Maria Taboada1, David Melnick2, Joseph P Iaconis3, Fang Sun4, Nan Shan Zhong5, Thomas M File6, Lily Llorens7, H David Friedland7, David Wilson8. 1. AstraZeneca Research & Development, Biometrics & Information Sciences, Parklands, Alderley Park, Macclesfield, SK10 4TG, UK maria.taboada@astrazeneca.com. 2. AstraZeneca, 1800 Concord Pike, Wilmington, DE 19803, USA. 3. AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA. 4. AstraZeneca China, 1168 Nan Jing Xi Road, Shanghai, 200041, P.R. China. 5. State Key Laboratory of Respiratory Diseases, 1st Affiliate Hospital of Respiratory Disease, Guangzhou Medical University, 151 Yan Jiang Road, Guangzhou, 501120, P.R. China. 6. Northeast Ohio Medical University, Rootstown, OH 44272, USA Summa Health System, Akron, OH 44304, USA. 7. Cerexa Inc., 2100 Franklin St, Oakland, CA 94612, USA. 8. AstraZeneca Research & Development, Biometrics & Information Sciences, Parklands, Alderley Park, Macclesfield, SK10 4TG, UK.
Abstract
BACKGROUND: We conducted a meta-analysis of clinical trials of adults hospitalized with pneumonia outcomes research team (PORT) risk class 3-4 community-acquired pneumonia (CAP) receiving ceftaroline fosamil versus ceftriaxone. METHODS: Three Phase III trials (clinicaltrials.gov registration numbers NCT00621504, NCT00509106 and NCT01371838) including 1916 hospitalized patients with CAP randomized 1:1 to empirical ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (1-2 g every 24 h) for 5-7 days were included in the meta-analysis. Primary outcome was clinical response at the test-of-cure visit (8-15 days after end of treatment) in the PORT risk class 3-4 modified ITT (MITT) and clinically evaluable (CE) populations. Data were tested for heterogeneity (χ(2) test) and, if not significant, results were pooled and OR and 95% CI constructed. A logistic regression analysis assessed factors impacting cure rate and treatment interactions. RESULTS: Clinical cure rates in each trial consistently favoured ceftaroline fosamil versus ceftriaxone, with no evidence of heterogeneity. In the meta-analysis, ceftaroline fosamil was superior to ceftriaxone in the MITT (OR: 1.66; 95% CI 1.34, 2.06; P < 0.001) and CE (OR: 1.65; 95% CI 1.26, 2.16; P < 0.001) populations. Results were consistent across various patient- and disease-related factors including patients' age and PORT score. Prior antimicrobial use within 96 h of starting study treatment was associated with diminished differences in cure rates between treatments. CONCLUSIONS: Ceftaroline fosamil was superior to ceftriaxone for empirical treatment of adults hospitalized with CAP. Receipt of prior antimicrobial therapy appeared to diminish the observed treatment effect.
BACKGROUND: We conducted a meta-analysis of clinical trials of adults hospitalized with pneumonia outcomes research team (PORT) risk class 3-4 community-acquired pneumonia (CAP) receiving ceftaroline fosamil versus ceftriaxone. METHODS: Three Phase III trials (clinicaltrials.gov registration numbers NCT00621504, NCT00509106 and NCT01371838) including 1916 hospitalized patients with CAP randomized 1:1 to empirical ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (1-2 g every 24 h) for 5-7 days were included in the meta-analysis. Primary outcome was clinical response at the test-of-cure visit (8-15 days after end of treatment) in the PORT risk class 3-4 modified ITT (MITT) and clinically evaluable (CE) populations. Data were tested for heterogeneity (χ(2) test) and, if not significant, results were pooled and OR and 95% CI constructed. A logistic regression analysis assessed factors impacting cure rate and treatment interactions. RESULTS: Clinical cure rates in each trial consistently favoured ceftaroline fosamil versus ceftriaxone, with no evidence of heterogeneity. In the meta-analysis, ceftaroline fosamil was superior to ceftriaxone in the MITT (OR: 1.66; 95% CI 1.34, 2.06; P < 0.001) and CE (OR: 1.65; 95% CI 1.26, 2.16; P < 0.001) populations. Results were consistent across various patient- and disease-related factors including patients' age and PORT score. Prior antimicrobial use within 96 h of starting study treatment was associated with diminished differences in cure rates between treatments. CONCLUSIONS:Ceftaroline fosamil was superior to ceftriaxone for empirical treatment of adults hospitalized with CAP. Receipt of prior antimicrobial therapy appeared to diminish the observed treatment effect.
Authors: M Edlinger-Stanger; V Al Jalali; M Andreas; W Jäger; M Böhmdorfer; M Zeitlinger; D Hutschala Journal: Antimicrob Agents Chemother Date: 2021-07-19 Impact factor: 5.191
Authors: Benedikt Huttner; Bernadette Cappello; Graham Cooke; Sumanth Gandra; Stephan Harbarth; Monica Imi; Mark Loeb; Marc Mendelson; Lorenzo Moja; Céline Pulcini; Mike Sharland; Evelina Tacconnelli; Mei Zeng; Nicola Magrini Journal: Am J Respir Crit Care Med Date: 2020-05-15 Impact factor: 21.405