Liposomal amikacin: Improved treatment of Mycobacterium avium complex infection in the beige mouse model

E. A. Petersen, J. B. Grayson, Evan M Hersh, Robert T Dorr, S. M. Chiang, M. Oka, R. T. Proffitt

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4°C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 107 cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

Original languageEnglish (US)
Pages (from-to)819-828
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume38
Issue number5
StatePublished - 1996

Fingerprint

Mycobacterium avium Complex
Amikacin
Infection
Mycobacterium avium
Therapeutics
Serum
Liposomes
Pharmaceutical Preparations
Half-Life
Veins
Phospholipids
Buffers
Acquired Immunodeficiency Syndrome
Spleen
Placebos
Pharmacology
Morbidity
Mortality
Liver

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

Cite this

Liposomal amikacin : Improved treatment of Mycobacterium avium complex infection in the beige mouse model. / Petersen, E. A.; Grayson, J. B.; Hersh, Evan M; Dorr, Robert T; Chiang, S. M.; Oka, M.; Proffitt, R. T.

In: Journal of Antimicrobial Chemotherapy, Vol. 38, No. 5, 1996, p. 819-828.

Research output: Contribution to journalArticle

Petersen, E. A. ; Grayson, J. B. ; Hersh, Evan M ; Dorr, Robert T ; Chiang, S. M. ; Oka, M. ; Proffitt, R. T. / Liposomal amikacin : Improved treatment of Mycobacterium avium complex infection in the beige mouse model. In: Journal of Antimicrobial Chemotherapy. 1996 ; Vol. 38, No. 5. pp. 819-828.
@article{e214d655e2104079ab91784f3113e0b2,
title = "Liposomal amikacin: Improved treatment of Mycobacterium avium complex infection in the beige mouse model",
abstract = "Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4°C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 107 cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.",
author = "Petersen, {E. A.} and Grayson, {J. B.} and Hersh, {Evan M} and Dorr, {Robert T} and Chiang, {S. M.} and M. Oka and Proffitt, {R. T.}",
year = "1996",
language = "English (US)",
volume = "38",
pages = "819--828",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Liposomal amikacin

T2 - Improved treatment of Mycobacterium avium complex infection in the beige mouse model

AU - Petersen, E. A.

AU - Grayson, J. B.

AU - Hersh, Evan M

AU - Dorr, Robert T

AU - Chiang, S. M.

AU - Oka, M.

AU - Proffitt, R. T.

PY - 1996

Y1 - 1996

N2 - Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4°C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 107 cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

AB - Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4°C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 107 cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

UR - http://www.scopus.com/inward/record.url?scp=0029822737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029822737&partnerID=8YFLogxK

M3 - Article

C2 - 8961051

AN - SCOPUS:0029822737

VL - 38

SP - 819

EP - 828

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 5

ER -