Appropriate empirical antibiotic therapy and mortality: Conflicting data explained by residual confounding

Autoři: Romy Schuttevaer aff001;  Jelmer Alsma aff001;  Anniek Brink aff001;  Willian van Dijk aff001;  Jurriaan E. M. de Steenwinkel aff002;  Hester F. Lingsma aff003;  Damian C. Melles aff002;  Stephanie C. E. Schuit aff001
Působiště autorů: Department of Internal Medicine, Section Acute Medicine, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands aff001;  Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands aff002;  Department of Public Health, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands aff003;  Department of Medical Microbiology and Immunology, Meander MC, Amersfoort, The Netherlands aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225478



Clinical practice universally assumes that appropriate empirical antibiotic therapy improves survival in patients with bloodstream infection. However, this is not generally supported by previous studies. We examined the association between appropriate therapy and 30-day mortality, while minimizing bias due to confounding by indication.


We conducted a retrospective cohort study between 2012 and 2017 at a tertiary university hospital in the Netherlands. Adult patients with bloodstream infection attending the emergency department were included. Based on in vitro susceptibility, antibiotic therapy was scored as appropriate or inappropriate. Primary outcome was 30-day mortality. To control for confounding, we performed conventional multivariable logistic regression and propensity score methods. Additionally, we performed an analysis in a more homogeneous subgroup (i.e. antibiotic monotherapy).


We included 1.039 patients, 729 (70.2%) received appropriate therapy. Overall 30-day mortality was 10.4%. Appropriately treated patients had more unfavorable characteristics, indicating more severe illness. Despite adjustments, we found no association between appropriate therapy and mortality. For the antibiotic monotherapy subgroup (n = 449), patient characteristics were more homogeneous. Within this subgroup, appropriate therapy was associated with lower mortality (Odds Ratios [95% Confidence Intervals] ranging from: 0.31 [0.14; 0.67] to 0.40 [0.19; 0.85]).


Comparing heterogeneous treatment groups distorts associations despite use of common methods to prevent bias. Consequently, conclusions of such observational studies should be interpreted with care. If possible, future investigators should use our method of attempting to identify and analyze the most homogeneous treatment groups nested within their study objective, because this minimizes residual confounding.

Klíčová slova:

Antibiotics – Blood – Body temperature – Critical care and emergency medicine – Intensive care units – Oxygen – Respiratory infections


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2019 Číslo 11