Impact of routine bedside infectious diseases service on clinical management and prognosis of patients with Candida fungemia - an example for Antifungal Stewardship at university level in Germany.

BACKGROUND: Candidemia is rare and has a high mortality rate. This study analyses the impact of bedside antifungal stewardship (AFS) on clinical management and prognosis of patients with candidemia at a university hospital in Germany. METHODS: All patients with at least one positive blood culture with Candida species between 2014 and 2016 received bedside AFS with standardized recommendations. Medical records were retrospectively analyzed. Results from the intervention period from 2014-2016 (n=109), with focus on 2016 (n=39), were compared with those from the pre-intervention period in 2013 (n=30). RESULTS: Bedside AFS was performed in 24/35 (69%) surviving patients in 2016 within the first 3 days after diagnosis of candidemia. All surviving patients (n=35) in 2016 received antifungal treatment compared with 24/28 (86%) in 2013 (p=0.0344). Follow-up blood cultures were performed in 25/35 (71%) in 2016 compared with 10/25 (40%) in 2013 (p=0.0046). Survival in the intervention compared with the pre-intervention group did not differ significantly (p=0.58) one year after the diagnosis of candidemia was made. However, patients with candidemia often have multiple serious comorbidities. CONCLUSIONS: Individualized bedside AFS significantly improves adherence to recommendations for patients with Candida fungemia, especially guideline-oriented diagnostics and therapy. Improving the prognosis of patients with candidemia remains a huge challenge for AFS.

Intrathecal Antibacterial and Antifungal Therapies.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Self-assembled nanocages for hydrophilic guest molecules.

Reverse polymeric micelles are obtained following the association of polymeric amphiphiles in apolar media. To this date, reports of pharmaceutical applications for such micelles have been scarce, mainly because these systems have been studied in solvents that are not suitable for medical use. Here, alkylated star-shaped poly(glycerol methacrylate) polymers have been proposed in the design of oil-soluble reverse polymeric micelles. Micellar behavior was studied in various apolar solvents, including ethyl oleate, a pharmaceutically acceptable vehicle. The polymers were shown to assemble into spherical nanostructures (<40 nm) as determined by cryogenic transmission electron microscopy and atomic force microscopy studies. Interestingly, the reverse micelles were able to encapsulate various peptides/proteins (vasopressin, myoglobin, and albumin) in substantial amounts and facilitate their solubilization in oil. The nature of both the polymer used in micelle formation and the guest molecules was found to influence the ability of the micelle to interact with hydrophilic compounds.