The online version of this article (doi:10.1007/s40121-014-0036-8) contains supplementary material, which is available to authorized users.
Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the “Ceftaroline Assessment Program and Teflaro® Utilization Registry” (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6–11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, −0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution.
Teflaro (ceftaroline fosamil) [full prescribing information]. New York: Forest Laboratories; 2010.
File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010;51:1395–405. PubMedCrossRef
File TM Jr, Low DE, Eckburg PB, et al. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011;66(Suppl 3:iii):19–32.
Low DE, File TM Jr, Eckburg PB, et al. FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011;66(Suppl 3:iii):33–44.
Huang X, Jandourek A, Cole P, Friedland D. Current use of ceftaroline for community-acquired bacterial pneumonia (cabp) in us hospitals: length of stay and total cost from the capture study. Chest J. 2013;144:259A-A. CrossRef
Jandourek A, Udeani G, Smith A, Friedland HD. CAPTURE Study experience in patients with community acquired pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) and treatment with ceftaroline. European Congress on Clinical Microbiology and Infectious Diseases. Berlin, Germany, 2013.
Maggiore C, Pasquale T, Cole P, Smith A, Friedland HD. Ceftaroline fosamil for treatment of acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia in patients with renal insufficiency: CAPTURE study experience. American Society of Health-System Pharmacists’ Midyear Meeting. Orlando: American Society of Health-System Pharmacists; 2013.
Maggiore C, Pasquale T, Jandourek A, Smith A, Friedland HD. Experience with ceftaroline fosamil as monotherapy and combination therapy with vancomycin in acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. ASHP Midyear Meeting 2013 Orlando, FL American Society of Health-System Pharmacists; 2013. p. 5–112.
Udeani G, Evans J, Jandourek A, Friedland HD. Ceftaroline fosamil for the treatment of community-acquired bacterial pneumonia (CABP): CAPTURE Year 1 (H 46). American Thoracic Society International Conference. Philadelphia, PA, 2013.
Udeani G, Evans J, Jandourek A, Friedland HD. CAPTURE: Ceftaroline fosamil for the treatment of community acquired bacterial pneumonia (CABP): Year 1. A49 community acquired pneumonia and healthcare-associated pneumonia: treatment and outcomes. American Thoracic Society; 2013. p. A1688-A.
van Hal SJ, Fowler VG, Jr. Is it time to replace vancomycin in the treatment of methicillin-resistant Staphylococcus aureus infections? Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;56:1779–88.
Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;54:621–9. CrossRef
Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis Off Publ Infect Dis Soc Am. 2003;37:1405–33. CrossRef
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;44(Suppl 2):S27–72. CrossRef
Antimicrobial hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia: developing drugs for treatment. 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM234907.pdf. Accessed Aug 25, 2011.
Guidance for industry. Community-acquired bacterial pneumonia: developing drugs for treatment, draft guidance. Food and Drug Administration, Center for Drug Evaluation and Research, Washington, DC. 2009. http://www.fda.gov.elibrary.amc.edu/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm123686.pdf. Accessed Aug 8, 2014.
Pertel PE, Bernardo P, Fogarty C, et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin infect Dis Off Publ Infect Dis Soc Am. 2008;46:1142–51. CrossRef
Bartlett JG. Diagnostic tests for agents of community-acquired pneumonia. Clin infect Dis Off Publ Infect Dis Soc Am. 2011;52(Suppl 4):S296–304. CrossRef
National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32:470–85.
Eckberg PB, Friedland DH, Llorens L, et al. Day 4 clinical response of ceftaroline fosamil versus cefriaxone for community-acquired bacterial pneumonia. Infect Dis Clin Pract. 2012;20:254–60. CrossRef
Zhanel GG, Yachison C, Nichol K, et al. Assessment of the activity of ceftaroline against clinical isolates of penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs of ceftaroline using an in vitro pharmacodynamic model. J Antimicrob Chemother. 2012;67:1706–11. PubMedCrossRef
Ramani A, Udeani G, Evans J, et al. Contemporary use of ceftaroline fosamil for the treatment of community-acquired bacterial pneumonia: CAPTURE study experience. J Chemother. 2014 (1973947814Y0000000184).
- Ceftaroline Fosamil for the Treatment of Community-Acquired Pneumonia: from FOCUS to CAPTURE
Joseph J. Carreno
Thomas P. Lodise
- Springer Healthcare
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