[Studies on the problems of resistance to antituberculous drugs. II--1. Clinically applicable criteria of drug-resistance to rifampicin].
Preliminary studies showed that some strains of tubercle bacilli were inhibited even by 2 micrograms/ml of rifampicin (RFP), but 10 micrograms/ml or higher concentrations were needed for the inhibition of all strains. Of 5,100 patients with pulmonary tuberculosis who were admitted to our hospital during 12 years since January 1970 through 1981, 1,344 patients had no previous antituberculous drug therapy. All of the strains of Mycobacterium tuberculosis isolated from such 1,344 patients showed no or less than 10% growth of control on 10 micrograms-RFP medium by indirect susceptibility tests. But, I defined the clinically applicable criteria of resistance to RFP as "more than 1% growth of control on 10 micrograms-RFP medium" because of following reasons: 1) the growth more than 1% and less than 10% of control on 10 micrograms-RFP medium could be reasonably explained as the results of some technical failures, 2) the results of follow-up observations of respective cases, 3) our previous studies on the distribution of RFP-susceptibility of natural resistant strains. Among total 5,100 cases, 605 cases had been treated with antituberculous drugs previously but failed to achieve negative conversion of the bacilli, and restarted the treatment with regimen including RFP (retreatment group), and the remains had no previous treatment (initial treatment group). The negative conversion rates within three months of treatment were almost same (more than 95%) in both groups, but the rates of RFP-resistance were 5.6% for the initial treatment group and 92.8% for the retreatment group. Among 605 retreated cases 129 were susceptible to RFP at the start of the treatment but became resistant to RFP, of which 11 were resistant to 10 micrograms/ml and 118 to 50 micrograms/ml RFP. Two of the 11 10 micrograms-resistant cases remained to be 10 micrograms-resistant until their death (8 and 15 months after the start of the therapy, respectively) though their critical proportions showed some fluctuations. Remaining 9 cases later became resistant to 50 micrograms/ml RFP. By the 50 micrograms-resistant cases with lower critical proportion, the increase of critical proportion was rarely observed and did not reach even 50%. "Fall-and-rise" phenomena were observed rather frequently during the course of treatment with regimens including RFP. The decrease of the number of bacilli in sputa, sometimes to culture-negativity, at the initial phase of the treatment may be an evidence of killing of susceptible bacilli. If bacilli reappeared or increased their number, it is a critical time to reassess the treatment schedule.(ABSTRACT TRUNCATED AT 400 WORDS)
Baba
H
H
National Nakano Chest Hospital, Tokyo, Japan.
D000328:Adult; D000368:Aged; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology
D012293:Rifampin