Risk of hepatic events in patients treated with vancomycin in clinical studies: a systematic review and meta-analysis

Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events.

To conduct a meta-analysis of published randomized controlled clinical trials (RCTs) to better understand if the use of vancomycin is potentially associated with an increased risk of hepatic events.

A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library from 1950 to June 2010 was conducted.

The inclusion criteria consisted of (i) published RCTs comparing vancomycin with/without other additional treatments to other comparators; and (ii) studies that reported hepatic events.

The data related to any hepatic events reported in RCTs were extracted and examined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio (RR) with a 95% CI and number needed to harm. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger's test.

A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with other comparators (pooled RR=1.95; 95% CI 1.62, 2.36; p<0.001), but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe drug-induced liver injury.

Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested.