Safety and efficacy of low-dose liposomal amphotericin B as empirical antifungal therapy for patients with prolonged neutropenia.
BACKGROUND
Liposomal amphotericin B (L-AmB) is recommended as an empirical antifungal treatment for patients at increased risk of fungal infections although renal toxicity remains a clinical problem. We therefore conducted a pilot study to evaluate the safety and efficacy of low-dose L-AmB as an empirical antifungal therapy for patients with prolonged neutropenia.


METHODS
High-risk patients with hematological malignancies were eligible to enroll in this study provided they had: exhibited neutropenia for at least 1 week; suffered from high-grade fever for 4 days despite treatment with a broad-spectrum antibacterial; and no identified fever-causing pathogen. Low-dose L-AmB (1 mg/kg) was administrated as empirical antifungal therapy.


RESULTS
Sixteen patients were registered and, of these, data from the13 patients who did not receive allogeneic stem cell transplantation were analyzed. The median duration of low-dose L-AmB treatment was 8 days. Hypokalemia was seen in one patient: administration of potassium supplements for 10 days restored potassium levels to the normal range. A two-fold increase in creatinine levels was not found in any patients even those taking concomitant nephrotoxic drugs (e.g., amynoglycoside) during the study. One patient stopped receiving the drug due to an infusion-related adverse event. No patients showed breakthrough fungal infections or died during therapy or within 7 days after the end of the study. Increase in the L-AmB dose was necessary due to persistent fever in three patients who withdrew from the study. The satisfactory response rate for low-dose L-AmB was 69 %.


CONCLUSIONS
This study suggests that low-dose L-AmB may be an effective option as empirical antifungal therapy for high-risk patients with febrile neutropenia.
Department of Hematology, Nephrology, and Rheumatology, Akita University Hospital, Akita, Japan.
Shinsuke
S
Noguchi
Naoto
N
Takahashi
Mitsugu
M
Ito
Kazuaki
K
Teshima
Takaya
T
Yamashita
Yoshihiro
Y
Michishita
Hideaki
H
Ohyagi
Seiji
S
Shida
Takayo
T
Nagao
Masumi
M
Fujishima
Sho
S
Ikeda
Isuzu
I
Ito
Naohito
N
Fujishima
Yoshihiro
Y
Kameoka
Hirobumi
H
Saitoh
Hiroyuki
H
Tagawa
Makoto
M
Hirokawa
Kenichi
K
Sawada
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000935:Antifungal Agents; D008081:Liposomes; D000666:Amphotericin B