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Pulmonary disease caused by M. malmoense in HIV negative patients: 5-yr follow-up of patients receiving standardised treatment.

The literature concerning the management of pulmonary disease caused by Mycobacterium malmoense consists of retrospective reports on small series of patients. A recent multicentre trial conducted by the British Thoracic Society provided an opportunity to prospectively document the clinical features and response to treatment of this relatively rare but challenging disease in a substantial number of patients. When two positive cultures were confirmed by the Mycobacterium Reference Units for England, Wales, Scotland or Scandinavia, the coordinating physician invited the patient's physician to enrol the patient, who was then treated on a random basis with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid for 2 yrs. Clinical, bacteriological and radiological progress were monitored at set intervals for 5 yrs. In over 5 yrs a total of 106 patients were recruited to the study. The mean age was 58 yrs, range 24-89 A total of 58% were male and just over half previously or at the time ofthe study had other lung diseases. Sputum was positive on direct smear in 58%. Cavitation was seen on the chest radiographs of 74%, the majority having cavities of > or = 2 cm in diameter. Less than half of the patients showed bilateral disease, 26% having involvement of more than three lung zones. Disease was confined to the upper zone(s) in 30%. Other lung diseases were evident in 52%. Although clinical response was judged satisfactory at most reviews (90%), one in three patients died within 5 yrs and <5% were thought to have died primarily because of M. malmoense. There were three failures of treatment and eight relapses after the end of treatment. There was no correlation between failure of treatment/relapse and in vitro resistance. A total of 63 (59%) of patients were alive at 5 yrs, of whom 44 (42% of the total entry) were known to be cured. Pulmonary disease caused by Mycobacterium malmoense is a serious condition that is associated with high morbidity and mortality. The results of standard susceptibility tests do not correlate with the bacteriological response of the disease to chemotherapy. Rifampicin and ethambutol, with or without isoniazid, cured only 42% of patients but were better tolerated than previously described, more complex regimens of equal or lesser efficacy. There is a need for more effective regimens that will reduce mortality and failure of treatment/relapse rates, but, in addition, attention should be directed at improving management of comorbid conditions and improving the general health of the patient.

Adult↗

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↗

[Effect of antitubercular preparations on the function of the ciliary epithelium of the respiratory tract mucosa].

The effect of various concentrations of streptomycin, isoniazid, rifampicin and ethambutol on the function of the siliated epithelium of the frog oral mucosa was studied (110 experiments with 50 frogs). The level of inhibition of the siliated epithelium function depended on the properties of the drugs and their concentration in solution. More pronounced inhibition was induced by 15 per cent ethambutol solution and 10 per cent isoniazid solution. The least inhibition of the siliated epithelium function was observed with the use of 6.25 per cent streptomycin solution, 5 per cent isoniazid solution, 7.5 per cent ethambutol solution and 3.75 per cent rifampicin solution.

Animals↗

[Tuberculosis and pregnancy].

Tuberculosis is neither more frequent, nor more serious in pregnant than non-pregnant women. The risks for the child are threefold: a doubling in the mortality level on account of the illness in the mother if she is not treated; a risk of toxicity linked to the anti-tuberculous drugs and a risk of tuberculous infection at birth. Isoniazid (INH) and ethambutol have a weak toxicity. These two antibiotics can be prescribed during pregnancy (after confirming the absence of Vitamin B6 deficiency in the mother). Rifampicin is teratogenic in high doses in animals, but epidemiological studies do not reveal any notable risk in man. For prudence it is only prescribed in the first trimester of pregnancy, in confirmed cases of tuberculosis. The data on the teratogenicity of pyrazinamide is insufficient and it should not be used in pregnancy. Thus the treatment of tuberculosis in pregnancy will be rifampicin + isoniazid + ethambutol (the ethambutol being stopped after two months and the isoniazid and rifampicin after 9 months of treatment). At the moment of confinement, if maternal tuberculosis is confirmed bacteriologically at the time of microscopy, chemoprophylaxis will be started in the new born with isoniazid, in a dose of 5 mg/kg until the mother is bacteriologically negative on microscopic examination, the new born should then be vaccinated with BCG. If the treatment of the mother is correctly prescribed and followed breast-feeding is possible and no isolation of either mother or child is necessary. The amount of antibiotic that passes in the mothers milk is minimal and such specific nourishment should not be dispensed with if the treatment is necessary.

Antitubercular Agents↗

[Resistance of Mycobacterium tuberculosis in Mexican patients. I. Clinical features and risk factors].

OBJECTIVE: To determine the clinical manifestations associated with resistant M. tuberculosis infection and the antimicrobial resistance in isolates from Mexican patients. STUDY DESIGN: Epidemiological surveillance. PATIENTS: Tuberculosis confirmed cases. METHODS: Primary resistance: no history of treatment prior to diagnosis. The following critical concentrations (micrograms/mL) were used for susceptibility: isoniazid 0.2 and 1; rifampin 1 and 5; ethambutol 5 and 10; streptomycin 2 and 10; ethionamide 5; kanamycin 6; and para-aminosalicylic acid (PAS) 2 and 10. RESULTS: Eighty-four patients with a mean age of 44.7 years were included; 54 men (64%) and 30 women (36%); most patients were from the Mexico City metropolitan area. In 34 patients there was clinical information available, 26 presented fever and weight loss and 8 respiratory symptoms. Fifty-nine patients (70%) were infected by pan-susceptible M. tuberculosis, and 25 (30%) by a resistant isolate; 17 (68%) of them were resistant to at least two drugs, 16 (64%) to isoniazid and rifampin. The proportion of resistance was: isoniazid 24%, rifampin 19%, streptomycin 12%, ethambutol 10%, PAS 9%, etionamide 7%, and kanamycin 6%. Of 47 patients without previous treatment, eight had a resistant microorganism (17%): 9% resistant to isoniazid, 6% to rifampin, 2% to streptomycin, 6% to PAS and 6% multiresistant. Of 37 patients with history of previous treatment for tuberculosis, 17 (46%) had a resistant isolate; 44% were resistant to isoniazid, 35% to rifampin, 24% to streptomycin, 19% to ethambutol, 12% to PAS and 35% multiresistant. Of the 84 patients, four were physicians infected by a resistant isolate, and seven HIV-infected patients, one with a multiresistant isolate, and another with isoniazid resistance. CONCLUSIONS: Antimicrobial resistance among M. tuberculosis is alarmingly high in Mexico City; these results emphasize the importance of case detection and early isolation of patients.

Adolescent↗

Antituberculosis drug resistance in Keelung area-1993 to 1994.

Patterns of drug resistance of 176 isolates of Mycobacterium tuberculosis collected from 1993 to 1994 were reviewed retrospectively. The rates of resistance to isoniazid, rifampicin, ethambutol and streptomycin were 84.1%, 17.6%, 23.3% and 11.9% respectively and the incidence of multidrug-resistant M. tuberculosis was 17.0%. Comparisons between 1993 and 1994 showed decrease in rates of resistance to rifampicin (25% vs. 7.5%) and ethambutol (36.5% vs. 7.5%) and the incidence of multidrug-resistant tuberculosis (25% vs. 7.5%). In contrast, the rate of resistance to isoniazid increased from 79.2% to 84.1%. Due to the high frequency of resistance to multiple drugs in tuberculosis isolates at Chang Gung Memorial Hospital, Keelung, three-combined (isoniazid+rifampicin+ethambutol) regimen of antituberculosis drugs may be ineffective as initial therapy for one-fourth of patients in our hospital. Of epidemiological factors, previous treatment was found to influence the rates of drug resistance. Of roentgenographic features, stage of chest roentgenography was found to be a positive predictor of infection with multidrug-resistant tuberculosis. The information provided in this study may help us understanding the epidemiology of M. tuberculosis in Keelung and refining antituberculosis treatment for our patients.

Adult↗

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

The prevalence and mortality rate of pulmonary tuberculosis in adults are high in Taiwan. Because the emergence of drug-resistant tuberculosis is one of the major causes of this sustained high tuberculosis mortality, surveillance of initial drug resistance is important. We tested Mycobacterium tuberculosis isolates from 1,935 newly diagnosed tuberculosis patients from January 1990 through December 1995 at the Taiwan Provincial Chronic Disease Control Bureau. The overall initial drug resistance rate was 12.3%; 8.7% of isolates were resistant to only one drug, 2.6% to two drugs, 0.7% to three drugs, and 0.3% to four drugs. The resistance rates to individual drugs were: streptomycin, 5.7%; isoniazid, 9.2%; ethambutol, 0.7%; and rifampin, 1.5%. The frequency of multidrug-resistant M. tuberculosis (resistant to at least isoniazid and rifampin) was 1.2%. In view of the high initial isoniazid resistance rate and low initial ethambutol resistance rate, ethambutol should be added to the regimen for the initial treatment of tuberculosis in Taiwan. The emergence of multidrug-resistant M. tuberculosis is ominous and should be considered when treating patients in Taiwan.

Adolescent↗

Osteomyelitis and tenosynovitis due to Mycobacterium marinum in a fish dealer.

Osteomyelitis caused by nontuberculous mycobacteria is rarely reported. We describe a case of tenosynovitis and osteomyelitis of the right middle finger and metacarpal bone caused by Mycobacterium marinum in a fish dealer. This 52-year-old woman suffered progressive pain, numbness, tenderness, and erythematous swelling of the right middle finger over a 2-month period. A radiograph of the right hand disclosed osteolytic lesions at the third metacarpal bone and the third proximal phalanx. She was treated successfully with repeated surgical debridement and antimicrobial agents, including clarithromycin, ethambutol, rifampin, and doxycycline for 1 month, followed by ethambutol and clarithromycin. Pathologic examination of the debrided tissue disclosed epithelioid granuloma, caseous necrosis, and numerous acid-fast bacilli, which were later identified as M. marinum using conventional biochemical tests and by the characteristic gas-liquid chromatogram of esterified cellular fatty acid. The wound healed completely after 7 months of treatment. The patient is still under treatment, and clarithromycin and ethambutol will be given for a total of 18 months.

Animals↗

Pattern of secondary acquired drug resistance to antituberculosis drug in Mumbai, India--1991-1995.

A retrospective observational study was conducted to find out whether secondary acquired drug resistance to isoniazid and ethambutol is high and to rifamycin and pyrazinamide is low, as is commonly believed in India. There were 2033 patients, whose sputum samples (6099) were reviewed from a specimen registry of the microbiology laboratory for the years 1991 to 1995. Of these, 521 (25.6%) patients [335 males and 186 females; age ranged from 11 to 75 years] had sputum positive culture and sensitivity for acid-fast bacilli (AFB). The drug resistance patterns in our study were: isoniazid (H) 15%, rifamycin (R) 66.8%, pyrazinamide (Z) 72.2%, ethambutol (E) 8.4%, streptomycin (S) 53.6%, cycloserine (C) 39.2% kanamycin (K) 25.1% and ethionamide (Eth) 65.3%. The resistance to streptomycin showed a significant fall over a year while there was a rise in resistance to cycloserine and kanamycin which is significant. The rate of secondary acquired resistance of isoniazid and ethambutol was low, and the rate of secondary acquired resistance to rifamycin and pyrazinamide was high, which is contarary to the common belief regarding these drugs in India. This implies that isoniazid is still a valuable drug in the treatment of multidrug resistance in India.

Adolescent↗

Mycobacterium marinum skin infections. Report of 31 cases and review of the literature.

BACKGROUND: Mycobacterium marinum is a rare cause of skin infections, and its treatment has been based primarily on the personal experience and preferences of individual investigators without the benefit of large studies. METHODS: Thirty-one patients with confirmed M marinum infection were identified at 33 Kaiser Permanente Northern California Region medical centers by microbiologic records, and their charts were reviewed. RESULTS: The upper extremity was affected in 90% of cases, and lymphatic or local spread was seen during the initial examination or during observation in 25 patients (81%). Granuloma was present in 22 (63%) of 35 biopsy specimens, and staining for acid-fast bacteria yielded positive results in two of 22 specimens. Cure or improvement occurred in 22 (81%) of 27 patients in whom outcome could be evaluated. Treatment with ethambutol plus rifampin appeared more successful (effective in five [100%] of five cases) than minocycline treatment (effective in 10 [71%] of 14 cases), although not significantly so (P = .28). Adverse reactions, most of which were gastrointestinal, occurred in five patients (18%). CONCLUSION: Ethambutol plus rifampin appears more useful than minocycline in treating cutaneous M marinum infection. This result remains to be confirmed by larger clinical studies, which may be difficult because this infection is relatively rare.

Adult↗

Susceptibility of mycobacteria to fusidic acid.

Fusidic acid was shown to be effective in vitro against 30 clinical isolates of Mycobacterium tuberculosis at concentrations of 32-64 mg/l, concentrations which are readily achieved in serum. All but one of 17 Mycobacterium avium complex strains were resistant to fusidic acid at concentrations up to 64 mg/l. However, synergistic effects were shown for 11 of the 17 strains when fusidic acid was combined with ethambutol. Five of the strains were fully susceptible to the combination of fusidic acid (64 mg/l) and ethambutol (4 mg/l). It is suggested that fusidic acid should be evaluated clinically as a potential supplementary drug for treatment of mycobacterial infections.

Drug Resistance, Microbial↗

Activity of subinhibitory concentrations of dapsone alone and in combination with cell-wall inhibitors against Mycobacterium avium complex organisms.

MICs of dapsone (p-p'-diaminodiphenylsulfone) were determined radiometrically for ten strains each of the Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis. MICs ranged from 50 to 250 micrograms/ml for Mycobacterium tuberculosis and from 2 to 100 micrograms/ml for MAC. However, at a concentration as low as 1.5 micrograms/ml dapsone significantly inhibited growth of MAC bacteria when used in combination with other drugs specifically acting at the mycobacterial cell-wall level. The latter drugs were used in subinhibitory concentrations, and included m-fluorophenylalanine (an inhibitor of mycoside-C biosynthesis), ethambutol (an inhibitor of arabinogalactan biosynthesis), and ethionamide (an inhibitor of mycolic acid biosynthesis). Using a radiometric method (Bactec 460-TB), the activity of dapsone was found to be enhanced for 2/10 strains in the presence of m-fluorophenylalanine, for 3/10 strains in the presence of ethambutol and for 5/10 strains in the presence of ethionamide. A satisfactory correlation between the radiometric data and bacterial viable counts was established.

Cell Wall↗

Tuberculoid tenosynovitis and carpal tunnel syndrome caused by Mycobacterium szulgai.

Mycobacterium szulgai, a scotochromogenic mycobacterium, is a newly recognized pathogen of man and has been reported to cause pulmonary infections, olecranon bursitis and cervical adenitis. We isolated M. szulfai from granulomatous tissue removed at surgery from a young florist with the carpal tunnel syndrome. The organism was susceptible to ethambutol and rifampin but resistant to isoniazid. Cure was achieved by debridement and chemotherapy with ethambutol and rifampin. Neither the source in our patient nor the natural habitat of M. szulgai is known. Because it resembles M. gordonae and M. flavescens, common scotochromogenic mycobacteria in tapwater, care must be taken to avoid dismissing M. szulgai as a contaminant when it is isolated from tissue.

Adult↗

A controlled trial of six months chemotherapy in pulmonary tuberculosis. First Report: results during chemotherapy. British Thoracic Association.

The results of six-month courses of chemotherapy with daily isoniazid and rifampicin, supplemented for the first two months by either streptomycin and pyrazinamide (EHRZ6 regimen), or by ethambutol and pyrazinamide (EHRZ6 regimen), in patients with culture-positive pulmonary tuberculosis have been studied. These results have been compared with those of a nine-month regimen of daily isoniazid and rifampicin supplemented by ethambutol for the first two months (EHR9 regimen). All patients in the three regimens achieved negative cultures before the end of chemotherapy but the rate of sputum conversion was significantly more rapid with the two pyrazinamide-containing regimens. Of the 287 patients on the SHRZ6 and EHRZ6 regimens who completed chemotherapy, 77% had achieved negative cultures at two months and 98% at three months, compared with 64% and 88% respectively of the 157 patients on the EHR9 regimen. Adverse drug reactions were not a serious problem. Of the 234 patients who started treatment with the SHRZ6 and EHRZ6 regimens, 14 (4%) developed hepatitis; among the 177 patients in the EHR9 group (who did not receive pyrazinamide), the incidence of hepatitis was also 4%. Thus the addition of pyrazinamide to regimens containing rifampicin and isoniazid did not increase the incidence of hepatitis. However, the incidence of adverse effect other than hepatitis was increased in the pyrazinamide-containing regimens, the most common being skin rashes. These results indicate that six-month regimens containing pyrazinamide do not produce undue toxicity and are worthy of further study. Their usefulness in routine clinical practice will not become clear until a further period of follow-up of patients in this study had established the incidence of subsequent relapse.

Adolescent↗

Gynecological tuberculosis in the west of Scotland.

Between 1st January 1950 and 15th June 1978, 638 women with proved tuberculosis of the genital tract were investigated. 7 different drug programmes were used to treat 581 patients. Apart from the most recent regimens employing ethambutol and rifampicin, the best results were obtained with a combination of streptomycin, PAS and isoniazid for 18 mth or 2 yr. Today the treatment of choice is a combination of rifampicin, ethambutol and isoniazid for 1 yr. Surgery should be employed where drug treatment has failed. It is essential that women with tuberculosis of the pelvic organs should be followed up indefinitely after drug treatment.

Aminosalicylic Acid↗

Lymph node tuberculosis: a comparison of various methods of treatment.

The treatment of lymph node tuberculosis has been studied in 108 patients. Chemotherapy consisted of 18 months' isoniazid with either rifampicin or ethambutol, plus an initial supplement of streptomycin. These 2 regimens were randomly allocated to 19 patients who had previously undergone excision of the lymph nodes, 56 patients who had undergone biopsy and 33 patients who had not had any surgical procedures. The majority of patients were of Indian or Pakistani origin (80%). Histological evidence of tuberculosis was obtained in 64% of the 108 patients and M. tuberculosis was cultured in 30%. No other mycobacteria were grown. Progress during treatment was uneventful in 65% of patients. Fresh nodes appeared during treatment in 12%, existing nodes enlarged in 13% and fluctuation developed in 11% of patients. Discharge and/or sinus formation was infrequent (7%), as was breakdown of a surgical scar (4%). Excision or aspiration after the start of chemotherapy was performed in 19% of patients. In the period up to the end of chemotherapy no difference emerged between the patients who received rifampicin with isoniazid and those who received ethambutol with isoniazid. Satisfactory results were obtained in 98% of the patients by the end of treatment although 13% still had slight node enlargement. The place of surgery is discussed. Follow-up will continue for 18 months after the end of chemotherapy.

Adolescent↗

Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study.

An analysis is presented of the side effects which occurred in 530 patients treated with 6 months chemotherapy for newly detected pulmonary tuberculosis. Five treatment regimens were used. The initial phase of treatment consisted of daily isoniazid, rifampicin and ethambutol (HRE) or isoniazid, rifampicin, streptomycin and pyrazinamide (HRSZ) given for 2 months. The second phase of treatment consisted of isoniazid and rifampicin given twice weekly (H2R2) or isoniazid, rifampicin and ethambutol given daily (4HRE) or intermittently (H1R1E1 or H2R2E2) for 4 months. Side effects were detected in 66 (12.4%) patients. Hepatotoxic reactions occurred in 48 (9%) patients, mainly of amild and transient nature and the majority were attributable to isoniazid. The 'flu like' syndrome occurred in only 2 patients both during the daily phase of treatment, and it was not encountered in patients taking rifampicin intermittently (dose 600 mg). Inclusion of pyrazinamide in the initial phase of 1 regimen did not result in an increase of frequency of side effects. In 56% of patients on pyrazinamide the serum uric acid concentration was elevated but there was no arthralgia. Drug toxicity leading to alteration or withdrawal of treatment occurred in only 10 (1.8%) patients. This study shows that with these 6 month regimens the overall risk of drug toxicity was low, and less than that associated with more conventional treatment regimens.

Adolescent↗

Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya.

There is evidence that in human immunodeficiency virus 1 (HIV-1) infected patients with tuberculosis the rate of recurrence of tuberculosis is increased in those patients treated with a standard thiacetazone-containing regimen. To assess the impact of HIV-1 on tuberculosis in Kenya, patients with tuberculosis were studied prospectively. After treatment with either a standard thiacetazone plus isoniazid regimen or a short-course thiacetazone-containing regimen, overall recurrence rate of tuberculosis was 34 times greater in 58 HIV-1-positive patients than in 138 HIV-1-negative patients (adjusted rate ratio 33.8, 95% CI 4.3-264). Recurrence in the HIV-1-positive group was strongly associated with a cutaneous hypersensitivity reaction due to thiacetazone during initial treatment (rate ratio 13.2, 95% CI 3.1-56.2). In all patients with a cutaneous hypersensitivity reaction ethambutol was substituted for thiacetazone. No significant association was found between recurrence among HIV-1-positive patients and initial resistance, initial treatment regimen, a diagnosis of AIDS (WHO definition), or poor compliance. DNA fingerprinting suggested that both relapse and new infection may have produced recurrence of tuberculosis. In patients who had a cutaneous hypersensitivity reaction, increased recurrence rate may have been related to interruption of treatment, subsequent poor compliance, or more advanced immunosuppression. Alternatively, a change to the combination of ethambutol and isoniazid in the continuation phase for 11 months only may not be adequate.

AIDS-Related Opportunistic Infections↗