さまよう薬剤師のブログ

感染症治療を考える素材を提供します。最近は意思決定への応用が関心領域。双子と0歳の育児奮闘中。I have Ph.D. but less sense a ID pharmacist (ICPS). Another face is an investor.

IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs. Meropenem in the Treatment of Complicated Intra-Abdominal Infections

CIDから報告された、cIAIに対するRCT P3。

 

academic.oup.com

感想

 

耐性菌と戦える抗菌薬が開発されたことは、素晴らしいです。

本試験は、エラバサイクリンが、カルバペネムと非劣勢を示しました。

ただし、試験デザインにおいて、投与期間が4から14日って大味な気がしますね。

 

なお、エラバサイクリンは、テトラサイクリン系の全合成フルオロサイクリンで、30Sリボソームサブユニットに結合することによって細菌タンパク質合成を阻害し、CREなどにも活性を有します。

 

Abstract

Background
Increasing antimicrobial resistance among pathogens that cause complicated intra-abdominal infections (cIAI) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae (CRE).

Methods
IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg q12h or meropenem 1 g q8h intravenously for 4–14 days. The prospectively defined primary objective was to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (25–31 days from start of therapy) in the micro-ITT population using a noninferiority margin of –12.5%. Microbiological outcomes and safety were also evaluated.

Results
Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference –0.5%; 95% confidence interval [CI] –6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified intent-to-treat population (231/250 [92.4%] vs 228/249 [91.6%]; (difference 0.8; CI -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference 0.8; CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline in this and our previous trials saw relatively low rates of adverse events (AEs) for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively.

Conclusions
Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens.

 

 

抗菌薬の考え方,使い方 ver.4   魔弾よ、ふたたび…

抗菌薬の考え方,使い方 ver.4 魔弾よ、ふたたび…