Elizabeth Dodds Ashley

Study Objective: To determine the true institutional cost of treating invasive fungal infections in light of recent advances in diagnostic techniques and antifungal therapies for both treatment and prophylaxis of these infections.Design: Economic analysis.Setting: Academic medical center.Patients: A total of 200 patients discharged from the hospital during 2004–2005 with a diagnosis of proven, probable, or possible aspergillosis, cryptococcosis, invasive candidiasis, or zygomycosis (cases). Patients were matched in a 1:1 fashion with patients having similar underlying disease states but no invasive fungal infections (controls).Measurements and Main Results: Data on demographic and clinical characteristics were collected from patients' medical records. In addition, information concerning each patient's hospitalization was recorded. Resource utilization data for a patient's entire hospitalization were collected from the hospital's charge databases and converted to costs. These data were compared between the cases and the controls. After adjusting for race‐ethnicity, sex, age, and comorbid illnesses, mean total hospital cost for cases was $32,196 more than for controls (p<0.0001). Nonpharmacy costs accounted for the majority (63%) of this difference, and an additional $3996 was attributed to systemic antifungal drugs. The mean length of hospital stay was longer for cases than controls (25.8 vs 18.4 days).Conclusion: Treatment of patients with invasive fungal infections was associated with a significantly higher inpatient hospital cost compared with controls. However, due to new diagnostic techniques and effective antifungal therapy, the relative cost of these infections appears to be at least stable compared with the previous decade. These findings can help assess the utility of cost‐avoidance strategies such as antifungal prophylaxis and application of appropriate treatment.

By controlling and changing how antimicrobial agents are selected and administered, antimicrobial stewardship programs (ASPs) aim to prevent or slow the emergence of antimicrobial resistance; optimize the selection, dosing, and duration of antimicrobial therapy; reduce the incidence of drug-related adverse events; and lower rates of morbidity and mortality, length of hospitalization, and costs. There is an abundant and growing body of evidence demonstrating that ASPs change the quantity and quality of antimicrobial prescriptions; however, measuring whether, when, and how ASPs improve patient outcomes and change patterns of antimicrobial resistance—which is the ultimate goals of ASPs—has been difficult, but the totality of evidence indicates that ASPs are capable of achieving these goals. In this article, we review the existing data on ASPs and their effects on patient care and antimicrobial resistance, as well as strategies for establishing ASPs in different types of hospitals.

Purpose of review Invasive fungal infections are a significant cause of morbidity, mortality, and rising healthcare costs. An increasing number of antifungal agents are available to manage these infections, and many of these have a high acquisition price. However, the more important consideration when choosing among therapeutic agents is the overall cost of treating these infections. Recent findings Both traditional and newer antifungal agents are available for the prevention and treatment of invasive fungal infections. Various pharmacoeconomic strategies have been used to evaluate the cost of invasive fungal infections and the relative economic benefits of the different antifungal therapies. The high cost of treating these infections is primarily driven by length of hospital stay and nature of the underlying disease. Inadequate or delayed therapy is associated with worse clinical outcomes and longer lengths of stay, both of which drive up costs of care. A growing number of pharmacoeconomic studies explore the comparative costs of antifungal therapies for invasive infections focusing on differences in treatment choice. An important consideration is that drug costs may be a relatively small percentage of the total treatment-related healthcare costs, and more expensive agents may be more cost-effective than agents with lower acquisition prices that may be less effective or more toxic. Summary Cost is an increasingly important consideration in antifungal drug selection. Emerging data point to drivers of treatment-related costs and the relative economic benefits of some regimens. Determining the best strategy for one's own institution includes a careful analysis of local epidemiology and drug use trends in addition to information from the published literature in order to make the most appropriate evidence-based decision.

Azole antifungal agents are frequently used in hematopoietic stem cell and solid organ transplant recipients for prevention or treatment of invasive fungal infections. However, because of metabolism by or substrate activity for various isoenzymes of the cytochrome P450 system and/or P‐glycoprotein, azole antifungals have the potential to interact with many of the drugs commonly used in these patient populations. Thus, to identify drug interactions that may result between azole antifungals and other drugs, we conducted a literature search of the MEDLINE database (1966‐December 2009) for English‐language articles on drug interaction studies involving the azole antifungal agents fluconazole, itraconazole, voriconazole, and posaconazole. Another literature search between each of the azoles and the immunosuppressants cyclosporine, tacrolimus, and sirolimus, as well as the corticosteroids methylprednisolone, dexamethasone, prednisolone, and prednisone, was also conducted. Concomitant administration of azoles and immunosuppressive agents may cause clinically significant drug interactions resulting in extreme immunosuppression or toxicity. The magnitude and duration of an interaction between azoles and immunosuppressants are not class effects of the azoles, but differ between drug combinations and are subject to interpatient variability. Drug interactions in the transplant recipient receiving azole therapy may also occur with antibiotics, chemotherapeutic agents, and acid‐suppressive therapies, among other drugs. Initiation of an azole antifungal in transplant recipients nearly ensures a drug‐drug interaction, but often these drugs are required. Management of these interactions first involves knowledge of the potential drug interaction, appropriate dosage adjustments when necessary, and therapeutic or clinical monitoring at an appropriate point in therapy to assess the drug‐drug interaction (e.g., immunosuppressive drug concentrations, signs and symptoms of toxicity). These aspects of drug interaction management are essential not only at the initiation of azole antifungal therapy, but also when these agents are removed from the regimen.