Evan J Zasowski1, Matteo Bassetti2, Francesco Blasi3, Herman Goossens4, Jordi Rello5, Giovanni Sotgiu6, Lara Tavoschi7, Mick R Arber8, Rachael McCool8, Jacoby V Patterson8, Christopher M Longshaw9, Sara Lopes9, Davide Manissero10, Sean T Nguyen9, Keiko Tone9, Stefano Aliberti11. 1. Department of Clinical Sciences, Touro University California College of Pharmacy, Vallejo, CA. 2. Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino-IRCCS per l'Oncologia, Genoa, Italy. 3. Respiratory Unit and Cystic Fibrosis Adult Center, Internal Medicine Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 4. Laboratory of Clinical Microbiology, Antwerp University Hospital, Edegem and Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. 5. Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), Barcelona, Spain; Clinical Research and Epidemiology in Pneumonia and Sepsis (CRIPS), Vall d'Hebron Institute of Research, Barcelona, Spain. 6. Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy. 7. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. 8. York Health Economics Consortium, University of York, York, United Kingdom. 9. Shionogi BV, London, United Kingdom. 10. Global Health, University College London, UCL, United Kingdom. 11. Respiratory Unit and Cystic Fibrosis Adult Center, Internal Medicine Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. Electronic address: stefano.aliberti@unimi.it.
Abstract
BACKGROUND: Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes. RESEARCH QUESTION: What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections? STUDY DESIGN AND METHODS: Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vs no delay in receiving appropriate therapy; duration of delay; and inappropriate vs appropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay. RESULTS: The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95% CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30 days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95% CI, 0.43-0.76]; OR, 0.47 [95% CI, 0.27-0.80]; and OR, 0.54 [95% CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P = .09), but heterogeneity between studies was high. INTERPRETATION: Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42018104669; URL: www.crd.york.ac.uk/prospero/.
BACKGROUND:Patients with severe bacterial infections often experience delay in receiving appropriate treatment. Consolidated evidence of the impact of delayed appropriate treatment is needed to guide treatment and improve outcomes. RESEARCH QUESTION: What is the impact of delayed appropriate antibacterial therapy on clinical outcomes in patients with severe bacterial infections? STUDY DESIGN AND METHODS: Literature searches of MEDLINE and Embase, conducted on July 24, 2018, identified studies published after 2007 reporting the impact of delayed appropriate therapy on clinical outcomes for hospitalized adult patients with bacterial infections. Where appropriate, results were pooled and analyzed with delayed therapy modeled three ways: delay vs no delay in receiving appropriate therapy; duration of delay; and inappropriate vs appropriate initial therapy. This article reports meta-analyses on the effect of delay and duration of delay. RESULTS: The eligibility criteria were met by 145 studies, of which 37 contributed data to analyses of effect of delay. Mortality was significantly lower in patients receiving appropriate therapy without delay compared with those experiencing delay (OR, 0.57; 95% CI, 0.45-0.72). Mortality was also lower in the no-delay group compared with the delay group in subgroups of studies reporting mortality at 20 to 30 days, during ICU stay, or in patients with bacteremia (OR, 0.57 [95% CI, 0.43-0.76]; OR, 0.47 [95% CI, 0.27-0.80]; and OR, 0.54 [95% CI, 0.40-0.75], respectively). No difference was found in time to appropriate therapy between those who died and those who survived (P = .09), but heterogeneity between studies was high. INTERPRETATION: Avoiding delayed appropriate therapy is essential to reduce mortality in patients with severe bacterial infections. CLINICAL TRIAL REGISTRATION: PROSPERO; No.: CRD42018104669; URL: www.crd.york.ac.uk/prospero/.
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