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      Vancomycin in ICU Patients with Gram-Positive Infections: Initial Trough Levels and Mortality

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          Vancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU).


          This retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15–20 mg/L for severe infections and 10–15 mg/L for less severe infections were considered therapeutic.


          The patients were relatively older with a mean age of 60 (SD ±20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068).


          The study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.

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          Most cited references 31

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          Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

          To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".
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            Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.

            Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.
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              Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

              A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P 373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥ 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                14 October 2020
                : 16
                : 979-987
                [1 ]Pharmaceutical Care Department, Ministry of National Guard- Health Affairs , Riyadh, Saudi Arabia
                [2 ]Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences , Riyadh, Saudi Arabia
                [3 ]Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, MD, USA
                [4 ]King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences , Riyadh, Saudi Arabia
                [5 ]Intensive Care Department, College of Medicine King Saud Bin Abdulaziz University for Health Sciences , Riyadh, Saudi Arabia
                Author notes
                Correspondence: Nadiyah Alshehri Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences , P.O. Box: 47323, Riyadh11552, Saudi Arabia Email alshehrina2@ngha.med.sa
                © 2020 Alshehri et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 10, References: 32, Pages: 9
                This research did not receive any funding.
                Original Research


                vancomycin dosage, pharmacokinetics, renal function, serum trough levels, mortality


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