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b; South Texas Veterans Health Care System, San Antonio, Texas, USA c Interest in antifungal therapeutic-drug monitoring has increased due to studies demonstrating associations between concentrations and outcomes. We reviewed the antifungal drug concentration database at our institution to gain a better understanding of achievable triazole drug levels. Antifungal concentrations were measured by high-performance liquid chromatography (HPLC), ultraperformance liquid chromatography and single-quadrupole mass spectrometry (UPLC/MS), or a bioassay. For this study, only confirmed human bloodstream (serum or plasma) and cerebral spinal fluid (CSF) concentrations of voriconazole, posaconazole, and itraconazole were analyzed. The largest numbers of bloodstream and CSF samples were found for voriconazole (14,370 and 173, respectively). Voriconazole bloodstream concentrations within the range of 1 to 5.5 g/ml represented 50.6% of samples. Levels below the lower limit of quantification (0.2 g/ml) were observed in 14.6% of samples, and 10.4% of samples had levels of >5.5 g/ml. CSF voriconazole levels ranged from undetectable to 15.3 g/ml and were <0.2 g/ml in 11% of samples. Posaconazole bloodstream concentrations were >0.7 and >1.25 g/ml in 41.6% and 18.9% of samples, respectively. Posaconazole was detected in only 4 of 22 CSF samples (undetectable to 0.56 g/ml). Itraconazole levels, as measured by UPLC/MS, were >0.5 g/ml in 43.3% and were undetectable in 33.9% of bloodstream samples. In contrast, when measured by a bioassay, itraconazole/hydroxyitraconazole bloodstream concentrations were >1.0 g/ml in 72.9% of samples and were undetectable in 18% of samples. These results indicate that there is marked variability in bloodstream concentrations achieved with these three azoles. In addition, many levels within the bloodstream for each azole and for voriconazole and posaconazole in the CSF were undetectable or below thresholds associated with efficacy. O ver the last 5 years, there has been increased interest in therapeutic-drug monitoring of systemic antifungals. Much of this interest stems from clinical evidence that suggests that this practice may improve outcomes for patients treated with voriconazole and posaconazole. For both agents, studies have reported a relationship between clinical response and certain threshold concentrations (1-6). In addition, marked interpatient variability has been observed with both of these antifungals (1, 7-11). For voriconazole, a clear relationship also exists between elevated concentrations and certain toxicities (1, 12, 13). Monitoring of voriconazole concentrations has also been suggested as part of patient management in the fungal meningitis outbreak associated with contaminated steroids due to the high doses of this agent that are recommended (14, 15). Although this practice has garnered recent attention, therapeutic-drug monitoring is not new, as previous studies have suggested relationships between itraconazole and flucytosine concentrations and clinical outcomes (16)(17)(18)(19).On...

We report the attainment of micafungin concentrations from brain tissue and pancreatic pseudocyst fluid from two patients with invasive candidiasis. Micafungin was present in low levels at both body sites, indicating limited penetration into central nervous system (CNS) tissue and pancreatic fluid. Further studies are needed to fully characterize its pharmacokinetics at these locations, as micafungin may potentially serve as an alternative antifungal therapy for CNS or pancreatic candidal infections for which the currently recommended first-line therapy fails.Micafungin is an echinocandin widely used for the treatment of invasive candidiasis (2,6,7,8,10). Little information exists regarding its penetration into human brain tissue and pancreatic fluid. We report the measurement of micafungin levels from these sites in 2 patients during treatment of invasive candidiasis.Patient 1. A 79-year-old male with a history of dysphagia secondary to cricopharyngeal achalasia was transferred from an outside hospital with an esophageal rupture, pneumomediastinum, and left pneumothorax. He was initiated on antimicrobial therapy with ciprofloxacin, fluconazole, piperacillintazobactam, and vancomycin, and bilateral pleural catheters were placed. Cultures from the pleural catheters on hospital day (HD) 9 grew fluconazole-resistant Candida glabrata (MIC ϭ 64 g/ml). Echinocandin susceptibility was not determined. Fluconazole was discontinued, and micafungin (100 mg daily; 1.69 mg/kg of body weight) was initiated. Computed tomographic (CT) imaging was consistent with an esophagealpleural fistula and mediastinitis. The patient underwent a left thoracotomy and decortication on HD 13, and pleural tissue cultures also grew fluconazole-resistant Candida glabrata. He subsequently developed left hemiparesis, and CT imaging of the head revealed a frontal lobe lesion concerning for an abscess on HD 29. Brain tissue specimens were obtained on HDs 31 and 53 via craniotomy and tissue biopsy. Bacterial, mycobacterial, and fungal cultures were negative, and pathology was inconsistent with malignancy. Micafungin plasma and brain tissue levels were obtained simultaneously during the second neurosurgical procedure, 23 h after the previous dose. Micafungin concentrations were assayed (lower limit of quantification, 0.05 g/ml; Beckman Coulter, Fullerton, CA) using highperformance liquid chromatography (11). The plasma level was 1.58 g/ml, and the corresponding brain tissue level was 0.28 g/ml (0.26 g/g). The patient was stabilized and eventually discharged to a long-term care facility on HD 81.Patient 2. A 31-year-old male with a history of biliary pancreatitis and pancreatic pseudocysts was readmitted for further management of an enlarging pancreatic pseudocyst. Upon admission, his renal function and nutritional status were within normal limits, but liver function tests demonstrated an elevated aspartate aminotransferase level, total bilirubin, and alkaline phosphatase. A culture of pancreatic pseudocyst fluid from the pseudocyst catheter on HD 1 rev...

Thiobarbituric acid reacting (TBAR) substances were measured in washed platelets before and after ingesting 120 mg of standardized Gingko biloba extract daily for 3 months, in both normocholesterolemic (total cholesterol, 160 +/- 27 mg/dl; age 40 +/- 13 years; n = 18) and hypercholesterolemic subjects (total cholesterol, 229 +/- 35; age, 45 +/- 8 years, n = 12). Gingko biloba extract significantly reduced cellular content of TBAR substances; 42 +/- 21 vs. 28 +/- 16 pmol/10(7 platelets (p < 0.0025) and 50 +/- 17 vs. 29 +/- 13 pmol/10(7) platelets (P < 0.004), for the normo- and hypercholemic subjects, respectively. In conclusion, Gingko biloba extract is a potent antioxidant for both groups, reducing TBAR substances possibly by inhibiting platelet COX-1 isoform activity.