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PubMed1998

Antibacterial spectra of drugs used for chemotherapy of mycobacterial infections.

The mechanism of action of many antimycobacterial agents is poorly understood. To obtain preliminary information on whether the targets for some of these drugs might also occur in other bacteria, the in vitro activities of selected agents against Escherichia coli, Bacillus subtilis and Staphylococcus aureus were determined. Dapsone, p-aminosalicylic acid and thiacetazone failed to inhibit the above organisms (MIC values > 100 micrograms/ml) that may therefore lack targets for these drugs. Capreomycin, viomycin and clofazimine demonstrated activity against some of the organisms (MIC values < 100 micrograms/ml) suggesting that the targets of these drugs may not be restricted to mycobacterial species. The agents were all potent inhibitors of Mycobacterium bovis bacille Calmette-Guérin (MIC values 0.08-0.5 microgram/ml).

Aminosalicylic Acid↗
PubMed2003

In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with anti-tuberculosis agents.

OBJECTIVES: To examine the effect of first-line and second-line anti-tuberculosis agents on the ability of fluoroquinolones to kill mycobacteria. METHODS: A clinical isolate of Mycobacterium tuberculosis and a laboratory strain of Mycobacterium smegmatis were grown in liquid medium and treated with a fluoroquinolone in the presence or absence of anti-tuberculosis agents. Bacterial survival was determined by viable colony counts on agar medium. RESULTS: When moxifloxacin activity was examined in two-drug combinations containing traditional anti-tuberculosis agents, activity was greater than either compound alone with isoniazid, capreomycin and low, but not high, concentrations of rifampicin. Cycloserine contributed no additional activity, and ethambutol interfered with the lethal action of moxifloxacin and gatifloxacin. Experiments with M. smegmatis confirmed that both rifampicin and ethambutol reduce fluoroquinolone lethality. Moreover, ethambutol increased the recovery of fluoroquinolone-resistant mutants newly created by ethyl methanesulphonate treatment. CONCLUSIONS: The intrinsic bactericidal activity of C-8-methoxy fluoroquinolones can be adversely affected by some agents currently used for treatment of tuberculosis.

Anti-Bacterial Agents↗
PubMed1988

MIC as a quantitative measurement of the susceptibility of Mycobacterium avium strains to seven antituberculosis drugs.

MICs of isoniazid, rifampin, ethionamide, streptomycin, amikacin, kanamycin, and capreomycin were determined for Mycobacterium avium complex strains by two methods: broth dilution in 7H12 medium radiometrically and agar dilution on 7H10 agar plates. The broth-determined MICs of all drugs with the exception of isoniazid were two to eight times lower than the agar-determined MICs for most of the tested M. avium strains, which is probably due to the higher absorption and degradation of the drugs in solid media. The MICs, especially those determined in broth, are suggested as quantitative measurements of the degree of susceptibility of M. avium complex strains. For a certain percentage of the M. avium strains the broth-determined MICs were within the limits of MICs found for wild susceptible Mycobacterium tuberculosis strains. These M. avium strains were classified as presumably susceptible. In contrast to M. tuberculosis, the MICs for M. avium strains had a wide range. When the MICs for M. avium strains were only one dilution higher than those for M. tuberculosis, they were tentatively classified as moderately susceptible. The designation moderately resistant or resistant, respectively, is suggested for those M. avium strains for which the MICs were at or above the concentrations achievable in blood. The quantitation of the degree of susceptibility by the MICs and the tentative interpretation of the MICs are suggested for future use in clinical trials as a means of evaluating the patients' responses to chemotherapy compared with the degree of susceptibility of the initial strain isolated before treatment.

Amikacin↗
PubMed1983

Identification of Mycobacterium fortuitum and Mycobacterium chelonei.

The study of 52 strains of rapidly growing mycobacteria showed that Mycobacterium fortuitum and M. chelonei were clearly distinguished by the aid of seven key tests (nitrate reductase, iron uptake, beta-glucosidase, penicillinase, growth on fructose, resistance to pipemidic acid, and resistance to capreomycin) and by analysis of their respective mycolic acids. However, the subdivision of these species into M. fortuitum var. fortuitum and M. fortuitum var. peregrinum and M. chelonei subsp. chelonei and M. chelonei subsp. abscessus was not satisfactorily accomplished.

Capreomycin↗
PubMed1982

Drug-resistant Mycobacterium tuberculosis in Korean isolates.

Tuberculosis is a common disease in developing countries. An increasing incidence of resistance to isoniazid (INH) and streptomycin in organisms isolated from patients who contracted their disease in these countries, particularly in the Far East, is well recognized. This drug resistance has led to the recommendation of empirically beginning a regimen in patients with tuberculosis from the Far East of INH, ethambutol, and rifampin. This report documents the increasing incidence of resistance in isolates from Korea to ethambutol and rifampin in addition to INH and streptomycin. It suggests that the empiric use of INH, ethambutol, and rifampin in this group of patients could potentially lead to resistance to all of these drugs because of a significant amount of multidrug resistance. A regimen of INH, rifampin, pyrazinamide, and capreomycin is suggested as appropriate initial therapy in these patients based on the in vitro sensitivity data presented and initial clinical experience.

Adult↗
PubMed2004

Hypokalemia among patients receiving treatment for multidrug-resistant tuberculosis.

INTRODUCTION: Between January 1999 and December 2000, 125 patients in Lima, Peru were enrolled in individualized treatment for multidrug-resistant tuberculosis (MDR-TB). Hypokalemia was observed to be an important adverse effect encountered in this cohort. OBJECTIVE: To identify risk factors associated with the development and persistence of hypokalemia during MDR-TB therapy, and to review the incidence and management of hypokalemia in patients receiving MDR-TB therapy. METHODS: A retrospective case series of 125 patients who received individualized therapy for MDR-TB between January 1, 1999, and December 31, 2000. RESULTS: Among 115 patients who were screened for electrolyte abnormalities, 31.3% had hypokalemia, defined as a potassium level of < 3.5 mEq/L. Mean serum potassium at time of diagnosis was 2.85 mEq/L. Diagnosis of low serum potassium occurred, on average, after 5.1 months of individualized therapy. Multivariate analysis of risk factors for this adverse reaction identified two causes: administration of capreomycin, and low initial body weight. Normalization of potassium levels was achieved in 86% of patients. CONCLUSIONS: Electrolyte disturbance was frequently encountered in our cohort of patients with MDR-TB. Successful screening and management of hypokalemia was facilitated by training the health-care team in the use of a standardized algorithm. Morbidity from hypokalemia can be significant; however, effective management of this side effect is possible without sacrificing MDR-TB treatment efficacy.

Adult↗
PubMed1983

Antibacterial activity of palmitoyltuberactinamine N and di-beta-lysylcapreomycin IIA.

Palmitoyltuberactinamine N (Pal-Tua N) and di-beta-lysylcapreomycin IIA (di-beta-Lys-Cpm IIA), which are synthetic derivatives of the antituberculous agent tuberactinomycin (Tum) and capreomycin (Cpm) respectively, were tested for anti-bacterial activity. Pal-Tua N inhibited not only tuberactinomycin-resistant Mycobacterium smegmatis but also Escherichia coli, Corynebacterium diphtheriae, Staphylococcus aureus, Streptococcus pyogenes, although it has lost activity against Mycobacterium tuberculosis. Di-beta-Lys-Cpm IIA inhibited the growth of laboratory-derived Tum-resistant M. smegmatis and M. tuberculosis as well as Tum-resistant M. tuberculosis from patients with one exceptional case.

Anti-Bacterial Agents↗
PubMed2005

Treatment outcome of multidrug-resistant tuberculosis among Vietnamese immigrants.

OBJECTIVE: To review the outcome for MDR-TB treatment among potential migrants from Vietnam. SETTING: All cases of documented MDR-TB treated by the International Organization of Migration (IOM) in Vietnam from 1989 to 2000 were reviewed. METHODS: MDR-TB was defined as isoniazid- and rifampicin-resistant Mycobacterium tuberculosis. All cases of TB treated by the IOM and recorded in the computerised database were reviewed to identify MDR-TB cases. Demographics, chest radiograph results, drug resistance, drug use and dosage, duration of treatment, and outcome were analysed. RESULTS: Forty-four cases of MDR-TB were identified. Treatment consisted of ambulatory directly observed treatment with an 8-drug protocol: isoniazid, rifampicin, pyrazinamide, ethambutol, capreomycin, ethionamide, ofloxacin and cycloserine. This initial protocol was modified due to drug availability or drug intolerance. Patients were treated with a median of 8 drugs (range 6-12). Mean duration of treatment for MDR-TB was 23.0 (SD+/-11.4) months. Thirty-eight (86%) patients were cured and emigrated, one failed treatment (2%), three were lost to follow-up (7%) and two died (4%). CONCLUSION: Treatment for MDR-TB provided by the IOM was effective in preparing a low-income population for migration.

Capreomycin↗
PubMedDate not supplied

[The rates of resistance to second-line drugs in multidrug resistant Mycobacterium tuberculosis strains].

The treatment of multidrug resistant tuberculosis (MDR-TB) requires the use of minor antituberculosis drugs, thus susceptibilities against these minor drugs should be performed. The aim of this study was to establish and standardize the susceptibility testing methods for minor antituberculosis drugs in this laboratory and to obtain data about the resistance rates. Drug susceptibility tests were performed by proportion method in Lowenstein-Jensen media for 50 MDR Mycobacterium tuberculosis isolates that have been collected from different regions of our country. Resistance rates to ethionamide, cycloserin, kanamycin, p-aminosalicylic acid, ofloxacin, thiacetasone, and capreomycin were found as 22%, 8%, 6%, 6%, 2%, 2%, and 0%, respectively. Multidrug resistance was observed in 8% of the isolates. As a result, the resistance rates of multidrug resistant M. tuberculosis strains against the tested minor antituberculosis drugs seem to be low in this study.

Aminosalicylic Acid↗
PubMed1991

Renal magnesium wasting associated with therapeutic agents.

Renal magnesium wasting is an important cause of hypomagnesemia observed in hospitalized patients. The purpose of this review is to present an index case of symptomatic hypomagnesemia associated with renal magnesium wasting during capreomycin therapy, and to survey the available literature regarding the various therapeutic agents associated with the causation of this syndrome. Finally, we have considered the pathophysiologic mechanisms that may contribute to the development of the multiple electrolyte abnormalities observed in these patients, and have outlined the current strategies to treat this syndrome.

Aminoglycosides↗
PubMed1975

[Sensitivity of m. kansasii strains to various antibiotics and chemotherapeutics in vitro and in vivo (author's transl)].

Sensitivity of 40 strains of M. kansasii (var. luciflava) to various antibiotics and chemotherapeutics in vitro and in vivo was examined. The strains showed considerable individual variability in their susceptibility in vitro, most were more resistant to isoniazid and PAS and about one half of the investigated strains to streptomycin, too, if correlated to "wild" strains of M. tuberculosis. Susceptibility to ethionamide, thiosemicarbazone (Conteben), viomycin, kanamycin and cycloserine appears to be the same as in the case of M. tuberculosis strains, but the resistance to pyrazinamide is higher. Good effect has been observed in vitro with rifampicin, ethambutol, capreomycin and phenazine derivative B 663. Oleandomycin and gentamycin are ineffectual in the dosages of drugs we used. The activity of most of these drugs was observed in experimental infections of white mice--in mono-therapy and in various combinations-provoked by different strains of M. kansasii. The main criterion of the effectivity of the treatment was the enumeration of viable mycobacterial units in the lungs of the mice in ten-days intervals; in one part of the experiments the histological examination of the various organs of the mice was performed. The drugs of the I. and II. line of antituberculotics were ineffective or showed only a slight effect. A very good effect of rifampicin, ethambutol and phenazine derivative B 663 in monotherapy and in multiply drug therapy was observed.

Animals↗
PubMedDate not supplied

Studies on pyrazine derivatives. Part X. Synthesis and tuberculostatic activity of some 6-cyclamino-, 6-imidazolyl--and triazolylpyrazine-2-carboxylic acids derivatives.

The 6(2'-methylpiperidine-, 2',6'-dimethylmorpholino-, imidazolyl- and triazolyl)-2-cyanopyrazines were prepared from 2-cyano-6-chloropyrazine. The -CN group was then transformed into COOH, CONH2, CSNH2, CONHNH2, CONHOH and C(NOH)NH2 functions. All compounds obtained were of weak tuberculostatic activity. Comp. 13 was active against isoniazide, capreomycin and ethionamide resistent strains at the concentration range of 31.2--62.5 microgram/cm3.

Antitubercular Agents↗
PubMed1978

[Atypical mycobacterial infection due to Mycobacterium fortuitum].

The case is presented of a 48-year-old woman who, in association with repeated septic temperatures, developed abscesses in the region of the right shoulder and in the right ankly. Histological examination from excisates revealed caseous tuberculoid granulomas. Mycobacterium fortuitum was isolated from the pus of both abscesses. Although the Mycobacterium fortuitum was resistant to nine commonly used tuberculostatics, it was found to be sensitive to ethionamide and capreomycine. The use of these two drugs in combination with local measures proved successful.

Ankle↗
PubMedDate not supplied

The efficacy of certain anti-tuberculosis drugs is affected by binding to alpha-1-acid glycoprotein.

One of the most ubiquitous plasma proteins, alpha-1-acid glycoprotein (AGP), has a high affinity, low capacity binding for basic drugs positively charged at physiological pH. Moreover, as an acute phase protein its level is increased in various disease states in a manner that is likely to influence the free plasma level of a drug, the ability to attain minimum effective concentration and overall in vivo effectiveness. AGP is a glycoprotein known to display disease specific changes in glycosylation and although this secondary modification is not directly involved in drug binding, it may influence the conformation of the binding site. Binding studies reveal that alpha-1-acid glycoprotein bind mainly to the tuberculosis drugs: rifampicin; isoniazid; pyrazinamide; p-aminosalicylic acid; capreomycin; ethionamide; levofloxacin and ofloxacin out with the therapeutic plasma range tested. These results are however still considered significant as not only are alpha-1-acid glycoprotein levels increased during the acute phase response but specific alpha-1-acid glycoprotein from tuberculosis samples are subject to glycosylation changes which can increase the binding affinity and cause binding to occur at the therapeutic concentration.

Antitubercular Agents↗
PubMed2006

Comparison of CID spectra of singly charged polypeptide antibiotic precursor ions obtained by positive-ion vacuum MALDI IT/RTOF and TOF/RTOF, AP-MALDI-IT and ESI-IT mass spectrometry.

Various classes of polypeptide antibiotics, including blocked linear peptides (gramicidin D), side-chain-cyclized peptides (bacitracin, viomycin, capreomycin), side-chain-cyclized depsipeptides (virginiamycin S), real cyclic peptides (tyrocidin, gramcidin S) and side-chain-cyclized lipopeptides (polymyxin B and E, amfomycin), were investigated by low-energy collision induced dissociation (LE-CID) as well as high-energy CID (HE-CID). Ion trap (IT) based instruments with different desorption/ionization techniques such as electrospray ionization (ESI), atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) and vacuum MALDI (vMALDI) as well as a vMALDI-time-of-flight (TOF)/curved field-reflectron instrument fitted with a gas collision cell were used. For optimum comparability of data from different IT instruments, the CID conditions were standardized and only singly charged precursor ions were considered. Additionally, HE-CID data obtained from the TOF-based instrument were acquired and compared with LE-CID data from ITs. Major differences between trap-based and TOF-based CID data are that the latter data set lacks abundant additional loss of small neutrals (e.g. ammonia, water) but contains product ions down to the immonium-ion-type region, thereby allowing the detection of even single amino-acid (even unusual amino acids) substitutions. For several polypeptide antibiotics, mass spectrometric as well as tandem mass spectrometric data are shown and discussed for the first time, and some yet undescribed minor components are also reported. De novo sequencing of unusually linked minor components of (e.g. cyclic) polypeptides is practically impossible without knowledge of the exact structure and fragmentation behavior of the major components. Finally, the described standardized CID condition constitutes a basic prerequisite for creating a searchable, annotated MS(n)-database of bioactive compounds. The applied desorption/ionization techniques showed no significant influence on the type of product ions (neglecting relative abundances of product ions formed) observed, and therefore the type of analyzer connected with the CID process mainly determines the type of fragment ions.

Anti-Bacterial Agents↗
PubMed1976

Effect of viomycin on dihydrostreptomycin binding to bacterial ribosomes.

Viomycin, a peptide antibiotic, reduced the amounts of dihydrostreptomycin bound to ribosomes of Myobacterium smegmatis and Escherichia coli, although they have different modes of action. The [3H]dihydrostreptomycin binding to ribosomes could not exchanged with streptomycin or dihydrostreptomycin, but not with unrelated antibiotics, namely, kanamycin, neomycin, spectinomycin, capreomycin, tuberactinomycin-N, chloramphenicol and erythromycin. We suggest that there is a significant interaction between the binding sites of viomycin and streptomycin on ribosomes.

Anti-Bacterial Agents↗
PubMed1995

[Multidrug-resistant tuberculosis. Epidemiology, treatment, prevention and diagnostic research].

The recent augmentation of the prevalence of multidrug resistant (MDR) tuberculosis is related to the high incidence of tuberculosis in HIV infected people, especially in those with low social status and no medical care; several nosocomial epidemics of MDR tuberculosis were observed in American and European institutions where HIV-infected persons were hospitalized; these MDR tuberculosis were associated with a high mortality-rate and frequent nosocomial transmission to immunocompromised contacts and care workers. The rapid institution of an adequate treatment with ancient antituberculosis agents (cycloserin, capreomycin, aminoglycosides) and/or new drugs (rifabutine, ofloxacin, sparfloxacin, etc) is necessary to avoid mortality and to diminish transmission. Prevention of MDR tuberculosis transmission is very important: patient isolation, adequate and prolonged therapy, better detection of resistance with gene-amplification methods (PCR) which are under investigation.

Comorbidity↗
PubMed2026

A Pilot Study on the Utility of Whole Genome Sequencing for Detecting Drug Resistance in Mycobacterium tuberculosis in the Current Scenario.

PURPOSE: Whole Genome Sequencing (WGS) comprehensively detects all drug-resistant mutants, which can help in the early initiation of specific treatment for the patient. But there is a need to evaluate the performance of WGS in comparison with Line Probe Assays (LPA) and Phenotypic Drug Susceptibility Tests (pDST). METHODS: Consecutive sputum samples (58) found positive for Mycobacterium tuberculosis (MTB) by GeneXpert were tested for first-and second-line LPA, pDST and WGS for anti-tubercular drugs. RESULTS: Of 58, 34 (58.6%) culture isolates were resistant to one or more drugs. Resistance detected by WGS was as follows: Isoniazid 23(39.6%), Rifampicin 21(36.2%), FQs 21(36.2%), Ethambutol 18(31%), Linezolid 12(20.6%), Streptomycin 8(13.8%), Kanamycin 6(10.3%), Amikacin and Capreomycin 5(8.6%), Para-amino salicylic acid 1(1.7%) and Ethionamide 1(1.7%). No resistance was detected to Pyrazinamide, Bedaquiline, Clofazimine, Delamanid and Pretomanid. Lineage 3(EAI) was the most predominant 23(39.6%) followed by Lineage 2: 13(22.4%). Intermediate Resistance (IR) and potential novel mutations were observed in a few cases, CONCLUSION: Overall accuracy for first-line drugs between pDST vs WGS was >98% &pDST vs LPA >95%, while for second-line drugs accuracy was >96% and >90% respectively. IR and potential novel mutations should be followed up closely to understand their clinical significance.

IR↗