This study systematically reviewed vancomycin treatment data from 1066 critically ill patients, analyzing the impact of obesity on continuous-infusion serum concentrations and clinical outcomes. It found that severe obesity increases supratherapeutic concentrations and elevates 28-day and 90-day mortality rates. The research emphasizes the importance of ideal body weight (IBW)-adjusted dosing and highlights the necessity of therapeutic drug monitoring (TDM) in obese patients.
Literature Overview
This article 'Impact of Obesity on Serum Concentrations of Vancomycin Administered as Continuous Infusion and on Clinical Outcomes in Critically Ill Patients' evaluates the distribution of vancomycin concentrations (<20 mg L−1, 20–25 mg L−1, >25 mg L−1) across different BMI groups. The study also assesses disease severity scores, mechanical ventilation requirements, renal replacement therapy (RRT) utilization rates, and mortality outcomes in these groups.
Background Knowledge
Vancomycin, a glycopeptide antibiotic, is commonly used to treat severe Gram-positive infections like methicillin-resistant Staphylococcus aureus (MRSA). Due to its narrow therapeutic window, both underdosing and overdosing can lead to suboptimal efficacy or toxicity risks, including acute kidney injury (AKI). Pharmacokinetics (PK) in obese patients are complex, involving altered volume of distribution (Vd) and fluctuating renal clearance rates, making standard dosing inappropriate. This study employs an IBW-based continuous infusion strategy to mitigate vancomycin overexposure in obese patients. While guidelines recommend continuous infusion for optimizing serum concentrations, its effectiveness in obese populations remains uncertain. The research conducts retrospective analysis to investigate the relationship between continuous-infusion vancomycin concentrations and clinical outcomes across BMI categories, underscoring the importance of TDM in obese patients.
Research Methods and Experiments
This retrospective observational study included 1066 patients treated at the ICU of University Hospital Leipzig, Germany, between 2009 and 2015, who received IBW-guided continuous vancomycin infusion. Patients without TDM, unrecorded loading doses, or unreliable data were excluded. Primary endpoints included supratherapeutic concentration (>25 mg L−1), while secondary endpoints encompassed subtherapeutic concentrations (<20 mg L−1), time to target attainment, AKI incidence, RRT requirements, and 28-day and 90-day mortality. Multivariate analysis evaluated the impact of BMI, RRT, and their interaction on vancomycin exposure.
Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first large-sample evaluation of IBW-guided continuous vancomycin infusion in obese critically ill patients. Results support IBW-adjusted dosing strategies to minimize supratherapeutic concentrations and toxicity. Prospective controlled trials are needed to validate this approach in obese populations, particularly regarding long-term AKI and mortality outcomes. Optimal TDM monitoring frequencies and AUC-guided dose adjustments across BMI groups require further investigation.
Conclusion
This retrospective analysis evaluated IBW-guided continuous vancomycin infusion in 1066 critically ill patients. While the regimen didn't significantly accelerate target attainment time, severe obesity correlated with increased supratherapeutic concentrations and elevated short-term mortality. The study underscores the necessity of TDM-guided individualized dosing in obese patients. Future research should focus on optimizing TDM protocols, validating AUC-directed dose adjustments, and assessing long-term outcomes and nephrotoxicity risks. Additional pharmacokinetic parameters (e.g., renal function, fluid status) should be considered for enhanced therapeutic safety.
