Keighley, C.L., Manii, P., Larsen, S.R., & van Hal, S. (2017). Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era. European Journal of Clinical Microbiology and Infectious Diseases, 36, 213–217.

To examine the rate of probable and proven breakthrough invasive fungal infections (bIFI) with the use of itraconazole prophylaxis as well as the effectiveness and tolerability of itraconazole in patients with acute myeloid leukemia (AML)

All patients admitted to the Royal Prince Albert Hospital who had AML and were undergoing chemotherapy and who were receiving itraconazole for antifungal prophylaxis were given itraconazole 200 mg oral solution twice daily starting 1-2 days prior to the chemotherapy and continuing until the neutrophil count was greater than 500.

• N = 175 episodes total; 148 episodes of febrile neutropenia   
• AGE: Median age was 59 years (range = 44-65)
• MALES: 67.4%  
• FEMALES: 32.6%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All have AML (primary 62.3%; secondary 9.7%; relapsed 17.1%; refractory 10.9%)
• OTHER KEY SAMPLE CHARACTERISTICS: Neutropenia for more than 7 days in 80.6%; for more than 14 days in 54.3%; median duration of neutropenia was 15 days; mucositis was present in 53.1%; total parenteral nutrition required in 7.4%; febrile neutropenia was present in 84.6%; bacterial infections were present in 60%; mycobacterial infections were present in 0.6%; viral infections were present in 4%; median length of stay was 27 days (range = 22-34).

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Royal Prince Albert Hospital; Sydney Australia

PHASE OF CARE: Active anti-tumor treatment

Retrospective study

Onset of invasive fungal infection; this was determined three different ways:

1. Starting empiric antifungal therapy
2. High resolution CT that was thought to show invasive fungal infection (IFI)
3. Positive microbiology on biopsy by bronchoalveolar lavage.

bIFI were classified as possible, probable, or proven; a bIFI was one that was diagnosed at least five days after starting antifungal prophylaxis.

Itraconazole was shown to be tolerable with few side effects. CT scans were performed in 55 patients and a bronchoalveolar lavage (BAL) was performed in 20 episodes that were shown to be abnormal on CT scan. Four of those undergoing BAL had positive results constituting probable bIFI. Empiric antifungal therapy was started in 33 patients; there was no evidence of bIFI in 16 of those patients. These possible IFI infections were treated for a median of 19 days with no progression to definitive IFI. Overall bIFI rate was 3.4%. Patients with bIFI have significantly longer length of stays and higher 30-day mortality (11%).

The use of itraconazole is reasonable with low side effects and low rates of bIFI noted in this group. Account of local epidemiology must be considered when choosing an antifungal agent overall.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Other limitations/explanation: Only patients with AML receiving chemotherapy

Cost of the intervention in some areas may be problematic. Nurses should work with their pharmacy colleagues to identify the most common fungal epidemiology before the choice of antifungal therapy is chosen. Education with patients is needed about the importance of taking the medications for prophylaxis to prevent bIFI.