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PubMed1992

Cerebrospinal fluid isoniazid concentrations in children with tuberculous meningitis: the influence of dosage and acetylation status.

Cerebrospinal fluid (CSF) and plasma isoniazid (INH) concentrations were determined on 96 occasions in 38 children (median age 1.5 years) with tuberculous meningitis, and the effects of INH elimination status and test dosages of 10 mg/kg body weight and 20 mg/kg body weight was studied. Maximum cerebrospinal fluid INH concentrations were reached during the period 2 to 4 hours after dosing and cerebrospinal fluid and plasma INH concentrations did not differ significantly during this period. Cerebrospinal fluid INH concentrations following a dosage of 10 mg/kg (4.6 +/- 2.4 micrograms/mL) were, however, significantly lower than those following a dosage of 20 mg/kg (11.6 +/- 2.7 micrograms/mL). Cerebrospinal fluid INH concentrations in faster acetylators at a dosage of 10 mg/kg (3.2 +/- 1.1 micrograms/mL) were significantly lower than in slower acetylators (7.7 +/- 1.3 micrograms/mL), as was the case with a dosage of 20 mg/kg, where faster acetylators had cerebrospinal fluid INH concentrations of 10.5 +/- 2.5 micrograms/mL compared with 14.1 +/- 1.4 microgram/mL in slower acetylators. Following dosages of both 10 mg/kg and 20 mg/kg, INH concentrations in excess of the minimal inhibitory concentration for Mycobacterium tuberculosis persisted in the CSF 12 to 14 hours later. Despite the patients' being young and frequently malnourished, suffering from advanced forms of tuberculous meningitis, and receiving high dosages of INH, rifampicin, and pyrazinamide, none developed any clinical signs of hepatotoxicity and in only one child did the serum bilirubin level rise to 19 micrograms/mL.

Acetylation↗

PubMed1991

Tuberculosis in the intensive care unit: a chemotherapeutic controversy.

A survey of 150 practicing pulmonary physicians was conducted to determine chemotherapy preferences for the treatment of the patient suffering respiratory insufficiency secondary to active nonmiliary tuberculosis. An equal sample was selected from both the private sector and academic medicine in order to determine if antituberculous agent selection differed between these two groups. The majority of the 109 physicians who responded to the questionnaire (64.2%) indicated that they would use isoniazid, rifampin, and a third agent. There was no statistical difference in the choice of ethambutol, pyrazinamide, or streptomycin as the third drug. There was no difference between university and community based physicians in the use of three drug combinations or in the selection of the specific third agent. This study suggests that, although the majority of pulmonologists responding would treat the patient with respiratory insufficiency from tuberculosis with an aggressive three drug approach, there is no consensus as to which agent should be the third drug.

Antitubercular Agents↗

PubMed1991

[The hepatotoxicity of tuberculosis treatment].

BACKGROUND: The hepatic toxicity of antituberculous drugs used for the therapy of initial cases was evaluated, assessing the incidence and severity and its relation with each drug, age, other associated hepatic risks and the chronological time of therapy. METHODS: 1235 patients with tuberculosis were prospectively assessed with a protocol including periodical clinical and laboratory controls. RESULTS: Hepatic toxicity was found in overall 16.5%, with 3.5% of severe forms and need for a definitive change in therapy in 1.5%. Differences in toxicity between the 6-month and the 9-month schedules were not found. The most commonly incriminated drugs was isoniazid followed by pyrazinamide. All severe forms presented with symptoms, although some were nonspecific and insidious. Other associated hepatic risks implied an increased frequency of iatrogenic reactions. Age did not have a determining influence in severe forms, which predominantly developed within the first two months of therapy. CONCLUSIONS: Moderate, transient and asymptomatic increase in transaminase activity not requiring a change a therapy is common. Severe and dangerous forms are uncommon and predominate at the beginning of therapy and in persons with associated hepatic risk factors. Therefore, although the clinical controls should be maintained throughout treatment, laboratory controls should only be carried out during the first two months, except when symptoms are present or in patients with associated hepatic risk factors, where they should be more frequent and carried out throughout treatment.

Age Factors↗

PubMed1991

[Studies about the therapy of tuberculosis in East Germany (former GDR)].

On the basis of a questionnaire the therapy of 2285 patients with tuberculosis was evaluated for the years 1987-1989. The data of the GDR National Tuberculosis Register (9827 patients) were used for statistical comparison. 85% of the patients had a pulmonary tuberculosis, 947 patients (41% of all) excreted tubercle bacilli in the sputum. The average duration of treatment was 31.8 weeks, 94.7% of the patients were hospitalised for treatment for an average time of 12.4 weeks, the following outpatient treatment was 19.4 weeks in average. The initial phase (daily-treatment) in all cases of tuberculosis was 8.6 weeks, the follow-up phase was 23.2 weeks (all data are averages). The intermittent outpatient drug administration was made in 95% of cases under nurse control in outpatient departments. The initial treatment was started in 92.1% with 3 or 4 drugs (H/R/Z/S or E). Isoniacid and rifampicin were prescribed in 89.7% and pyrazinamide was used as a 4th drug. In the follow-up phase the combination isoniacid and rifampicin was employed intermittent in 75.7%. The delaytime for the evaluated cases was 38.8 days in average. The result of study shows, in most cases the patients were treated according to the recommendation of therapy. The clinical stay of patients is too long.

Adolescent↗

PubMed1991

[Treatment with antitubercular agents after kidney transplantation].

After kidney transplantation 1-3.6% of patients develop tuberculosis. At early diagnosis and addressly applied treatment the disease is not life threatening. On the basis of the author's own experience and literary data, suitable combinations of antituberculotics are recommended. At normal or reduced function of the kidney transplant a combination of isoniazid, rifampicin, and pyrazinamide is advocated. In deranged liver function the combination of choice consists of isoniazid, streptomycin, and ethambutol. (Ref. 9).

Antitubercular Agents↗

PubMed1991

[Antitubercular agents. LIV. 3-Alkyl(or -alkyl) thio-2,5-pyrazindicarboxamides].

From 5-cyano-3-chloro-2-pyrazinecarboxamide) (II) hydrolysis in acid medium) yielded 3-chloro-2,5-pyrazinedicarboxamide (III), which in a reaction with sodium hydrogensulfide in dimethyl-formamide) yielded 3-mercapto-2,5-pyrazinedicarboxamide (IV). This compound through condensations with alkyl- and arylhalogenides in triethylamine) yielded 3-alkyl(or aryl) thio-2,5-pyrazinedicarboxamides of type I. The structure of compounds was confirmed by elemental analysis, IR and 1H NMR spectra. A microbiological evaluation was carried out; the antituberculous effect of these compounds is not higher than that of pyrazinamide.

Mycobacterium tuberculosis↗

PubMed1991

[The usefulness of systematic follow-up of tuberculosis for the diagnosis of relapse in French Polynesia between 1971 and 1984].

Standard chemotherapy for one year was proposed for the treatment of tuberculous patients in French Polynesia between 1971 and 1978, and for nine months with the addition of pyrazinamide from 1979 to 1984. After treatment, the patients were followed up systematically for a period of 5 years. The aim of this study was to evaluate the value of the follow up measures to detect relapses. Of 1,065 patients treated between 1971 and 1984 at the centre for the control of tuberculosis 35 (3%) presented with a relapse, of whom 30 were confirmed either by bacteriological examination or histological examination. The level of relapse seen was not linked to age, sex, nor type of treatment received (one year or nine months). However, the level of relapse in non compliant patients to the initial treatment (7%) was significantly greater than those observed in patients who were totally compliant (2%) (p less than 0.0001). Of the 35 relapses 9 (26%) were discovered during routine follow up visits, of whom 8 were detected during the first year. The median delay separating apparent recovery from relapse was 8 months. 28 patients (80%) presented with symptoms suggestive of a relapse. Over 5 years 5773 consultations were carried out, which meant 642 consultations to detect one relapse. The authors suggest that in French Polynesia a systematic follow up limited to one year after apparent cure should be adequate.

Adult↗

PubMed1991

[Tuberculosis treatment today].

In West and East Germany the incidence of tuberculosis is declining. However, with an incidence of 22 per 100,000 inhabitants in West Germany and 17 new diseases per 100,000 inhabitants in East Germany it is not a rare disease. In the chemotherapy of pulmonary tuberculosis, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), streptomycin (SM), pyrazinamide (PZA) and prothionamide (PTH) are the most relevant drugs. The chemotherapy of tuberculosis is always carried out as a combination therapy of at least three drugs. A rapid cultural conversion of the sputum as well as low rates of failures and relapses are regarded as parameters of quality. Therefore six-month-regimens with initially four drugs (INH + RMP + PZA + SM or EMB) or nine-(twelve-) month-regimens with initially three medicaments (INH + RMP + PZA, or INH + RMP + EMB or INH + RMP + SM) may be recommended. Peculiarities of the therapy in patients with AIDS, with drug resistance, with relapses.

Antitubercular Agents↗

PubMed1991

The management of extra-pulmonary tuberculosis.

Most cases of extra-pulmonary tuberculosis respond well to chemotherapy. The standard regimen is isoniazid + rifampicin daily for 6 months, with the addition of pyrazinamide for the first 2 months. Chemotherapy is given for 9 or 12 months in meningitis, and in some cases of lymphadenitis and bone and joint disease. If initial drug resistance is suspected, either streptomycin or ethambutol should be added to the first phase of treatment. Only a minority of cases need surgical treatment but surgical diagnostic procedures are often useful. Corticosteroids are not recommended for routine use but can be valuable in lymphadenitis, meningitis, pericarditis and genito-urinary disease.

Antitubercular Agents↗

PubMed1991

Clinical features, diagnoses, and management of tuberculosis in immunocompromised hosts.

For many years tuberculosis has been known to occur with greater frequency among persons with disorders that impair host defenses. In most instances these processes interfere with the immune response to Mycobacterium tuberculosis, whereas, in a few, such as silicosis, the probable abnormality is a nonimmune defect in macrophage function. Infection with the human immunodeficiency virus (HIV) causes progressive and ultimately profound depression of both humoral and cell-mediated immunity and, thus, is an extremely potent risk-factor for tuberculosis. Presumably the major effect of HIV infection that predisposes persons to developing tuberculosis is the reduction in circulating T-helper (CD4+) lymphocytes which causes a reduction in cytokine production and a consequent decrease in the functional capabilities of macrophages. However, a number of questions concerning pathogenesis of tuberculosis related to HIV remain. Available data suggest that the magnitude of the risk for developing tuberculosis among persons infected with both HIV and M. tuberculosis is very high, 8% in one prospective study. Because of the epidemic of HIV infection, the progressive downward trend in the incidence of tuberculosis in the United States has reversed and in 1989 there was a 5% increase in the number of cases. Preliminary data for 1990 suggest that there will be an 8 to 10% increase over 1989. Also in the United States approximately 3% of tuberculosis patients have been found to be HIV seropositive. The clinical features of tuberculosis in patients with HIV infection vary depending on the degree of immunosuppression. With mild immunosuppression early in the course of HIV infection tuberculosis presents in a "typical" way with positive tuberculin skin tests, upper lobe cavitary infiltrates on chest film and positive sputum smears and cultures. As the HIV infection progresses, the mode of presentation of tuberculosis becomes more "atypical" with negative skin tests, multiple sites of involvement, chest films showing diffuse noncavitary infiltrates often accompanied by intrathoracic lymphadenopathy. The key to diagnosis is maintaining a high index of suspicion for tuberculosis, especially in patients with advanced HIV disease and including appropriate laboratory examinations in the evaluations of such persons. Regardless of the stage of HIV infection the response to treatment for tuberculosis is generally favorable if it is begun promptly. Standard therapy utilizing isoniazid, rifampin, and pyrazinamide with or without ethambutol have been associated with high rates of cure. Relapse has been uncommon. There has been, however, at least one outbreak of tuberculosis caused by isoniazid and rifampin resistant organisms in which the response to therapy was very poor.(ABSTRACT TRUNCATED AT 400 WORDS)

HIV Infections↗

PubMed1991

Tuberculous pericarditis.

Tuberculosis is responsible for approximately 4% of cases of acute pericarditis, 7% of cases of cardiac tamponade, and, in older studies, 6% of instances of constrictive pericarditis. However, in some nonindustrialized countries, tuberculosis is a leading cause of pericarditis. The diagnosis is based on demonstration of tubercle bacilli in pericardial fluid or on histologic section of the pericardium, or proof of tuberculosis elsewhere in a patient with otherwise unexplained pericarditis. Treatment consists of triple drug therapy for at least 9 months (isoniazid, rifampin, and streptomycin or ethambutol). Pyrazinamide can be used for the first 2 months, and the total therapeutic period can then be shortened to 6 months after culture conversion. Three months of corticosteroid therapy may be useful in patients in whom pericardial effusion persists or recurs despite the use of antituberculous drugs. Surgical resection of the pericardium is indicated for recurrent or life-threatening tamponade, or when there is persistent elevation of systemic venous pressure unrelieved by pericardiocentesis. As many as one third to one half of patients will eventually require pericardiectomy despite adequate drug therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Treatment of tuberculosis.

The incidence of tuberculosis is increasing in the United States. Although the lung is still the most common site of infection, extrapulmonary disease is becoming more prevalent, particularly in patients infected with human immunodeficiency virus (HIV). Clinically active tuberculosis is treated with a combination of drugs. Recommended therapy consists of a six-month regimen of isoniazid and rifampin, with pyrazinamide given for the first two months. Longer regimens are used in patients infected with HIV. Monthly monitoring for adverse effects and treatment response is necessary. Compliance is the most important factor for successful treatment. Treatment failure usually requires the use of more toxic second-line drugs. In such cases, drug susceptibility studies may be useful.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Short course chemotherapy for pulmonary tuberculosis in routine service in Kenya.

The results are reported of the application of a short-course regimen for pulmonary tuberculosis in routine service in three districts in Kenya. All patients were treated in hospital for one month receiving Streptomycin, Isoniazid, Rifampicin and Pyrazinamide daily and followed by Rifampicin and Isoniazid daily on outpatient basis for five months. There was no failure of chemotherapy among 194 patients with pre-treatment sensitive strains at the end of chemotherapy. Six (3.9%) had a doubtful status but none relapsed during follow-up. Among 123 patients assessed after completion of follow-up only one (0.8%) relapsed and 16 of 22 patients with pretreatment resistant strains had a favourable response at the end of chemotherapy and follow-up. The therapeutic results achieved are excellent under programme conditions though of necessity with some amount of supervision that is not routinely available. Considering the advantages of short course regimens, a case for the choice of an appropriate short regimen to be used nationwide in the near future is made.

Adolescent↗

PubMed1990

[Follow-up study of short course chemotherapy of pulmonary tuberculosis complicated with diabetes mellitus].

A retrospective analysis was made for 644 patients with pulmonary tuberculosis newly diagnosed during the time of 1977 to 1985 to evaluate the influence of diabetes mellitus (DM) on the drug response rate and the long-term relapse rate in the treatment of tuberculosis. These patients were divided into four groups: (1) 123 patients with DM on 9- to 12-month short course regimens; (2) 79 with DM on 13- to 36-month long-term regimens; (3) 379 nondiabetic patients on short-term regimens; and (4) 63 nondiabetics on long-term regimens. Bacteriological relapse after chemotherapy was defined as positive cultures growing at least 20 or more colonies. 1) Bacteriological negative conversion rates were similar in both diabetic and nondiabetic patients who had received combination regimens including INH and RFP. The degree of control of DM did not affect the conversion rate. 2) Of 297 patients who had received short-course chemotherapy and the information for analysis were available as of August 1989, 8 (10.3%) had relapses in 78 diabetic, and patients 23 (10.5%) in 219 non-diabetic patients; the difference was not statistically significant. There were also no discernible differences in the relapse rates between patients on the short-course regimens and those on the long-term regimens. 3) Most of the relapses occurred around 6 months and 30 months after completing the short-course chemotherapy. Similar pattern of relapses was observed also in the long-term therapy group. 4) Pretreatment radiographic findings and quantity of the acid-fast bacilli in the sputum, and the presence of cavitary lesions at the completion of therapy bore no significant relation to the development of relapse. 5) In the diabetic patients the degree of control of DM contributed little to the development of recurrence. 6) Although most of the patients without DM relapsed with sensitive strains and achieved a good response to retreatment, diabetic patients frequently relapsed with resistant strains and had a grave prognosis. 7) Of 41 patients who died after having been on the short-course regimens, two were attributed to tuberculosis. Only one was attributed to tuberculosis of 25 patients who died after receiving the long-term regimens. 8) The data obtained here confirmed that the 12-month regimen for diabetic patients could achieve favorable results in the response rate and the long-term relapse rate, as that for nondiabetic patients. However the cases of tuberculosis complicated with DM frequently showed a poor prognosis once the relapse took place. These results suggest that pyrazinamide-containing 4-drug combination regimens in an initial intensive phase is the preferred treatment for the patients with DM.

Adult↗

PubMed1990

Determination of antitubercular drugs in human plasma by HPLC through direct injection.

A simple and efficient method is described for the direct determination of Isoniazide (INH) and Pyrazinamide (PZAm) in human plasma, based on reversed-phase HPLC. A number of other antitubercular drugs such as p-Aminosalycylic acid (PAS), Streptomycin (STM) and Ethambutol (ETH) and the major metabolites of the two investigated drugs, namely N-Monoacetylisoniazide (AcINH) and Pyrazinoic acid (PZAc), were shown not to interfere with the assay method. A potential application of the method to routine clinical monitoring of antitubercular drugs is discussed.

Antitubercular Agents↗

PubMed1990

Study on hepatotoxicity and other side-effects of antituberculosis drugs.

A prospective study of different side-effects and toxicity of different antituberculosis drugs was made on 125 cases of pulmonary tuberculosis, divided into 3 groups according to the regime of treatment. Group A consisted of 50 patients, taking streptomycin, ethambutol and isoniazid. Group B of 50 patients received streptomycin plus ethambutol plus isoniazid and rifampicin and 25 patients comprising group C received streptomycin plus isoniazid plus ethambutol and pyrazinamide. The group B showed hepatotoxicity in 30% cases, out of which clinical jaundice with abnormal liver function tests being 26% and rest 4% cases were of anicteric hepatitis, while group A showed only 6% hepatotoxicity with 4% clinical jaundice and 2% anicteric hepatitis. In group A out of 50 cases only 2 patients complained of colour blindness, which reversed with the stoppage of drugs. In group C out of 25 cases 3 patients had gouty problems and responded with stoppage of drugs. Patients in group A developed jaundice in a mean of 50 days while those in group B developed jaundice in 17 days.

Adult↗

PubMed1990

Anti-tuberculous drugs and sideroblastic anaemia.

Two cases of sideroblastic anaemia associated with antituberculous therapy are reported. The first, in whom there was a constitutional chromosomal abnormality and peripheral neuropathy, recovered on withdrawal of isoniazid and pyridoxine treatment. The other, who had been given a four-drug combination including isoniazid and pyrazinamide and recovered on the withdrawal of isoniazid alone, highlights the increasing likelihood of this complication in patients treated for tuberculosis, since this drug combination has regained popularity in recent years.

Adult↗

PubMed1990

Hepatotoxicity to different antituberculosis drug combinations.

Hepatotoxicity to different combinations of anti-tuberculosis drugs containing, Rifampicin (R), Streptomycin (S), Isoniazid (H), Pyrazinamide (Z) and Myambutol (E) is described in 47 patients who completed 6 to 9 months therapy. Seven cases (15%) showed signs of toxicity and in 4 patients (8.5%) the drugs had to be withdrawn. Two patients developed hepatitis, one with jaundice and the other with fever and deranged liver functions, while others 2 developed severe hypersensitivity reactions. Burning palms, difficulty in micturition, itching and giddiness were complained of by one patient each, which settled in due course without recourse to withdrawal of drugs.

Antitubercular Agents↗