Lown Livia, Peters Brian M, Walraven Carla J, Noverr Mairi C, Lee Samuel A
Section of Infectious Diseases, New Mexico Veterans Healthcare System, Albuquerque, New Mexico, United States of America.
Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, New Mexico, United States of America.
PLoS One. 2016 Jul 18;11(7):e0159225. doi: 10.1371/journal.pone.0159225. eCollection 2016.
Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies.
白色念珠菌是导管相关血流感染的主要原因，与高发病率和死亡率相关。由于白色念珠菌易于形成耐药生物膜，目前的护理标准包括拔除导管；然而，重新插入在技术上可能具有挑战性或存在风险。已尝试通过在导管内长时间暴露抗真菌封管溶液并结合全身治疗来挽救导管。此前，我们证明了米卡芬净、乙醇和高剂量强力霉素作为单一药物在预防和治疗白色念珠菌生物膜方面具有出色的体外活性。因此，我们试图研究米卡芬净、乙醇和/或强力霉素作为封管溶液的最佳组合。我们进行了两药和三药棋盘试验，以确定两两组合或三种药物联合用于预防或治疗白色念珠菌生物膜的体外活性。对最佳封管溶液针对白色念珠菌临床分离株、参考菌株以及白色念珠菌-金黄色葡萄球菌混合生物膜的活性进行了测试。一种含有20%（v/v）乙醇、0.01565μg/mL米卡芬净和800μg/mL强力霉素的溶液在用于预防真菌生物膜形成时，代谢活性降低了98%且无真菌再生长；然而，与单独使用20%乙醇相比并无优势。该溶液在抑制成熟混合生物膜中白色念珠菌的再生长方面也取得了成功，尽管它并非完全杀菌。含有5%乙醇以及低浓度米卡芬净和强力霉素的溶液在用于预防单一白色念珠菌生物膜形成时表现出协同活性。在这些研究中，米卡芬净、乙醇和强力霉素的联合溶液在预防白色念珠菌生物膜形成方面非常有效，但与单独使用20%乙醇相比并无优势。
