Prophylactic, empirical, pre-emptive and targeted antibacterial therapy all play a role in invasive aspergillosis
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Prophylactic, empirical, pre-emptive and targeted antibacterial therapy all play a role in invasive aspergillosis Invasive aspergillosis is an acute and lethal fungal infection affecting immunocompromised patients, usually adults. Clinicians must decide when and how to intervene when treating patients at risk for invasive aspergillosis (i.e. prophylactic, empirical, pre-emptive or targeted treatment). Voriconazole is recommended as first-line targeted therapy, with poor tolerability making amphotericin B a second-line option. Posaconazole appears promising when prophylaxis is warranted and echinocandins are effective for salvage therapy.
Acute fungal infection … Invasive aspergillosis is an acute fungal infection (notably pulmonary disease with or without dissemination) that usually occurs in immunocompromised patients.[1,2] Aspergillus spp. are ubiquitous, and infection occurs through the inhalation of airborne conidia, which are lightweight, easily dispersed 3–5 μm particles.[3] The respiratory route of infection means invasive aspergillosis most commonly affects the lungs and sinuses.[3] Aspergillosis spp. may also cause chronic disease (e.g. chronic necrotizing aspergillosis, pulmonary/sinus aspergilloma and allergic bronchopulmonary aspergillosis).[1] Table I summarizes the characteristics of several pathogenic Aspergillus spp.[1] Table I. Characteristics of various pathogenic Aspergillus spp.[1] Species (frequency in clinical infection)
Clinical significance
A. fumigatus (65%)
Most common cause of invasive pulmonary aspergillosis Resistance to triazoles reported
A. flavus (14%)
Frequent cause of sinusitis and skin infections Resistance to triazoles reported
A. niger (5%)
Role in invasive infections less well established Less pathogenic probably because larger conidia do not reach the alveoli
A. terreus (5%)
Usually susceptible to triazoles Increasing reports of resistance to amphotericin B Blood cultures may be positive
A. ustus (1%)
Intrinsically higher minimum inhibitory concentration values (resistance) to triazoles and polyenes
Drugs Ther Perspect 2009; Vol. 25, No. 1
… that infects the immunocompromised … Subject to diagnostic uncertainty, invasive aspergillosis affects 5–24% of immunosuppressed patients, particularly those with acute leukaemia, those undergoing allogeneic haematopoietic stem cell transplant (HSCT) or those who have received solid organ transplant.[3] The incidence of invasive aspergillosis has increased with advances in bone marrow and solid organ transplantation,[3] but is also high in a heterogeneous group of patients whose state of immunosuppression is not related to a haematological malignancy or solid organ transplant (e.g. patients with AIDS or severe burns, in intensive care units, or receiving certain drugs [e.g. purine analogues or alemtuzumab]).[2,3] However, the risk of invasive aspergillosis is low in children, and in patients undergoing autologous HSCT or receiving high-dose chemotherapy.[3,4] Fatality rates after treatment are 30–40% in patients with acute le
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