Background. The sensitivity of blood cultures for diagnosing invasive candidiasis (IC) is poor. Methods. We performed a validated Candida real-time polymerase chain reaction (PCR) and the Fungitell 1,3-b-D-glucan (BDG) assay on blood samples collected from prospectively identified patients with IC (n 5 55) and hospitalized controls (n 5 73). Patients with IC had candidemia (n 5 17), deep-seated candidiasis (n 5 33), or both (n 5 5). Controls had mucosal candidiasis (n 5 5), Candida colonization (n 5 48), or no known Candida colonization (n 5 20). Results. PCR using plasma or sera was more sensitive than whole blood for diagnosing IC (P 5 .008). Plasma or sera PCR was more sensitive than BDG in diagnosing IC (80% vs 56%; P 5 .03), with comparable specificity (70% vs 73%; P 5 .31). The tests were similar in diagnosing candidemia (59% vs 68%; P 5 .77), but PCR was more sensitive for deep-seated candidiasis (89% vs 53%; P 5 .004). PCR and BDG were more sensitive than blood cultures among patients with deep-seated candidiasis (88% and 62% vs 17%; P 5 .0005 and .003, respectively). PCR and culture identified the same Candida species in 82% of patients. The sensitivity of blood cultures combined with PCR or BDG among patients with IC was 98% and 79%, respectively. Conclusions. Candida PCR and, to a lesser extent, BDG testing significantly enhanced the ability of blood cultures to diagnose IC.

Patients with therapeutic voriconazole serum concentrations were twice as likely to achieve successful outcomes. The likelihood of toxicity associated with supratherapeutic voriconazole serum concentrations was 4-fold that of therapeutic concentrations. Our findings suggest that the use of voriconazole TDM to aim for serum concentrations between 1.0 and 6.0 mg/L during therapy may be warranted to optimize clinical success and minimize toxicity.

ABSTRACTVoriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n= 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n= 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (P= 0.005). Patients that were ≥60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (P= 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤1.5 μg/ml (P= 0.01) and among patients with no trough of >1.5 μg/ml (P= 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P= 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.

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