Infectious Disease Service, Brooke Army Medical Center/San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
J Orthop Trauma. 2013 Aug;27(8):428-36. doi: 10.1097/BOT.0b013e3182830bf9.
Posttraumatic invasive fungal infections threaten critically injured combat-related injuries and require a combination of extensive surgery and systemic antifungal therapy, along with topical antimicrobials used adjunctively to control the infection. We evaluated the in vitro activity of topical agents in varying combinations and concentrations against molds from patients that were responsible for wound invasive fungal infections and the topical agents' toxicity to human cells.
Mafenide acetate solutions (2.5%, 5%, and 7.5%), amphotericin B solutions (2 µg/mL, 2 mg/mL, and 20 mg/mL), SMAT (5% mafenide acetate in combination with 2 µg/mL, 2 mg/mL, and 20 mg/mL amphotericin B), and Dakin's solutions (buffered sodium hypochlorite) (0.5%, 0.25%, and 0.125% and 10-fold serial dilutions of 0.25%-0.00000025%) were evaluated for antifungal activity against 4 molds using a time-kill assay using standard conidial suspensions of 5 × 10(4) colony-forming units per milliliter. To assess cellular toxicity, confluent monolayers of human keratinocytes, dermal fibroblasts, and osteoblasts were exposed to these topical agents. Based upon efficacy and toxicity ratios, an additional 10 molds were screened with selected concentrations of the topical agents for antifungal activity and toxicity.
All the topical agents seemed to have a dose-dependent killing with only mafenide acetate showing time killing associated with prolonged contact. There was overall evidence of dose-dependent cytotoxicity of the various topical agents against the various cell lines tested, but there did not seem to be increased cell death with continued exposure to the agents over time. Dakin's solution exhibited dose-dependent toxicity and efficacy with 0.00025% appearing to optimize those parameters.
Mafenide acetate and amphotericin B did not seem to persistently meet the toxicity and efficacy balance as consistently as Dakin's solution.
创伤后侵袭性真菌感染威胁着严重创伤的战伤患者，需要广泛的手术和全身性抗真菌治疗，同时联合局部使用抗菌药物来控制感染。我们评估了不同浓度和组合的局部用药对导致伤口侵袭性真菌感染的患者的真菌的体外活性，以及这些局部用药对人细胞的毒性。
评估醋酸磺胺米隆溶液（2.5%、5%和 7.5%）、两性霉素 B 溶液（2μg/ml、2mg/ml 和 20mg/ml）、SMAT（5%醋酸磺胺米隆联合 2μg/ml、2mg/ml 和 20mg/ml 两性霉素 B）和达金溶液（缓冲次氯酸钠）（0.5%、0.25%和 0.125%以及 0.25%-0.00000025%的 10 倍系列稀释液）对 4 种真菌的抗真菌活性，使用标准的 5×10(4)cfu/ml 的分生孢子悬浮液进行时间杀伤试验。为了评估细胞毒性，将人角质形成细胞、真皮成纤维细胞和骨细胞的汇合单层暴露于这些局部用药。基于疗效和毒性比值，用选定浓度的局部用药对另外 10 种真菌进行抗真菌活性和毒性筛选。
所有局部用药似乎都有剂量依赖性的杀菌作用，只有醋酸磺胺米隆显示出与延长接触相关的时间杀伤作用。各种局部用药对不同的细胞系均有剂量依赖性的细胞毒性，但随着时间的推移，细胞暴露于药物中似乎没有增加细胞死亡。达金溶液显示出剂量依赖性的毒性和疗效，0.00025%似乎能优化这些参数。
醋酸磺胺米隆和两性霉素 B 似乎不像达金溶液那样始终如一地保持毒性和疗效的平衡。
