Antifungal Therapy in Neutropenic Oncohemopatic Patients. A Single Centre Retrospective Analysis.
Authors: Bonini Alessandro , Tieghi Alessia , Bulgarelli Simona , Gugliotta Luigi 
Published: October 2019

Abstract
Infections are the most frequent complication during chemotherapy-induced neutropenia and fungal infections are a cause of morbility and mortality. We have retrospectively analysed our patients who received an antifungal treatment for a possible, probable or proven fungal infection. Between April 1998 and July 2005 we analysed 750 consecutive phases of treatment for 309 patients admitted at our Institution. The treatment phases were for: acute leukemia 253, lymphoma 168, multiple myeloma 215, chronic leukemia 19, severe aplastic anemia 12, solid tumors (breast, renal, testis cancer) 44, multiple sclerosis 5, others 34. Among them 474 (63.2%) were at high risk for infections (the risk was considered high for lenght of neutropenia, diagnosis of acute leukemia, allogeneic BMT). There were 31 allo-BMT and 145 autologous BMT. The antifungal therapy was for a first short period (until mid-1999) an empirical treatment (when fever persisted more than 4 days despite antibiotic therapy during neutropenia); after, only when another sign (clinical or radiological or microbiological) of fungal infection was present, the patients received an antifungal treatment. We treated also a small cohort of patients with a secondary prophylactic regimen (they were patients who developed a fungal infection during a previous treatment). Seventy-four patients received an antifungal treatment (10% of all phases and 15.6% of high-risk phases). The infection was possible (empiric treatment) in 4 cases, probable (presumptive therapy) in 37 cases, proven in 16 cases; 17 cases of secondary prophylaxis. The first administered drug was Amphotericin B deoxycholate (AMB) in 31/74 cases (41.9%), Abelcet (ABCT) in 6/74 (8%), Liposomal Amphotericin B (LAMB) in 18/74 cases (24.4%), Voriconazole (VCZ) in 3/74 cases (4%) and Caspofungin (Caspo) in 16/74 cases (21.7%). The schedule of treatment was: AMB 0.7–1 mg/Kg in 6 hours, ABCT 5 mg/Kg in 3 hours, LAMB 3 mg/Kg in 1 hour, VCZ 6 mg/Kg bid iv in 2 hours for 3 days then 4 mg/Kg bid orally, Caspo 70 mg iv on the first day and then 50 mg in 1 hour. For the empiric treatment the first drug was AMB 3 and Caspo 1; for presumptive therapy AMB 18, ABCT 4, LAMB 4, VCZ 1 and Caspo 10. For proven infections AMB 8, ABCT 1, LAMB 5, VCZ 1, Caspo 1; for secondary prophylaxis AMB 2, ABCT 1, LAMB 9, VCZ 1 and Caspo 4. The isolated fungi were Candida albicans 4, Aspergillus spp 4, Scedosporium 2, Fusarium solani 1, others (only histological isolation) 5. The days of treatment were 7.64 for AMB, 6.88 for ABCT, 14.22 for l-AMB, 14.1 for Caspo and 30 for VCZ. Adverse events with AMB and ABCT were similar: mild to moderate renal insufficiency (50%), fever (50%), ipokalemia (75%), chills (30%); with VCZ visual disturbances (80%) and mild hepatic insufficiency (20%); with LAMB mild renal insufficiency (10%) and low back pain (5%); no adverse events with Caspo were noted. AMB was discontinued 9/31 times (29%), ABCT 1/6 (17%) for adverse events. Our conclusions are that AMB and ABCT are problematic drugs for their poor tolerability, they need an important premedication, a hyperhydration regimen and a long-time administration; moreover for a great cohort of patients we have had to discontinue the drug. The other drugs seems to be better tolerated; no organ failures were seen and the treatment duration was longer for Caspo and LAMB. Even if the cost of these two drugs is major than others the lack of adverse events and the new mechanism of action of Caspo make these drugs probably better than ABCT, AMB and VCZ.