- Volume 60 , Number 2
- Page: 276–7
Minimal bactericidal dietary concentration of minocycline for Mycobacterium leprae-infected mice is very low and similar to its minimal inhibitory dietary concentration
To the Editor:
Previously it was found, by both the kinetic and proportional bactericidal method, that minocycline was consistently bactericidal for Mycobacterium leprae in infected mice (2, 4). This activity was obtained at levels which were exceeded several fold by standard doses in man (2). Furthermore, we found that for seven different M. leprae isolates continuous administration of 0.01% and 0.04% w/w minocycline in the mouse diet consistently inhibited the growth of M. leprae (serum levels 0.11 µ g/ml and 0.31 Mg/ml, respectively), while 0.004% inhibited 5 of 7 strains and 0.001% was consistently inactive (serum levels < 0.08 µ m/ml) (3). These present studies were initiated to determine by the proportional bactericidal method (1) minocycline's minimal bactericidal dietary concentration for a single strain of M. leprae.
In this study, groups of BALB/c female mice (Jackson Laboratories, Bar Harbor, Maine, U.S.A.) were infected in both hind foot pads with 101, 102, or 103 M . leprae and fed diets for 60 days thereafter containing various concentrations of minocycline (0.004%, 0.01%, 0.04%, 0.06%, 0.1%); controls = 0%. One year after the discontinuation of therapy, foot pads of 8 or more mice (generally 10) from each group of mice were harvested, and the number of M . leprae counted microscopically (6). If > 105 M. leprae were found, multiplication was considered to have occurred (6). From these results the percentage of bacteria killed was quantitated by the method of Spearman and Karber (5).
The results of these studies are summarized in The Table. Minocycline 0.004% was found to have had no significant bactericidal activity for M. leprae (p = 0.14). On the other hand, all other dietary levels of mino cycline tested (0.01%, 0.04%, 0.06%, and 0.1%) were bactericidal for M. leprae (p < 0.02).
Unfortunately, in this study the control inoculum itself had low viability. This may account for why the percentage of M . leprae killed was less than had been found in previous studies (2, 4). Nonetheless, it would appear that concentrations of minocycline required to inhibit and kill M . leprae are similar (2, 3) and easily attainable in man.
- Robert H. Gelber, M.D.
Patricia Siu
Mabel Tsang
Lydia P. Murray
Kuzell Institute for Arthritis and Infectious Disease
Medical Research Institute of San Francisco
2200 Webster Street
San Francisco, California 94115-1896, U.S.A.
GWL Hansen's Disease Center (Dr. Gelber only)
5445 Point Clair Road
Carville, Louisiana 70721, U.S.A.
Acknowledgment. This investigation received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR).
REFERENCES
1. COLSTON, M. J., HILSON, G. R. and BANERJEE, D. K. The "proportional bactericidal test": a method for assessing bactericidal activity in drugs against Mycobacterium leprae in mice. Lepr. Rev. 49(1978)7-15.
2. GELBER, R. H. Activity of minocycline in Mycobacterium leprae -infected mice. J. Infect. Dis. 156(1987)236-239.
3. GELBER, R. H., SIU, P., TSANG, M., ALLEY. P. and MURRAY, L. P. Effect of low-level and intermittent minocycline therapy on the growth of Mycobacterium leprae in mice. Antimicrob. Agents Chemother. 35(1991)992-994.
4. Ji, B., PERANI, E. G. and GROSSET, J. H. Effectiveness of clarithromycin and minocycline alone and in combination against experimental Mycobacterium leprae infection in mice. Antimicrob. Agents Chemother. 35(1991)579-581.
5. SHEPARD, C. C. Statistical analysis of results obtained by two methods for testing drug activity against Mycobacterium leprae. Int. J. Lepr. 50(1982)96-101.
6. SHEPARD, C. C. and MCRAE, D. H. A method for counting acid-fast bacteria. Int. J. Lepr. 36(1968)78-82.