Akers Kevin S, Rowan Matthew P, Niece Krista L, Graybill John C, Mende Katrin, Chung Kevin K, Murray Clinton K
United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA.
Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, 3698 Chambers Pass, JBSA Fort Sam Houston, TX, 78234, USA.
BMC Infect Dis. 2015 Apr 15;15:184. doi: 10.1186/s12879-015-0918-8.
Survivors of combat trauma can have long and challenging recoveries, which may be complicated by infection. Invasive fungal infections are a rare but serious complication with limited treatment options. Currently, aggressive surgical debridement is the standard of care, with antifungal agents used adjunctively with uncertain efficacy. Anecdotal evidence suggests that antifungal agents may be ineffective in the absence of surgical debridement, and studies have yet to correlate antifungal concentrations in plasma and wounds.
Here we report the systemic pharmacokinetics and wound effluent antifungal concentrations of five wounds from two male patients, aged 28 and 30 years old who sustained combat-related blast injuries in southern Afghanistan, with proven or possible invasive fungal infection. Our data demonstrate that while voriconazole sufficiently penetrated the wound resulting in detectable effluent levels, free amphotericin B (unbound to plasma) was not present in wound effluent despite sufficient concentrations in circulating plasma. In addition, considerable between-patient and within-patient variability was observed in antifungal pharmacokinetic parameters.
These data highlight the need for further studies evaluating wound penetration of commonly used antifungals and the role for therapeutic drug monitoring in providing optimal care for critically ill and injured war fighters.
战斗创伤幸存者的康复过程漫长且充满挑战,可能会因感染而复杂化。侵袭性真菌感染是一种罕见但严重的并发症,治疗选择有限。目前,积极的手术清创是标准治疗方法,抗真菌药物作为辅助使用,疗效不确定。轶事证据表明,在没有手术清创的情况下,抗真菌药物可能无效,而且研究尚未将血浆和伤口中的抗真菌浓度关联起来。
在此,我们报告了两名年龄分别为28岁和30岁的男性患者五个伤口的全身药代动力学和伤口流出液中的抗真菌浓度。这两名患者在阿富汗南部遭受了与战斗相关的爆炸伤,患有已证实或可能的侵袭性真菌感染。我们的数据表明,虽然伏立康唑能够充分渗透到伤口中,导致流出液中可检测到药物水平,但尽管循环血浆中有足够的浓度,伤口流出液中却不存在游离两性霉素B(未与血浆结合)。此外,在抗真菌药代动力学参数方面,观察到患者之间和患者体内存在相当大的变异性。
这些数据凸显了进一步研究评估常用抗真菌药物伤口渗透情况以及治疗药物监测在为重症和受伤战士提供最佳护理方面作用的必要性。