Universität zu Köln

Groll, Andreas H., Silling, Gerda, Young, Charlotte, Schwerdtfeger, Rainer, Ostermann, Helmut, Heinz, Werner J., Gerss, Joachim, Kolve, Hedwig, Lanvers-Kaminsky, Claudia, Pinheiro, Joao Paulo Vieira, Gammelin, Sibylle, Cornely, Oliver A. and Wuerthwein, Gudrun (2010). Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients. Antimicrob. Agents Chemother., 54 (10). S. 4143 - 4150. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Groll, Andreas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Silling, Gerda UNSPECIFIED UNSPECIFIED UNSPECIFIED Young, Charlotte UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwerdtfeger, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Ostermann, Helmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinz, Werner J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerss, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Kolve, Hedwig UNSPECIFIED UNSPECIFIED UNSPECIFIED Lanvers-Kaminsky, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinheiro, Joao Paulo Vieira UNSPECIFIED UNSPECIFIED UNSPECIFIED Gammelin, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerthwein, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494614
DOI:	10.1128/AAC.00425-10
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	54
Number:	10
Page Range:	S. 4143 - 4150
Date:	2010
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INVASIVE FUNGAL-INFECTION; PREEMPTIVE ANTIFUNGAL THERAPY; HIGH-RISK; NEUTROPENIC PATIENTS; PERSISTENT FEVER; EFFICACY; ASPERGILLOSIS; MICAFUNGIN; AMBISOME; FEBRILE Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49461