Vaccine and Infectious Disease Division

The value of monitoring drug levels in persons with aspergillosis

Invasive fungal infections (IFIs) can be caused by environmental fungi, such as Aspergillus fumigatus, that do not usually cause disease. However, when a host’s immune system is compromised as a result of “injuries” like hematopoietic transplant, AIDS or cancer these organisms can proliferate and cause serious and sometimes fatal disease. Voriconazole, a member of the azole class of antifungal compounds, is the preferred treatment for many IFIs such as aspergillosis. Assuring drug levels remain within the therapeutic range in a patient is a harder task for some drugs than others. Voriconazole levels, or “bioavailability,” can fluctuate during the course of therapy, thereby affecting the intended benefits and adverse effects of treatment. Therapeutic drug monitoring (TDM), which is sampling drug levels within a patient over time, allows clinicians to determine if there is a correlation between drug levels and clinical outcome. TDM may be useful for recognizing adverse events resulting from drug toxicity; a noted problem of voriconazole.

VIDD member Dr. David Fredricks together with colleagues from the University of Washington performed a retrospective cohort study of 108 individuals who were treated with voriconazole and underwent TDM between the years 2007 and 2009 at UWMC, SCCA and Harborview Medical Center. These patients, the majority of whom had hematologic malignancies, were put on voriconazole therapy for suspected or confirmed aspergillosis. The researchers performed an electronic chart review to obtain voriconazole dosage, drug monitoring information, subsequent drug levels and clinical outcome for each patient. The median time of voriconazole treatment was 35 days. The authors found no significant difference in response to therapy between patients with therapeutic drug levels (1-5 mg/L) and those with subtherapeutic (< 1 mg/L) voriconazole in their blood, which contrasts with previously published studies. Additionally, no statistically significant correlation was found between high levels of voriconazole (> 5.5 mg/L) and adverse events such as liver toxicity or confusion (encephalopathy), though there was a trend towards greater toxicity in those with higher levels. The authors concluded that voriconazole levels in this cohort did not affect clinical outcome of aspergillosis or voriconazole-related adverse events. Therefore, this study calls into question the use of routine TDM in our patients at Fred Hutch and SCCA.

Chu HY, Jain R, Xie H, Pottinger P, Fredricks DN. Voriconazole therapeutic drug monitoring: retrospective cohort study of the relationship to clinical outcomes and adverse events. BMC Infect Dis. 2013 Feb 26;13(1):105. [Epub ahead of print]