Joseph R Paonessa1, Raj D Shah2, Chiagozie I Pickens1, Bryan D Lizza3, Helen K Donnelly1, Michael Malczynski4, Chao Qi5, Richard G Wunderink6. 1. Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL. 2. Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL; Northwest Hospital and Medical Center, University of Washington Medicine, Seattle, WA. 3. Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL. 4. Department of Pathology, Northwestern Memorial Hospital, Chicago, IL. 5. Department of Pathology, Northwestern Memorial Hospital, Chicago, IL; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL. 6. Department of Medicine, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address: r-wunderink@northwestern.edu.
Abstract
BACKGROUND: Guidelines recommend empirical vancomycin or linezolid for patients with suspected pneumonia at risk for methicillin-resistant Staphylococcus aureus (MRSA). Unneeded vancomycin or linezolid use may unnecessarily alter host flora and expose patients to toxicity. We therefore sought to determine if rapid testing for MRSA in BAL can safely decrease use of vancomycin or linezolid for suspected MRSA pneumonia. METHODS: Operating characteristics of the assay were initially validated against culture on residual BAL. A prospective, unblinded, randomized clinical trial to assess the effect of antibiotic management made on the basis of rapid diagnostic testing (RDT) compared with usual care was subsequently conducted, with primary outcome of duration of vancomycin or linezolid administration. Secondary end points focused on safety. RESULTS:Sensitivity of RPCR was 95.7%, with a negative likelihood ratio of 0.04 for MRSA. The clinical trial randomized 45 patients: 22 to antibiotic management made on the basis of RDT and 23 to usual care. Duration of vancomycin or linezolid administration was significantly reduced in the intervention group (32 h [interquartile range, 22-48] vs 72 h [interquartile range, 50-113], P < .001). Proportions with complications and length of stay trended lower in the intervention group. Hospital mortality was 13.6% in the intervention group and 39.1% for usual care (95% CI of difference, -3.3 to 50.3, P = .06). Standardized mortality ratio was 0.48 for the intervention group and 1.18 for usual care. CONCLUSIONS: A highly sensitive BAL RDT for MRSA significantly reduced use of vancomycin and linezolid in ventilated patients with suspected pneumonia. Management made on the basis of RDT had no adverse effects, with a trend to lower hospital mortality. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT02660554; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: Guidelines recommend empirical vancomycin or linezolid for patients with suspected pneumonia at risk for methicillin-resistant Staphylococcus aureus (MRSA). Unneeded vancomycin or linezolid use may unnecessarily alter host flora and expose patients to toxicity. We therefore sought to determine if rapid testing for MRSA in BAL can safely decrease use of vancomycin or linezolid for suspected MRSA pneumonia. METHODS: Operating characteristics of the assay were initially validated against culture on residual BAL. A prospective, unblinded, randomized clinical trial to assess the effect of antibiotic management made on the basis of rapid diagnostic testing (RDT) compared with usual care was subsequently conducted, with primary outcome of duration of vancomycin or linezolid administration. Secondary end points focused on safety. RESULTS: Sensitivity of RPCR was 95.7%, with a negative likelihood ratio of 0.04 for MRSA. The clinical trial randomized 45 patients: 22 to antibiotic management made on the basis of RDT and 23 to usual care. Duration of vancomycin or linezolid administration was significantly reduced in the intervention group (32 h [interquartile range, 22-48] vs 72 h [interquartile range, 50-113], P < .001). Proportions with complications and length of stay trended lower in the intervention group. Hospital mortality was 13.6% in the intervention group and 39.1% for usual care (95% CI of difference, -3.3 to 50.3, P = .06). Standardized mortality ratio was 0.48 for the intervention group and 1.18 for usual care. CONCLUSIONS: A highly sensitive BAL RDT for MRSA significantly reduced use of vancomycin and linezolid in ventilated patients with suspected pneumonia. Management made on the basis of RDT had no adverse effects, with a trend to lower hospital mortality. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT02660554; URL: www.clinicaltrials.gov.
Authors: S E Trevino; M A Pence; J Marschall; M H Kollef; H M Babcock; C-A D Burnham Journal: Eur J Clin Microbiol Infect Dis Date: 2016-12-21 Impact factor: 3.267
Authors: Pervin Korkmaz Ekren; Otavio T Ranzani; Adrian Ceccato; Gianluigi Li Bassi; Eva Muñoz Conejero; Miquel Ferrer; Michael S Niederman; Antoni Torres Journal: Am J Respir Crit Care Med Date: 2018-03-15 Impact factor: 21.405
Authors: J Y Fagon; J Chastre; M Wolff; C Gervais; S Parer-Aubas; F Stéphan; T Similowski; A Mercat; J L Diehl; J P Sollet; A Tenaillon Journal: Ann Intern Med Date: 2000-04-18 Impact factor: 25.391
Authors: Victor I Band; Emily K Crispell; Brooke A Napier; Carmen M Herrera; Greg K Tharp; Kranthi Vavikolanu; Jan Pohl; Timothy D Read; Steven E Bosinger; M Stephen Trent; Eileen M Burd; David S Weiss Journal: Nat Microbiol Date: 2016-05-09 Impact factor: 17.745
Authors: Evelien de Jong; Jos A van Oers; Albertus Beishuizen; Piet Vos; Wytze J Vermeijden; Lenneke E Haas; Bert G Loef; Tom Dormans; Gertrude C van Melsen; Yvette C Kluiters; Hans Kemperman; Maarten J van den Elsen; Jeroen A Schouten; Jörn O Streefkerk; Hans G Krabbe; Hans Kieft; Georg H Kluge; Veerle C van Dam; Joost van Pelt; Laura Bormans; Martine Bokelman Otten; Auke C Reidinga; Henrik Endeman; Jos W Twisk; Ewoudt M W van de Garde; Anne Marie G A de Smet; Jozef Kesecioglu; Armand R Girbes; Maarten W Nijsten; Dylan W de Lange Journal: Lancet Infect Dis Date: 2016-03-02 Impact factor: 25.071
Authors: Megan K Proulx; Samantha G Palace; Sumanth Gandra; Brenda Torres; Susan Weir; Tracy Stiles; Richard T Ellison; Jon D Goguen Journal: J Infect Dis Date: 2015-10-26 Impact factor: 5.226
Authors: Andrew F Shorr; Daniela E Myers; David B Huang; Brian H Nathanson; Matthew F Emons; Marin H Kollef Journal: BMC Infect Dis Date: 2013-06-06 Impact factor: 3.090
Authors: Marc Leone; François Malavieille; Laurent Papazian; Bertrand Meyssignac; Nadim Cassir; Julien Textoris; François Antonini; Bernard La Scola; Claude Martin; Bernard Allaouchiche; Sami Hraiech Journal: Crit Care Date: 2013-08-06 Impact factor: 9.097
Authors: Laura Evans; Andrew Rhodes; Waleed Alhazzani; Massimo Antonelli; Craig M Coopersmith; Craig French; Flávia R Machado; Lauralyn Mcintyre; Marlies Ostermann; Hallie C Prescott; Christa Schorr; Steven Simpson; W Joost Wiersinga; Fayez Alshamsi; Derek C Angus; Yaseen Arabi; Luciano Azevedo; Richard Beale; Gregory Beilman; Emilie Belley-Cote; Lisa Burry; Maurizio Cecconi; John Centofanti; Angel Coz Yataco; Jan De Waele; R Phillip Dellinger; Kent Doi; Bin Du; Elisa Estenssoro; Ricard Ferrer; Charles Gomersall; Carol Hodgson; Morten Hylander Møller; Theodore Iwashyna; Shevin Jacob; Ruth Kleinpell; Michael Klompas; Younsuck Koh; Anand Kumar; Arthur Kwizera; Suzana Lobo; Henry Masur; Steven McGloughlin; Sangeeta Mehta; Yatin Mehta; Mervyn Mer; Mark Nunnally; Simon Oczkowski; Tiffany Osborn; Elizabeth Papathanassoglou; Anders Perner; Michael Puskarich; Jason Roberts; William Schweickert; Maureen Seckel; Jonathan Sevransky; Charles L Sprung; Tobias Welte; Janice Zimmerman; Mitchell Levy Journal: Intensive Care Med Date: 2021-10-02 Impact factor: 17.440
Authors: Barbara Ellen Jones; Jian Ying; Vanessa Stevens; Candace Haroldsen; Tao He; McKenna Nevers; Matthew A Christensen; Richard E Nelson; Gregory J Stoddard; Brian C Sauer; Peter M Yarbrough; Makoto M Jones; Matthew Bidwell Goetz; Tom Greene; Matthew H Samore Journal: JAMA Intern Med Date: 2020-04-01 Impact factor: 21.873
Authors: Andrew T Peters; Chiagozie I Pickens; Michael J Postelnick; Teresa R Zembower; Chao Qi; Richard G Wunderink Journal: Infect Control Hosp Epidemiol Date: 2021-08-13 Impact factor: 6.520
Authors: Julio A Ramirez; Daniel M Musher; Scott E Evans; Charles Dela Cruz; Kristina A Crothers; Chadi A Hage; Stefano Aliberti; Antonio Anzueto; Francisco Arancibia; Forest Arnold; Elie Azoulay; Francesco Blasi; Jose Bordon; Steven Burdette; Bin Cao; Rodrigo Cavallazzi; James Chalmers; Patrick Charles; Jean Chastre; Yann-Erick Claessens; Nathan Dean; Xavier Duval; Muriel Fartoukh; Charles Feldman; Thomas File; Filipe Froes; Stephen Furmanek; Martin Gnoni; Gustavo Lopardo; Carlos Luna; Takaya Maruyama; Rosario Menendez; Mark Metersky; Donna Mildvan; Eric Mortensen; Michael S Niederman; Mathias Pletz; Jordi Rello; Marcos I Restrepo; Yuichiro Shindo; Antoni Torres; Grant Waterer; Brandon Webb; Tobias Welte; Martin Witzenrath; Richard Wunderink Journal: Chest Date: 2020-06-16 Impact factor: 9.410
Authors: Richard G Wunderink; Arjun Srinivasan; Philip S Barie; Jean Chastre; Charles S Dela Cruz; Ivor S Douglas; Margaret Ecklund; Scott E Evans; Scott R Evans; Anthony T Gerlach; Lauri A Hicks; Michael Howell; Melissa L Hutchinson; Robert C Hyzy; Sandra L Kane-Gill; Erika D Lease; Mark L Metersky; Nancy Munro; Michael S Niederman; Marcos I Restrepo; Curtis N Sessler; Steven Q Simpson; Sandra M Swoboda; Christina Vazquez Guillamet; Grant W Waterer; Curtis H Weiss Journal: Ann Am Thorac Soc Date: 2020-05
Authors: Charles S Dela Cruz; Scott E Evans; Marcos I Restrepo; Nathan Dean; Antonio Torres; Isabel Amara-Elori; Shanjana Awasthi; Elisabet Caler; Bin Cao; James D Chalmers; Jean Chastre; Taylor S Cohen; Alan H Cohen; Kristina Crothers; Y Peter Di; Marie E Egan; Charles Feldman; Samir Gautam; E Scott Halstead; Susanne Herold; Barbara E Jones; Carlos Luna; Michael S Niederman; Raul Mendez; Rosario Menendez; Joseph P Mizgerd; Roomi Nusrat; Julio Ramirez; Yuichiro Shindo; Grant Waterer; Samantha M Yeligar; Richard G Wunderink Journal: Ann Am Thorac Soc Date: 2021-07