Influence of fungicidal activity against Candida tropicalis on the efficacy of micafungin and liposomal amphotericin B in a neutropenic murine lethal infection model. 2012

Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan. koji-takemoto@ds-pharma.co.jp

OBJECTIVE To investigate the correlation between in vitro killing activity and in vivo efficacy of micafungin (MCFG) and liposomal amphotericin B (L-AMB) against Candida tropicalis in a neutropenic murine lethal infection model. METHODS Candida albicans (one strain) and C. tropicalis (three strains) were tested in time-kill studies. Cyclophosphamide-treated mice were inoculated intravenously with each strain. One day after inoculation, antifungals were administered intravenously once daily for 1 or 3 days. RESULTS MCFG exhibited fungicidal activity against C. albicans ATCC 90029 and C. tropicalis SP-20142, and fungistatic activity against C. tropicalis ATCC 42678 and SP-20047. The ED(50)s (dosage that results in 50% survival) of MCFG for C. tropicalis ATCC 42678 and SP-20047 (4.1-50 mg/kg) were higher than those for other strains (1.6-12 mg/kg). A 1-day course of MCFG was not effective against C. tropicalis ATCC 42678 and SP-20047 at the clinical dose (5 mg/kg), which achieved an AUC level almost equal to that of 100 mg in humans, whereas a 3-day course of 5 mg/kg MCFG was efficacious against all strains. In contrast, L-AMB showed fungicidal activity against all strains tested and the ED(50)s of L-AMB were 0.08-0.65 mg/kg. In both treatment regimens, the minimum effective doses of L-AMB (≤0.5 mg/kg) were less than the clinical dosage (≤5 mg/kg). CONCLUSIONS The in vivo efficacy of MCFG and L-AMB showed a correlation with the in vitro killing activity. At the clinical dose, L-AMB exerted anti-C. tropicalis activity within a shorter treatment period than MCFG.

UI MeSH Term Description Entries
D008297 Male Males
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009503 Neutropenia A decrease in the number of NEUTROPHILS found in the blood. Neutropenias
D002177 Candidiasis Infection with a fungus of the genus CANDIDA. It is usually a superficial infection of the moist areas of the body and is generally caused by CANDIDA ALBICANS. (Dorland, 27th ed) Candida Infection,Moniliasis,Candida Infections,Candidiases,Infection, Candida,Moniliases
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000077551 Micafungin A cyclic lipo-hexapeptide echinocandin antifungal agent that is used for the treatment and prevention of CANDIDIASIS. FK 463,FK-463,FK463,Micafungin Sodium,Mycamine
D000666 Amphotericin B Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. Amphocil,Amphotericin,Amphotericin B Cholesterol Dispersion,Amphotericin B Colloidal Dispersion,Fungizone
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
June 2010, The Japanese journal of antibiotics,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
December 2002, The Journal of antimicrobial chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
September 2016, The Journal of antimicrobial chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
November 2008, Antimicrobial agents and chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
December 2010, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
November 1994, Antimicrobial agents and chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
September 2015, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
October 1992, Clinical and investigative medicine. Medecine clinique et experimentale,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
May 2008, Antimicrobial agents and chemotherapy,
Koji Takemoto, and Tatsuo Nakayama, and Katsunori Kanazawa, and Yutaka Ueda
December 2020, The Lancet. Microbe,
Copied contents to your clipboard!