0
May 12, 1975, Vol 232, No. 6 >
ARTICLE | May 12, 1975

Amphotericin B: Title and subTitle BreakOld Drug, New Therapy FREE

Gerald Medoff, MD; George S. Kobayashi, MD
[+] Author Affiliations

Reprint requests to Division of Infectious Disease, Washington University School of Medicine, St. Louis, MO 63110 (Dr. Medoff).


JAMA. 1975;232(6):619-620. doi:10.1001/jama.1975.03250060015012
Text Size: A A A
Published online
Article
References

RECENT animal experiments1-4 support our earlier in vitro work on the synergistic action of amphotericin B and second agents against a variety of fungi.5-9 Before these results lead to the indiscriminate use of amphotericin B and flucytosine for the treatment of all fungal infections in human beings, we would like to review some old and recent information, which might encourage some circumspection in the use of combination therapy.

Amphotericin B is a polyene macrolide that binds to sterols in eukaryotic cell membranes.10 It is the only polyene antibiotic that is sufficiently nontoxic to be useful itself in the treatment of systemic fungal infections. The relative specificity of amphotericin B for fungi is likely due to its greater avidity for ergosterol, the principal sterol in fungal cell membranes, than cholesterol, the principal sterol in animal cell membranes.11 Unfortunately, the specificity of amphotericin B for fungi compared to animal

REFERENCES

1 +
Block ER, Bennett JE:  The combined effect of 5-fluorocytosine and amphotericin B in the therapy of murine Cryptococcus . Proc Soc Exp Biol Med 142:476-480, 1973;.
2 +
Titsworth E, Gruneberg E:  Chemotherapeutic activity of 5-fluorocytosine and amphotericin B against Candida albicans in mice . Antimicrob Agents Chemother 4:306-308, 1973;.
3 +
Rabinovich S, Shaw BD, Bryant T, et al:  Effect of 5-fluorocytosine and amphotericin B on Candida albicans infection in mice . J Infect Dis 130:28-31, 1974;.
4 +
Huppert M, Sun SH, Vukovich KR:  Combined amphotericin B-tetracycline therapy for experimental coccidiodomycosis . Antimicrob Agents Chemother 5:473-478, 1974;.
5 +
Medoff G, Comfort M, Kobayashi GS:  Synergistic action of amphotericin B and 5-fluorocytosine against yeast-like organisms . Proc Soc Exp Biol Med 138:571-574, 1971;.
6 +
Medoff G, Kwan CN, Schlessinger D, et al:  Potentiation of rifampicin and 5-fluorocytosine as antifungal antibiotics by amphotericin B . Proc Natl Acad Sci USA 69:196-199, 1972;.
7 +
Kwan CN, Medoff G, Kobayashi GS, et al:  Potentiation of the antifungal effects of antibiotics by amphotericin B . Antimicrob Agents Chemother 2:61-65, 1972;.
8 +
Kobayashi GS, Medoff G, Schlessinger G, et al:  Amphotericin B potentiating of rifampicin as an antifungal agent against the yeast phase of Histoplasma capsulatum . Science 177:709-710, 1972;.
9 +
Kobayashi GS, Cheung SC, Schlessinger D, et al:  Effects of rifamycin derivatives, alone and in combination with amphotericin B, against Histoplasma capsulatum . Antimicrob Agents Chemother 5:16-18, 1974;.
10 +
Kinsky SC:  Antibiotic interactions with model membrane . Ann Rev Pharmacol 10:119-142, 1970;.
11 +
Brajtburg JK, Price HD, Medoff G, et al:  The molecular basis for the selective toxicity of amphotericin B for yeast and filipin for animal cells . Antimicrob Agents Chemother 5:377-382, 1974;.
12 +
Garriques IL, Sande MA, Utz JP, et al:  Combined amphotericin Bflucytosine chemotherapy in human cryptococcosis , abstracted, in Thirteenth Interscience Conference on Antimicrobial Agents and Chemotherapy , Washington, DC, American Society of Microbiology, 1973;, vol 2.
13 +
Medoff G, Kwan CN, Schlessinger D, et al:  Permeability control in animal cells by polyenes: A possibility . Antimicrob Agents Chemother 3:441-443, 1973;.
14 +
Medoff G, Kwan CN, Schlessinger D, et al:  Potentiation of rifampicin, rifampicin analogs and tetracycline against animal cells by amphotericin B and polymyxin B . Cancer Res 33:1146-1149, 1973;.
15 +
Medoff G, Schlessinger D, Kobayashi GS:  Polyene potentiation of antitumor agents . J Natl Cancer Inst 50:1047-1050, 1973;.
16 +
Medoff G, Kobayashi GS, Schlessinger D:  Sensitivity of transformed and nontransformed cells to amphotericin B and several rifamycin derivatives . Cancer Res 34:823-826, 1974;.
17 +
Medoff G, Valeriote F, Lynch RG, et al:  Synergistic effect of amphotericin B and 1,3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) against a syngeneic transplantable AKR leukemia . Cancer Res 34:974-978, 1974;.
18 +
Thomas M, Medoff G, Kobayashi GS:  Resistance to Listeria monocytogenes infection induced by amphotericin B . J Infect Dis 127:373-377, 1973;.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Block ER, Bennett JE:  The combined effect of 5-fluorocytosine and amphotericin B in the therapy of murine Cryptococcus . Proc Soc Exp Biol Med 142:476-480, 1973;.
2 +
Titsworth E, Gruneberg E:  Chemotherapeutic activity of 5-fluorocytosine and amphotericin B against Candida albicans in mice . Antimicrob Agents Chemother 4:306-308, 1973;.
3 +
Rabinovich S, Shaw BD, Bryant T, et al:  Effect of 5-fluorocytosine and amphotericin B on Candida albicans infection in mice . J Infect Dis 130:28-31, 1974;.
4 +
Huppert M, Sun SH, Vukovich KR:  Combined amphotericin B-tetracycline therapy for experimental coccidiodomycosis . Antimicrob Agents Chemother 5:473-478, 1974;.
5 +
Medoff G, Comfort M, Kobayashi GS:  Synergistic action of amphotericin B and 5-fluorocytosine against yeast-like organisms . Proc Soc Exp Biol Med 138:571-574, 1971;.
6 +
Medoff G, Kwan CN, Schlessinger D, et al:  Potentiation of rifampicin and 5-fluorocytosine as antifungal antibiotics by amphotericin B . Proc Natl Acad Sci USA 69:196-199, 1972;.
7 +
Kwan CN, Medoff G, Kobayashi GS, et al:  Potentiation of the antifungal effects of antibiotics by amphotericin B . Antimicrob Agents Chemother 2:61-65, 1972;.
8 +
Kobayashi GS, Medoff G, Schlessinger G, et al:  Amphotericin B potentiating of rifampicin as an antifungal agent against the yeast phase of Histoplasma capsulatum . Science 177:709-710, 1972;.
9 +
Kobayashi GS, Cheung SC, Schlessinger D, et al:  Effects of rifamycin derivatives, alone and in combination with amphotericin B, against Histoplasma capsulatum . Antimicrob Agents Chemother 5:16-18, 1974;.
10 +
Kinsky SC:  Antibiotic interactions with model membrane . Ann Rev Pharmacol 10:119-142, 1970;.
11 +
Brajtburg JK, Price HD, Medoff G, et al:  The molecular basis for the selective toxicity of amphotericin B for yeast and filipin for animal cells . Antimicrob Agents Chemother 5:377-382, 1974;.
12 +
Garriques IL, Sande MA, Utz JP, et al:  Combined amphotericin Bflucytosine chemotherapy in human cryptococcosis , abstracted, in Thirteenth Interscience Conference on Antimicrobial Agents and Chemotherapy , Washington, DC, American Society of Microbiology, 1973;, vol 2.
13 +
Medoff G, Kwan CN, Schlessinger D, et al:  Permeability control in animal cells by polyenes: A possibility . Antimicrob Agents Chemother 3:441-443, 1973;.
14 +
Medoff G, Kwan CN, Schlessinger D, et al:  Potentiation of rifampicin, rifampicin analogs and tetracycline against animal cells by amphotericin B and polymyxin B . Cancer Res 33:1146-1149, 1973;.
15 +
Medoff G, Schlessinger D, Kobayashi GS:  Polyene potentiation of antitumor agents . J Natl Cancer Inst 50:1047-1050, 1973;.
16 +
Medoff G, Kobayashi GS, Schlessinger D:  Sensitivity of transformed and nontransformed cells to amphotericin B and several rifamycin derivatives . Cancer Res 34:823-826, 1974;.
17 +
Medoff G, Valeriote F, Lynch RG, et al:  Synergistic effect of amphotericin B and 1,3-Bis (2-chloroethyl)-1-nitrosourea (BCNU) against a syngeneic transplantable AKR leukemia . Cancer Res 34:974-978, 1974;.
18 +
Thomas M, Medoff G, Kobayashi GS:  Resistance to Listeria monocytogenes infection induced by amphotericin B . J Infect Dis 127:373-377, 1973;.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems