抗真菌活性对浮游生物和生物膜白色念珠菌在异物感染的实验模型。
Antifungal activity against planktonic and biofilm Candida albicans in an experimental model of foreign-body infection.
机构信息
Charité - University Medicine Berlin, Center for Musculoskeletal Surgery, Berlin, Germany; Septic Surgical Unit, Department of Surgery and Anesthesiology, Lausanne University Hospital, Lausanne, Switzerland.
Septic Surgical Unit, Department of Surgery and Anesthesiology, Lausanne University Hospital, Lausanne, Switzerland.
出版信息
J Infect. 2016 Mar;72(3):386-92. doi: 10.1016/j.jinf.2015.12.008. Epub 2015 Dec 24.
OBJECTIVES
The treatment of Candida implant-associated infections remains challenging. We investigated the antifungal activity against planktonic and biofilm Candida albicans in a foreign-body infection model.
METHODS
Teflon cages were subcutaneously implanted in guinea pigs, infected with C. albicans (ATCC 90028). Animals were treated intraperitoneally 12 h after infection for 4 days once daily with saline, fluconazole (16 mg/kg), amphotericin B (2.5 mg/kg), caspofungin (2.5 mg/kg) or anidulafungin (20 mg/kg). Planktonic Candida was quantified, the clearance rate and cure rate determined.
RESULTS
In untreated animals, planktonic Candida was cleared from cage fluid in 25% (infected with 4.5 × 10(3) CFU/cage), 8% (infected with 4.8 × 10(4) CFU/cage) and 0% (infected with 6.2 × 10(5) CFU/cage). Candida biofilm persisted on all explanted cages. Compared to untreated controls, caspofungin reduced the number of planktonic C. albicans to 0.22 and 0.0 CFU/ml, respectively, and anidulafungin to 0.11 and 0.13 CFU/ml, respectively. Fluconazole cured 2/12 cages (17%), amphotericin B and anidulafungin 1/12 cages (8%) and caspofungin 3/12 cages (25%).
CONCLUSION
Echinocandins showed superior activity against planktonic C. albicans. Caspofungin showed the highest cure rate of C. albicans biofilm. However, no antifungal exceeded 25% cure rate, demonstrating the difficulty of eradicating Candida biofilms from implants.
目的
白色念珠菌定植相关性感染的治疗仍然具有挑战性。我们在异物感染模型中研究了抗浮游和生物膜白色念珠菌的抗真菌活性。
方法
将特氟龙笼皮下植入豚鼠，用白色念珠菌（ATCC 90028）感染。感染后 12 小时，动物每天经腹腔内给予生理盐水、氟康唑（16 mg/kg）、两性霉素 B（2.5 mg/kg）、卡泊芬净（2.5 mg/kg）或阿尼芬净（20 mg/kg），连续治疗 4 天。定量浮游白色念珠菌，确定清除率和治愈率。
结果
在未治疗的动物中，浮游白色念珠菌分别从笼液中清除了 25%（感染 4.5×103 CFU/笼）、8%（感染 4.8×104 CFU/笼）和 0%（感染 6.2×105 CFU/笼）。所有取出的笼子上都有白色念珠菌生物膜。与未治疗的对照组相比，卡泊芬净将浮游白色念珠菌的数量分别减少到 0.22 和 0.0 CFU/ml，阿尼芬净分别减少到 0.11 和 0.13 CFU/ml。氟康唑治愈了 12 个笼子中的 2 个（17%），两性霉素 B 和阿尼芬净治愈了 12 个笼子中的 1 个（8%），卡泊芬净治愈了 12 个笼子中的 3 个（25%）。
结论
棘白菌素类药物对浮游白色念珠菌具有更好的活性。卡泊芬净对白色念珠菌生物膜的治愈率最高。然而，没有一种抗真菌药物的治愈率超过 25%，这表明从植入物中根除白色念珠菌生物膜具有一定难度。
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