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学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense a ID pharmacist. Another face is an investor.

Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for acute bacterial skin and skin structure infections: a Phase 3, double-blind, randomized study

JACに報告された、皮膚感染に対する、delafloxacin vs vancomycin plus aztreonamのP3。

academic.oup.com

 

Abstract

Background

Delafloxacin is an investigational anionic fluoroquinolone in development for oral or intravenous administration for the treatment of infections caused by Gram-positive (including MRSA), Gram-negative, atypical and anaerobic organisms.

Objectives

To establish the non-inferiority of delafloxacin compared with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections and to compare the safety of the two antimicrobials.

Patients and methods

A Phase 3, multicentre, randomized, double-blind, active-controlled study with 660 patients compared delafloxacin 300 mg or vancomycin 15 mg/kg plus aztreonam 2 g each administered twice daily intravenously for 5–14 days. Non-inferiority was evaluated by objective response (≥20% erythema reduction) at 48–72 h after initiation of study drug, investigator subjective assessment of outcome and microbiological responses. Clinical Trials Registration: NCT01811732. EudraCT number: 2012-001767-71.

Results

In the ITT analysis set, the objective response was 78.2% in the delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment difference, −2.6%; 95% CI, −8.78% to 3.57%). Investigator-assessed cure was similar between the two groups at follow-up (52.0% versus 50.5%) and late follow-up (70.4% versus 66.6%). Bacterial eradication of MRSA was 100% and 98.5% in the delafloxacin group and the vancomycin/aztreonam group, respectively. Frequency of treatment-emergent adverse events in the delafloxacin and vancomycin/aztreonam groups was similar. Treatment-emergent adverse events leading to study drug discontinuation were higher in the vancomycin/aztreonam group compared with the delafloxacin group (4.3% versus 0.9%).

Conclusions

Delafloxacin, an anionic fluoroquinolone, was statistically non-inferior to vancomycin/aztreonam at 48–72 h following the start of therapy and was well tolerated as monotherapy in the treatment of acute bacterial skin and skin structure infections.

 

PECO

 

P : 

age ≥18 years and a diagnosis of ABSSSI classified as cellulitis/erysipelas, wound infection, major cutaneous abscess or burn infection with ≥75 cm2 of erythema and ≥2 signs of systemic infection.

E : delafloxacin 300 mg for 5–14 days

C : vancomycin 15 mg/kg plus aztreonam 2 g each administered twice daily intravenously for 5–14 days

O : 

the objective response was 78.2% in the delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment difference, −2.6%; 95% CI, −8.78% to 3.57%).

Treatment-emergent adverse events leading to study drug discontinuation were higher in the vancomycin/aztreonam group compared with the delafloxacin group (4.3% versus 0.9%).

 

T : A Phase 3, multicentre, randomized, double-blind, active-controlled study.

     Non-inferiority. ITT.

 

f:id:akinohanayuki:20171207055159p:plain

 

f:id:akinohanayuki:20171207055250p:plain

 

Summary of AEs affecting either treatment group: safety population

Summary of AE, n (%) 

Treatment group


 

delafloxacin, N =324 

vancomycin +  aztreonam, N =326 

Overall TEAEs 

154 (47.5) 

193 (59.2) 

TEAEs affecting ≥5% of patients 

 diarrhoea 

27 (8.3) 

10 (3.1) 

 headache 

10 (3.1) 

25 (7.7) 

 infection 

28 (8.6) 

25 (7.7) 

infusion-site extravasation 

28 (8.6) 

44 (13.5) 

 nausea 

24 (7.4) 

28 (8.6) 

TEAEs by intensity 

 mild 

90 (27.8) 

126 (38.7) 

 moderate 

53 (16.4) 

60 (18.4) 

 severe 

11 (3.4) 

7 (2.1) 

TEAEs related to study drug 

 total related to study drug 

78 (24.1) 

107 (32.8) 

 possibly 

56 (17.3) 

75 (23.0) 

 probably 

14 (4.3) 

23 (7.1) 

 definitely 

8 (2.5) 

9 (2.8) 

TEAEs leading to early discontinuation of study drug 

3 (0.9) 

14 (4.3) 

Related TEAEs leading to early discontinuation of study drug 

1 (0.3) 

8 (2.5) 

Overall serious AEs 

12 (3.7) 

12 (3.7) 

Deaths 

1 (0.3) 

1 (0.3) 

 

感想

 

Delafloxacinがバンコマイシン+アズトレと非劣勢となり、脅威が増している皮膚感染の武器が増えたことは良かったのですが、パッとしない結果かなと印象。