Invasive pulmonary aspergillosis complicating severe influenza: epidemiology, diagnosis and treatment

Bacterial super-infection of critically ill influenza patients is well known, but in recent years, more and more reports describe invasive aspergillosis as a frequent complication as well. This review summarizes the available literature on the association of invasive pulmonary aspergillosis (IPA) with severe influenza [influenza-associated aspergillosis (IAA)], including epidemiology, diagnostic approaches and treatment options.Though IPA typically develops in immunodeficient patients, non-classically immunocompromised patients such as critically ill influenza patients are at high-risk for IPA as well. The morbidity and mortality of IPA in these patients is high, and in the majority of them, the onset occurs early after ICU admission. At present, standard of care (SOC) consists of close follow-up of these critically ill influenza patients with high diagnostic awareness for IPA. As soon as there is clinical, mycological or radiological suspicion for IAA, antifungal azole-based therapy (e.g. voriconazole) is initiated, in combination with therapeutic drug monitoring (TDM). Antifungal treatment regimens should reflect local epidemiology of azole-resistant Aspergillus species and should be adjusted to clinical evolution. TDM is necessary as azoles like voriconazole are characterized by nonlinear pharmacokinetics, especially in critically ill patients.In light of the frequency, morbidity and mortality associated with influenza-associated aspergillosis in the ICU, a high awareness of the diagnosis and prompt initiation of antifungal therapy is required. Further studies are needed to evaluate the incidence of IAA in a prospective multicentric manner, to elucidate contributing host-derived factors to the pathogenesis of this super-infection, to further delineate the population at risk, and to identify the preferred diagnostic and management strategy, and also the role of prophylaxis.