Aminoglycoside계 항균제 1일 1회 투여법과 1일 다회 투여법에서 신독성의 발생 비교
Comparison of two dosing regimens of aminoglycosides for the development of nephrotoxicity: once versus multiple daily dosing
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목적 : Aminoglycoside계 항균제는 주로 호기성 그람음성막대균 감염증의 치료에 유용하나 치료지수가 좁고 신독성과 이독성을 일으킬 위험이 있다. 농도의존형 살균효과, post-antibiotic effect 등의 약역학적 특성이 밝혀져 최근에는 1일 1회 투여법이 사용되고 있다. 이 연구는 aminoglycoside계 항균제의 1일 다회 투여법과 1일 1회 투여법에서 신독성의 발생률을 비교하였다. 방법 : 2005년 3∼8월 사이 aminoglycoside계 항균제가 4일 이상 투여된 내과 환자를 대상으로 하였고, 4월까지 1일 다회 투여법(MDD군)이 5월부터는 1일 1회 투여법(ODD군)이 사용되었다. 신독성의 발생은 aminoglycoside계 항균제를 투여 중이거나 투여를 종료한 지 7일 안에 기저 혈청 creatinine치가 3.0 mg/dL 미만인 경우 혈청 creatinine치가 처음보다 0.5 mg/dL 이상 상승하거나 기저치가 3.0 mg/dL 이상인 경우 혈청 creatinine치가 1.0 mg/dL 이상 상승하는 것으로 정의하였다.결과 : MDD군(45명)과 ODD군(40명)의 인구통계학적 특성, 감염증의 종류와 중증도, 사용된 항균제의 종류에 유의한 차이는 없었다. 투여된 aminoglycoside계 항균제는 tobramycin (43:38명), amikacin (2:1명), gentamicin (0:1명) 등이었으며, tobramycin의 경우 하루 평균 투여량(mg)은 MDD군이 129.3±29.1이었고, ODD군은 205.3±57.2이었다(p<0.001). 평균 투여기간(일)은 MDD군이 8.0 (3-31)이었으며 ODD군이 7.7 (3-19)이었다(p=0.83). Aminoglycoside계 항균제 투여에 의한 신독성은 MDD군에서 0명, ODD군에서 1명에서 발생하였다(p=0.48).
Abstract
Background : Aminoglycosides are useful for the treatment of aerobic gram-negative infections, and this is despite the narrow therapeutic index and the potential nephrotoxicity and ototoxicity. Once daily dosing of aminoglycosides has recently been suggested as an alternative method to multiple daily dosing. We compared the two dosing regimens of aminoglycosides for the development of nephrotoxicity. Methods : This study was conducted as part of an ongoing quality improvement program. For the administration of aminoglycosides in adult patients with suspected or documented gram-negative infection, multiple daily dosing was used until April 2005 and thereafter once daily dosing was recommended. Results : A total of 85 patients who received aminoglycoside for more than 3 days from March to August 2005 were available for analysis (40 in the once daily dosing group and 45 in the multiple daily dosing group). The mean duration of administration was 7.7 (range: 3-19) days in the once daily dosing group and 8.0 (range: 3-31) days in the multiple daily dosing group (p=0.83). Aminoglycoside-associated nephrotoxicity was observed in a patient in the once daily dosing group (2.5% vs 0%, respectively, p=0.48). Conclusions : No significant difference in the development of nephrotoxicity was found between the two dosing regimens for aminoglycosides, but this finding had low statistical power. This may be due to underdosing of aminoglycosides in the multiple daily dosing group.(Korean J Med 71:543-550, 2006)
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