Efficacy and Safety of Continuous Infusion of Vancomycin in Critically Ill Adults: A Systematic Review

Abstract

AbstractBackgroundVancomycin is an antibiotic to empirically treat gram-positive infections in critically ill adults in the intensive care unit (ICU). 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.ObjectivesTo investigate the impact of steady-state serum concentration (Css) of CI on the safety and efficacy of therapy in adults in the intensive care unit: a systematic literature review.MethodsAccording to the PRISMA statement, relevant literature was identified by searching three electronic databases (MEDLINE through the PubMed interface, Cochrane Library and Google Scholar) from inception until March 2022, focussing on studies reporting measured steady-state serum concentration of vancomycin (Css) and treatment outcomes (mortality, nephrotoxicity) with CI. Due to the heterogeneity of the study designs and outcome measures, it was not possible to summarise the results in a meta-analysis. Therefore, a narrative synthesis of the evidence was performed.ResultsTwenty-one publications were included with a total of 2,949 patients (pts) with CI. In two studies (n=388 pts) mortality rates were reported and cohorts with different Css compared. Mortality was higher with a Css <15 mg/L measured approximately 24 hours after initiation of therapy with CI (C24). An adequate loading dose appeared most important for maintaining higher C24. Acute kidney injury (AKI) in cohorts with different Css was described in four studies (n=863 pts). In one study (n=129 pts), a mean Css throughout the duration of therapy (Cmean) of >30 mg/L was found to predict AKI. No clear cutoff value for Css has been identified in the other studies, but higher concentrations led to higher rates of AKI. We calculated that a Css <25 mg/L was preferable compared to a concentration ≥25 mg/L for reducing nephrotoxicity. Data on target attainment and Css was mentioned in eleven studies (n=1,391 pts). We noticed higher target attainment rates in the studies if the defined target ranges were lower and broader. No association between target attainment and effectiveness (e.g. mortality) of therapy with CI has been observed so far. In two studies (n=101 pts) data on clinical response was presented and compared in cohorts with different Css of which in one study (n=40 pts) higher clinical cure was detected with a C24 >15 mg/L while in the other study (n=61 pts), treatment success was reported at higher Cmean, with sparing out a clear cutoff calculation.ConclusionDespite sparse data availability, it seems that for continuous infusion of vancomycin the mortality was increased if C24 was <15 mg/L, AKI may be reduced if Cmean was <25 mg/L, clinical cure was more likely to occur at C24 >15 mg/L, while no relationship between target attainment and efficacy has yet been established. In future research, vancomycin serum concentration cohorts should be formed to allow evaluation of the impact of serum concentration of CI on treatment outcomes.