title: Inappropriate empirical antimicrobial therapy for multidrug-resistant organisms in critically ill patients with pneumonia is not an independent risk factor for mortality: Results of a prospective observational study of 758 patients.
abstract: The benefits of broad-spectrum initial empirical antibiotic therapy for all patients in intensive care units (ICUs) with high rates of multidrug-resistant organisms (MDROs) have not been critically evaluated. In this study, 758 ICU patients with pneumonia were prospectively evaluated. Of 349 positive respiratory cultures, 119 (34.1%) were with MDRO isolates. These were associated with increased mortality [adjusted hazard ratio (HR)=1.65, 95% confidence interval (CI) 1.01-2.68; P=0.04] as was increasing age and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Among the patients with MDRO-associated pneumonia, increasing age, APACHE II score and inappropriate definitive antimicrobial therapy (IDAT) were found to be significant risk factors for mortality (in-ICU mortality, adjusted HR=2.8, 95% CI 1.3-5.8; P=0.007), but inappropriate empirical antimicrobial therapy (IEAT) was not (in-ICU mortality, unadjusted HR=1.6, 95% CI 0.7-3.6; P=0.3). In conclusion, we found that among critically ill patients with MDRO-associated pneumonia, IEAT is not an independent risk factor for ICU mortality. Hence, we do not recommend the use of broad-spectrum initial empirical antimicrobial therapy for all patients, as its benefits may not outweigh the potential risks. Early microbiological diagnosis to facilitate implementation of early definitive antimicrobial therapy through use of novel technologies is likely to have a major impact.
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Anupama
authors.initials: A
authors.lastname: Vasudevan
authors.affiliation: Department of Medicine, Alexandra Hospital, Jurong Health Services, Singapore. Electronic address: leyland_chuang@nuhs.edu.sg.
authors.forename: Leyland
authors.initials: L
authors.lastname: Chuang
authors.affiliation: Department of Statistics and Applied Probability, National University of Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Jialiang
authors.affiliation: Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Health System, Singapore.
authors.forename: Amartya
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Anaesthesia, National University Health System, Singapore.
authors.forename: Eugene Yu-Yuen
authors.initials: EY
authors.lastname: Goh
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. Electronic address: paul_anantharajah_tambyah@nuhs.edu.sg.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tambyah
keywords: Antibiotic resistance; Critically ill; Inappropriate antibiotic; Mortality; Pneumonia