PMID- 21482566 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 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. PG - iii19-32 LID - 10.1093/jac/dkr096 [doi] AB - OBJECTIVES: 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. 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. 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). RESULTS: 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. CONCLUSIONS: 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. FAU - File, Thomas M Jr AU - File TM Jr AD - Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, USA. filet@summahealth.org FAU - Low, Donald E AU - Low DE FAU - Eckburg, Paul B AU - Eckburg PB FAU - Talbot, George H AU - Talbot GH FAU - Friedland, H David AU - Friedland HD 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 1 investigators LA - eng SI - ClinicalTrials.gov/NCT00621504 PT - Clinical Trial, Phase III PT - Comparative Study 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 - Pullman, John IR - Pullman J FIR - Giordano, Philip IR - Giordano P FIR - Welker, James IR - Welker J FIR - Manos, Paul IR - Manos P FIR - Mehra, Purvi IR - Mehra P FIR - File, Thomas IR - File T FIR - De Santo, Joseph IR - De Santo J FIR - Venkateswaralu, Bhaskar IR - Venkateswaralu B FIR - Gerald Schrock, Christian IR - Gerald Schrock C FIR - Tillis, William IR - Tillis W FIR - Winetz, Jan Alan IR - Winetz JA FIR - Gonzalez, J Mario IR - Gonzalez JM FIR - Ramage, Anthony IR - Ramage A FIR - Eisenhower, Dwight D IR - Eisenhower DD FIR - Koegelenberg, Coenie IR - Koegelenberg C FIR - Engelbrecht, Ingrid IR - Engelbrecht I FIR - Jurgens, Jaco IR - Jurgens J FIR - Mitha, Ishmail IR - Mitha I FIR - Breedt, Johannes IR - Breedt J FIR - Gani, Mashra IR - Gani M FIR - Roos, Johannes IR - Roos J FIR - Basson, Matthys IR - Basson M FIR - Van Zyl, Louis IR - Van Zyl L FIR - Meeding, Ronel IR - Meeding R FIR - Fulat, Muhammed IR - Fulat M FIR - Le Roux, Marius IR - Le Roux M FIR - Bonvehi, Pablo Eduardo IR - Bonvehi PE FIR - Ganaha, Maria Cristina IR - Ganaha MC FIR - Gurini, Ana Leticia IR - Gurini AL FIR - Daniel Lopardo, Gustavo IR - Daniel Lopardo G FIR - Cristina, Lucia IR - Cristina L FIR - Edwardo Prieto, Sergio IR - Edwardo Prieto S FIR - Rodiguez, Claudia Gabriela IR - Rodiguez CG FIR - Augusto Teijeiro, Ricardo IR - Augusto Teijeiro R FIR - Carmen Pallone, Elida IR - Carmen Pallone E FIR - Pryluka, Daniel Horacio IR - Pryluka DH FIR - da Cunha, Clovis Arns IR - da Cunha CA FIR - da Silva, Nilton Brandao IR - da Silva NB FIR - de Faria Freire, Antonio Tarcisio IR - de Faria Freire AT FIR - Ferreira Starling, Carlos Ernesto IR - Ferreira Starling CE FIR - Costa Fiterman, Jussara IR - Costa Fiterman J FIR - Gongora Rubio, Fernando IR - Gongora Rubio F FIR - Carlos Losso, Luis IR - Carlos Losso L FIR - Patelli, Maria IR - Patelli M FIR - Souza Lima, Juliani IR - Souza Lima J FIR - Zimermann Teixeira, Paulo Jose IR - Zimermann Teixeira PJ FIR - Carmo Moreira, Maria Auxiliadora IR - Carmo Moreira MA FIR - Abreu de Oliveira, Julio Cesar IR - Abreu de Oliveira JC FIR - Roudas, Vsevolod IR - Roudas V FIR - Gamal, Evgeny A IR - Gamal EA FIR - Leschenko, Igor IR - Leschenko I FIR - Rudnov, Vladimir A IR - Rudnov VA FIR - Yevdokimova, Anna G IR - Yevdokimova AG FIR - Vertkin, Arkadiy L IR - Vertkin AL FIR - Ambalov, Yuriy M IR - Ambalov YM FIR - Dvoryashina, Irina V IR - Dvoryashina IV FIR - Zilber, Elmira IR - Zilber E FIR - Khamitov, Rustem F IR - Khamitov RF FIR - Galustyan, Anna N IR - Galustyan AN FIR - Reshetko, Olga V IR - Reshetko OV FIR - Senior, Victoria Arama IR - Senior VA FIR - Grosan, Mihaela Flavia IR - Grosan MF FIR - Jimborean, Gabriela IR - Jimborean G FIR - Lupse, Mihaela IR - Lupse M FIR - Aron, Gheorgita IR - Aron G FIR - Olteanu, Dan IR - Olteanu D FIR - Puschita, Maria IR - Puschita M FIR - Gavris, Claudia IR - Gavris C FIR - Tudorache, Voicu Mircea IR - Tudorache VM FIR - Youroukova, Vania IR - Youroukova V FIR - Petkova, Mila IR - Petkova M FIR - Troshanova, Evelina IR - Troshanova E FIR - Dzhabalyan, Mari IR - Dzhabalyan M FIR - Kavtaradze, George IR - Kavtaradze G FIR - Makhviladze, Manana IR - Makhviladze M FIR - Tabukashvili, Revaz IR - Tabukashvili R FIR - Pons, Marco IR - Pons M FIR - Garbino, Jorge IR - Garbino J FIR - Genne, Daniel IR - Genne D FIR - Rothen, Madeleine IR - Rothen M FIR - de Saracho, Juan Oriz IR - de Saracho JO FIR - Capelastegui, Alberto IR - Capelastegui A FIR - Menendez, Rosario IR - Menendez R FIR - Torres, Antoni IR - Torres A FIR - Shum, Conrado IR - Shum C FIR - Falco, Vincenc IR - Falco V FIR - Bouza, Emilio IR - Bouza E FIR - Bru, Jean-Pierre IR - Bru JP FIR - Misset, Benoit IR - Misset B FIR - Megarbane, Bruno IR - Megarbane B FIR - Sollet, Jean Pierre IR - Sollet JP FIR - Molina, Jean-Michel IR - Molina JM FIR - Dalhoff, Klaus IR - Dalhoff K FIR - Lorenz, Joachim IR - Lorenz J FIR - Petermann, Wolfgang IR - Petermann W FIR - Rohde, Gernot IR - Rohde G FIR - Schumann, Christian IR - Schumann C FIR - Tasci, Selcuk IR - Tasci S FIR - Zerbst, Joachim IR - Zerbst J FIR - Auch-Schwelk, Wolfgang IR - Auch-Schwelk W FIR - Suttorp, Norbert IR - Suttorp N FIR - Henrich, Rolf IR - Henrich R FIR - Fertl, Andreas IR - Fertl A FIR - Grohe, Christian IR - Grohe C FIR - Jakobeit, Christian IR - Jakobeit C FIR - Deppermann, Karl-Matthius IR - Deppermann KM FIR - Batura-Gabryel, Halina IR - Batura-Gabryel H FIR - Pupek-Musialik, Danuta IR - Pupek-Musialik D FIR - Piotrowicz, Pawe IR - Piotrowicz P FIR - Marcisz, Czeslaw IR - Marcisz C FIR - Czarnobilski, Krzysztof IR - Czarnobilski K FIR - Jankowska, Renata IR - Jankowska R FIR - Janik, Krzysztof IR - Janik K FIR - Gutowska-Jablonska, Malgorzata IR - Gutowska-Jablonska M FIR - Hamankiewicz, Maciej IR - Hamankiewicz M FIR - Kus, Jan IR - Kus J FIR - Rydzewski, Andrzej IR - Rydzewski A FIR - Dulawa, Jan IR - Dulawa J FIR - Ziolko, Ewa IR - Ziolko E FIR - Baranska, Eliza IR - Baranska E FIR - Wendland, Marian IR - Wendland M FIR - Trebas-Pietras, Ewa IR - Trebas-Pietras E FIR - Tyszkiewic, Ireneusz IR - Tyszkiewic I FIR - Bonelli, Johannes IR - Bonelli J FIR - Baliko, Zoltan IR - Baliko Z FIR - Bisits, Marta IR - Bisits M FIR - Losonczy, Gyorgy IR - Losonczy G FIR - Mark, Zsuzsa IR - Mark Z FIR - Albert, Istvan IR - Albert I FIR - Francovszky, Eva IR - Francovszky E FIR - Fonay, Karoly IR - Fonay K FIR - Tetiana Pertseva, Tetiana IR - Tetiana Pertseva T FIR - Yefimov, Volodymyr IR - Yefimov V FIR - Havrysyuk, Volodymyr IR - Havrysyuk V FIR - Melnyk, Vasyl IR - Melnyk V FIR - Yashyna, Lyudmyla IR - Yashyna L FIR - Monogarova, Nadiya IR - Monogarova N FIR - Kolchyn, Yuriy IR - Kolchyn Y FIR - Dutka, Roman IR - Dutka R FIR - Smolyanyi, Oleksandr IR - Smolyanyi O FIR - Tryshchuk, Nadiya IR - Tryshchuk N FIR - Kaydashev, Igor IR - Kaydashev I FIR - Rodionova, Victoria IR - Rodionova V FIR - Neyko, Vasyl IR - Neyko V FIR - Chopey, Ivan IR - Chopey I FIR - Alekniene, Birute IR - Alekniene B FIR - Kramilius, Ginataras IR - Kramilius G FIR - Naudziunas, Stanislovas IR - Naudziunas S FIR - Miliauskas, Skaidrius IR - Miliauskas S FIR - Nausediene, Vitalija IR - Nausediene V FIR - Valavicius, Arvydas IR - Valavicius A FIR - Mitic-Milikic, Marija IR - Mitic-Milikic M FIR - Celeketic, Dusica IR - Celeketic D FIR - Lazic, Zorica IR - Lazic Z FIR - Milinic, Nikola IR - Milinic N FIR - Pejcic, Tatjana IR - Pejcic T FIR - Sukles, Kai IR - Sukles K FIR - Jaanus, Martti IR - Jaanus M FIR - Meriste, Sulev IR - Meriste S FIR - Ahmad Mahayiddin, Datin Hjh Aziah IR - Ahmad Mahayiddin DH FIR - Bin Abdul Muttalif, Abdul Pazak IR - Bin Abdul Muttalif AP FIR - Kuang Kiat, Kiew IR - Kuang Kiat K FIR - Binte, Roslina IR - Binte R FIR - Manap, Abdul IR - Manap A FIR - Bt Md Tarekh, Noor Aliza IR - Bt Md Tarekh NA FIR - Anekthananon, Thanomsak IR - Anekthananon T FIR - Mootsikapun, Piroon IR - Mootsikapun P FIR - Intalapaporn, Poj IR - Intalapaporn P FIR - Pothirat, Chaicharn IR - Pothirat C FIR - Horsin, Pinyo IR - Horsin P FIR - Churchottaworn, Charoen IR - Churchottaworn C FIR - Wattanathum, Anan IR - Wattanathum A FIR - Dukat, Andrej IR - Dukat A FIR - Plutinsky, Jan IR - Plutinsky J 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 - dkr096 [pii] AID - 10.1093/jac/dkr096 [doi] PST - ppublish SO - J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii19-32. doi: 10.1093/jac/dkr096.