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スルバクタム/アンピシリンの高用量と低用量の安全性の比較。日本人肺炎患者を対象としたレトロスペクティブ観察研究
Comparison of safety between high and low doses of sulbactam/ampicillin: A retrospective observational study in Japanese patients with pneumonia.
PMID: 32622622 DOI: 10.1016/j.jiac.2020.06.004.
抄録
日本ではスルバクタム/アンピシリン（SBT/ABPC）12g/日投与が承認されているが，従来用量（6g/日以下）と高用量（9g/日以上）による副作用発現頻度の違いは不明なままである。我々は、2015年10月から2018年1月までにSBT/ABPC治療を受けた成人肺炎患者を対象に、高用量と低用量の安全性を比較するためのレトロスペクティブ観察研究を行った。患者を高用量（≧9g/日，n=200）群と低用量（≦6g/日，n=246）群に分けた。ロジスティック回帰を用いて高用量群と低用量群の傾向スコアを決定し、傾向スコア調整後の副作用の発生率を比較した（各群n=200）。プロペンシティスコア調整後も、アラニンアミノトランスフェラーゼ（ALT）値の上昇頻度は高用量群の方が低用量群よりも有意に高かった（21％対11％、p=0.006）。一方、アルカリホスファターゼ、アスパラギン酸アミノトランスフェラーゼ、血清クレアチニン値の上昇頻度、白血球数・血小板数の減少、貧血の発生率には変化はなかった。血中尿素窒素値、赤血球数、ヘマトクリットの変化は両投与群間で有意差は認められなかった。高用量群で副作用として医薬品医療機器総合機構に報告された発疹は2例であった。30 日間死亡率は，傾向スコア調整後も有意差は認められなかった。我々の解析では、1日量9g以上のSBT/ABPCを投与された患者では、ALTグレードの上昇がより頻繁にみられたことが示唆された。
Although 12 g/day sulbactam/ampicillin (SBT/ABPC) is approved in Japan, differences in the frequency of adverse effects induced by conventional (≤6 g/day) and high (≥9 g/day) doses remain unclear. We performed a retrospective observational study on SBT/ABPC-treated hospitalized adult patients with pneumonia from October 2015 to January 2018 to compare the safety between high and low doses. Patients were divided into high-dose (≥9 g/day, n = 200) and low-dose (≤6 g/day, n = 246) groups. We used logistic regression to determine propensity scores for the high-dose and low-dose groups and compared the incidence of adverse effects after propensity score adjustment (n = 200 in each group). Following propensity score adjustment, the frequency of elevated alanine aminotransferase (ALT) level was still significantly higher in the high-dose group than in the low-dose group (21% versus 11%, p = 0.006). In contrast, the frequencies of elevated alkaline phosphatase, aspartate aminotransferase, and serum creatinine levels and decreased white blood cell and platelet counts, and incidence of anemia, were not. Changes in blood urea nitrogen levels, erythrocyte count, and hematocrit were not significantly different between the two dose groups. There were two cases of rash reported to the Pharmaceuticals and Medical Devices Agency as an adverse effect in the high-dose group. Thirty-day mortality rates were not significantly different after propensity score adjustment. Our analysis suggests that an increase in the ALT grade was more frequent in patients treated with a daily dose of SBT/ABPC of ≥9 g.
Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.