Gonzalez Pedro L, Rappo Urania, Mas Casullo Veronica, Akinapelli Karthik, McGregor Jennifer S, Nelson Jennifer, Nowak Michael, Puttagunta Sailaja, Dunne Michael W
AbbVie, Madison, NJ, USA.
Independent Consultant, Hamden, CT, USA.
Infect Dis Ther. 2021 Mar;10(1):471-481. doi: 10.1007/s40121-021-00402-0. Epub 2021 Jan 30.
Dalbavancin is a lipoglycopeptide antibiotic approved as a single- and two-dose regimen for adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. We present nephrotoxicity rates for patients with ABSSSI who received dalbavancin in three pivotal clinical trials and compare the rates with vancomycin.
In a phase 3b clinical trial (DUR001-303), patients were randomized to dalbavancin single-dose (1500 mg intravenous [IV]) or two-dose regimen (1000 mg IV on day 1, 500 mg IV on day 8). In two phase 3 clinical trials (DISCOVER 1 and DISCOVER 2), patients were randomized to dalbavancin (two-dose regimen) or vancomycin 1 g (or 15 mg/kg) IV every 12 h for at least 3 days with an option to switch to orally administered linezolid 600 mg every 12 h for 10-14 days. Patients on dalbavancin with a creatinine clearance below 30 mL/min not on regular dialysis received a reduced dose of 1000 mg (single-dose arm) or 750 mg IV on day 1, 375 mg IV on day 8 (two-dose arm). Nephrotoxicity was defined as a 50% increase from baseline serum creatinine (SCr) or an absolute increase in SCr of 0.5 mg/dL at any time point. P values were obtained using the Cochran-Mantel-Haenszel test.
In dalbavancin-treated patients, rates of nephrotoxicity were low. The safety population with available creatinine values included 1325/1347 patients on any regimen of dalbavancin, and 54/651 patients who received vancomycin intravenously for at least 10 days and were not switched to orally administered linezolid. Patients on any regimen of dalbavancin had a lower rate of nephrotoxicity compared with patients receiving vancomycin intravenously for at least 10 days (3.7% vs 9.3%, respectively; P = 0.039).
Nephrotoxicity rates were lower in patients on dalbavancin relative to vancomycin for at least 10 days. On the basis of this experience, dalbavancin may be less nephrotoxic than intravenously administered vancomycin.
达巴万星是一种脂糖肽类抗生素，已被批准用于治疗由敏感革兰氏阳性菌引起的成人急性细菌性皮肤及皮肤结构感染（ABSSSI），采用单剂量和两剂量方案。我们在三项关键临床试验中给出了接受达巴万星治疗的ABSSSI患者的肾毒性发生率，并与万古霉素的发生率进行比较。
在一项3b期临床试验（DUR001 - 303）中，患者被随机分为达巴万星单剂量组（静脉注射1500毫克）或两剂量组（第1天静脉注射1000毫克，第8天静脉注射500毫克）。在两项3期临床试验（DISCOVER 1和DISCOVER 2）中，患者被随机分为达巴万星组（两剂量方案）或万古霉素组，万古霉素1克（或15毫克/千克）静脉注射，每12小时一次，至少持续3天，可选择改为口服利奈唑胺600毫克，每12小时一次，持续10 - 14天。肌酐清除率低于30毫升/分钟且未进行规律透析的达巴万星治疗患者，单剂量组剂量减为1000毫克，两剂量组第1天静脉注射750毫克，第8天静脉注射375毫克。肾毒性定义为血清肌酐（SCr）较基线水平升高50%或在任何时间点SCr绝对值升高0.5毫克/分升。P值采用 Cochr an - Mantel - Haenszel检验获得。
在接受达巴万星治疗的患者中，肾毒性发生率较低。有可用肌酐值的安全人群包括接受任何达巴万星治疗方案的1325/1347例患者，以及静脉注射万古霉素至少10天且未改为口服利奈唑胺的54/651例患者。接受任何达巴万星治疗方案的患者肾毒性发生率低于静脉注射万古霉素至少10天的患者（分别为3.7%和9.3%；P = 0.039）。
达巴万星治疗患者的肾毒性发生率低于万古霉素至少10天的患者。基于这一经验，达巴万星的肾毒性可能低于静脉注射的万古霉素。
