para>Amphotericin B (including lipid formulations) may cause significant renal insufficiency and electrolyte abnormalities. A. terreus, the second most common cause of IA, is resistant to amphotericin B.
Itraconazole: Normal-to-low gastric pH is necessary for absorption; may alter serum levels of hepatically metabolized drugs; potentiates the adrenal suppressing effects of corticosteroids
Voriconazole: can cause transient visual disturbances during dosing and may alter serum levels of hepatically metabolized drugs. Other adverse effects: nausea, vomiting, diarrhea, fever, rash, headaches, fatigue, and decreased libido. Increased risk of cutaneous squamous cell carcinoma with cumulative long-term use; surveillance is indicated.
Second Line
- Itraconazole (200 mg PO TID for 3 days, followed by 200 mg BID) is useful as an alternative agent but is rarely used in immunosuppressed patients.
- Caspofungin (70 mg IV loading dose on day 1, followed by 50 mg IV once daily) is approved for patients with aspergillosis unresponsive to other therapy or with unacceptable toxicity to other agents.
- Alternative regimens: posaconazole 200 mg PO QID or micafungin 100 to 150 mg IV daily (8)[A].
ISSUES FOR REFERRAL
Patients with IA should be managed by specialists with expertise in treating invasive fungal infections (IFI).
SURGERY/OTHER PROCEDURES
- Bronchial artery embolization may temporarily control bleeding in cases of hemorrhage due to aspergilloma.
- Although surgical resection of aspergilloma offers definitive cure, it is a technically difficult procedure. Ideal candidates are those with a single aspergilloma. Lobectomy is most frequently performed.
- Patients with invasive disease may benefit from resection of Aspergillus-infected tissue, particularly if lesions involve the great vessels, pericardium, or if lesions are eroding into the pleural space or ribs.
- Extensive/necrotic skin lesions require excision (1)[A].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Significant respiratory distress or ongoing oxygen requirement, regardless of disease type.
- Hemoptysis due to aspergilloma, due to the risk of massive pulmonary hemorrhage
- High clinical suspicion of invasive disease in immunocompromised patients
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- ABPA: Serum IgE levels (goal: to decrease levels by 25-50%), CXR, pulmonary function test, every 6 to 8 weeks to objectively assess for remission or recurrence of AH or ABPA. Patients with mucoid impaction should have repeated imaging in 3 weeks.
- Aspergilloma: Monitor recurrence by CXR.
- IA: Optimal duration of therapy has not been defined; continue until radiologic (>25% reduction compared with baseline), clinical (resolution of symptoms), and mycologic (clearance of cultures) response.
PROGNOSIS
- ABPA has good overall prognosis if properly treated.
- Allogeneic stem cell transplant recipients and patients with extrapulmonary aspergillosis have the poorest response to antifungal therapy.
- Guarded prognosis for invasive disease; mortality >90% depending on comorbidities and affected organs
COMPLICATIONS
- ABPA may lead to bronchiectasis, pulmonary fibrosis, and obstructive lung disease.
- Massive hemoptysis occurs in up to 83% of patients with aspergilloma and may be life-threatening.
- Untreated/undertreated pulmonary invasive disease may disseminate (CNS, GI tract, skin).
REFERENCES
11 Bernardeschi C, Foulet F, Ingen-Housz-Oro S, et al. Cutaneous invasive aspergillosis: retrospective multicenter study of the French Invasive-Aspergillosis Registry and Literature Review. Medicine (Baltimore). 2015;94(26):e1018.22 Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873.33 Shin B, Koh WJ, Jeong BH, et al. Serum galactomannan antigen test for the diagnosis of chronic pulmonary aspergillosis. J Infect. 2014;68(5):494-499.44 Leeflang MM, Debets-Ossenkopp YJ, Visser CE, et al. Galactomannan detection for invasive aspergillosis in immunocompromized patients. Cochrane Database Syst Rev. 2008;(4):CD007394.55 Fisher CE, Stevens AM, Leisenring W, et al. Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis. Transpl Infect Dis. 2014;16(3):505-510.66 Prattes J, Flick H, P ¼ller F, et al. Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases. Am J Respir Crit Care Med 2014;190(8):922-999.77 Hoenigl M, Prattes J, Spiess B, et al. Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device, conventional culture, and PCR tests with bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. J Clin Microbiol. 2014;52(6):2039-2045.88 Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327-360.99 Siopi M, Mavridou E, Mouton JW, et al. Susceptibility breakpoints and target values for therapeutic drug monitoring of voriconazole and Aspergillus fumigatus in an in vitro pharmacokinetic/pharmacodynamic model. J Antimicrob Chemother. 2014;69(6):1611-1619.
ADDITIONAL READING
- Playford EG, Webster AC, Sorrell TC, et al. Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients. Cochrane Database Syst Rev. 2006;(1):CD004920.
CODES
ICD10
- B44.9 Aspergillosis, unspecified
- B44.1 Other pulmonary aspergillosis
- B44.81 Allergic bronchopulmonary aspergillosis
- B44.89 Other forms of aspergillosis
- B44.0 Invasive pulmonary aspergillosis
- B44.2 Tonsillar aspergillosis
- B44.7 Disseminated aspergillosis
ICD9
- 117.3 Aspergillosis
- 484.6 Pneumonia in aspergillosis
- 518.6 Allergic bronchopulmonary aspergillosis
SNOMED
- Aspergillosis (disorder)
- Pulmonary aspergillosis (disorder)
- Allergic bronchopulmonary aspergillosis (disorder)
- chronic necrotizing pulmonary aspergillosis (disorder)
- Invasive pulmonary aspergillosis (disorder)
CLINICAL PEARLS
- Although Aspergillus spp. are ubiquitous, most immunocompetent people do not acquire disease.
- Diagnosis of aspergillosis can be challenging and is based on history, physical exam, and a combination of laboratory, histopathologic and radiographic findings.
- If clinical suspicion for invasive aspergillosis is high, consult an experienced infectious disease specialist and institute empiric antifungal therapy, using voriconazole as the accepted first-line drug.