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PubMed2004

[Frequency and pattern of adverse reactions due to treatment of patients with pulmonary tuberculosis with antitubercular reserve drugs].

Two hundred and fifty-four patients with pulmonary tuberculosis, treated with reserve antituberculous drugs due to multidrug resistance, the ineffective prior stage of treatment, or intractable adverse reactions, were examined. Aminoglycosides and capreomycin were administered. Combinations simultaneously included 5-7 drugs. Adverse reactions were developed in 72.8% of the patients to different drugs and in different periods. Adverse gastrointestinal, renal, central nervous system, and auditory reactions of reserve drugs were most commonly detected. Essential were also electrolyte metabolic disturbances, hypothyroidism (when reserve drugs were given), intestinal dysbacteriosis, and allergic reactions. The paper analyzes the pattern of adverse reactions caused by each preparation, the time of their occurrence, and methods for their elimination in detail. Adverse reactions to reserve drugs exerted a negative effect of the efficiency of the chemotherapy performed.

Adolescent↗
PubMed2005

Analysis of Mycobacterium tuberculosis isolates from treatment failure patients living in East Timor.

SETTING: In the first 2 years of the East Timor National TB Control Programme, 7960 new patients were treated (2RHZE/6HE) and 224 received a retreatment regimen (2SRHZE/1RHZE/4R3H3Z3E3). OBJECTIVE: To determine the nature and extent of drug-resistant tuberculosis (TB) in treatment failure cases in East Timor. METHODS: Sputum specimens from retreatment failure cases were processed and inoculated into a BACTEC MGIT960 tube and onto Löwenstein-Jensen media. Isolates were identified by Ziehl-Neelsen staining, hybridisation with nucleic acid probes and biochemical investigations. Susceptibility testing was performed using the radiometric proportion method. Pyrazinamide testing was performed using the Wayne indirect method. RESULTS: Eighteen patients failed retreatment (0.7% of new cases) and 14 were available for analysis. Mycobacterium tuberculosis was cultured from all specimens, despite considerable transport delays. Nine (64.3%) had multiple drug resistance (MDR-TB) and four (28.6%) had other drug resistance. All MDR-TB isolates were susceptible to amikacin, capreomycin and ethionamide, with most also susceptible to ciprofloxacin and para-aminosalicylic acid (PAS). CONCLUSIONS: An excellent TB control programme has been established in East Timor. If funds are available, East Timor provides an ideal setting for a small-scale DOTS-Plus programme to treat prevalent cases of MDR-TB, and this study could inform the second-line drug regimen.

Antitubercular Agents↗
PubMed2006

A community-based TB drug susceptibility study in Mimika District, Papua Province, Indonesia.

SETTING: A district level tuberculosis (TB) control programme in Papua Province, Indonesia. OBJECTIVE: To determine the nature and extent of drug-resistant TB in newly diagnosed sputum smear-positive patients. METHODS: Sputum was collected from previously untreated smear-positive pulmonary TB patients diagnosed in the district over a 10-month period. Sputum specimens were processed and inoculated into a BACTEC MGIT960 tube. Isolates were identified by Ziehl-Neelsen staining, hybridisation with nucleic acid probes and biochemical investigations. Susceptibility testing was performed using the radiometric proportion method. Pyrazinamide testing was performed using the Wayne indirect method. RESULTS: One hundred and seven patients had sputum sent to a reference laboratory; 101 (94.4%) were culture-positive for Mycobacterium tuberculosis, with 87 (86.1%) fully sensitive to first-line anti-tuberculosis drugs. Two per cent were multidrug-resistant (MDR-TB) and 12 (11.9%) had other drug resistance. Each of the MDR-TB isolates was susceptible to amikacin, capreomycin, ciprofloxacin and para-aminosalicylic acid (PAS), but were resistant to rifabutin. One isolate was also resistant to ethionamide. CONCLUSIONS: MDR-TB is present in Indonesia but is not a major problem for TB control in this district. Generalisability to other districts in Indonesia, particularly large urban areas, needs to be confirmed by future studies.

Adolescent↗
PubMed1991

[In vitro experiment showing that chemotherapy of tuberculosis by aminoglycoside antibiotics may influence successive chemotherapy with rifampicin].

When Mycobacterium tuberculosis strain H37Rv was cultivated in Ogawa egg medium containing 5 micrograms/ml streptomycin and/or 10 micrograms/ml kanamycin, which were considered as subinhibitory, it was observed that growing bacterial population contained several times more rifampicin-resistant mutants than did the parent strain. The ratio of isoniazid-resistant mutants did not change by the above treatment. The finding suggests that, even without the use of rifampicin, the bacterial population of patients becomes more resistant to rifampicin by chemotherapy in the past with streptomycin or kanamycin. Furthermore, it was shown that the ratio of streptomycin-resistant mutants increased by pre-treatment with kanamycin and the ratio of kanamycin-resistant mutants by pre-treatment with streptomycin. Parent, susceptible bacterial population develops 4R-phenotype mutants which are resistant to four drugs, high concentrations of kanamycin, lividomycin and paraomomycin and a low concentration of capreomycin, whereas streptomycin-resistant mutant population does not develop the 4R mutants but develops only mutants with the KR phenotype which is almost mono-resistant to kanamycin.

Anti-Bacterial Agents↗
PubMed1988

[Interactions of antitubercular drugs].

Antituberculous drugs are never used alone but are often given concomitantly with drugs prescribed for other diseases. We have therefore reviewed the potential interactions of antituberculous drugs between themselves and with other drugs. Rifampicin being a potent enzyme inducer will decrease the plasma levels of a wide range of drugs. This in turn will decrease the effectiveness of these drugs if they are unmetabolized and active, or increase drug toxicity if the metabolites are toxic. Within the first category are the oral contraceptives, steroids, oral antidiabetics, oral anticoagulants and digitalis. Within the second category is thought to be isoniazid on account of its hepatotoxicity. In contrast, isoniazid (INH) is an enzyme inhibitor. Drugs with hepatic metabolism will tend to accumulate, although this seems clinically relevant only with antiepileptic drugs, diazepam, triazolam and oral anticoagulants (with high INH doses). Many other cases of drug interaction have been described, but they seem to be rare and may not be clinically relevant. INH and rifampicin do not seem to modify each other's metabolism consistently, but it may be wise to check the serum INH levels during coadministration. As said above, rifampicin does increase the hepatotoxicity of INH. INH also inhibits monoamine oxidase and will interact with other MAOI, as well as with fish, cheese or wine with high histamine or tyramine contents. The only interaction found with ethambutol is with diazepam: it increases its clearance and free fraction. Obviously, streptomycin potentiates the ototoxicity of other amino-glycosides, such as capreomycin, kanamycin or viomycin, so that combining them is strictly contra-indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗
PubMedDate not supplied

[Skin ulcer caused by Mycobacterium ulcerans in Cameroon. II. Bacteriological study].

Nine stains of Mycobacterium ulcerans isolated in Kamerun, in Congo and in France, were compared with six reference strains found in Zaïre, Australia and Mexico and M. intracellulare, M. simiae, M. paratuberculosis. These fiveteen strains constitutets an species whose typical features were: the difficult and slow growth at the optimum temperature of 30 degrees C, the biochemical tests and the sensitivity to rifampin, streptomycin, kanamycin, viomycin, cycloserin and probably capreomycin. In mice inoculated by the intravenous route, M. ulcerans gives ulcerations of external teguments and sometimes, internal lesions.

Anti-Bacterial Agents↗
PubMedDate not supplied

Studies on pyrazine derivatives. Part VIII. Synthesis and tuberculostatic activity of some 6-alkylthio- and 6-phenylthiopyrazine-2-carboxylic acids.

2-Cyano-6-alkylthio- and 6-phenylthiopyrazines were prepared from 2-cyano-6-chloropyrazine (CCP) in the reaction with mercaptans. By the transformation of the -CN group the corresponding amides, thioamides, amidoximes, acids, esters and hydroxamic acids and hydrazides were obtained. The oxidation of sulfur in the above mentioned compounds led to sulfoxy- and sulfonyl derivatives. In the screening for antituberculous activity compounds 30 and 42 showed the greatest activity (MIC = 31.2 microgram/cm3) against H37Rv strain and compund 8 so did against saprophytic ATCC 607 strain. The compounds with 6-benzylthio grouping were more active against ethionamide, isoniazide and capreomycine resistant strains.

Antitubercular Agents↗
PubMed1978

[Antibiotic action on the embryonic development of the fetuses of amphibians].

The effect on the embrionic development of Tr. cristatus of 16 antibiotics (keflin, penicillin, benzazillin, ampicillin, nystatin, kanamycin, streptomycin, novobiocin, brunomycin, erythran, oleandomycin, tetracyclin, chlornytromycin, gentamycin, rimactan, and capreomycin) administered in 3 concentrations was studied. It was established that except kanamycin, keflin and rimactan all the rest damage the embryonic development showing certain phase specifity. Gastrulation turned to be the most sensitive embryonic period.

Amphibians↗
PubMed1981

[Recommendations to otolaryngologists for patients with antituberculotic chemotherapy (author's transl)].

With long-time antituberculotic chemotherapy aminoglycosid-antibiotics (Streptomycin, Neomycin, Kanamycin, Gentamycin) and polypeptid-antibiotics (Polymyxin B, Viomycin, Capreomycin) will endanger the nervus statoacusticus. After discussing manner and frequency of possible troubles recommendations are given to the ENT-physician, how to minimize the damage for the cochleovestibular system.

Antitubercular Agents↗
PubMed1994

Antimycobacterial drugs.

This review consists of the following three sections: (1) General principles in selecting antimycobacterial drugs for the treatment regimens, (2) The antimicrobial activity in vitro with an emphasis on inhibitory and bactericidal potency of various agents, and (3) Drug susceptibility testing including methodology and interpretation of the test results. Each of these sections addresses three groups of antimycobacterial agents: (1) against tuberculosis, (2) against Mycobacterium avium complex infections, and (3) against infections caused by M. fortuitum and M chelonae. The following are the drugs examined in the sections and subsections of this review: isoniazid, ethionamide, thiacetazone, rifampin, rifabutin, rifapentine, KRM-1648, pyrazinamide, streptomycin, kanamycin, amikacin, capreomycin, gentamicin, tobramycin, ethambutol, para-aminosalicylic acid, D-cycloserine, ofloxacin, levofloxacin, ciprofloxacin, sparfloin, clofazimine, clarithromycin, azithromycin, erythromycin, cefoxitin, cefmetazole, imipenem, sulfamethoxazole, sulfisoxazole, sulfadiazine, sulfathiazole, trimethoprim, and doxycycline.

Antitubercular Agents↗
PubMed1996

Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family.

OBJECTIVE: To determine whether isolates of Mycobacterium tuberculosis from New York and elsewhere that are resistant to four or more primary antimicrobial agents and responsible for widespread disease in the 1990s represent a newly emerged clone or a heterogeneous array of unrelated organisms. SETTING: New York City area and selected locations in the United States. PATIENTS: M tuberculosis isolates from 1953 patients in New York and multidrug-resistant isolates from six patients from other US communities. DESIGN: Convenience sample of all M tuberculosis strains (M tuberculosis isolates resistant to rifampin, streptomycin, isoniazid, and ethambutol, and sometimes ethionamide, kanamycin, capreomycin, or ciprofloxacin) submitted to the Public Health Research Institute Tuberculosis Center since 1991 and samples submitted to the Centers for Disease Control and Prevention from throughout the United States. The samples submitted were representative of the New York City strains of M tuberculosis. MAIN OUTCOME MEASURE: Characterization of resistant M tuberculosis strains studied by IS6110 and polymorphic GC-rich repetitive sequence (PGRS) hybridization patterns, multiplex polymerase chain reaction (PCR) analysis, and automated DNA sequencing of genes containing mutations associated with resistance to rifampin (rpoB), isoniazid (katG and inhA locus), and streptomycin (strA and rrs). RESULTS: Multidrug-resistant M tuberculosis isolates were recovered from 253 New York City patients and had the same or closely allied IS6110 and PGRS patterns, multiplex PCR type, and gene mutations associated with resistance to rifampin, isoniazid, and streptomycin. Isolates with these same molecular characteristics were recovered from patients in Florida and Nevada, health care workers in Atlanta, Ga, and Miami, Fla, and an individual who recently moved from New York City to Denver, Colo, and caused disease or skin test conversion in at least 12 people in a nursing home environment. CONCLUSIONS: The results document the molecular origin and spread of progeny of a closely related family of multidrug-resistant M tuberculosis strains that have recently shared a common ancestor and undergone clonal expansion. The multidrug-resistant phenotype in these organisms arose by sequential acquisition of resistance-conferring mutations in several genes, most likely as a consequence of antibiotic selection of randomly occurring mutants in concert with inadequately treated infections. Dissemination of these difficult-to-treat bacteria throughout New York City and to at least four additional US cities has adverse implications for tuberculosis control in the 21st century.

Antitubercular Agents↗
PubMed1996

A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes.

OBJECTIVE: To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome. DESIGN: Epidemiologic investigation of every tuberculosis case reported in New York City. SETTING: Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months). PATIENTS: We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W. MAIN OUTCOME MEASURES: Patient survival and the conversion of sputum cultures from positive to negative. RESULTS: Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who received medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+ T-lymphocyte count greater than 0.200 x 10(9)/L (200/microL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival. CONCLUSIONS: This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival.

Adolescent↗
PubMed1998

Outcome of second-line tuberculosis treatment in migrants from Vietnam. International Organization for Migration (IOM) Tuberculosis Working Group.

From 1990 to 1995, 410,441 prospective migrants were screened for tuberculosis (TB) in Ho-Chi-Minh City (Vietnam), within the framework of the Orderly Departure Programme. 161 individuals had multidrug-resistant (MDR) TB and were treated with a seven-drug regimen (isoniazid, rifampicin, ethambutol, pyrazinamide, capreomycin, cycloserine, and ethionamide) for at least 12 months. In January 1996, 31 of these patients were still on treatment. The cumulative percentage of cure was 21% at 18 months, 71.6% at 36 months, and 81.2% at 55 months. Sex, age, presence of cavities, and previous tuberculosis treatment did not affect the chance of cure, but age > 45 years significantly affected the chance of treatment failure (nonadherence, death, treatment stopped due to side effects).

Adult↗
PubMed1985

Chromatographic analysis of antituberculosis drugs in biological samples.

Numerous chromatographic and non-chromatographic methods of analysis for anti-tuberculosis drugs and metabolites in biological tissues have been discussed in this review. Depending upon the analytical methodology selected, limits of detection range from microgram to picogram levels. A number of examples have been given of the correlation between different types of assay procedures. The metabolism and pharmacokinetics have been described along with some of the commonly associated problems of sample collection and storage.

Aminosalicylic Acids↗