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A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities.
J Antimicrob Chemother. 2016 12; 71(12):3575-3584.JA

Abstract

OBJECTIVES

Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting.

METHODS

Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days. Clinical cure was assessed at the test of cure (TOC) visit (8-15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than -10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135.

RESULTS

Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference -1.0%, 95% CI -6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI -4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups.

CONCLUSIONS

Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified.

Links

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Authors+Show Affiliations

Dryden M
Royal Hampshire County Hospital, Winchester SO22 5DG, UK matthew.dryden@hhft.nhs.uk.
Zhang Y
Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Zhong Road, Shanghai 200040, P.R. China.
Wilson D
AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.
Iaconis JP
AstraZeneca, 35 Gatehouse Drive, Waltham, MA, USA.
Gonzalez J
AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.

MeSH

Administration, IntravenousAdolescentAdultAgedAged, 80 and overAnti-Bacterial AgentsAztreonamCephalosporinsDouble-Blind MethodDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedProspective StudiesSkin Diseases, BacterialSoft Tissue InfectionsSystemic Inflammatory Response SyndromeTreatment OutcomeVancomycinYoung Adult

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

27585969

Clinical Trial Links

Clinical trial which this article describes [1]
Clinical trial which this article describes [2]

Citation

Dryden, Matthew, et al. "A Phase III, Randomized, Controlled, Non-inferiority Trial of Ceftaroline Fosamil 600 Mg Every 8 H Versus Vancomycin Plus Aztreonam in Patients With Complicated Skin and Soft Tissue Infection With Systemic Inflammatory Response or Underlying Comorbidities." The Journal of Antimicrobial Chemotherapy, vol. 71, no. 12, 2016, pp. 3575-3584.
Dryden M, Zhang Y, Wilson D, et al. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. J Antimicrob Chemother. 2016;71(12):3575-3584.
Dryden, M., Zhang, Y., Wilson, D., Iaconis, J. P., & Gonzalez, J. (2016). A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. The Journal of Antimicrobial Chemotherapy, 71(12), 3575-3584.
Dryden M, et al. A Phase III, Randomized, Controlled, Non-inferiority Trial of Ceftaroline Fosamil 600 Mg Every 8 H Versus Vancomycin Plus Aztreonam in Patients With Complicated Skin and Soft Tissue Infection With Systemic Inflammatory Response or Underlying Comorbidities. J Antimicrob Chemother. 2016;71(12):3575-3584. PubMed PMID: 27585969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. AU - Dryden,Matthew, AU - Zhang,Yingyuan, AU - Wilson,David, AU - Iaconis,Joseph P, AU - Gonzalez,Jesus, Y1 - 2016/09/01/ PY - 2016/01/13/received PY - 2016/06/10/revised PY - 2016/07/18/accepted PY - 2016/9/3/pubmed PY - 2017/8/15/medline PY - 2016/9/3/entrez SP - 3575 EP - 3584 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 71 IS - 12 N2 - OBJECTIVES: Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting. METHODS: Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days. Clinical cure was assessed at the test of cure (TOC) visit (8-15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than -10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135. RESULTS: Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference -1.0%, 95% CI -6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI -4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups. CONCLUSIONS: Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/27585969/A_Phase_III_randomized_controlled_non_inferiority_trial_of_ceftaroline_fosamil_600_mg_every_8_h_versus_vancomycin_plus_aztreonam_in_patients_with_complicated_skin_and_soft_tissue_infection_with_systemic_inflammatory_response_or_underlying_comorbidities_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓27 ↑23]

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