Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus

Kimberly C Claeys, Evan J Zasowski, Trang D Trinh, Anthony M Casapao, Jason M Pogue, Nitin Bhatia, Ryan P Mynatt, Suprat S Wilson, Crystal Arthur, Robert Welch, Robert Sherwin, Wasif Hafeez, Donald P Levine, Keith S Kaye, George Delgado, Christopher A Giuliano, Robert Takla, Colleen Rieck, Leonard B Johnson, Kyle P Murray, James Gordon, Kate Reyes, Pamela Hartman, Susan L Davis, Michael J Rybak, Kimberly C Claeys, Evan J Zasowski, Trang D Trinh, Anthony M Casapao, Jason M Pogue, Nitin Bhatia, Ryan P Mynatt, Suprat S Wilson, Crystal Arthur, Robert Welch, Robert Sherwin, Wasif Hafeez, Donald P Levine, Keith S Kaye, George Delgado, Christopher A Giuliano, Robert Takla, Colleen Rieck, Leonard B Johnson, Kyle P Murray, James Gordon, Kate Reyes, Pamela Hartman, Susan L Davis, Michael J Rybak

Abstract

Introduction: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection.

Methods: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics.

Results: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%).

Conclusion: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes.

Trial registration: ClinicalTrials.gov identifier, NCT02582203.

Funding: Allergan plc.

Keywords: Acute bacterial skin and skin structure infection; Ceftaroline; Methicillin-resistant S. aureus; Vancomycin.

References

    1. Dryden MS. Complicated skin and soft tissue infection. J Antimicrob Chemother. 2010;65(Suppl 3):iii35–iii44.
    1. Edelsberg J, Taneja C, Zervos M, Haque N, Moore C, Reyes K, et al. Trends in US hospital admissions for skin and soft tissue infections. Emerg Infect Dis. 2009;15(9):1516–1518. doi: 10.3201/eid1509.081228.
    1. Pollack CV, Amin A, Ford WT, Finley R, Kaye KS, Nguyen HH, et al. Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital. J Emerg Med. 2015;48(4):508–519. doi: 10.1016/j.jemermed.2014.12.001.
    1. Hersh AL, Chambers HF, Maselli JH, Gonzales R. National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. Arch Intern Med. 2008;168(14):1585–1591. doi: 10.1001/archinte.168.14.1585.
    1. Kaye KS, Patel DA, Stephens JM, Khachatryan A, Patel A, Johnson K. Rising United States hospital admissions for acute bacterial skin and skin structure infections: recent trends and economic impact. PLoS One. 2015;10(11):e0143276. doi: 10.1371/journal.pone.0143276.
    1. Itani KMF, Merchant S, Lin S-J, Akhras K, Alandete JC, Hatoum HT. Outcomes and management costs in patients hospitalized for skin and skin-structure infections. Am J Infect Control. 2011;39(1):42–49. doi: 10.1016/j.ajic.2010.03.018.
    1. Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med. 2017;196(7):856–863. doi: 10.1164/rccm.201609-1848OC.
    1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):147–159. doi: 10.1093/cid/ciu444.
    1. Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P, Goldstein EJC, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373–1406. doi: 10.1086/497143.
    1. Food and Drug Administration (FDA). Non-inferiority clinical trials to establish effectiveness guidance for industry. [cited 2019 Jan 10].
    1. Wilcox MH, Corey GR, Talbot GH, Thye D, Friedland D, Baculik T, et al. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010;65(Suppl 4):iv53–iv65.
    1. Corey GR, Wilcox MH, Talbot GH, Thye D, Friedland D, Baculik T. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010;65(Suppl 4):iv41–iv51.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010.
    1. AHA Annual Survey | American Hospital Association’s Annual Survey Database | AHA Data Online [Internet]. [cited 2019 Jan 10]. .
    1. Davis SL, McKinnon PS, Hall LM, Delgado G, Rose W, Wilson RF, et al. Daptomycin versus vancomycin for complicated skin and skin structure infections: clinical and economic outcomes. Pharmacotherapy. 2007;27(12):1611–1618. doi: 10.1592/phco.27.12.1611.
    1. Kauf TL, McKinnon P, Corey GR, Bedolla J, Riska PF, Sims M, et al. An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection. BMC Infect Dis. 2015;15:503. doi: 10.1186/s12879-015-1261-9.
    1. Wolk DM, Struelens MJ, Pancholi P, Davis T, Della-Latta P, Fuller D, et al. Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays. J Clin Microbiol. 2009;47(3):823–826. doi: 10.1128/JCM.01884-08.
    1. Bruun T, Oppegaard O, Hufthammer KO, Langeland N, Skrede S. Early response in cellulitis: a prospective study of dynamics and predictors. Clin Infect Dis. 2016;63(8):1034–1041. doi: 10.1093/cid/ciw463.
    1. Dunne M. Abstract: concordance of clinical response at 48–72 hours after initiation of therapy and end of treatment (EOT) in patients with acute bacterial skin and skin structure infection (abSSSI) in the DISCOVER Studies (IDWeek 2013) [Internet]. Poster presented at: IDWeek 2013; 2013 [cited 2019 Jan 10]; San Fransisco. .
    1. Nathwani D, Dryden M, Garau J. Early clinical assessment of response to treatment of skin and soft-tissue infections: how can it help clinicians? Perspectives from Europe. Int J Antimicrob Agents. 2016;48(2):127–136. doi: 10.1016/j.ijantimicag.2016.04.023.
    1. Nathwani D, Corey R, Das AF, Sandison T, De Anda C, Prokocimer P. Early clinical response as a predictor of late treatment success in patients with acute bacterial skin and skin structure infections: retrospective analysis of 2 randomized controlled trials. Clin Infect Dis. 2017;64(2):214–217. doi: 10.1093/cid/ciw750.
    1. Food and Drug Administration (FDA). Guidance for industry acute bacterial skin and skin structure infections: developing drugs for treatment. [cited 2019 Jan 10].

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren