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      Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis

      review-article
      1 , , 2 , 3 , 4 , 5
      Drugs
      Springer International Publishing

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          Abstract

          Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.

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          Most cited references112

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          Aspects of immune dysfunction in end-stage renal disease.

          End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.
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            Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists

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              Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections.

              The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P MIC of MIC was <100%.
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                Author and article information

                Contributors
                christo.l.cimino@vumc.org
                Journal
                Drugs
                Drugs
                Drugs
                Springer International Publishing (Cham )
                0012-6667
                1179-1950
                16 February 2021
                : 1-20
                Affiliations
                [1 ]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Department of Pharmaceutical Services, , Vanderbilt University Medical Center, ; 1211 Medical Center Drive, Nashville, TN 37232 USA
                [2 ]GRID grid.419579.7, ISNI 0000 0000 8660 3507, St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis, ; 1 Pharmacy Place, St. Louis, MO 63110 USA
                [3 ]GRID grid.415952.e, ISNI 0000 0004 0434 5532, Department of Pharmacy, , Missouri Baptist Medical Center, ; 3015 N Ballas Road, St. Louis, MO 63131 USA
                [4 ]GRID grid.412726.4, ISNI 0000 0004 0442 8581, Department of Pharmacy, , Jefferson Health-New Jersey, ; Stratford, NJ 08084 USA
                [5 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Perelman School of Medicine, , University of Pennsylvania, ; 51 N. 39th Street, Philadelphia, PA 19104 USA
                Author information
                http://orcid.org/0000-0002-6290-0026
                Article
                1469
                10.1007/s40265-021-01469-2
                7884963
                33591549
                e0e343e6-90c6-42dd-80e2-bc7a8863c12a
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 16 January 2021
                Categories
                Review Article

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