さまよう薬剤師のブログ

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 ID pharmacist.

ESTABLISH-2 : Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial.

ESTABLISH-2 : Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial.

www.ncbi.nlm.nih.gov

 2014年 Lancet Inf Disに報告された、日本を含まない9カ国 58施設 によるABSSSIsに対するTedizolidとLinezolidを比較した第3相 RCT。

 

 

 

P : Patients (aged ≥12 years) with acute bacterial skin and skin-structure infections (cellulitis or erysipelas, major cutaneous abscess, or wound infection) that had a minimum lesion area of 75 cm(2) and were suspected or documented to be associated with a Gram-positive pathogen

E :  intravenous once-daily tedizolid (200 mg for 6 days) with optional oral step-down. 

      n=332

C :  intravenous twice-daily linezolid (600 mg for 10 days), with optional oral step-down. 

      n=334

O : 283 (85%) patients in the tedizolid group and 276 (83%) in the linezolid group achieved early clinical response (difference 2·6%, 95% CI -3·0 to 8·2)

T :  randomised, double-blind, phase 3, non-inferiority trial 

 

f:id:akinohanayuki:20170523053710p:plain

f:id:akinohanayuki:20170523053718p:plain

f:id:akinohanayuki:20170523053745p:plain

f:id:akinohanayuki:20170523053750p:plain

f:id:akinohanayuki:20170523053756p:plain

f:id:akinohanayuki:20170523053803p:plain

f:id:akinohanayuki:20170523053809p:plain

f:id:akinohanayuki:20170523053815p:plain

 Limitations

 

A potential limitation of our study concerns the reliability of lesion measurements. Manual measurement of lesion size of acute bacterial skin and skin-structure infections could introduce variability; however, this variability would be expected to be of similar size and direction between treatment groups.

 

Another potential limitation is that our study population, most of whom originated from the community setting, had a somewhat lower incidence of comorbidities than reported for patients admitted to or already in the hospital treated for complicatedskinandskin-structureinfectionsinclinical practice. Reasons include differences in how these patient populationshavetraditionallybeendefined,andtheethical requirement to exclude some highly comorbid patients from initial phase 3 studies. Because we showed the non- inferiority of tedizolid to linezolid for treatment of acute bacterial skin and skin-structure infections, the results might be applicable to a broad range of patients with these infections, including patients with renal or hepatic impairment. Further investigation is warranted to confirm this assumption. Data suggest that severe hepatic or renal insufficiency, even the need for haemodialysis, do not affect the pharmacokinetics of tedizolid

 

the study was not designed to assess this possibility, and the scarcity of available data about the reasons for de-escalation is a limitation of our trial. Future studies should aim to identify patient subsets that are likely to need sequential intravenous to oral or exclusively intravenous tedizolid treatment, rather than merely oral drug, to achieve successful treatment outcomes.

 

結論

ESTABLISH-2において、ABSSSIsに対してTedizolidスイッチ療法 6日 は Linezolidスイッチ療法 10日と比べ非劣勢であった。

 

感想

ESTABLISH-2と同様、日本において必要性は微妙です。LZDを選択することはまだ少ないです。しかし、スイッチ療法を比較した事は興味深いです。スイッチ療法の必要性は高まるはずです。

なお、 副作用において、LZDは吐き気が多い傾向です。しかし、ESTABLISH-1よりは気になりませんでした。一方、Tedizolidは、ESTABLISH-1同様にSecondary abscessが多い傾向でした。

 

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