Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
Authors: Liesbet De Bus, Pieter Depuydt, Johan Steen, Sofie Dhaese, Ken De Smet, Alexis Tabah, Murat Akova, Menino Osbert Cotta, Gennaro De Pascale, George Dimopoulos, Shigeki Fujitani, Jose Garnacho-Montero, Marc Leone, 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, Fernando Rios, Alejandro Risso Vazquez, Maria Gabriela Vidal, Graciela Zakalik, Antony George 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, Elias Pablo Arévalo, Mónica Crespo, Roberto Zelaya Flores, Petr Píza, Diego Morocho Tutillo, Andreas Elme, Anne Kallaste, Joel Starkopf, Jeremy Bourenne, Mathieu Calypso, Yves Cohen, Claire Dahyot-Fizelier, François Depret, Max Guillot, Nadia Imzi, Sebastien Jochmans, Achille Kouatchet, Alain Lepape, Olivier Martin, Markus Heim, Stefan J Schaller, Kostoula Arvaniti, Anestis Bekridelis, Panagiotis Ioannidis, Cornelia Mitrakos, Metaxia N. Papanikolaou, Sofia Pouriki, Anna Vemvetsou, Babu Abraham, Pradip Kumar Bhattacharya, Anusha Budugu, Subhal Dixit, Sushma Gurav, Padmaja Kandanuri, Dattatray Arun Prabhu, Darshana Rathod, Kavitha Savaru, Ashwin Neelavar Udupa, Sunitha Binu 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 Martin-Loeches, Jan Steiner, Maria Barbagallo, Anselmo Caricato, Andrea Cortegiani, Rocco D’Andrea, Cristian Deana, Abele Donati, Massimo Girardis, Giuliana Mandalà, Giovanna Panarello, Daniela Pasero, Lorella Pelagalli, Paolo Maurizio Soave, Savino Spadaro, Yoshihito Fujita, Shinsuke Fujiwara, Yuya Hara, Hideki Hashi, Satoru Hashimoto, Hideki Hashimoto, Katsura Hayakawa, Masash Inoue, Shutaro Isokawa, Shinya Kameda, Hidenobu Kamohara, Masafumi Kanamoto, Shinshu Katayama, Toshiomi Kawagishi, Yasumasa Kawano, Yoshiko Kida, Mami Kita, Atsuko Kobayashi, Akira Kuriyama, Takaki Naito, Hiroshi Nashiki, Kei Nishiyama, Shunsuke Shindo, Taketo Suzuki, Akihiro Takaba, Chie Tanaka, Komuro Tetsuya, Yoshihiro Tomioka, Youichi Yanagawa, Hideki Yoshida, Syamhanin Adnan, Mohd Shahnaz Hasan, Helmi Sulaiman, Gilberto A. Gasca Lopez, Carmen M. Hernández-Cárdenas, Silvio A. Ñamendys-Silva, Carina Bethlehem, Dylan de Lange, Nicole Hunfeld, Sandra Numan, Henk van Leeuwen, Daniel Owens, Mónica Almeida, Elsa Fragoso, Tiago Leonor, José-Manuel Pereira, Daniela Filipescu, Ioana Grigoras, Mihai Popescu, Dana Tomescu, Mohammed S. Alshahrani, Manuel Alvarez-Gonzalez, Irene Barrero-García, Miguel Angel Blasco-Navalpotro, Laura Claverias, Ángel Estella, Lorena Forcelledo Espina, Jose Luis Garcia Garmendia, Emilio García Prieto, Gracia Gómez-Prieto, Carlos Jiménez Conde, Fernando Martinez Sagasti, Alicia Muñoz Cantero, Alberto Orejas-Gallego, Elisabeth Papiol, Demetrio Pérez-Civantos, Juan Carlos Pozo Laderas, Josep Trenado Álvarez, Paula Vera-Artázcoz, Pablo Vidal Cortés, Anders Oldner, Martin Spångfors, Emine Alp, Iftihar Köksal, Volkan Korten, Arife Özveren, Anna Hall, Kevin W. Hatton, Krzysztof Laudanski
Journal: Intensive Care Medicine (2020)

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. 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. 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). 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.