Serum concentration of continuously administered vancomycin influences efficacy and safety in critically ill adults: a systematic review

Objectives: Vancomycin is used to treat Gram-positive infections in critically ill adults. For vancomycin administered by continuous infusion (CI), various target ranges have been used, ranging from 15-20 mg/L to 30-40 mg/L. This systematic literature review was conducted to investigate the impact of steady-state serum concentration (C-ss) of CI on safety and efficacy of therapy in critically ill adults.Methods: Relevant literature was identified by searching two electronic databases (PubMed, Cochrane Library) and Google Scholar from inception until July 2023, focusing on studies reporting measured C-ss and treatment outcomes (e.g. mortality, nephrotoxicity) with CI. Due to study heterogeneity, a narrative synthesis of the evidence was performed.Results: Twenty-one publications were included with a total of 2949 patients. Mortality was higher (two studies, n = 388 patients) and clinical cure was lower (one study, n = 40 patients) with C-ss < 15 mg/L measured 24 h after initiation of CI (C-24). An adequate loading dose appeared most important for maintaining higher C-24. Generally, higher C-ss was associated with higher rates of acute kidney injury (AKI) (15 studies, n = 2331 patients). It was calculated that C-ss < 25 mg/L (versus >= 25 mg/L) was preferable for reducing nephrotoxicity (three studies, n = 515 patients).Conclusions: Despite sparse data availability, the target range of 15-25 mg/L in CI may increase clinical cure and reduce mortality and AKI. In future research, vancomycin C-ss cohorts should be formed to allow evaluation of the impact of C-ss of CI on treatment outcomes.