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A prognostic score for the resolution of bacteremia by Gram-negative bacteria resistant to carbapenems

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Abstract

The management of bacteremia by carbapenem-resistant Gram-negative bacteria (CRGNB) necessitates a surrogate marker for response to treatment. We developed a prognostic score of bacteremia resolution using a test and a validation cohort. In the test cohort, five protein biomarkers were measured in serial daily serum samples from 39 patients with ventilator-associated pneumonia (VAP) and CRGNB bacteremia. Receiver operator characteristic curves were designed to identify cut-off of over-time changes that were associated with more than 80% specificity for resolution of bacteremia. The developed score was validated in a cohort of 24 patients mostly with primary bacteremia by carbapenem-resistant enterobacteria (CRE). Among the five tested biomarkers, only procalcitonin (PCT) was associated with resolution of bacteremia. More precisely, resolved bacteremia was considered if at least one of three situations occurred: (a) PCT on day 2 was decreased more than 30% and PCT on day 4 was below 0.5 ng/ml; (b) PCT on day 4 was decreased more than 40% and PCT on day 4 was below 0.5 ng/ml; and (c) PCT on day 2 was decreased more than 30% and PCT on day 4 was decreased more than 40%. Sensitivity, specificity, and positive and negative predictive values of the score were 66.7%, 83.3%, 90.0%, and 52.6% respectively. This score was fully validated (p values of comparison between the cohorts 0.623). The developed score is highly predictive of resolution of bacteremia by CRGNB. A prospective clinical study is mandatory to validate the results.

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Funding

Part of the study was supported by an unrestricted educational grant provided by Merck to the University of Athens [grant 70/3/11471]. The funders did not have any role in study design, analysis, and interpretation of data and drafting the manuscript.

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Authors and Affiliations

  1. 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece

    Evangelos J. Giamarellos-Bourboulis & Antigone Kotsaki

  2. 1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece

    Christina Routsi

  3. Infectious Diseases Clinic, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy

    Elena Graziano, Elda Righi & Matteo Bassetti

Authors
  1. Evangelos J. Giamarellos-Bourboulis
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  2. Antigone Kotsaki
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  3. Christina Routsi
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  4. Elena Graziano
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  5. Elda Righi
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  6. Matteo Bassetti
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Corresponding author

Correspondence to Evangelos J. Giamarellos-Bourboulis.

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Conflict of interest

EJ Giamarellos-Bourboulis has received honoraria (paid to the University of Athens) from AbbVie USA, Abbott CH, Biotest Germany, Brahms GmbH, InflaRx GmbH, the Medicines Company, MSD Greece, and XBiotech Inc. He has received independent educational grants from AbbVie, Abbott, Astellas Pharma, AxisShield, bioMérieux Inc., InflaRx GmbH, the Medicines Company, and XBiotech Inc. He has received funding from the FrameWork 7 program HemoSpec and from the Horizon2020 Marie-Curie project European Sepsis Academy (granted to the National and Kapodistrian University of Athens).

M Bassetti serves on scientific advisory boards for Angelini, AstraZeneca, Bayer, Cubist, Pfizer, Menarini, MSD, Nabriva, Paratek, Roche, Shionogi, Tetraphase, The Medicine Company, and Astellas Pharma Inc.; has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer MSD, Gilead Sciences, Menarini, Novartis, Ranbaxy, and Teva. The other authors declare no conflict of interest.

Ethical approval

The study was approved by the Ethics Committees of the hospitals of the participating study sites and by the National Organization of Medicines of Greece (http://clinicaltrials.gov: registration number NCT00297674).

Informed consent

Patients were enrolled after written consent provided by first-degree relatives.

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Giamarellos-Bourboulis, E.J., Kotsaki, A., Routsi, C. et al. A prognostic score for the resolution of bacteremia by Gram-negative bacteria resistant to carbapenems. Eur J Clin Microbiol Infect Dis 37, 2083–2089 (2018). https://doi.org/10.1007/s10096-018-3342-3

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  • DOI: https://doi.org/10.1007/s10096-018-3342-3

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