Study protocol of REpeat versus SIngle ShoT Antibiotic prophylaxis in major Abdominal Surgery (RESISTAAS I): a prospective observational study of antibiotic prophylaxis practice for patients undergoing major abdominal surgery.

INTRODUCTION: Surgical site infections (SSIs) are among the most common complications after abdominal surgery and develop in approximately 20% of patients. These patients suffer a 12% increase in mortality, underlying the need for strategies reducing SSI. Perioperative antibiotic prophylaxis is paramount for SSI prevention in major abdominal surgery. Yet, intraoperative redosing criteria are subjective and whether patients benefit from it remains unclear. METHODS AND ANALYSIS: The REpeat versus SIngle ShoT Antibiotic prophylaxis in major Abdominal Surgery (RESISTAAS I) study is a single-centre, prospective, observational study investigating redosing of antibiotic prophylaxis in 300 patients undergoing major abdominal surgery. Adult patients scheduled for major abdominal surgery will be included. Current practice of redosing regarding number and time period will be recorded. Postoperative SSIs, nosocomial infections, clinically relevant infection-associated bacteria, postoperative antibiotic treatment, in addition to other clinical, pharmacological and economical outcomes will be evaluated. Differences between groups will be analysed with analysis of covariance. ETHICS AND DISSEMINATION: RESISTAAS I will be conducted in accordance with the Declaration of Helsinki and internal, national and international standards of GCP. The Medical Ethics Review Board of Heidelberg University has approved the study prior to initiation (S-404/2021). The study has been registered on 7 February 2022 at German Clinical Trials Register, with identifier DRKS00027892. We plan to disseminate the results of the study in a peer-reviewed journal. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00027892.

Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Dalbavancin.

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.

Antibiotic Stewardship and Therapeutic Drug Monitoring of ß-Lactam Antibiotics: Is There a Link? An Opinion Paper.

PURPOSE: In critically ill patients, changes in the pharmacokinetics (PK) of ß-lactams can lead to significant variations in serum concentrations, with possibly detrimental effects on outcomes. The utilization of individually calculated doses, extended infusion regimen, and therapeutic drug monitoring (TDM)-guided dose adjustments can mitigate the PK changes and help to achieve and attain an individual PK target. METHODS: We reviewed relevant literature from 2004 to 2021 using 4 search engines (PubMed, Web of Science, Scopus, and Google Scholar). Unpublished clinical data were also examined. RESULTS: TDM-guided, individualized dosing strategies facilitated PK target attainment and improved patient outcomes. TDM-guided therapy is a core concept of individualized dosing that increases PK target attainment and identifies possible toxic ß-lactam concentrations. CONCLUSIONS: Individualized dosing and TDM facilitate the rational use of ß-lactams and are integral for antibiotic stewardship interventions in critical care, affording the optimal exposure of both pathogen and drugs, along with enhanced treatment efficacy and reduced emergence of antimicrobial resistance.