Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study
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Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB).
Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression.
One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25 %) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95 % confidence interval [CI] [0.39–2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95 % CI [0.47–4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome.
In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.
KeywordsStaphylococcus aureus Bloodstream infection Antimicrobial Antibiotic Adequate Empiric Appropriate
Data acquisition was supported by H. Birkholz (University of Cologne), M. Gensler (Saarland University Hospital, Homburg), M. Holl (University Hospital Ulm), G. Peyerl-Hofmann (University Hospital Freiburg), and C. Feind (University Hospital Düsseldorf). This study was mainly funded by the Deutsche Forschungsgemeinschaft (DFG, grant number KA 3104/1-1 to A.J.K.). The following individuals received support from the German Federal Ministry of Education and Research: A.J.K, S.R., P.K., F.M.B.; grant number BMBF 01KI1017, 01EO0803, 01KI0772, and 01EO1002, respectively. F.M.B. was supported by the Thuringian Ministry of Education, Science and Culture (PE 108-2), the Thuringian Foundation for Technology, Innovation and Research (STIFT), and the German Sepsis Society (GSS). B.S. was supported by the DFG (IRTG1522, SFB-TR34). The funding agencies did not have any role in the study design, collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.
Conflict of interest
All authors none to declare.
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