Effect of delays in concordant antibiotic treatment on mortality in patients with hospital-acquired Acinetobacter spp. bacteremia: a 13-year retrospective cohort
Lim C., Yin M., Teparrukkul P., Hongsuwan M., Day NPJ., Limmathurotsakul D., Cooper B.
Background Therapeutic options for multidrug-resistant Acinetobacter spp. are limited, and resistance to last resort antibiotics in hospitals is increasing globally. Quantifying the impact of delays in concordant antibiotic treatment on patient mortality is important for designing hospital antibiotic policies. Methods We included patients with Acinetobacter spp. hospital-acquired bacteremia (HAB) in a hospital in Thailand over a 13-year period. For each day of stay following the first positive blood culture we considered antibiotic treatment to be concordant if the isolated organism was susceptible to at least one antibiotic given. We used marginal structural models with inverse-probability weightings to determine the association between delays in concordant treatment and 30-day mortality. Results Between January 2003 and December 2015, 1,203 patients had HAB with Acinetobacter spp., of which 682 patients (56.7%) had one or more days of delay in concordant treatment. These delays were associated with an absolute increase in 30-day mortality of 6.6% (95% CI 0.2%-13.0%), from 33.8% to 40.4%. Crude 30-day mortality was substantially lower in patients with three or more days of delays in concordant treatment compared to those with one to two days of delays. Accounting for confounders and immortal time bias resolved this paradox, and showed similar 30-day mortality for one, two and three or more days of delays. Conclusions Delays in concordant antibiotic treatment were associated with a 6.6% absolute increase in mortality among patients with hospital-acquired Acinetobacter spp. bacteremia. If this association is causal, switching fifteen patients from discordant to concordant initial treatment would be expected to prevent one death. Funding The Mahidol Oxford Tropical Medicine Research Unit (MORU) is funded by the Wellcome Trust [grant number 106698/Z14/Z]. CL is funded by a Wellcome Trust Research Training Fellowship [grant number 206736/Z/17/Z]. MY is supported by a Singapore National Medical Research Council Research Fellowship [grant number NMRC/Fellowship/0051/2017]. BSC is funded by the UK Medical Research Council and Department for International Development [grant number MR/K006924/1]. DL is funded by a Wellcome Trust Intermediate Training Fellowship [grant number 101103]. The funder has no role in the design and conduct of the study, data collection, or in the analysis and interpretation of the data.