Objectives To investigate the performance and risk associated with the usage of Chat Generative Pre-trained Transformer (ChatGPT) to answer drug-related questions. Methods A 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). Results Overall, 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. Conclusion In 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.

Optimization of antibiotic dosing is a treatment intervention that is likely to improve outcomes in severe infections. The aim of this retrospective study was to describe the therapeutic exposure of steady state piperacillin concentrations (c_PIP) and clinical outcome in critically ill patients with sepsis or septic shock who received continuous infusion of piperacillin with dosing personalized through software-guided empiric dosing and therapeutic drug monitoring (TDM). Therapeutic drug exposure was defined as c_PIP of 32–64 mg/L (2–4× the ‘MIC breakpoint’ of Pseudomonas aeruginosa). Of the 1544 patients screened, we included 179 patients (335 serum concentrations), of whom 89% achieved the minimum therapeutic exposure of >32 mg/L and 12% achieved potentially harmful c_PIP > 96 mg/L within the first 48 h. Therapeutic exposure was achieved in 40% of the patients. Subsequent TDM-guided dose adjustments significantly enhanced therapeutic exposure to 65%, and significantly reduced c_PIP > 96 mg/L to 5%. Mortality in patients with c_PIP > 96 mg/L (13/21; 62%) (OR 5.257, 95% CI 1.867–14.802, p = 0.001) or 64–96 mg/L (30/76; 45%) (OR 2.696, 95% CI 1.301–5.586, p = 0.007) was significantly higher compared to patients with therapeutic exposure (17/72; 24%). Given the observed variability in critically ill patients, combining the application of dosing software and consecutive TDM increases therapeutic drug exposure of piperacillin in patients with sepsis and septic shock.

Dalbavancin is emerging as a promising alternative in the ambulant treatment of gram-positive infections that require long-term antibiotic treatment such as osteomyelitis, prosthetic joint infections, and endocarditis. The aim of the current study was to develop and validate a simple, rapid, and cost-effective high-performance liquid chromatography–ultraviolet spectrometry (HPLC–UV) method for the quantification of dalbavancin. Sample clean-up included a protein precipitation protocol, followed by chromatographic separation on a reverse phase HPLC column (C-18) with gradient elution of the mobile phase. Quantification was performed with the internal standard (caffeine) method. Linear relationships between peak area responses and drug concentrations were obtained in the range of 12.5–400 mg/L. The variation coefficient of precision and the bias of accuracy (both inter- and intraday) were less than 10%. The limit of quantification (LOQ) was 12.5 mg/L. The simple and reliable HPLC–UV assay described is a powerful tool for routine therapeutic drug monitoring (TDM) of dalbavancin in human serum in clinical laboratories. With a total process time of approximately 20 min, it allows for accurate and selective quantification up to the expected pharmacokinetic peak concentrations. The method was successfully used to analyze subsequent serum samples of three patients and showed good performance in monitoring serum levels.

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The optimal dosing strategy for beta-lactams in critically ill patients, particularly in septic patients, is an ongoing matter of discussion. This retrospective study aimed to evaluate the success of software-guided empiric meropenem dosing (CADDy, Calculator to Approximate Drug-Dosing in Dialysis) with subsequent routine meropenem measurements and expert clinical pharmacological interpretations. Adequate therapeutic drug exposure was defined as concentrations of 8–16 mg/L, whereas concentrations of 16–24 mg/L were defined as moderately high and concentrations >24 mg/L as potentially harmful. A total of 91 patients received meropenem as a continuous infusion (229 serum concentrations), of whom 60% achieved 8–16 mg/L, 23% achieved 16–24 mg/L, and 10% achieved unnecessarily high and potentially harmful meropenem concentrations >24 mg/L in the first 48 h using the dosing software. No patient showed concentrations 24 mg/L with TDM-guided dose adjustments. The combined use of dosing software and consecutive TDM promised a high rate of adequate therapeutic drug exposures of meropenem in patients with sepsis and septic shock.

Background: Prophylactic antibiotics are frequently administered after major abdominal surgery including hepatectomies aiming to prevent infective complications. Yet, excessive use of antibiotics increases resistance in bacteria. The aim of this systematic review and meta-analysis is to assess the efficacy of prophylactic antibiotics after hepatectomy (postoperative antibiotic prophylaxis, POA). Method: This systematic review and meta-analysis were completed according to the current PRISMA guidelines. The protocol has been registered prior to data extraction (PROSPERO registration Nr: CRD42021288510). MEDLINE, Web of Science and CENTRAL were searched for clinical reports on POA in hepatectomy restrictions. A random-effects model was used for synthesis. Methodological quality was assessed with RoB2 and ROBINS-I. GRADE was used for the quality of evidence assessment. Results: Nine comparative studies comprising 2987 patients were identified: six randomized controlled trials (RCTs) and three retrospectives. POA did not lead to a reduction in postoperative infective complications or have an effect on liver-specific complications—post-hepatectomy liver failure and biliary leaks. POA over four or more days was associated with increased rates of deep surgical site infections compared to short-term administration for up to two days (OR 1.54; 95% CI [1.17;2.03]; p = 0.03). Routine POA led to significantly higher MRSA incidence as a pathogen (p = 0.0073). Overall, the risk of bias in the studies was low and the quality of evidence moderate. Conclusion: Routine POA cannot be recommended after hepatectomy since it does not reduce postoperative infection or liver-specific complications but contributes to resistance in bacteria. Studies into individualized risk-adapted antibiotic prophylaxis strategies are needed to further optimize perioperative treatment in liver surgery.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.