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FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia

2011; Oxford University Press; Volume: 66; Issue: Supplement 3 Linguagem: Inglês

10.1093/jac/dkr096

1460-2091

Thomas M. File, Donald E. Low, Paul B. Eckburg, George H. Talbot, H. David Friedland, Jon Lee, Lily Llorens, Ian A. Critchley, Dirk Thye, John Pullman, Philip Giordano, James Welker, Paul Manos, P. Mehra, Thomas M. File, J. De Santo, B. Venkateswaralu, C. G. Schrock, William Tillis, Jan A. Winetz, Javier González, Andrew G. Ramage, Dwight D. Eisenhower, Coenraad F.N. Koegelenberg, Ingrid Engelbrecht, Julie A. Jurgens, Ismail Mitha, J. Breedt, Mashra Gani, Jack Roos, Marc D. Basson, Louis van Zyl, Ronel Meeding, Muhammed Ameen Fulat, M. Le Roux, Pablo Bonvehí, María Cristina Ganaha, A. L. Gurini, Gustavo Lopardo, Laura Cristina, Sergio Prieto, Celestino Rodíguez, Ricardo Teijeiro, E Pallone, Daniel Pryluka, Clóvis Arns da Cunha, N. B. da Silva, António Freire, Cláudia Starling, J. Costa Fiterman, Fernando Gôngora Rubio, L. Carlos Losso, Marco Patelli, J. Souza Lima, Paulo José Zimermann Teixeira, Marta Moreira, J. C. Abreu de Oliveira, V. Roudas, E. A. Gamal, I. V. Leschenko, В. А. Руднов, A. G. Yevdokimova, A. L. Vertkin, Y. M. Ambalov, I. V. Dvoryashina, E. Zilber, R. F. Khamitov, A. N. Galustyan, О.V. Reshetko, Victoria Senior, M. F. Grosan, Gabriela Jimborean, M. Lupse, G. Aron, Dan Olteanu, Maria Puşchiţă, Claudia Gavriș, V. M. Tudorache, Vania Youroukova, M Petkova, E. Troshanova, M. Dzhabalyan, G Kavtaradze, M. Makhviladze, R. Tabukashvili, Marco Pons, Jorge Garbino, Daniel Genné, Madeleine Rothen, J. O. de Saracho, A. Capelastegui, Rosario Menéndez, Antoní Torres, C. Shum, Vicenç Falcó, Emilio Bouza, J.P. Bru, Benoît Misset, Bruno Mégarbane, J.-P. Sollet, J.-M. Molina, K. Dalhoff, J. Lorenz, W Petermann, Gernot Rohde, C. Schumann, Sultan Taşçı, J. Zerbst, Wolfgang Auch–Schwelk, Norbert Suttorp, Rolf Henrich, Andreas Fertl, C. Grohe, C. Jakobeit, K.-M. Deppermann, Halina Batura‐Gabryel, Danuta Pupek‐Musialik, Pawel Piotrowicz, Czesław Marcisz, K Czarnobilski, Renata Jankowska, Krzysztof Janik, M. Gutowska-Jablonska, Maciej Hamankiewicz, Jan Kuś, Andrzej Rydzewski, Jan Duława, Ewa Ziółko, Edyta Barańska, Michael F. Wendland, Ewa Trębas-Pietraś, I. Tyszkiewic, J Bonelli, Zoltán Balikó, M. Bisits, G. Losonczy, Z. Mark, I. Albert, E. Francovszky, Károly Fónay, Tetiana Pertseva, Valentyn Yefimov, V. Havrysyuk, Victor Melnyk, L. A. Yashyna, Н. Е. Моногарова, Y. Kolchyn, R.Ya. Dutka, O. Smolyanyi, Nadiya Tryshchuk, І. P. Kaydashev, Valeria Rodionova, Vasyl Neyko, Ivan V. Chopey, B. Alekniene, G. Kramilius, S. Naudziunas, Skaidrius Miliauskas, V. Nausediene, Arvydas Valavičius, Marija Mitić-Milikić, Dušica Čeleketić, Zorica Lazić, Nikola Milinić, Tatjana Pejčić, Kai Sukles, Martin Jaanus, Sirli Meriste, D. H. A. Ahmad Mahayiddin, A. P. Bin Abdul Muttalif, Kiew Kuang Kiat, R. Binte, Abreeza Manap, N. A. bt Md Tarekh, T. Anekthananon, Piroon Mootsikapun, Poj Intalapaporn, Chaicharn Pothirat, Pinyo Horsin, C. Churchottaworn, Anan Wattanathum, Andrej Dukát, Ján Plutinský,

Nosocomial Infections in ICU

Ceftaroline, the active form of the prodrug ceftaroline fosamil, is a novel cephalosporin with bactericidal activity against important pathogens associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and common Gram-negative pathogens. FOCUS 1 is a randomized, double-blinded, Phase III study that was conducted to evaluate the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ −10%] in clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations. Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Patients also received two 500 mg doses of oral clarithromycin every 12 h administered on day 1. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 1 registration number NCT00621504 (http://clinicaltrials.gov/ct2/show/NCT00621504). Of 613 enrolled patients, 298 received ceftaroline fosamil and 308 received ceftriaxone. Baseline characteristics between treatment groups were comparable. Clinical cure rates were as follows: CE population, 86.6% (194/224) for ceftaroline fosamil and 78.2% (183/234) for ceftriaxone [difference (95% CI), 8.4% (1.4, 15.4)]; and MITTE population, 83.8% (244/291) for ceftaroline fosamil and 77.7% (233/300) for ceftriaxone [difference (95% CI), 6.2% (−0.2, 12.6)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE population were 88.9% (24/27) and 66.7% (20/30) for ceftaroline fosamil and ceftriaxone, respectively. Both agents were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations because of an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, insomnia and nausea, and the most common AEs for ceftriaxone-treated patients were hypokalaemia, hypertension, nausea and diarrhoea. Ceftaroline fosamil demonstrated high clinical cure and microbiological response rates in hospitalized patients with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile similar to that of ceftriaxone and consistent with the cephalosporin class. In this study, ceftaroline fosamil was an effective and well-tolerated treatment option for CAP.