PMID- 21482568 OWN - NLM STAT- MEDLINE DCOM- 20110718 LR - 20231213 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 66 Suppl 3 DP - 2011 Apr TI - FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. PG - iii33-44 LID - 10.1093/jac/dkr097 [doi] AB - OBJECTIVES: Ceftaroline (active form of the prodrug ceftaroline fosamil) is a novel cephalosporin with activity against pathogens commonly associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Gram-negative pathogens. This randomized, double-blind, Phase III study evaluated 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%] of 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. METHODS: 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. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 2 registration number NCT00509106 (http://clinicaltrials.gov/ct2/show/NCT00509106). RESULTS: The study enrolled 627 patients, 315 of whom received ceftaroline fosamil and 307 of whom received ceftriaxone. Patients in both treatment groups had comparable baseline characteristics. Clinical cure rates were as follows: CE population, 82.1% (193/235) for ceftaroline fosamil and 77.2% (166/215) for ceftriaxone [difference (95% CI), 4.9% (-2.5, 12.5)]; and MITTE population, 81.3% (235/289) for ceftaroline fosamil and 75.5% (206/273) for ceftriaxone [difference (95% CI), 5.9% (-1.0, 12.7)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE (mMITTE) population were 83.3% (35/42) and 70.0% (28/40) for ceftaroline fosamil and ceftriaxone, respectively. Ceftaroline fosamil and ceftriaxone were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations due to an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, hypokalaemia, insomnia and phlebitis, and the most common AEs for ceftriaxone-treated patients were diarrhoea, insomnia, phlebitis and hypertension. CONCLUSIONS: Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP. FAU - Low, Donald E AU - Low DE AD - Mount Sinai Hospital/University Health Network, Toronto, Ontario, Canada. dlow@mtsinai.on.ca FAU - File, Thomas M Jr AU - File TM Jr FAU - Eckburg, Paul B AU - Eckburg PB FAU - Talbot, George H AU - Talbot GH FAU - David Friedland, H AU - David Friedland H FAU - Lee, Jon AU - Lee J FAU - Llorens, Lily AU - Llorens L FAU - Critchley, Ian A AU - Critchley IA FAU - Thye, Dirk A AU - Thye DA CN - FOCUS 2 investigators LA - eng SI - ClinicalTrials.gov/NCT00509106 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Cephalosporins) RN - 75J73V1629 (Ceftriaxone) SB - IM MH - Aged MH - Aged, 80 and over MH - Bacteria/isolation & purification MH - Ceftriaxone/administration & dosage/adverse effects MH - Cephalosporins/*administration & dosage/*adverse effects MH - Community-Acquired Infections/*drug therapy MH - Double-Blind Method MH - Female MH - Humans MH - Infusions, Intravenous MH - Male MH - Middle Aged MH - Pneumonia, Bacterial/*drug therapy MH - Treatment Outcome MH - Ceftaroline FIR - Corral, Jorge IR - Corral J FIR - Giugno, Eduardo IR - Giugno E FIR - Gonzalez Arzac, Maria Del Rosario IR - Gonzalez Arzac Mdel R FIR - Maurizi, Diego IR - Maurizi D FIR - Altclas, Javier IR - Altclas J FIR - Ambasch, German IR - Ambasch G FIR - Jasovich, Abel IR - Jasovich A FIR - Minguez, Angel Ramon IR - Minguez AR FIR - Oliva, Maria Eugenia IR - Oliva ME FIR - Teglia, Osvaldo IR - Teglia O FIR - Bergallo, Carlos IR - Bergallo C FIR - Mastruzzo, Maria Antonia IR - Mastruzzo MA FIR - Isabel Morera, Graciana IR - Isabel Morera G FIR - Scapellato, Pabio Gustavo IR - Scapellato PG FIR - Lamberghini, Ricardo IR - Lamberghini R FIR - Mykietiuk, Analia IR - Mykietiuk A FIR - Remolif, Christian IR - Remolif C FIR - Barros Monge, Manuel Jose IR - Barros Monge MJ FIR - Enriqueta Campos Barker, Maria Isabel IR - Enriqueta Campos Barker MI FIR - Chernilo Steinmann, Sara Mireya IR - Chernilo Steinmann SM FIR - Gaete Gutierrez, Pablo Antonio IR - Gaete Gutierrez PA FIR - Munoz Vejar, Sylvia Susana IR - Munoz Vejar SS FIR - Calvo Arellano, Mario Andres IR - Calvo Arellano MA FIR - Chahin Anania, Carolina Eugenia IR - Chahin Anania CE FIR - Jauregui Cruz, Arturo IR - Jauregui Cruz A FIR - Amaya Tapia, Gerardo IR - Amaya Tapia G FIR - Acuna Kaldman, Moises IR - Acuna Kaldman M FIR - Noriega, Eduardo IR - Noriega E FIR - Matos Prado, Eduardo Demetrio IR - Matos Prado ED FIR - Ramos, Carlos IR - Ramos C FIR - Andreeva, Irina IR - Andreeva I FIR - Abyshev, Rashad IR - Abyshev R FIR - Antonovsky, Yuri A IR - Antonovsky YA FIR - Balyuzek, Marina IR - Balyuzek M FIR - Esina, Alla L IR - Esina AL FIR - Gorelov, Alexander IR - Gorelov A FIR - Khrustalev, Oleg A IR - Khrustalev OA FIR - Kozlov, Roman S IR - Kozlov RS FIR - Novozhenok, Vladislav IR - Novozhenok V FIR - Popova, Veronika B IR - Popova VB FIR - Sobchenko, Svetlana IR - Sobchenko S FIR - Trofimov, Vasily IR - Trofimov V FIR - Yakovlev, Sergey IR - Yakovlev S FIR - Zhidkov, Konstantin IR - Zhidkov K FIR - Ambert, Luminta Gabriela IR - Ambert LG FIR - Fierbinteau, Carmen Georgeta IR - Fierbinteau CG FIR - Ionescu, Valentina IR - Ionescu V FIR - Muresan, Mihai Marius IR - Muresan MM FIR - Tanaseanu, Cristina Mihaela IR - Tanaseanu CM FIR - Georgiev, Ognian IR - Georgiev O FIR - Hodzhev, Valdimir IR - Hodzhev V FIR - Marinov, Rosen IR - Marinov R FIR - Metev, Hristo IR - Metev H FIR - Peneva, Marinka IR - Peneva M FIR - Popov, Dimitar IR - Popov D FIR - Simeonova, Milkana IR - Simeonova M FIR - Krastins, Ivars IR - Krastins I FIR - Lovcinovsk, Viktors IR - Lovcinovsk V FIR - Silins, Viesturs IR - Silins V FIR - Svarcberga, Vita IR - Svarcberga V FIR - Bargon, Joachim IR - Bargon J FIR - Bauer, Thorsten IR - Bauer T FIR - Bergmann, Rolf IR - Bergmann R FIR - Meyer, F J IR - Meyer FJ FIR - Mueller, Thomas IR - Mueller T FIR - Welte, Tobias IR - Welte T FIR - Glaeser, Sven IR - Glaeser S FIR - Hammerl, Peter IR - Hammerl P FIR - Kern, Hartmut IR - Kern H FIR - Krueger, Stefan IR - Krueger S FIR - Kujath, Peter IR - Kujath P FIR - Lies, Achim IR - Lies A FIR - Schaberg, Tom IR - Schaberg T FIR - Schmalz, Oliver IR - Schmalz O FIR - Schutte, Wolfgang IR - Schutte W FIR - Chazan, Ryszarda IR - Chazan R FIR - Gorecka, Dorota IR - Gorecka D FIR - Rogala, Barbara IR - Rogala B FIR - Antczak, Adam IR - Antczak A FIR - Grodzicki, Tomasz IR - Grodzicki T FIR - Jahnz-Ro, Karina IR - Jahnz-Ro K FIR - Milanowski, Janusz IR - Milanowski J FIR - Nalepa, Piotr IR - Nalepa P FIR - Wrobel-Rajzer, Malgorzata IR - Wrobel-Rajzer M FIR - Szelerska-Twardosz, Hanna IR - Szelerska-Twardosz H FIR - Grzelewska-Rzymowska, Iwona IR - Grzelewska-Rzymowska I FIR - Kachel, Tomasz IR - Kachel T FIR - Marciniak, Andrzej IR - Marciniak A FIR - Panaszek, Bernard IR - Panaszek B FIR - Szczeklik, Andrzej IR - Szczeklik A FIR - Kozielski, Jerzy IR - Kozielski J FIR - Harat, Rafal IR - Harat R FIR - Jastrzebsk, Dariusz IR - Jastrzebsk D FIR - Juszczak, Jacek IR - Juszczak J FIR - Labij, Violetta IR - Labij V FIR - Vetter, Norbert IR - Vetter N FIR - Bolitschek, Josef IR - Bolitschek J FIR - Eckmayr, Josef IR - Eckmayr J FIR - Molnar, Sandor IR - Molnar S FIR - Papai-Szekely, Zsolt IR - Papai-Szekely Z FIR - Szegedi, Janos IR - Szegedi J FIR - Vinkler, Ilona IR - Vinkler I FIR - Borscchivskyy, Mykhaylo IR - Borscchivskyy M FIR - Dziublyk, Oleksandr IR - Dziublyk O FIR - Dzyak, Georgiy V IR - Dzyak GV FIR - Kraydaschenko, Oleg IR - Kraydaschenko O FIR - Mostovoy, Yuriy M IR - Mostovoy YM FIR - Rudyk, Iurii S IR - Rudyk IS FIR - Sushko, Viktor IR - Sushko V FIR - Vizir, Vadim IR - Vizir V FIR - Bhattacharya, Amal Kumar IR - Bhattacharya AK FIR - Chakrapan, Mahabala IR - Chakrapan M FIR - D'Souza, George IR - D'Souza G FIR - Malpani, G S IR - Malpani GS FIR - Mehta, Parthiv IR - Mehta P FIR - Rao, K N Mohar IR - Rao KN FIR - Talwar, Deepak IR - Talwar D EDAT- 2011/04/26 06:00 MHDA- 2011/07/19 06:00 CRDT- 2011/04/13 06:00 PHST- 2011/04/13 06:00 [entrez] PHST- 2011/04/26 06:00 [pubmed] PHST- 2011/07/19 06:00 [medline] AID - dkr097 [pii] AID - 10.1093/jac/dkr097 [doi] PST - ppublish SO - J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii33-44. doi: 10.1093/jac/dkr097.