Treatment of breakthrough fungal infections: Is there one best drug strategy?

Abstract

Widespread use of antifungal drugs in prophylactic and therapeutic settings is associated with breakthrough infections primarily due to Aspergillus and non-Aspergillus molds and non-albicans Candida. Reasons for breakthrough include worsening of initial infection, superinfection, and co-infection; subtherapeutic drug levels, emergence of antifungal resistance, and host factors may contribute to progression of the initial infection. Establishing an etiologic diagnosis is crucial because clinical and radiological features are nonspecific, and empirically chosen drug(s) may not provide appropriate antimicrobial coverage. Evidence-based data do not exist for the management of breakthrough infection. Current treatment strategies include switching therapy to a drug of another class, dose optimization, and combinations of drugs. Dosage adjustment of triazoles guided by serum concentrations may ensure optimal efficacy and avoidance of toxicity. A combination of an echinocandin plus a triazole or polyene appears to be synergistically effective against invasive aspergillosis. The treatment strategy needs to be individualized. For an optimal outcome, reversal of immunosuppression is essential.