Predicting the outcome of therapy for pulmonary tuberculosis.

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.

Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.

Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.

Rapid radiometric method for pyrazinamide susceptibility testing of Mycobacterium tuberculosis.

Pyrazinamide (PZA) is one of the most important drugs in modern chemotherapy of tuberculosis. Since PZA is active only at an acid pH, testing the susceptibility of Mycobacterium tuberculosis to PZA is difficult and timeconsuming. Therefore, we evaluated the BACTEC system for rapid testing of PZA susceptibility at pH 6. A total of 91 M. tuberculosis strains and 2 different strains of M. bovis BCG were screened for susceptibility to PZA. Each strain was tested in special 7H12 broth supplemented with polyoxyethylene stearate containing 25, 50 and 100 micrograms PZA/ml. Strains resistant to 100 micrograms/ml were retested against 25-100 micrograms/ml and at an extended range of PZA concentrations from 200-6,400 micrograms/ml. The MIC was determined with all strains within 4-20 (mean 7) days. Of the 77 susceptible strains, based on the pyrazinamidase test, MIC were less than or equal to 25 micrograms/ml for 34 strains, 50 for 38 and 100 for 2 strains. Three pyrazinamidase-positive strains had still higher MIC, 1 at 800 and 2 at 3,200 micrograms/ml. PZA-resistant strains had MIC of 800 or greater. Monoresistance to PZA has not been detected to date. The clear bimodal distribution of MIC in this method could enable the routine clinical microbiology laboratory to perform PZA susceptibility testing as easily as the 4 drugs now tested in the BACTEC system.

[Effect of antimicrobial preparations on thermogenesis in yeast-like fungi and in staphylococcus]. / Vliianie antimikrobnykh preparatov na termogenez u drozhzhepodobnykh gribov i stafilokokka

The results of the investigation of the effect of various concentrations of levorin and decamethoxin on the curves of thermogenesis in cultures of Candida albicans 688 and Staph. aureus 209 are presented in the paper. It was found that the above drugs in the concentration ranges within 0.0001--1 gamma/ml had different inhibitory effect on thermoproduction in the microorganisms. In the presence of higher concentrations of the drugs, i.e. above 1 gamma/ml thermoproduction practically ceased. It is supposed that determination of the levels of thermoprocesses in the presence of antimicrobial drugs provided predistination of the state of the biochemical reactions in the microorganisms at various stages of their cultivation.