Freundlich Morten, Thomsen Reimar W, Pedersen Lars, West Hans, Schønheyder Henrik C
Anaesthesiology Sector North Jutland, 4th Department, Department of Intensive Care R, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
J Antimicrob Chemother. 2007 Nov;60(5):1115-23. doi: 10.1093/jac/dkm354. Epub 2007 Sep 19.
The effectiveness and safety of aminoglycoside (AG)/beta-lactam combination therapy has been questioned in several meta-analyses. We examined the association between AG combination therapy and mortality and increase in serum creatinine in adult patients with bacteraemia given appropriate empirical antibiotic therapy.
Historical cohort study based on prospective registration of bacteraemias in a Danish hospital 1996-2002. AG + beta-lactam was the recommended empirical therapy for severe sepsis. We identified 1,257 patients, of whom 969 received gentamicin or tobramycin (AG cohort); 288 patients not given AGs formed the non-AG cohort. We used Cox regression analysis to compare adjusted mortality rates; the association between AG therapy and increase in serum creatinine was analysed by logistic regression.
The cumulative 30 day mortality in the AG cohort was 17.3% versus 18.1% in the non-AG cohort [adjusted mortality rate ratio (MRR) 1.02; 95% CI 0.74-1.39]. The adjusted 31-180 day MRR in the AG cohort was 1.72 (95% CI 1.15-2.55). AG therapy was associated with lower 30 day mortality in patients with an abdominal focus (adjusted 30 day MRR 0.52; 95% CI 0.24-1.10) or a urinary tract focus (adjusted 30 day MRR 0.48; 95% CI 0.22-1.08), but with a worse prognosis in patients with a respiratory tract focus (adjusted 30 day MRR 2.06; 95% CI 0.93-4.53). An increase in serum creatinine of >or=45 micromol/L was observed similarly often in AG- and non-AG-treated patients [14.1% versus 12.4%, adjusted odds ratio 1.06; 95% CI 0.63-1.79].
Among patients with bacteraemia receiving appropriate empirical coverage, AG combination therapy was not associated with increased 30 day mortality and only a modest risk of raised serum creatinine. The longer-term prognosis should, however, be explored further.
氨基糖苷类(AG)/β-内酰胺类联合治疗的有效性和安全性在多项荟萃分析中受到质疑。我们研究了在接受适当经验性抗生素治疗的成年菌血症患者中,AG联合治疗与死亡率及血清肌酐升高之间的关联。
基于丹麦一家医院1996 - 2002年菌血症前瞻性登记的历史性队列研究。AG + β-内酰胺类是严重脓毒症的推荐经验性治疗方案。我们确定了1257例患者,其中969例接受庆大霉素或妥布霉素治疗(AG队列);288例未接受AG治疗的患者组成非AG队列。我们使用Cox回归分析比较调整后的死亡率;通过逻辑回归分析AG治疗与血清肌酐升高之间的关联。
AG队列30天累积死亡率为17.3%,非AG队列为18.1%[调整后死亡率比(MRR)1.02;95%置信区间(CI)0.74 - 1.39]。AG队列31 - 180天调整后的MRR为1.72(95% CI 1.15 - 2.55)。AG治疗与腹部感染源患者较低的30天死亡率相关(调整后30天MRR 0.52;95% CI 0.24 - 1.10)或泌尿道感染源患者(调整后30天MRR 0.48;95% CI 0.22 - 1.08),但与呼吸道感染源患者较差预后相关(调整后30天MRR 2.06;95% CI 0.93 - 4.53)。在接受AG治疗和未接受AG治疗的患者中,血清肌酐升高≥45微摩尔/升的情况同样常见[14.1%对12.4%,调整后优势比1.06;95% CI 0.63 - 1.79]。
在接受适当经验性覆盖治疗的菌血症患者中,AG联合治疗与30天死亡率增加无关且血清肌酐升高风险仅适度增加。然而,长期预后应进一步探索。