Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
Liesbet De Bus, Pieter Depuydt, Johan Steen, Sofie Dhaese, Ken De Smet, Alexis Tabah, Murat Akova, Menino Osbert Cotta, Gennaro De Pascale, George Dimοpoulos, Shigeki Fujitani, José Garnacho‐Montero, Marc Léone, Jeffrey Lipman, Marlies Ostermann, José-Artur Paiva, Jeroen Schouten, Fredrik Sjövall, Jean‐François Timsit, Jason A. Roberts, Jean‐Ralph Zahar, Farid Zand, Kapil Zirpe, Jan J. De Waele, DIANA study group, Fernando Rios, Alejandro Risso Vazquez, María Gabriela Vidal, Graciela Zakalik, Antony Attokaran, Iouri Banakh, Smita Dey-Chatterjee, Julie Ewan, Janet Ferrier, Loretta Forbes, Cheryl Fourie, Anne Leditschke, Lauren Murray, Philipp Eller, Patrick Biston, Stephanie Bracke, Luc De Crop, Nicolas De Schryver, Eric Frans, Herbert Spapen, Claire Van Malderen, Stijn Vansteelandt, Daisy Vermeiren, Esteban Arevalo, Mónica Crespo, Roberto Zelaya Flores, Petr Píza, Diego Morocho Tutillo, Andreas Elme, Anne Kallaste, Joel Starkopf, Jérémy Bourenne, Mathieu Calypso, Y. Cohen, Claire Dahyot‐Fizelier, François Dépret, Max Guillot, Nadia Imzi, Sébastien Jochmans, Achille Kouatchet, Alain Lepape, O. Martin, Markus Heim, Stefan J. Schaller, Kostoula Arvaniti, A Bekridelis, Panagiotis Ioannidis, Cornelia Mitrakos, Metaxia Papanikolaou, Sofia Pouriki, Anna Vemvetsou, Babu K. Abraham, Pradip Bhattacharya, Anusha Budugu, Subhal Dixit, Sushma Gurav, Padmaja Kandanuri, Dattatray Prabhu, Darshana Rathod, Kavitha Savaru, Ashwin Neelavar Udupa, Sunitha Varghese, Hossein Haddad Bakhodaei, Gholamreza Dabiri, Mohammad Javad Fallahi, Farnia Feiz, Mohammad Firoozifar, Vahid Khaloo, Behzad Maghsudi, Mansoor Masjedi, Reza Nikandish, Golnar Sabetian, Brian Marsh, Ignacio Martín‐Loeches, Jan Steiner
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.