Gerber, B., Koppel, J., Paul, M., Nguyen-Kim, T.D., Frauenfelder, T., Nair, G., . . . Manz, M.G. (2014). Efficacy of anti-fungal but not anti-bacterial prophylaxis in intensive primary AML therapy: a real-world, retrospective comparative single-centre study. Swiss Medical Weekly, 144, w13985. 

To assess the effect of primary prophylaxis with posaconazole and levofloxacin on the incidence of invasive fungal infections (IFI) and bacteremia

This was a retrospective, single-center study that evaluated two groups of adult patients with acute myeloid leukemia/acute promyelocytic leukemia (AML/APL) and high-grade myelodysplastic syndrome (MDS) receiving intensive chemotherapy. The primary endpoint was IFI and bacteremia with secondary endpoints of overall survival at day 100 and at two years, time from the initiation of chemotherapy to the onset of IFI, the use of intravenous and oral antifungal and antibacterial therapy, and total duration of antifungal and antibacterial medication.

• N = 88 (43 no prophylaxis and 45 prophylaxis)
• AVERAGE AGE = 49.8 years (no prophylaxis); 53.5 years (prophylaxis)
• MALES: 51.2% (no prophylaxis); 51.1% (prophylaxis)
• KEY DISEASE CHARACTERISTICS: Patients with AML, APL, or high-grade MDS receiving intensive chemotherapy

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: University Hospital Zurich

• PHASE OF CARE: Active antitumor treatment

Retrospective 

• Radiologic diagnosis of IFI determined by two independent evaluators
• Possible or proven IFI defined according to European Organisation for Research and Treatment of Cancer and ​Mycoses Study Group (EORTC/MSG) criteria

IFIs were significantly less common in the prophylaxis group after the first chemotherapy cycle (33.3% versus 65.8%; p = 0.0088). IFIs were significantly less common in the prophylaxis group after the last chemotherapy cycle (53.9% versus 88.9%; p = 0.0021). Chemotherapy cycles that were complicated with bacteremia occurred at a rate of 34.6% with prophylaxis and 32.3% in the nonprophylaxis group; p = 0.8. Positive blood cultures were 50 and 43, respectively, with a nonsignificant trend to more gram-negative infections in the nonprophylaxis group (42% versus 14%; p = 0.073) and to more gram-positive infection in the prophylaxis group (86% versus 58%; p = 0.092). Overall survival at 100 days and at two years, as well as the use of antiviral medications, did not differ between the two arms. Fewer fever days (5.6 versus 9.2;  p = 0.00032) and less cytarabine toxicity (18.3% versus 35%; p = 0.025) were observed in the prophylaxis arm.

This single-center retrospective study of posaconazole prophylaxis was efficient in reducing the possible IFIs with a number needed to treat to prevent one IFI of only three. This institution had a relatively high rate of IFIs when compared to published data. Posaconazole for prophylaxis was cost-effective. There was no benefit seen in the use of levofloxacin in preventing bacteremia.

• Small sample (< 100)
• Measurement/methods not well described
• Findings not generalizable
• Other limitations/explanation: The rate of IFIs in this institution was higher compared to other published data, and the inclusion of possible IFIs may have led to an overdiagnosis of IFIs, which might not reflect the true outcomes of IFI.

Oncology nurses should be aware of facility policies relating to the use of prophylaxis for IFI and bacteremia and should understand the local climate that may affect the rate of IFIs. This facility used posaconazole and levofloxacin as prophylaxis agents. Other agents exist and are currently in use that may produce different outcomes.