論文No1070
"Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials"
Jason A. Roberts, Mohd-Hafiz Abdul-Aziz, Joshua S. Davis, Joel M. Dulhunty, Menino O. Cotta, John Myburgh, Rinaldo Bellomo, and Jeffrey Lipman
American Journal of Respiratory and Critical Care Medicine, Vol. 194, No. 6 (2016), pp. 681-691.
doi: 10.1164/rccm.201601-0024OC
＜背景＞
重症患者に対するβラクタム系抗菌薬の最適化は
重症敗血症の転帰を改善するかもしれない介入である。
＜目的＞
この重症敗血症の個人データのメタ解析において、我々はβラクタム系抗菌薬の持続点滴vs間欠点滴の臨床効果を比較した。
＜方法＞
ランダム化コントロール試験を検索した。
４つの基準によって研究の質を評価した。
研究から個人データを結合し、共通のベースラインの臨床背景、研究の目的（３０日院内死亡、臨床的治癒を含む）に対してデータの整合性を評価した。
その後、累積効果評価を行い、多変量解析で院内死亡と関連する因子を検討した。
＜結果＞
重症敗血症６３２名のデータを３つのランダム化コントロール試験から得た。
持続vs間欠的投与は年齢、性別、疾患重症度がマッチしていた。
持続vs間欠で、
院内死亡率は19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56–1.00; P = 0.045)、
臨床的治癒は55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03–1.40; P = 0.021)であった。
多変量モデルにおいて、間欠的βラクタム点滴、APACHE-Ⅱスコア高値、腎移植、非発酵性グラム陰性桿菌は院内死亡と有意に関連していた。
βラクタムの持続点滴は臨床的治癒と独立には関連しなかった。
＜感想＞
通常、βラクタム系抗菌薬は６時間ごと、８時間ごとなど間欠的に投与します。
このメタ解析では、持続的に投与した方が重症敗血症の院内死亡率を改善したという結果でした。
Rationale: Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.
Objectives: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.
Methods: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.
Measurements and Main Results: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56–1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03–1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.
Conclusions: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201601-0024OC#.V-Jp2s-a27Q