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Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study

  • Clinical and Epidemiological Study
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Abstract

Objectives

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).

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

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.

Author information

Author notes

  1. T. Widmann

    Present address: Department of Oncology, Ruland Kliniken, 75335, Dobel, Germany

  2. S. Reuter

    Present address: Department of Medicine 4, Klinikum Leverkusen, 51375, Leverkusen, Germany

  3. B. Sinha

    Present address: Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9713, GZ, Groningen, The Netherlands

Authors and Affiliations

  1. Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstr. 19–21, 50935, Cologne, Germany

    A. J. Kaasch & H. Seifert

  2. Department of Medicine, Center for Infectious Diseases and Travel Medicine, University Hospital of Freiburg, 79106, Freiburg, Germany

    S. Rieg & W. V. Kern

  3. Department of Infectious Diseases, J. W. Goethe University Hospital, 60596, Frankfurt, Germany

    J. Kuetscher & H.-R. Brodt

  4. Institute of Medical Microbiology and Hygiene, Saarland University Hospital, 66421, Homburg, Germany

    T. Widmann & M. Herrmann

  5. Department of Respiratory Medicine, Hannover Medical School, 30625, Hannover, Germany

    C. Meyer & T. Welte

  6. Comprehensive Infectious Diseases Center, University Hospitals, 89081, Ulm, Germany

    P. Kern

  7. Department of Gastroenterology, Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, 40225, Düsseldorf, Germany

    U. Haars & S. Reuter

  8. Department of Medicine 1, University Hospital Erlangen, 91054, Erlangen, Germany

    I. Hübner & R. Strauss

  9. Institute of Hygiene and Microbiology, University of Würzburg, 97080, Würzburg, Germany

    B. Sinha

  10. Paul-Martini Sepsis Research Group, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07743, Jena, Germany

    F. M. Brunkhorst

  11. Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, 50924, Cologne, Germany

    M. Hellmich

  12. Department of Internal Medicine, University of Cologne, 50924, Cologne, Germany

    G. Fätkenheuer

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  1. A. J. Kaasch
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  2. S. Rieg
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  18. W. V. Kern
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The preSABATO study group*

Corresponding author

Correspondence to A. J. Kaasch.

Additional information

* This article was written by members of the preSABATO study group. Other members of this study group, who collaborated to this research, are: C. MacKenzie (University Hospital Düsseldorf, Düsseldorf, Germany), C. Bogdan (University Hospital Erlangen, Erlangen, Germany), G. Häcker, C. Schneider (University Hospital of Freiburg, Freiburg, Germany), T. Wichelhaus, J. Kessel (J. W. Goethe University Hospital, Frankfurt, Frankfurt, Germany), S. Ziesing (Hannover Medical School, Hannover, Germany), L. von Müller (Saarland University Hospital, Homburg, Homburg Germany), and S. Stenger (University Hospital Ulm, Ulm, Germany).

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Kaasch, A.J., Rieg, S., Kuetscher, J. et al. Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study. Infection 41, 979–985 (2013). https://doi.org/10.1007/s15010-013-0428-9

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  • DOI: https://doi.org/10.1007/s15010-013-0428-9

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