Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
- PMID: 32519003
- PMCID: PMC7334278
- DOI: 10.1007/s00134-020-06111-5
Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
Abstract
Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation.
Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure.
Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64).
Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely.
Keywords: Antimicrobial de-escalation; Bacterial infection; Clinical cure; Empirical therapy; Intensive care unit.
Conflict of interest statement
LDB, PD, SD, KDS, JSteen, AT, MA, MOC, GDP, GD, SF, JGM, JAP, JSchouten, FS, FZ, KZ have no conflicts of interest to declare. ML: consulting Amomed, Aguettant; lectures MSD, Pfizer, 3 M, Aspen, Orion, 3 M, Edwards. JL: board membership: Bayer ESICM Advisory Board, MSD Antibacterials Advisory Board; honorarium for lectures: Pfizer South Africa, MSD South Africa; committee: Pfizer International: 2018 Anti-Infectives. MO: speaker honoraria Fresenius Medical, Baxter and Biomerieux; research funding from Fresenius Medical, Baxter and LaJolla Pharma; member of an advisory committee for Biomerieux, AM Pharma and NxStage. JFT declares COI outside the submitted work: scientific board: Pfizer, Paratek, Nabriva, Merck; research grants to my university: Pfizer, Merck, Biomerieux; lectures fees: Merck, Pfizer, Biomerieux, Gilead. JR: consultancies/advisory boards: MSD (2019), QPEX (2019), Discuva Ltd (2019), Accelerate Diagnostics (2017), Bayer (2017), Biomerieux (2016); speaking fees: MSD (2018), Biomerieux (2018); industry grants: MSD (2017), The Medicines Company (2017), Cardeas Pharma (2016), Biomerieux (2019). JRZ: research grants: Pfizer, Merck; scientific board participation: Merck, BioMerieux, Eumedica, Pfizer; lecture fees: Merck, Pfizer, Correvio, Gilead. JDW: grant from the Flanders Research Foundation during the conduct of the study (Senior Clinical Investigator Grant); consulted for Accelerate, Bayer Healthcare, Cubist, Grifols, MSD, Pfizer (honoraria were paid to his institution).
