was adherence to guideline pocket cards for community-acquired pneumonia, cystitis, pyelonephritis and COVID-19-associated bacterial pneumonia. Secondary outcomes were reduction in antibiotic consumption and adherence to AMS specialist recommendations. Results: The study included 1324 patients. Guideline adherence increased in P2 for each of the infectious diseases entities. After 3 years (P3), guideline adherence decreased again, but was mostly on a higher level than in P1. AMS ward rounds resulted in an additional increase in guideline adherence (P1/P2: 47% versus 58.6%, P = 0.005; P2/P3: 58.6% versus 57.3%, P = 0.750; P3/P4: 57.3% versus 72.5%, P < 0.001). Adherence increased significantly, not only during workdays but also on weekends/nightshifts. Adherence to AMS specialist recommendations was excellent (91.3%). We observed an increase in use of narrow-spectrum antibiotics and a decrease in the application of fluoroquinolones and cephalosporins. Conclusions: Establishing treatment guidelines in the ED is effective. However, positive effects can be diminished over time. Daily AMS ward rounds are useful, not only to restore but to further increase guideline adherence significantly.

Comparison of ß-D-Glucan and Galactomannan in Serum for Detection of Invasive Aspergillosis: Retrospective Analysis with Focus on Early Diagnosis.

The early diagnosis of invasive aspergillosis (IA) relies mainly on computed tomography imaging and testing for fungal biomarkers such as galactomannan (GM). We compared an established ELISA for the detection of GM with a turbidimetric assay for detection of the panfungal biomarker ß-D-glucan (BDG) for early diagnosis of IA. A total of 226 serum specimens from 47 proven and seven probable IA cases were analysed. Sensitivity was calculated for samples obtained closest to the day of IA-diagnosis (d0). Additional analyses were performed by including samples obtained during the presumed course of disease. Most IA cases involved the respiratory system (63%), and Aspergillus fumigatus was the most frequently isolated species (59%). For proven cases, sensitivity of BDG/GM analysis was 57%/40%. Including all samples dating from -6 to +1 weeks from d0 increased sensitivities to 74%/51%. Sensitivity of BDG testing was as high as or higher than GM testing for all subgroups and time intervals analysed. BDG testing was less specific (90-93%) than GM testing (99-100%). Combining BDG and GM testing resulted in sensitivity/specificity of 70%/91%. Often, BDG testing was positive before GM testing. Our study backs the use of BDG for diagnosis of suspected IA. We suggest combining BDG and GM to improve the overall sensitivity.

Evaluation of a Novel Aspergillus Antigen Enzyme-Linked Immunosorbent Assay.

Invasive aspergillosis (IA) is a life-threatening infection that mainly occurs in immunocompromised patients. Here, we compared the novel Aspergillus-specific galactomannoprotein (GP) enzyme-linked immunosorbent assay (ELISA) (Euroimmun Medizinische Labordiagnostika AG) to the established Platelia Aspergillus galactomannan (GM) ELISA (Bio-Rad Laboratories) for the detection of IA. A total of 267 serum samples from 45 cases of proven and 4 episodes of probable IA (according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] criteria) and 156 sera from patients without evidence of IA were tested. Pearson's correlation statistics, as well as sensitivity and specificity, were calculated using manufacturer-recommended (GM) or optimized (GP) cutoff levels. Aspergillus fumigatus was found in 88% of culture-positive infections. When we analyzed all 423 serum samples, GM and GP tests correlated strongly (r = 0.82, P < 0.0001). Among proven IA cases using samples obtained as closely as possible to the day of proven diagnosis, the sensitivity for both tests was 40%. All cases of probable IA (defined by positive GM testing) were also GP positive. Concordant results of the two ELISAs were obtained in 43 of 49 samples (88%). Extending measurements to all sera available in the time frame of 7 days prior to 7 days after the day of proven diagnosis, 47% and 56% of the cases were detected by the GM and GP tests, respectively. Specificity was 99% for GM and 96% for GP testing. For the diagnosis of IA, sensitivity and specificity of the novel GP ELISA are similar to those of the Platelia GM ELISA. The low sensitivities of both tests underline the need for serial testing in patients at risk for IA.

Improving quality of antifungal use through antifungal stewardship interventions.

PURPOSE: In recent years antifungal stewardship (AFS) programmes have been increasingly recommended to provide optimal antifungal treatment. In a previous study (study I) in the department of haematology and oncology of a German tertiary care hospital we found areas for improvement concerning antifungal prescription. Subsequently, AFS measures were implemented and their impact on quality of antifungal use was assessed in this study. METHODS: AFS measures included medical training (two sessions), a pocket card summarising main recommendations for antifungal use, and daily pharmaceutical counselling on the ward. In a 6-month observational study, antifungal prescriptions were analysed and compared to the previously collected data (study I) concerning indication, choice of drug, dosing, duration and drug-drug interactions. The study was approved by the university hospital ethical review board. RESULTS: Antifungal agents were prescribed for 103/1169 inpatients. Compared to study I, a significant increase in dosage accuracy (+ 19.3%; p < 0.05) and correct choice of drug (+ 15.9%; p < 0.05) was noted, as well as a decrease in potential clinically relevant drug-drug interactions with concomitant medication (- 13.9%; p < 0.05). However, no significant improvement in indication and duration of antifungal treatment was identified. 56 recommendations were given to the prescribing physicians (acceptance rate: 66.1%). CONCLUSIONS: The implementation of AFS interventions based on pharmaceutical presence on the ward was associated with an improvement in antifungal use; however, indication and duration of therapy need to be communicated by infectious disease specialists. Considering the proportionally short observation period, the long-term effects of our AFS interventions need to be further investigated.

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.

Antifungal prophylaxis in newly diagnosed AML patients-Adherence to guidelines and feasibility in a real life setting.

Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients.