Serum Concentration of Continuously administered Vancomycin influences Efficacy and Safety in Critically Ill Adults: A Systematic Review

Vancomycin is an antibiotic to treat gram-positive infections in critically ill adults. For continuously administered vancomycin (CI), various target ranges have been used in the past, 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 (Css) of CI on the safety and efficacy of therapy in critically ill adults. According to the PRISMA statement, relevant literature was identified by searching two electronic databases (PubMed, Cochrane Library) and Google Scholar from inception until July 2023, focussing on studies reporting measured Css and treatment outcomes (e.g. mortality, nephrotoxicity) with CI. Due to the heterogeneity of the studies, a narrative synthesis of the evidence was performed. Twenty-one publications were included with a total of 2,949 patients with CI (pts). Mortality was higher (two studies, n=388 pts) and clinical cure lower (one study, n=40 pts) with a Css <15 mg/L measured 24 hours after initiation of CI (C24). An adequate loading dose appeared most important for maintaining higher C24. Generally, higher Css were associated with higher rates of acute kidney injury (AKI) (fifteen studies, n=2,331 pts). We calculated that a Css <25 mg/L (vs. ≥25 mg/L) was preferable for reducing nephrotoxicity (three studies, n=515 pts). 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 Css cohorts should be formed to allow evaluation of the impact of Css of CI on treatment outcomes.