TY - JOUR
T1 - Experimental short-course preventive therapy of tuberculosis with rifampin and pyrazinamide
AU - Lecoeur, H. F.
AU - Truffot-Pernot, C.
AU - Grosset, J. H.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - In a first experiment, the efficacy of a 6-month course of isoniazid (INH) alone in comparison with 2-month courses of rifampin (RMP) alone, RMP + pyrazinamide (PZA), or RMP + PZA + INH as preventive therapy of tuberculosis was evaluated in the mouse. To simulate the infected, non-diseased state of humans, a nonreplicating bacillary population of limited size was developed in the mouse. Mice were vaccinated intravenously with 2.74 log10 M. bovis BCG and infected a month later with 3.38 log10 M. tuberculosis. Treatment began 2 wk after infection when the mean size of the M. tuberculosis population was 4.98 ± 0.26 log10 cfu in the spleen. After 2 months of therapy, the proportion of mice with positive spleen cultures was 100%, 50%, 0%, and 20% in those animals treated, respectively, with INH alone, RMP alone, RMP + PZA, or RMP + PZA + INH. After 6 months of therapy with INH alone, the proportion of mice with positive spleen cultures was 38%. In order to confirm the extreme activity of the combination RMP + PZA and to assess the value of 3 months of therapy with RMP, a second experiment was performed following similar procedures. On completion of treatment, the proportion of mice with positive spleen cultures was 100%, 20%, 0%, and 80% in those animals treated, respectively, for 6 months with INH alone, 3 months with RMP alone, or 2 months with RMP + PZA, or RMP + PZA + INH. Six months after the end of treatment, the respective proportions of mice with positive spleen cultures were 100%, 60%, 56%, or 95%, suggesting that 2 months of therapy with RMP + PZA or 3 months of therapy with RMP alone were more effective than 6 months of therapy with INH alone.
AB - In a first experiment, the efficacy of a 6-month course of isoniazid (INH) alone in comparison with 2-month courses of rifampin (RMP) alone, RMP + pyrazinamide (PZA), or RMP + PZA + INH as preventive therapy of tuberculosis was evaluated in the mouse. To simulate the infected, non-diseased state of humans, a nonreplicating bacillary population of limited size was developed in the mouse. Mice were vaccinated intravenously with 2.74 log10 M. bovis BCG and infected a month later with 3.38 log10 M. tuberculosis. Treatment began 2 wk after infection when the mean size of the M. tuberculosis population was 4.98 ± 0.26 log10 cfu in the spleen. After 2 months of therapy, the proportion of mice with positive spleen cultures was 100%, 50%, 0%, and 20% in those animals treated, respectively, with INH alone, RMP alone, RMP + PZA, or RMP + PZA + INH. After 6 months of therapy with INH alone, the proportion of mice with positive spleen cultures was 38%. In order to confirm the extreme activity of the combination RMP + PZA and to assess the value of 3 months of therapy with RMP, a second experiment was performed following similar procedures. On completion of treatment, the proportion of mice with positive spleen cultures was 100%, 20%, 0%, and 80% in those animals treated, respectively, for 6 months with INH alone, 3 months with RMP alone, or 2 months with RMP + PZA, or RMP + PZA + INH. Six months after the end of treatment, the respective proportions of mice with positive spleen cultures were 100%, 60%, 56%, or 95%, suggesting that 2 months of therapy with RMP + PZA or 3 months of therapy with RMP alone were more effective than 6 months of therapy with INH alone.
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U2 - 10.1164/ajrccm/140.5.1189
DO - 10.1164/ajrccm/140.5.1189
M3 - Article
C2 - 2817579
AN - SCOPUS:0024434790
VL - 140
SP - 1189
EP - 1193
JO - American Review of Respiratory Disease
JF - American Review of Respiratory Disease
SN - 1073-449X
IS - 5
ER -