Department of Renal Medicine and Transplantation, The Royal London Hospital, London, UK.
Perit Dial Int. 2012 May-Jun;32(3):332-8. doi: 10.3747/pdi.2010.00294. Epub 2011 Nov 1.
For the treatment of peritoneal dialysis-associated peritonitis (PDP), it has been suggested that serum concentrations of vancomycin be kept above 12 mg/L-15 mg/L. However, studies correlating vancomycin concentrations in serum and peritoneal dialysate effluent (PDE) during active infection are sparse. We undertook the present study to investigate this issue and to determine whether achieving the recommended serum level of vancomycin results in therapeutic levels intraperitoneally.
We studied patients treated with intraperitoneal (i.p.) vancomycin for non-gram-negative PDP. We gave a single dose (approximately 30 mg/kg) at presentation, and we subsequently measured vancomycin levels in PDE on day 5; we wanted to determine if efflux of vancomycin from serum to PDE during a 4-hour dwell was consistent and resulted in therapeutic levels.
Of the 48 episodes of PDP studied, serum vancomycin concentrations exceeding 12 mg/L were achieved in 98% of patients, but in 11 patients (23%), a PDE vancomycin level below 4 mg/L--the minimal inhibitory concentration (MIC) of many gram-positive organisms--was observed at the end of a 4-hour dwell on day 5. The correlation between the concentrations of vancomycin in serum and PDE (from efflux of antibiotic over 4 hours) was statistically significant, but poor (R(2) = 0.18).
Our data support the International Society for Peritoneal Dialysis statement that adequate serum vancomycin concentrations can be achieved with intermittent dosing (single dose every 5 days), but cannot guarantee therapeutic PDE levels in the treatment of PDP. Intermittent dosing of vancomycin may not consistently result in PDE concentrations markedly greater than MIC of many important pathogens. Although the clinical significance of this finding remains to be determined, it may be preferable to give smaller but more frequent doses of PDE vancomycin (continuous dosing) for adults with PDP (as is currently recommended for children).
对于治疗腹膜透析相关性腹膜炎（PDP），有人建议将万古霉素的血清浓度保持在 12mg/L-15mg/L 以上。然而，关于活跃感染期间血清和腹膜透析液（PDE）中万古霉素浓度相关性的研究很少。因此，我们进行了本项研究来探讨这一问题，并确定是否达到推荐的血清万古霉素水平可导致腹膜内的治疗水平。
我们研究了接受腹腔内（i.p.）万古霉素治疗非革兰氏阴性 PDP 的患者。我们在初次就诊时给予单剂量（约 30mg/kg），随后在第 5 天测量 PDE 中的万古霉素水平；我们想确定万古霉素从血清到 PDE 的 4 小时驻留期间是否持续外排并达到治疗水平。
在研究的 48 例 PDP 中，98%的患者血清万古霉素浓度超过 12mg/L，但在 11 例患者（23%）中，在第 5 天的 4 小时驻留结束时，观察到 PDE 万古霉素水平低于 4mg/L（许多革兰氏阳性菌的最小抑菌浓度 [MIC]）。万古霉素在血清和 PDE 中的浓度（抗生素在 4 小时内的外排）之间的相关性具有统计学意义，但较差（R²=0.18）。
我们的数据支持国际腹膜透析学会的声明，即间歇性给药（每 5 天给予单剂量）可以达到足够的血清万古霉素浓度，但不能保证在治疗 PDP 时 PDE 达到治疗水平。万古霉素间歇性给药可能不会始终导致 PDE 浓度明显高于许多重要病原体的 MIC。尽管这一发现的临床意义仍有待确定，但对于患有 PDP 的成人，给予更小但更频繁的 PDE 万古霉素剂量（连续给药）可能更为可取（目前建议儿童使用）。
