Continuous versus intermittent beta-lactam antibiotic infusions in critically ill patients: The UK cohort of the BLING III trial.

BACKGROUND

There are theoretical reasons why beta-lactam antibiotics may be more effective in treating severe infections if administered by continuous infusion, rather than short intermittent infusions. The Beta-Lactam Infusion Group (BLING) III trial was a multinational randomised clinical trial (RCT) which tested this hypothesis in participants with sepsis who were cared for in an intensive care unit (ICU). The United Kingdom (UK) findings are reported here.

METHODS

The global trial was an open-label RCT conducted in the UK, Australia, New Zealand, Belgium, France, Sweden and Malaysia. Participants were critically ill adults being treated with meropenem or piperacillin/tazobactam due to a confirmed or presumed infection. Participants were randomised to receive the antibiotic by either continuous infusion or short intermittent infusion at equivalent daily doses as selected by the treating team. The primary outcome was 90-day all-cause mortality; secondary outcomes included clinical cure up to 14 days after randomisation, new infection and acquisition of resistant organisms, ICU and in hospital mortality.

RESULTS

Overall, 7202 participants were randomised, with 2900 from the UK. The UK cohort had very similar baseline characteristics and outcomes to the global trial. For continuous versus intermittent infusion, the global trial showed 24.9% versus 26.8% participants had died by 90 days (odds ratio 0.91, 95% CI: 0.81-1.01, p = 0.08); and in the UK 26.7% versus 29.3% participants had died (odds ratio 0.88, 95% CI: 0.75-1.04, p = 0.13). Although not statistically significant, all outcomes showed point estimates in favour of continuous infusion.

CONCLUSIONS

The findings in the UK cohort are consistent with the conclusions drawn from the global BLING III trial. It seems reasonable to conclude the finding are applicable to the UK.