Antimicrobial Stewardship with and without Infectious Diseases Specialist Services to Improve Quality-of-Care in Secondary and Tertiary Care Hospitals in Germany: Study Protocol of the ID ROLL OUT Study.

BACKGROUND: Antimicrobial stewardship (AMS) programs aim to secure the rational prescription of antibiotics through implementing department- or hospital-level activities. Infectious disease (ID) specialists improve the quality of care and outcomes in infection patients predominantly by individual consultations and patient-level interventions. While hospital AMS programs are established to various extents in Germany, ID specialist services are rarely available in this country. In the ID ROLL OUT study, we will implement and evaluate hospital-level AMS tools with and without ID specialist services in secondary and tertiary care hospitals. We aim to identify means to comprehensively and sustainably improve the quality of care of patients with infectious diseases. METHODS: This project is a clustered, two-armed intervention study, which will be conducted in ten secondary and tertiary (non-university) care hospitals in Germany. The intervention groups are stratified by key characteristics of the hospitals. We will compare two interventional strategies: implementation of AMS teams and implementation of AMS teams combined with the activities of ID specialists (AMS + IDS). PLANNED OUTCOMES: The primary outcome is the quality of care as measured in changes in a Staphylococcus aureus bacteremia (SAB) score (as an indicator of difficult-to-treat infections) and a community-acquired pneumonia (CAP) score (as an indicator of common infections) compared to a baseline pre-interventional period. Our secondary outcomes comprise patient- and hospital-level outcomes, such as the quality and frequency of antibiotic treatment, in-hospital mortality, duration of hospitalization, and C. difficile incidence (associated diarrhea episodes). The study may provide urgently needed key information for the aspired advancement of ID care in Germany. TRIAL REGISTRATION: DRKS00023710 (registered on 9th April 2021).

Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany.

OBJECTIVES: The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German-Austrian hospital ABS practice guideline. METHODS: Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability. RESULTS: Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration. CONCLUSIONS: Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.

[Shortened duration of antibiotic therapy in bacterial infections]. / Verkürzte Therapiedauer bei bakteriellen Infektionen.

The adequate duration of antibiotic therapy in the treatment of bacterial infections is often unclear. For many indications guidelines recommend intervals with ranges of several days instead of fixed courses of treatment, and physicians tend to choose longer rather than shorter durations. The emergence of infections due to multidrug-resistant bacteria and the valuation of avoidable side effects from antibiotic agents raised the question whether a shortened duration of therapy is appropriate in specific indications. Therefore clinical trials to investigate the effectiveness of shorter in comparison to prolonged antibiotic treatment have yet been of growing interest to current research. Recent studies have shown that, concerning clinical endpoints, shorter duration of antibiotic therapy is not inferior to longer treatment in the management of pyelonephritis, intraabdominal infections, community acquired pneumonia an also gramnegative bloodstream infections and febrile neutropenia.

Validation of adapted daily dose definitions for hospital antibacterial drug use evaluation: a multicentre study.

Background: The WHO/ATC (Anatomical Therapeutic Chemical) index DDD (WHO-DDD) is commonly used for drug consumption measurement. Discrepancies between WHO-DDD and actual prescribed daily doses (PDD) in hospitals have prompted alternative dose definitions adapted to doses recommended in hospital practice guidelines [recommended daily doses (RDD)]. Methods: In order to validate RDD we performed modified point prevalence surveys in 24 acute care hospitals and recorded 20620 PDD of antibiotics given to 4226 adult patients on the day of the survey and the 6 preceding days. We calculated RDD and WHO-DDD and compared them with PDD. Results: The rate of RDD corresponding to PDD was higher than the corresponding rate for WHO-DDD (pooled data, 55% versus 30%) and the differences were similar across the hospital sample, but varied according to drug/drug class, route of administration, indication and renal function. RDD underestimated actual consumption by 14% overall, while WHO-DDD overestimated total antibacterial consumption by 28% (pooled data; median values RDD -10% versus WHO-DDD +32%). The deviations of estimated from actual drug use volumes were largest for ß-lactams (RDD -11% versus WHO-DDD +49%), in particular for penicillins (-11% versus +64%), if WHO-DDD were used. Conclusions: Hospital antibiotic consumption surveillance systems using current WHO-DDD should address the uneven discrepancies between actual prescribing and consumption estimates according to drug class that may lead to misclassification in benchmark analyses. We recommend using validated RDD as a supplementary measure to the WHO-DDD for detailed analyses.

Membrane/Water Partition Coefficients of Bile Salts Determined Using Laurdan as a Fluorescent Probe.

The interaction of liposomal membranes composed of soybean phosphatidylcholine with the bile salts (BSs) cholate (Ch), glycocholate (GC), chenodeoxycholate (CDC), and glycochenodeoxycholate (GCDC) was studied. The BSs differed with regard to their lipophilicity, pKa values, and the size of their hydrophilic moiety. Their membrane interactions were investigated using Laurdan as a membrane-anchored fluorescent dye. The apparent membrane/water partition coefficient, D, at pH 7.4 was calculated from binding plots and compared with direct binding measurements using ultracentrifugation as a reference. The Laurdan-derived LogD values at pH 7.4 were found to be 2.10 and 2.25 for the trihydroxy BSs, i.e., Ch and GC, and 2.85 and 2.75 for the dihydroxy BSs, i.e., CDC and GCDC, respectively. For the membrane-associated glycine-conjugated GC and GCDC (pKa values of ∼3.9), no differences in the Laurdan spectra of the respective BS were found at pH 6.8, 7.4, and 8.2. Unconjugated Ch and CDC (pKa values of ∼5.0) showed pronounced differences at the three pH values. Furthermore, the kinetics of membrane adsorption and transbilayer movement differed between conjugated and unconjugated BSs as determined with Laurdan-labeled liposomes.

Interactions of beta-blockers with model lipid membranes: molecular view of the interaction of acebutolol, oxprenolol, and propranolol with phosphatidylcholine vesicles by time-dependent fluorescence shift and molecular dynamics simulations.

Since pharmacokinetic and pharmacodynamic activities of drugs are often related to their interactions with biomembranes, it is of high interest to establish an approach for the characterization of these interactions at the molecular level. For the present study, beta-blockers (oxprenolol, propranolol, and acebutolol) were selected due to their well described nonspecific membrane effects (NME). Their interactions with model lipid membranes composed of palmitoyloleoylphosphatidylcholine (POPC) were studied using Time-Dependent Fluorescence Shift (TDFS) and Generalized Polarization (GP) as well as molecular dynamics (MD) simulations. Liposomal vesicles were labeled with fluorescent membrane polarity probes (Laurdan, Prodan, and Dtmac). Increasing beta-blocker concentrations (0-10 mM for acebutolol and oxprenolol, and 0-1.5 mM for propranolol) significantly rigidifies the lipid bilayer at the glycerol and headgroup level, which was detected in the steady-state and in the time-resolved fluorescence data. The effects of propranolol were considerably stronger than those of the two other beta-blockers. The addition of fluorescent probes precisely located at different levels within the lipid bilayer revealed the insertion of the beta-blockers into the POPC bilayer at the glycerol backbone level, which was further confirmed by MD simulations in the case of propranolol.