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Treatment
Breakthrough Infection
Î The IDSA suggests an individualized approach that takes into
consideration the rapidity and severity of infection and local
epidemiology (W-M).
• As principles, the IDSA recommends an aggressive and prompt attempt to
establish a specific diagnosis with bronchoscopy and/or CT-guided biopsy for
peripheral lung lesions.
• Documentation of serum azole levels should be verified if TDM is available for
patients receiving mold-active triazoles.
• Antifungal therapy should be empirically changed to an alternative class of
antifungal with Aspergillus activity.
• Other considerations include reduction of underlying immunosuppression, if
feasible, and susceptibility testing of any Aspergillus isolates recovered from the
patient.
Empirical and Pre-emptive Strategies
Î Empirical antifungal therapy is recommended for high-risk patients
with prolonged neutropenia who remain persistently febrile despite
broad-spectrum antibiotic therapy (S-H).
• Antifungal options include a lipid formulation of AmB (S-H), an echinocandin
(caspofungin or micafungin) (S-H), or voriconazole (S-M).
Î Empirical antifungal therapy is NOT recommended for patients who
are anticipated to have short durations of neutropenia (duration of
neutropenia <10 days), unless other findings indicate a suspected
invasive fungal infection (S-M).
Î The use of serum or BAL fungal biomarkers such as GM or (1→3)-β-D-
glucan to guide antifungal therapy in asymptomatic or febrile high
risk patients (often referred to as pre-emptive or biomarker-driven
antifungal therapy) can reduce unnecessary antifungal therapy (S-M).
• The pre-emptive approach can result in more documented cases of IA without
compromise in survival and can be used as an alternative to empirical antifungal
therapy.
Î Early initiation of antifungal therapy in patients with strongly
suspected IPA is warranted while a diagnostic evaluation is
conducted (S-M).
Î Management of suspected or documented breakthrough IPA in the
context of mold-active azole prophylaxis or empirical suppressive
therapy is not defined by clinical trial data, but a switch to another
drug class is suggested (W-L).
