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PubMed1992

Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases.

Bacteriostatic and bactericidal activities of rifampicin, isoniazid, streptomycin, enviomycin and ethambutol against Mycobacterium tuberculosis, Mycobacterium avium--M. intracellulare complex and Mycobacterium kansasii were studied in different growth phases. Bacteriostatic activities of the drugs were similar in different growth phases, except isoniazid. M. tuberculosis was much less susceptible to isoniazid in the lag phase than in the log and the stationary phases. In contrast, bactericidal activity was influenced by the growth phase. M. tuberculosis was killed by isoniazid, streptomycin and rifampicin. The bactericidal activity of isoniazid was strongest. The bactericidal activity of isoniazid and streptomycin was most marked in the log phase. M. avium complex and M. kansasii resisted the bactericidal activity, but some strains of M. avium complex were killed by streptomycin and enviomycin, and the activities of these two drugs were most marked in the lag phase.

Antitubercular Agents↗

PubMed1988

Comparison of antituberculosis drug regimens for lung disease caused by Mycobacterium avium complex.

A total of 123 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously received different regimens of antituberculosis agents. The rate of sputum conversion (continuously negative cultures for six months or more) was compared among the regimens. It was shown that the regimens of rifampin + isoniazid + streptomycin and rifampin + isoniazid + enviomycin were superior to the regimens of streptomycin + isoniazid + p-aminosalicylate, isoniazid alone or isoniazid + p-aminosalicylate. This finding demonstrated that the regimens including rifampin, isoniazid and streptomycin or enviomycin were really effective in the initial treatment of lung disease caused by M avium complex.

Aminosalicylic Acid↗

PubMedDate not supplied

Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine.

The antituberculous activity of 27753-RP (RP), a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro. 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 microgram/ml in liquid media, showing no cross-resistance. However, loss of potency occurred in Ogawa's egg media, and 50 micrograms/ml of RP were required for inhibition of growth. 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect. In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required. When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy. 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs. Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage. 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M. intracellulare appeared to be extremely low.

Animals↗

PubMed2002

Comparative study on the use of solid media: Löwenstein-Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility.

A total of 53 Mycobacterium tuberculosis strains were examined to evaluate the consistency of susceptibility tests using two solid egg-based culture media, Ogawa and Löwenstein-Jensen (L-J), in order to assess the inter-media differences in susceptibility tests for anti-tuberculosis drugs. Fifty-three M. tuberculosis strains were tested for resistance against isoniazid, rifampicin, ethambutol, streptomycin and other alternative drugs on L-J and Ogawa media. Data from isoniazid (INH) revealed 31 strains were susceptible and 11 strains were resistant in L-J medium. On the other hand, one strain showed resistance against INH only on Ogawa medium. This gave a consistency ratio of 97.7% for INH between these two media. Similarly, the methods had 100% compatibility with rifampicin, 86.0% with ethambutol and 88.4% with streptomycin. When 41 of these strains were tested against ethionamide, enviomycin, para -aminosalicylate, sparfloxacin, and levofloxacin, the same numbers of strains were shown to be resistant or susceptible to L-J and Ogawa media. Similarly, the consistency ratio was 75.6% for kanamycin and 61.0% for capreomycin. There are inconsistencies between results obtained with L-J and Ogawa media, Ogawa medium had a tendency to produce results that indicated more resistant strains. However, the differences were statistically negligible.

Antitubercular Agents↗

PubMed1980

Studies on the cross-resistance of Mycobacterium tuberculosis, strain H37Rv, to aminoglycoside- and peptide-antibiotics.

Various phenotypes of the resistance to aminoglycoside- and peptide-antibodies of Mycobacterium tuberculosis strain H37Rv were produced by single- and/or two-step selection of the parent strain. Mutants obtained by single-step selection with antibiotics were classified into ten phenotypes; one of single resistance, two of triple resistance, three of quadruple resistance, and four of sextuple resistance. There were two kinds of sextuple resistance (high resistance to enviomycin, viomycin, capreomycin, kanamycin, lividomycin). One was isolated from the parent strain by single-step selection and could be eliminated by mutation to isoniazid resistance, the other was obtained by two-step selections and was not eliminated by mutation to isoniazid resistance. Interaction between mutation to streptomycin resistance and mutation to quadruple resistance (4R phenotype) was observed. Streptomycin resistance interfered with the formation of the 4R phenotype and produced a different phenotype, KR instead of the 4R phenotype. The existence of mutation of the 4R phenotype did not usually interfere with mutation to streptomycin resistance, but a small portion of the mutants with the 4R phenotype were altered in their phenotype from 4R to KR after addition of the mutation to streptomycin resistance. This effect of the mutation to streptomycin resistance was not observed in mutants which already had a mutation to klR phenotype (mutation to low concentrations of kanamycin only).

Aminoglycosides↗

PubMed1987

Two groups of Mycobacterium avium complex strains determined according to the susceptibility to rifampicin and ansamycin.

Mycobacterium avium complex strains previously not exposed to any antituberculosis agents could be divided into two groups according to their susceptibility to rifampicin and ansamycin; one group susceptible to 80 micrograms/ml rifampicin and to 1.25 micrograms/ml ansamycin, and another resistant to these concentrations. In each group, the ratio of the minimal inhibitory concentration of ansamycin against that of rifampicin was greatly different depending on the strain. This naturally occurring resistance to rifampicin and ansamycin was frequently correlated to naturally occurring resistance to ethambutol, kanamycin, enviomycin, kitasamycin, and minocycline, but not correlated to that to isoniazid and sulfadimethoxine. Ansamycin was more active than rifampicin against M. bovis, M. kansasii, M. marinum, M. xenopi, and M. haemophilum.

Anti-Bacterial Agents↗

PubMed1989

Different correlations of drug susceptibilities to colonial morphology in Mycobacterium avium complex strains.

In Mycobacterium avium and Mycobacterium intracellulare complex strains isolated from patients who were not treated previously by any antituberculosis drugs or from fowls, the colonial morphology, smooth, domed, opaque (SmD) or smooth, flat, transparent (SmT) colonial forms, significantly correlated with susceptibilities to rifampicin, minocycline, streptomycin, kanamycin, enviomycin, ethambutol, and sulfadimethoxine, whereas it did not correlate with susceptibilities to isoniazid, cycloserine, and ethionamide. Strains with the SmT colonial morphology were more resistant to the former seven drugs than strains with the SmD colonial morphology. Since the susceptibilities to antituberculosis drugs with large molecules correlated with the colonial morphology, it has been suggested that a permeability barrier that allows passage of small molecules but prevents passage of large molecules exists in the strains with the SmT colonial morphology.

Anti-Bacterial Agents↗

PubMed1988

Evidence that antituberculosis drugs are really effective in the treatment of pulmonary infection caused by Mycobacterium avium complex.

Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators. However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial. The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC. It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M. avium complex strain increased significantly. This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs. Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown. The M. avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect. The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection.

Antitubercular Agents↗

PubMed1989

[Evaluation of excised loach skin for studies on transdermal permeation of drugs in vitro].

Transdermal permeation of drug across the excised skin of Asian pond loach (Misgurnus anguillicaudatus Cantor) was studied in vitro. Ten kinds of drugs, D-glucose, L-glucose, sucrose, salicylic acid, cefazolin, urea, antipyrine, naphazoline, propranolol and enviomycin were permeated through the excised loach skin, whereas dextran, a polysaccharide, could not be permeated through the skin. The observed transdermal flux (J), the slope of the line obtained from plots of the cumulative amount of drug permeated vs. time, increased as the drug concentration in the donor compartment solution (50----300 mM), as the temperature of the skin (test solution) increased (4----37 degrees C), or as the molecular weight of compound decreased. These results suggested that the transport of drug across the loach skin was due to the passive diffusion mechanism. The effect of pH on the permeation of drug could not be elucidated since the loach skin was drastically impaired below pH 5.0. The J values of antipyrine and naphazoline varied in proportion to the drug concentration in the donor compartment solution at time zero (C0). The permeability constants (Kp, cm.h-1) of antipyrine and naphazoline were 12.9 x 10(-2) and 9.2 x 10(-2), respectively. However, the J values of salicylic acid and urea were not proportional to C0 in high concentration (300 mM). Probably, these results were related to the irritative effect of salicylic acid or urea on the skin.

Animals↗

PubMed1993

A clinical comparison between Mycobacterium avium and Mycobacterium intracellulare infections.

Susceptibility, clinical features, and response to treatment were compared between 29 cases of Mycobacterium avium infection and 43 cases of Mycobacterium intracellulare infection detected in the Nagasaki (Japan) area and identified by a DNA probe method. In vitro susceptibility of two species to antituberculous agents was determined by a microdilution method, and M avium was more resistant to enviomycin at 25 mg/L than M intracellulare, while M intracellulare was more resistant to isoniazid at 5 mg/L and to cycloserine at 20 mg/L. No significant difference was found between infections caused by two species as to background factors, laboratory data, clinical symptoms, and chest radiographic findings at the onset of the disease. Approximately 70 percent of the patients in each group had underlying diseases; among them, pulmonary tuberculosis was the most common. Negative conversion of bacilli during the 6-month treatment was seen in 17 of 29 patients (59 percent) with M avium infection and in 21 of 43 patients (49 percent) with M intracellulare infection. Bacilli-negative conversion was slightly faster in the former than in the latter. However, these differences were statistically not significant. In conclusion, most M avium-intracellulare complex organisms are clearly identified as M avium or M intracellulare by the DNA probe method, and there was no significant difference in clinical features and response to treatment between infections caused by the two species.

Aged↗

PubMed2001

[A case of drug-resistant pulmonary tuberculosis treated successfully following disappearance of rifampicin resistance after 17 years' chemotherapy].

A female who first acquired pulmonary tuberculosis in 1962 when she was 25 years old, admitted to the National Hiroshima Hospital in 1982. Her sputum has been smear positive for acid-fast bacilli for 3 years before admission in spite of continuous antituberculous chemotherapy, and were resistant to isoniazid (INH) and rifampicin (RFP). She was treated with a regimen containing ethambutol (EB), prothionamide (TH) and enviomycin (EVM) but continued to be culture positive. Though she was treated with various regimens which include one to three sensitive drugs, her sputum continued to be positive for M. tuberculosis in the following 14 years. During the course, resistance to EB, TH, cycloserine (CS) and streptomycin (SM) emerged. Resistance to RFP temporarily retracted in 1988, but her sputum was bacilli negative only for 2 months after the addition of RFP to previous regimen, and followed by resurgence of RFP resistance. In 1992, data of drug sensitivity tests showed sensitivity to TH, CS and RFP in turn, which were not used for 3 to 5 years. In 1993, she was treated with RFP, TH and EVM successfully and continued to be bacteriologically negative for 7 years so far. Drug resistance to M. tuberculosis is induced by inappropriate chemotherapy as seen in this case. Regimens with less than three drugs without RFP and INH was not only insufficient to get cure but, what was worse, also induced additional resistance to used drugs. The reason of successful chemotherapy in this case was spontaneous disappearance of drug resistance to RFP and TH. This case suggests that the disappearance of drug resistance is possible, when drugs are not used for more than a few years, hence the successful treatment could be expected. However it must be emphasized that the drug resistance is produced by incorrect treatment as seen in this case, and its prevention is of the prime importance.

Antitubercular Agents↗

PubMed2001

[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].

The thirty-two times of treatment in 27 patients with multidrug-resistant tuberculosis (MDR-TB) were analyzed retrospectively. In twenty-eight times of treatments cases had previous histories of antituberculosis chemotherapy. Drug sensitivity tests were performed by Microtiter method for isoniazid (INH), rifampicin (RFP), ethambutol, streptomycin, kanamycin, enviomycin, ethionamide, para-aminosalicylic acid and cycloserine. A drug is defined as 'active drug' when the drug was proved to be sensitive by the drug sensitivity tests or never used in the past or used for not more than 2 months in case of pyrazinamide (PZA) and less than one month for fluoroquinolones. Outcomes of treatments were grouped as follows; A: bacteriologically negative for more than 24 months, B: bacteriologically negative for more than 6 months but less than 24 months, C: bacteriologically relapsed after negative conversion, D: continuously bacilli positive for M. tuberculosis. Mean age of patients in each group were; 61.0 yrs for group A (n = 10), 61.0 yrs for group B (n = 7), 52.5 yrs for group C (n = 4), 57.9 yrs for group D (n = 11). All patients had cavitary disease and positive sputum smears for acid-fast bacilli. Mean numbers of 'active drugs' used per treatment in each group, were 3.6, 3.3, 2.5 and 1.8 respectively, while the mean number of resistant drug including INH and RFP were 2.8, 3.3, 2.5 and 3.7. The number of drugs, which was unable to use due to toxicity, were 0.20, 0.14, 0.50, and 0.73 per treatment respectively. All of 9 patients treated with four 'active drugs' were in group A or B and succeeded to achieve negative conversion. The duration of chemotherapy in group A was 13 to 44 months. Treatment had failed in 4 out of 11 patients treated with 3 'active drugs' and 11 out of 12 patients treated with less than 2 'active drugs'. Fluoroquinolones (ofloxacin, levofloxacin or sparfloxacin) were used in 7 out of 10 patients in group A and in 6 out of 9 patients treated with four-drug regimens while they were used only in 3 out of 11 patients in group D. Regimens with at least 4 sensitive drugs are mandatory for the successful treatment of MDR-TB and fluoroquinolones are needed in the majority of cases to ensure the four-drug regimen, because of frequent drug resistance or toxicity to other antituberculosis drugs.

Adult↗

PubMed2006

[A case of pulmonary Mycobacterium fortuitum infection successfully treated with Kampo treatments].

A 72-year-old male was referred to our hospital in August 2001 for his pulmonary M. fortuitum infection. His symptoms were coughing, pyrexia, hemoptysis, general malaise, and insomnia. He had been suffering from these symptoms since 1982, though the intensive anti-mycobacterial chemotherapy such as three-drug (RFP, SM, and INH), twice two-drug (KM and SM and cycloserine and enviomycin) and four-drug (CAM, EB, RFP, and KM) regimens were administered for 26 months from July 1999. His symptoms tentatively improved after chemotherapy, but soon recurred with smear positive sputum. We decided to withdraw all antibacterial agents to treat him with decoction of Ninjinyoueito according to the diagnostics Kampo medical science in September 2001. After this prescription, his subjective symptoms gradually improved, and ten months later his sputum converted to smear negative. Because of recurrence of his general malaise in August 2002, we replaced the Ninjinyoueito by Seishoekkito, based on the Kampo diagnostics. His physical conditions remained good until 2005. In addition, the sputum smear examination maintain the level below +/-. We evaluate that Kampo (Chinese traditional medicine) treatment resulted in favorable response. Though it is not common to prescribe Kampo-medicine for intractable infectious diseases, we believe that Kampo-medicine is effective in some cases associated with host defense mechanisms.

Aged↗

PubMed1990

[Determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex].

The determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) is influenced by the size of inoculation used in the determination. Such influences differ greatly according to the drugs. By increasing the number of colony-forming units (CFU) of the inoculation to 10(6)-fold, minimal inhibitory concentrations (MICs) of rifampicin and cycloserine have increased only 2-to 3-fold. However, MICs of ethionamide, streptomycin, enviomycin and ethambutol have increased 4-to 9-fold. In contrast, MICs of isoniazid and sulfadimethoxine have increased 30-to 35-fold. Since the determination of MICs of isoniazid and sulfadimethoxine are so greatly influenced by the size of inoculation, the determinations of MICs of these two drugs should be carried out by use of the "actual count" method (6, 7, 9) or the proportion method (8). In the actual count method, the MIC is determined by inoculating 20-100 CFU. The determination of isoniazid susceptibility of M. tuberculosis (H37Rv) was influenced only slightly by the size of inoculation, but that of M. bovis (BCG) was influenced greatly as occurred in the determination of MAI complex strains.

Antitubercular Agents↗

PubMed1990

[Bactericidal activity of antituberculosis drugs against Mycobacterium avium complex].

The bactericidal activity of antituberculosis drugs against two strains of M. avium complex 13008 (serotype 20) and 13016 (serotype 4), was observed using modified Dubos liquid medium (1.3 g of Dubos Broth Base (Difco) in 180 mil of distilled water plus 20 ml of bovine serum). The strains were most susceptible to antituberculosis drugs among M. avium complex strains (Table). The test strains were cultivated in Ogawa egg medium at 37 degrees C for 10 days, and growing colonies were homogenized by shaking with glass beads for 10 minutes and suspended in the modified Dubos liquid medium to a concentration of 2 mg wet weight per ml. The media containing drug and containing no drug were incubated at 37 degrees C for 24 hours under shaking (8 cm-moving range and 56 strokes per minute). After incubation, the medium was diluted by a 0.1% Tween 80 aqueous solution to 10(-7), and each 0.02 ml-sample of 10(-4) to 10(-7) suspensions was inoculated onto Ogawa egg medium. The Ogawa egg medium slants were incubated at 37 degrees C for 28 days, and the number of colonies was counted. The bactericidal activity was determined as a ratio of the number of colony-forming units in 10 ml-aliquot of drug-containing Dubos liquid medium against the number of colony-forming units in the control Dubos liquid medium. The results are shown in Figures 1 and 2. Under the condition tested, rifampicin, isoniazid, ethambutol, ethionamide and cycloserine did not exhibit any bactericidal activity, and only streptomycin and enviomycin exhibited bactericidal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

PubMed1989

[Cross-resistance relationships of antituberculosis drugs in Mycobacterium avium complex].

At present, infection caused by Mycobacterium avium complex is usually treated by chemotherapy of antituberculosis drugs. However, cross-resistance relationships of antituberculosis drugs in the M. avium complex have not yet been studied. In the present study, we studied on this subject using three strains which were isolated from sputum specimens of patients who were not treated by any antituberculosis drugs: strain 13008 (serotype 20), strain 13016 (serotype 4) and strain 13034 (serotype 18). The methods used for isolating mutants resistant to rifampicin, isoniazid, ethambutol, streptomycin, kanamycin and/or enviomycin were described previously (Tsukamura, M: Kekkaku 62: 445-458, 1987). Mutants resistant to ethionamide were isolated from strains 13008 and 13016 at a rate of 10(-6) and mutants resistant to kitasamycin at a rate of 10(-5) to 10(-6) (these were not isolated from strain 13034). In contrast, mutants resistant to minocycline were isolated from strain 13034 only at a rate of 10(-4). Susceptibility testings to antituberculosis drugs were carried out as follows. Bacterial suspensions, 10 mg wet weight/ml, were prepared from ten day-old cultures of the strains growing on Ogawa egg medium slants. Each 0.02 ml-sample of the suspensions was inoculated onto Ogawa egg medium with or without a drug by a spiral loop. The media inoculated were incubated at 37 degrees C for 14 days. Minimal inhibitory concentration was determined as a concentration, on which no membraneous growth could occur. The results are shown in Tables 1 to 3. Cross-resistance relationships were observed only between ethionamide and isoniazid. Ethionamide-resistant mutant strains were resistant to isoniazid.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

PubMed1998

[Multidrug-resistant tuberculosis. Additional comment: primary multidrug-resistant tuberculosis--diagnosis and treatment].

Primary drug resistance is defined as the presence of resistant strains of Mycobacterium tuberculosis in a patient with no history of prior anti-tuberculosis chemotherapy. In Japan, a recent study shows that the prevalence of primary resistance has been stable for two decades and that primary multidrug-resistant tuberculosis (MDR-TB) is rare, which suggests the effectiveness of tuberculosis control. We presented four cases of primary MDR-TB that we had experienced from 1984 to 1997, and discussed an issue about diagnosis and treatment of primary MDR-TB. Of the four patients, two young men received surgical resection, which has resulted in a favorable outcome. Of the other two patients, one responded to long-term chemotherapy with ethambutol, ofloxacin and enviomycin. There have been no recurrence so far in the three cases. The rest case died due to progression of tuberculosis. Two of the four patients had been in contact with relatives who had died of MDR-TB. In conclusion, all the tuberculosis patients should be suspected to be primary MDR-TB when they had a history of a contact with a tuberculosis patient in whom chemotherapy had not been successful, and once patients are diagnosed as MDR-TB, surgical intervention should be considered as an adjunctive treatment. To prevent the emergence of primary MDR-TB, it is important to treat MDR-TB patients appropriately and to implement the infection control program.

Adult↗

PubMed1995

Enhancement of Neurospora VS ribozyme cleavage by tuberactinomycin antibiotics.

Several examples of inhibition of the function of a ribozyme or RNA-protein complex have shown that certain antibiotics can interact specifically with RNA. There are, however, few examples of antibiotics that have a positive, rather than a negative, effect on the function of an RNA. We have found that micromolar concentrations of viomycin, a basic, cyclic peptide antibiotic of the tuberactinomycin group, enhance the cleavage of a ribozyme derived from Neurospora VS RNA. Viomycin decreases by an order of magnitude the concentration of magnesium required for cleavage. It also stimulates an otherwise insignificant transcleavage reaction by enhancing interactions between RNA molecules. The ability of viomycin to enhance some RNA-mediated reactions but inhibit others, including translation and Group I intron splicing, demonstrates the potential for natural selection by small molecules during evolution in the 'RNA world' and may have broader implications with respect to ribozyme expression and activity in contemporary cells.

Enviomycin↗