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      Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review

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          Abstract

          Ceftaroline is approved by the Food and Drug Administration for acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia, including cases with concurrent bacteremia. Use for serious methicillin-resistant Staphylococcus aureus (MRSA) infections has risen for a multitude of reasons. The aim of this article is to review the literature evaluating clinical outcomes and safety of ceftaroline prescribed for serious MRSA infections. We conducted a literature search in Ovid (Medline) and PubMed for reputable case reports, clinical trials, and reviews focusing on the use of ceftaroline for treatment of MRSA infections. Twenty-two manuscripts published between 2010 and 2016 met inclusion criteria. Mean clinical cure was 74% across 379 patients treated with ceftaroline for severe MRSA infections. Toxicities were infrequent. Ceftaroline treatment resulted in clinical and microbiologic cure for severe MRSA infections. Close monitoring of hematological parameters is necessary with prolonged courses of ceftaroline.

          Summary

          This article reviews and evaluates the existing literature describing clinical outcomes and safety of ceftaroline in severe methicillin-resistant Staphylococcus aureus infections.

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          Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter.

          Andrew Paterson, T. P. Lodise, T. van Tienen (2013)
          In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter. The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (≥ 15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of <15 mg/liter. The relationship between a trough of ≥ 15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37). The relationship between troughs of ≥ 15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy.
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            Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding.

            Abhay Dhand, Arnold S. Bayer, George Sakoulas … (2011)
            We used daptomycin plus antistaphylococcal β-lactams (ASBL) to clear refractory MRSA bacteremia. In vitro studies showed enhanced daptomycin bactericidal activity, increased membrane daptomycin binding, and decrease in positive surface charge induced by ASBLs against daptomycin nonsusceptible MRSA. Addition of ASBLs to daptomycin may be of benefit in refractory MRSA bacteremia. (Although the official designation is "daptomycin nonsusceptiblity," we will use the term "daptomycin-resistance" in this paper for facility of presentation.).
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              Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline.

              George Sakoulas, Pamela Moise, Anthony Casapao … (2014)
              Guidelines recommend daptomycin combination therapy as an option for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin failure. Recent data suggest that combining daptomycin with a β-lactam may have unique benefits; however, there are very limited clinical data regarding the use of ceftaroline with daptomycin.
              Article 0 comments Cited 51 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Open Forum Infect Dis
                Journal ID (iso-abbrev): Open Forum Infect Dis
                Journal ID (publisher-id): ofid
                Title: Open Forum Infectious Diseases
                Publisher: Oxford University Press (US )
                ISSN (Electronic): 2328-8957
                Publication date Collection: Spring 2017
                Publication date (Electronic): 02 May 2017
                Publication date PMC-release: 02 May 2017
                Volume: 4
                Issue: 2
                Electronic Location Identifier: ofx084
                Affiliations
                [1 ]Department of Pharmacy, Massachusetts General Hospital ,
                [2 ]Center for Drug Policy, Partners Healthcare ,
                [3 ]Department of Pharmacy , and
                [4 ]Division of Infectious Diseases, Brigham and Women’s Hospital , Boston, Massachusetts; and
                [5 ]Harvard Medical School , Cambridge, Massachusetts
                Author notes

                Correspondence: R. A. Cosimi, PharmD, BCPS, South Texas Veterans Health Care System, 7400 Merton Minter, San Antonio 78230, TX ( reese.cosimi@ 123456gmail.com ).

                Article
                Publisher ID: ofx084
                DOI: 10.1093/ofid/ofx084
                PMC ID: 5499876
                PubMed ID: 28702467
                SO-VID: 3952df90-da86-473e-98e4-21a61bdbe6f1
                Copyright © © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

                History
                Date received : 12 December 2016
                Date accepted : 21 April 2017
                Page count
                Pages: 7
                Categories
                Subject: Review Article

                Keywords: ceftaroline,methicillin-resistant staphylococcus aureus (mrsa),bacteremia,endocarditis,pneumonia.
                Data availability:
                Keywords: ceftaroline, methicillin-resistant staphylococcus aureus (mrsa), bacteremia, endocarditis, pneumonia.

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