Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented. Although, in contrast to the newer lipoglycopeptides, telavancin demonstrates a relatively short half-life and rapid total clearance, its apparent volume of distribution (V_d) is almost identical to that of dalbavancin. The accumulation of telavancin after repeated dosing is only marginal, whereas the pharmacokinetic values of the other glycopeptides show much greater differences after administration of multiple doses. Despite its high plasma–protein binding of 90% and relatively low V_d of approximately 11 L, telavancin shows near complete equilibration of the free fraction in plasma with soft tissue. The ratio of the area under the plasma concentration–time curve from time zero to 24 h (AUC₂₄) of unbound plasma concentrations to the minimal inhibitory concentration (MIC) required to inhibit growth of 90% of organisms (MIC₉₀) of Staphylococcus aureus and S. epidermidis of telavancin are sufficiently high to achieve pharmacokinetic/pharmacodynamic targets indicative for optimal bacterial killing. Considering both the AUC₂₄/MIC ratios of telavancin and the near complete equilibration of the free fraction in plasma with soft tissue, telavancin is an appropriate antimicrobial agent to treat soft tissue infections caused by Gram-positive pathogens. Although the penetration of telavancin into epithelial lining fluid (ELF) requires further investigations, the AUC₂₄/MIC ratio for S. aureus indicates that bactericidal activity in the ELF could be expected.

The current standard method for the analysis of potential drug–drug interactions (pDDIs) is time‐consuming and includes the use of multiple clinical decision support systems (CDSSs) and the interpretation by healthcare professionals. With the emergence of large language models developed with artificial intelligence, an interesting alternative arose. This retrospective study included 30 patients with polypharmacy, who underwent a pDDI analysis between October 2022 and August 2023, and compared the performance of Chat GPT and established CDSSs (MediQ®, Lexicomp®, Micromedex®) in the analysis of pDDIs. A multidisciplinary team interpreted the obtained results and decided upon clinical relevance and assigned severity grades using three categories: (i) contraindicated, (ii) severe, (iii) moderate. The expert review identified a total of 280 clinically relevant pDDIs (3 contraindications, 13 severe, 264 moderate) using established CDSSs, compared with 80 pDDIs (2 contraindications, 5 severe, 73 moderate) using Chat GPT. Chat GPT almost entirely neglected pDDIs with the risk to QTc prolongation (85 vs. 8), which could also not be sufficiently improved by using a specific prompt. To assess the consistency of the results provided by Chat GPT, we repeated each query and found inconsistent results in 90% of the cases. In contrast, Chat GPT provided acceptable and comprehensible recommendations for specific questions on side effects. The use of Chat GPT for the identification of pDDIs cannot be recommended currently, because clinically relevant pDDIs were not detected, there were obvious errors and results were inconsistent. However, if these limitations are addressed accordingly, it is a promising platform for the future.

About one-sixth of the world’s population is affected by a neglected tropical disease as defined by the World Health Organization and Center for Disease Control. Parasitic diseases comprise most of the neglected tropical disease list and they are causing enormous amounts of disability, morbidity, mortality, and healthcare costs worldwide. The burden of disease of the top five parasitic diseases has been estimated to amount to a total 23 million disability-adjusted life-years. Despite the massive health and economic impact, most drugs currently used for the treatment of parasitic diseases have been developed decades ago and insufficient novel drugs are being developed. The current review provides a compilation of the systemic and target-site pharmacokinetics of established antiparasitic drugs. Knowledge of the pharmacokinetic profile of drugs allows for the examination and possibly optimization of existing dosing schemes. Many symptoms of parasitic diseases are caused by parasites residing in different host tissues. Penetration of the antiparasitic drug into these tissues, the target site of infection, is a prerequisite for a successful treatment of the disease. Therefore, for the examination and improvement of established dosing regimens, not only the plasma but also the tissue pharmacokinetics of the drug have to be considered. For the current paper, almost 7000 scientific articles were identified and screened from which 429 were reviewed in detail and 100 were included in this paper. Systemic pharmacokinetics are available for most antiparasitic drugs but in many cases, not for all the relevant patient populations and only for single- or multiple-dose administration. Systemic pharmacokinetic data in patients with organ impairment and target-site pharmacokinetic data for relevant tissues and body fluids are mostly lacking. To improve the treatment of patients with parasitic diseases, research in these areas is urgently needed.

Objectives: Continuous infusion (CON) of fosfomycin has been proposed as potentially advantageous in certain clinical scenarios. However, no clinical data on the pharmacokinetics (PK) of fosfomycin after CON are available to date. This study aimed at investigating the PK of fosfomycin after CON and compare it with intermittent infusion (INT) of fosfomycin. Methods: A randomized two-way crossover study including 8 healthy male volunteers was performed. Each subject received fosfomycin as INT of 8g over 30 minutes every 8 hours and, separated by a wash-out period, as CON of 1g/hour preceded by a loading dose of 8g over 30 minutes. PK sampling was performed for 18 and 24 hours in the CON and INT group, respectively. Results: Fosfomycin was generally well tolerated. However, 2 out of 8 subjects (25%) developed thrombophlebitis at the infusion site following CON, which was prevented in the following subjects with simultaneous co-infusion of Ringer9s lactate. Steady-state C_max and AUC_{SS, 0-24} of fosfomycin after INT were 551.5 ± 67.8 mg/L and 3678.5 ± 601.9 h*mg/L, respectively. CON led to an average steady-state concentration of 183.8 ± 35.9 mg/L, resulting in a calculated AUC_{SS, 0-24} of 4411.2 ± 862.4 h*mg/L, which was 1.2-fold higher compared with INT. CON resulted in 100% T_>MIC for MICs ≤ 128 mg/L, whereas %T_>MIC for INT was only 44% for a MIC of 128 mg/L. Conclusions: CON of fosfomycin led to improved PK and PK/PD determinants in plasma of healthy volunteers. The clinical relevance of these findings remains to be investigated in patients.

Rationale: The present study set out to investigate if PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of two PET tracers and the corresponding target structures was assessed. The first tracer was [⁶⁸Ga]Ga-PSMAHBED-CC([⁶⁸Ga]PSMA), which is already implemented in clinical routine. The second tracer was [¹⁸F]-fluoro-5α-dihydrotestosterone([¹⁸F]FDHT) which binds to the androgen receptor (AR). The AR is particularly interesting in PC, since the AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient received a [⁶⁸Ga]PSMA-PET/MRI- and [¹⁸F]FDHT-PET/MRI-scan prior to prostatectomy. Cancer standardized uptake values (SUV) were determined and related to background SUVs. Following prostatectomy, tumor tissue was sampled and AR and prostate-specific membrane antigen (PSMA) expression determined. AR and PSMA expressions were evaluated quantitively with QuPath and additionally with a four-tiered rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [¹⁸F]FDHT, the SUV_max/SUVbackground ratio showed a significant, strong correlation (P-value=0.019, r=0.72) with AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [⁶⁸Ga]PSMA SUV_max/SUVbackground ratio was not significant (P-value=0.061), yet a positive correlation trend could be observed (r=0.61). SUV_max/SUVbackground ratios were higher for [⁶⁸Ga]PSMA (34.9±24.8) compared to [¹⁸F]FDHT (4.8±1.2). In line with this findings, the tumor detection rate of the Ga-PSMA-PET scan was 90%, but only 40% for the [¹⁸F]FDHT-PET scan. The four-tiered rating of PSMA staining intensity yielded very homogenous results with values of 3+ for most subjects (90%). The AR staining was rated with 1+ in two patients (20%), with 2+ in four patients (40%) and with 3+ in four patients (40%). Conclusion: [¹⁸F]FDHT-PET may be useful for monitoring AR expression and alterations of AR expression during treatment of PC patients. This may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [¹⁸F]FDHT-PET is inferior to [⁶⁸Ga]PSMA-PET for primary PC diagnosis, but the correlation between [⁶⁸Ga]PSMA SUVs and PSMA expression is weaker compared to [¹⁸F]FDHT and the AR.

Fungal central nervous system (CNS) infections show a high mortality rate and only a few antifungal agents are available to treat these infections. We hypothesize that the different biochemical properties of human cerebrospinal fluid (CSF) compared to the standard growth medium lead to the altered activity of antifungal agents in CSF. We investigated the in vitro activity of two of these agents, i.e., amphotericin B (AmB) and voriconazole (VOR), against three different fungi in CSF in comparison to sabouraud-dextrose broth (SDB).