3児の親さん薬剤師のブログ

とある薬剤師です。感染症治療を考える素材をちょこっと提供。https://note.mu/twin1980。

Omadacycline for Acute Bacterial Skin and Skin-Structure Infections

NEJMに報告された、OASIS-1 study

 

皮膚・皮膚組織感染症に対する、 omadacycline vs linezolid P3 RCT。

主要評価項目は、48〜72時間における早期臨床反応とされ。これはレスキュー抗菌薬なしで、少なくとも20%の病変サイズ縮小を伴う生存と定義。

 

3日後から内服スイッチ可で、投与期間は7から14日。

 

非劣性マージンは 10パーセント。

 

https://www.nejm.org/doi/full/10.1056/NEJMoa1800170

f:id:akinohanayuki:20190210050937j:plain

 

感想

 

皮膚・皮膚組織感染に対して、Omadacyclineは、linezolidと非劣勢でした。

内服スイッチもできていい感じですね。

肺炎スタディは、Omadacyclineの死亡率高い可能性が見えたので、慎重にウォッチ。

 

皮膚感染に対しては、 delafloxacin・oritavancin・Tedizolid・CLDM vs STなど、様々なRCTが近年報告されてます。

統一王者決定戦を希望します。

 

Abstract


BACKGROUND
Acute bacterial skin and skin-structure infections are associated with substantial morbidity and health care costs. Omadacycline, an aminomethylcycline antibiotic that can be administered once daily either orally or intravenously, is active against pathogens that commonly cause such infections, including antibiotic-resistant strains.

METHODS
In this double-blind trial, we randomly assigned adults with acute bacterial skin and skin-structure infections (in a 1:1 ratio) to receive omadacycline (100 mg given intravenously every 12 hours for two doses, then 100 mg given intravenously every 24 hours) or linezolid (600 mg given intravenously every 12 hours). A transition to oral omadacycline (300 mg every 24 hours) or oral linezolid (600 mg every 12 hours) was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was an early clinical response at 48 to 72 hours, defined as survival with a reduction in lesion size of at least 20% without rescue antibacterial therapy. A secondary end point was an investigator-assessed clinical response at the post-treatment evaluation 7 to 14 days after the last dose, with clinical response defined as survival with resolution or improvement in signs or symptoms of infection to the extent that further antibacterial therapy was unnecessary. For both end points, the noninferiority margin was 10 percentage points.

RESULTS
In the modified intention-to-treat population, omadacycline (316 patients) was noninferior to linezolid (311 patients) with respect to early clinical response (rate of response, 84.8% and 85.5%, respectively; difference, −0.7 percentage points; 95% confidence interval [CI], −6.3 to 4.9). Omadacycline also was noninferior to linezolid with respect to investigator-assessed clinical response at the post-treatment evaluation in the modified intention-to-treat population (rate of response, 86.1% and 83.6%, respectively; difference, 2.5 percentage points; 95% CI, −3.2 to 8.2) and in the clinical per-protocol population (96.3% and 93.5%, respectively; difference, 2.8 percentage points; 95% CI, −1.0 to 6.9). In both groups, the efficacy of the trial drug was similar for methicillin-susceptible and methicillin-resistant Staphylococcus aureus infections. Adverse events were reported in 48.3% of the patients in the omadacycline group and in 45.7% of those in the linezolid group; the most frequent adverse events in both groups were gastrointestinal (in 18.0% and 15.8% of the patients in the respective groups).

CONCLUSIONS
Omadacycline was noninferior to linezolid for the treatment of acute bacterial skin and skin-structure infections and had a similar safety profile. (Funded by Paratek Pharmaceuticals; OASIS-1 ClinicalTrials.gov number, NCT02378480.)

 

 

 






 

感染症プラチナマニュアル 2019

感染症プラチナマニュアル 2019