Wang S, Cunha B A, Hamid N S, Amato B M, Feuerman M, Malone B
Department of Pharmacy, Winthrop-University Hospital, Mineola, NY 11501, USA.
J Chemother. 2007 Aug;19(4):410-6. doi: 10.1179/joc.2007.19.4.410.
The purpose of the study was to compare the clinical efficacy of once-daily versus multiple dose regimens of metronidazole in inpatients with serious/systemic Bacteroides fragilis infections, i.e., intraabdominal/pelvic and diabetic foot infections. A retrospective chart review was performed on 145 adult inpatients who received combination therapy with metronidazole for B. fragilis abdominal/pelvic infection or diabetic (deep) foot infections/osteomyelitis. Exclusion criteria included metronidazole given for indications other than those mentioned, patients who received only one dose of metronidazole, and patients who received oral metronidazole only. The 145 patients were in two groups: 66 patients in the metronidazole 1 g (i.v.) q24h (Group A) and 79 patients who received metronidazole 500 mg (i.v./p.o.) q6-8h dosing (Group B). Patient demographics included age, gender, indications of metronidazole, concomitant, antibiotics, and co-morbidities. Data collection also included length of stay (LOS), antibiotic days, and clinical outcomes. The 145 patients in our study had a mean age of 66 years, 61% were female and 39% male. Most patients were being treated for definitive intraabdominal/pelvic infections (82%), or probable intraabdominal/pelvic infections (22%). Only 6% had deep diabetic foot infections of osteomyelitis (percentages exceed 100% since a patient can have more than one indication) and were included since B. fragilis is also and important pathogen in diabetic osteomyelitis. Group A patients had more concomitant antibiotics and co-morbidities (p < 0.0001 and p < 0.05 respectively, chi-square test for trend) than Group B patients. There were no statistically significant differences between groups A and B for LOS and antibiotic days (p = 0.42 and p = 0.92 respectively, by rank-sum test), but after adjusting for concomitant antibiotics and co-morbidities Group A patients had clinically shorter LOS and fewer antibiotic days. Unadjusted mortality and failure rates were non-significantly higher in group A (relative ratios of 12.1%/6.3% = 6.3% = 1.91 and 18.2%/ 10.1% = 1.80 respectively), but after adjusting for concomitant antibiotics and co-morbidities with stratification analysis, groups A and B were virtually the same (risk differences of </= 1%). The authors conclude that for B. fragilis infections, as part of combination therapy, metronidazole 1 g (i.v.) q 24h appears to eb as efficacious and not inferior to multiply-dosed metronidazole regimens. Once daily metronidazole, i.e., 1 g (i.v.) q24h for the treatment of serious systemic infections where B. fragilis is an important co-pathogen (intraabdominal/pelvic and deep diabetic foot infections) has pharmacokinetic and pharmaco-economic advantages.
本研究的目的是比较甲硝唑每日一次与多剂量方案治疗患有严重/全身性脆弱拟杆菌感染（即腹腔/盆腔感染和糖尿病足感染）的住院患者的临床疗效。对145例接受甲硝唑联合治疗脆弱拟杆菌腹腔/盆腔感染或糖尿病（深部）足部感染/骨髓炎的成年住院患者进行了回顾性病历审查。排除标准包括因上述以外的适应症使用甲硝唑、仅接受一剂甲硝唑的患者以及仅接受口服甲硝唑的患者。145例患者分为两组：66例患者接受甲硝唑1g（静脉注射）每24小时一次（A组），79例患者接受甲硝唑500mg（静脉注射/口服）每6 - 8小时给药一次（B组）。患者人口统计学特征包括年龄、性别、甲硝唑的适应症、合并使用的抗生素以及合并症。数据收集还包括住院时间（LOS）、抗生素使用天数以及临床结局。我们研究中的145例患者平均年龄为66岁，61%为女性，39%为男性。大多数患者接受确定性腹腔/盆腔感染治疗（82%），或可能的腹腔/盆腔感染治疗（22%）。只有6%患有深部糖尿病足感染或骨髓炎（百分比超过100%，因为患者可能有不止一种适应症），由于脆弱拟杆菌也是糖尿病骨髓炎的重要病原体，所以将这些患者纳入研究。A组患者比B组患者有更多的合并使用抗生素和合并症（分别为p < 0.0001和p < 0.05，趋势卡方检验）。A组和B组在住院时间和抗生素使用天数方面无统计学显著差异（分别为p = 0.42和p = 0.92，秩和检验），但在调整合并使用的抗生素和合并症后，A组患者的临床住院时间更短，抗生素使用天数更少。未调整的死亡率和失败率在A组略高（相对比率分别为12.1%/6.3% = 1.91和18.2%/10.1% = 1.80），但在通过分层分析调整合并使用的抗生素和合并症后，A组和B组基本相同（风险差异≤1%）。作者得出结论，对于脆弱拟杆菌感染，作为联合治疗的一部分，甲硝唑1g（静脉注射）每24小时一次似乎同样有效且不劣于多剂量甲硝唑方案。每日一次的甲硝唑，即1g（静脉注射）每24小时一次，用于治疗脆弱拟杆菌作为重要共同病原体的严重全身性感染（腹腔/盆腔感染和深部糖尿病足感染）具有药代动力学和药物经济学优势。
