Assessment of the anti-biofilm effect of micafungin in an animal model of catheter-related candidemia.

In cases where catheter-related candidemia (CRC) must be managed without catheter withdrawal, antifungal lock therapy using highly active anti-biofilm (HAAB) agents is combined with systemic treatment. However, the activity of HAAB agents has never been studied in in vivo models using bioluminescence. We assessed the efficacy of micafungin using a bioluminescent Candida albicans SKCA23-ACTgLuc strain in an animal model of CRC. We divided 33 female Wistar rats into five groups: sham (A), infected nontreated (B), treated with lock therapy (0.16 mg/ml) (C), systemically treated only (1 mg/kg) (D), and systemically treated+lock (E). Catheters were colonized 24 h before insertion into the femoral vein (day 0). Treatment started on day 1 and lasted 7 days, followed by 7 days of surveillance. Bioluminescence assays were carried out on days 1, 3, 5, and 14, together with daily monitoring of clinical variables. Postmortem microbiological cultures from the catheter and several tissue samples were also obtained. Overall, 28 rats (84.8%) completed the study. Group B animals showed significant weight loss at days 2, 4, and 5 compared with groups C and D (P < .05). In group B, no animals survived after day 7, 75% had CRC, and bioluminescence remained constant 5 days after catheter implantation. Positive catheter culture rates in groups C, D, and E were, respectively, 83.3%, 62.5%, and 25.0% (P = .15). Micafungin proved to be a HAAB agent when administered both systemically and in lock therapy in an animal model of CRC, although the bioluminescence signal persists after treatment. This persistence should be further analyzed.

Training should be the first step toward an antifungal stewardship program.

The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved.