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PubMed1999

[Diagnosis, clinical picture and treatment policy in acute progressive forms of pulmonary tuberculosis under present-day epidemiological conditions].

Among 103 examinees, the most common clinical type was caseous pneumonia (45.6%), progressive fibrocavernous tuberculosis (20.4%), infiltrative caseous pneumonia (17.5%), disseminated tuberculosis (16.5%). Progression was characterized by cavern formation in 91.1% of patients, with large and giant caverns containing nonspecific microbes forming in 79.6%. All the patients were found to isolate bacteria and 93.5% showed their excess. Drug-resistant microbes were identified in 62.1% of patients; polydrug resistance was seen in 37.5%. Chemotherapy was performed at the first stage by using 5 drugs: isoniazid, rifampicin, pyrazinamide, ethambutol plus kanamycin or amikacin. A combination of reserve drugs, including prothionamide, ofloxacin (ciprofloxacin) amikacin, pyrazinamide, and ethambutol, was used in patients with polyresistance. Symptomatic and pathogenetic therapies should aim at correcting complications and concomitant abnormalities. Following 6 months, 80% of patients stopped isolating bacteria, the process became stable and they could be prepared for planned surgical treatment. In 20% of cases, the process was progressive and it required salvage operations.

Acute Disease↗
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↗
PubMed2004

Results of a standardised regimen for multidrug-resistant tuberculosis in Bangladesh.

SETTING: Individualised regimens based on drug susceptibility test results, generally used to treat multidrug-resistant tuberculosis (MDR-TB), require often unavailable expertise and resources. OBJECTIVE: To evaluate a standardised regimen based on the susceptibility profiles of locally prevalent MDR-TB strains. DESIGN: The activities of a successful DOTS programme in Bangladesh were complemented by offering treatment with a standardised 21-month regimen to patients with laboratory-confirmed MDR-TB disease. The regimen contained kanamycin, ofloxacin, prothionamide, pyrazinamide, ethambutol, isoniazid and clofazimine. Clinical and bacteriological progress was monitored quarterly until treatment completion, then 6 monthly for 2 years. RESULTS: The status at the end of treatment of this cohort of 58 documented MDR-TB patients was as follows: eight (14%) deaths, seven (12%) defaults, three (5%) failures and 40 (69%) cures. One bacteriologically-confirmed relapse was recognised. Frequent and sometimes serious side effects proved to be the main problem, suggesting the need for a better tolerated but equally effective regimen. CONCLUSION: A standardised approach may provide a reasonable alternative to individualised treatment of MDR-TB in resource-poor settings. However, DOTS-plus programmes in resource-poor settings may confront significant difficulties in the enrolment, diagnosis and management of MDR-TB patients.

Adolescent↗
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↗
PubMed1990

[Resistance testing of M. avium-intracellulare and M. tuberculosis of AIDS patients with new drugs and drug combinations].

The minimal inhibitory concentration (MIC) of rifabutin for M. tuberculosis was 0.006 to 0.06 micrograms/ml, and 0.12 to 0.25 micrograms/l for clofazimine. Accordingly, M. tuberculosis is inhibited by concentrations of these two medications that are far lower than the levels normally found in the serum. In the case of M. avium, the MIC of the new drugs such as rifabutin and clofazimine are, in contrast to the MICs for M. tuberculosis, merely of the order of the achievable serum concentrations. The minimum bactericidal concentrations of these two substances are much higher than the bacteriostatic concentrations, which probably explains the frequent therapeutic failures, while in the case of ciprofloxacin, the prevailing situation is much more favourable. The growth of all M. avium strains is inhibited (= sensitive) when elevated concentrations (double "breakpoint" concentrations) of a triple-drug combination comprising rifampicin, ethambutol and ciprofloxacin, or a combination of ethambutol, rifampicin, ciprofloxacin and prothionamid are tested at "normal breakpoint" concentrations.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Joint chemotherapy trials in lepromatous leprosy conducted in Thailand, the Philippines, and Korea.

Chemotherapy trials in lepromatous leprosy using various combinations of existing antileprosy drugs were conducted jointly by Korea, The Philippines, and Thailand. The general objective of these trials was to determine the most effective and practicable regimen or regimens for field application. Lepromatous patients were divided into two groups: Group I was comprised of new, untreated patients infected with dapsone-sensitive Mycobacterium leprae and Group II consisted of relapsed patients with dapsone-resistant disease. Four different regimens were administered to each group for 5 years. Comparison among the regimens was based on antileprotic efficacy, drug safety, acceptability, field practicability, and economic feasibility. No significant differences were noted among the various regimens as judged by the reduction in the bacterial index (BI), clinical response, and change in biopsy index. Toxicity was seen only in the regimens containing prothionamide and rifampin. The regimens were acceptable to the patients and all were found practical for field use. Clofazimine, even in low doses, was found to suppress the frequency and severity of erythema nodosum leprosum. A multidrug regimen effective against both new and relapsed cases of lepromatous leprosy, whether dapsone sensitive or dapsone resistant, is recommended for field use. Given priority, the cost of the regimens is affordable in the three countries.

Adolescent↗
PubMed1985

An experimental study of the antileprosy activity of a series of thioamides in the mouse.

A series of substituted thioamides have been studied to establish whether their structure-activity pattern against Mycobacterium leprae is similar to that displayed against M. tuberculosis. Antileprosy activity was evaluated in the mouse foot pad using both the kinetic and continuous methods. Ethionamide and prothionamide were found to be the most active compounds and to be of approximately equal potency. Thioisonicotinamide was about five times less active. 2-t-Butyl-thioisonicotinamide, 2-dimethylamino-thioisonicotinamide, and pyrazine carbonic thioamide were inactive at the dosages tested. High-pressure liquid chromatographic methods were devised to study the potential influence of pharmacological factors on their in vivo activity. Fecal measurements suggested that all of the thioamides were well absorbed when fed in the diet. After intravenous administration, all of the thioamides were rapidly eliminated from the mouse. The differences in their elimination rates probably played only a minor role in affecting their relative antileprosy activities. It was concluded that the structural requirements for antileprosy and antituberculosis activity of the thioamides are probably similar.

Amides↗
PubMed1977

Drug resistance among Mycobacterium tuberculosis strains isolated in Taiwan during 1975.

455 strains of Mycobacterium tuberculosis were isolated from patients with history of treatment in Taiwan Provincial Tuberculosis Control Bureau and tested for resistance against various antituberculosis agents including streptomycin (SM), paraaminosalicylic acid (PAS), isoniazid (INH), cycloserine (CS), prothionamide (1321TH), kanamycin (KM), ethambutol (EMB), and rifampicin (RFP). In vitro resistance to SM and INH was more frequently found than others and the resistance to a single drug was more common than multiple resistance.

Antitubercular Agents↗
PubMed1979

[Sensivity of Mycobacterium kansaii and Mycobacterium marinum to different antituberculous drugs (author's transl)].

Mycobacteriosis includes clinical manifestations caused by especies of the genus Mycobacterium other than M. tuberculosis and M. bovis. Therapy for these conditions has not been clearly sistematized as it has for tuberculosis, particularly because of the natural resistance that the etiologic agents present to a large number of antituberculous drugs. The sensitivity of M. kansasii and M. marinum to eleven tuberculostatic agents was studied in order to determine which one were best suited for treatment of cases caused by these species. The drugs showing the strongest action against M. kansasii were rifampin, cycloserine, streptomycin, and prothionamide. M. marinum was even more sensitive except to isoniazid, which is ineffective. As a general rule, especially if the sensitivity of the isolated strain is unknown drugs with little or no action on M. kansasii and M. marinum should not be used. Particularly the use of isoniazid and PAS should be avoided.

Antitubercular Agents↗
PubMed1983

[Antibacterial treatment of bacteria-abundant leprosy].

A historic introduction reviews the start of DDS (diaminodiphenylsulphone) therapy in leprosy, stressing the fact that, far after the start of combined therapy in tuberculosis, leprosy continued to be treated with monotherapy of DDS. Reports about resistance of M. leprae to DDS initiated a review of policy. A complete breakthrough toward combined therapy started after 1962, when Shepard introduced mousefootpad inoculation of M. leprae to be used for therapeutic trials. Full attention is given to Freerksen's trial in Malta where combined treatment with rifampicin, INH, prothionamide, and DDS were given for 2 years only to all patients, while at resurvey after 4 years no relapse was found. The applicability of short-term combined therapy for endemic areas is discussed.

Dapsone↗
PubMed1983

Field application of combined therapy for infectious leprosy cases. A feasibility study in Bombay.

The practical problems related to dapsone monotherapy for a prolonged period to infectious leprosy patients are well known to the scientific community and combined treatment of dapsone with clofazimine, rifampicin or prothionamide has been successfully carried out by several workers in hospitalised leprosy patients. The application of polytherapy in field condition was hindered by the cost of the drugs and fear of side effects. 42 infectious leprosy patients attending 5 field leprosy clinics in the slums of Bombay city were put on combined drug schedule. The drug compliance of these patients was judged along with their regularity in attendance at clinics by the persons in charge and periodic and frequent check up of urines. 27 (65%) were regular in treatment from the beginning, 8(19%) who were initially irregular after motivation and 7(17%) remained irregular through out the period. The urine samples collected from leprosy patients on monotherapy and attending the same centres revealed 31% irregularity in drug consumption. The study indicates that advocating combined therapy in field conditions by paramedical workers is quite feasible. The patients on multiple drugs are more regular in drug consumption as compared to monotherapy group. The frequent check up of urine for drug content and advice to patients who are irregular in treatment improve their regularity in drug consumption.

Adolescent↗
PubMed1983

Hepatitis in leprosy patients treated by a daily combination of dapsone, rifampin, and a thioamide.

A 13% incidence of hepatitis was observed among 54 cases of multibacillary leprosy treated daily with the three-drug combination of dapsone, rifampin, and a thioamide (ethionamide or prothionamide). No hepatitis was observed among 109 cases of paucibacillary leprosy treated daily with the two-drug combination of dapsone and rifampin. Symptoms were jaundice in five cases and nausea plus vomiting associated with a significant increase of transaminase levels in two cases. In five cases, the symptoms appeared during the first two months of therapy and in two cases, later. Discontinuing treatment with rifampin and the thioamide but not dapsone resulted in recovery. When rifampin was resumed without the thioamide, the hepatitis did not recur. Viral etiology could be eliminated in six cases. Neither sex, age, weight nor the fact that the patient was a new case or a relapse case appeared to be a contributing factor. Hepatotoxicity caused by administration of a thioamide might have been potentiated by the concurrent administration of rifampin.

Adolescent↗
PubMed1982

Bacterial growth kinetics of "M. lufu" in the presence and absence of various drugs alone and in combination. A model for the development of combined chemotherapy against M. leprae?

Bacterial growth kinetic studies were performed in a series of potential inhibitors of M. leprae using "M. lufu" as a model strain. Reasons why "M. lufu" is considered to be a better model than M. tuberculosis are presented. The inhibitory power of the single drugs has been quantified, the activity constants are calculated, and the synergistic, additive, or antagonistic behavior of the combinations is evaluated. It is demonstrated that a combination consisting of dapsone (DDS), prothionamide (PTH), isoniazid (INH), and rifampin (RAMP) is a very powerful inhibitor of "M. lufu" and prevents or delays the development of resistance under the experimental conditions described. This finding is in agreement with the therapeutic effect of this combination (Isoprodian + rifampin) achieved in a leprosy eradication program on the Island of Malta. Whereas there is no direct proof that "M. lufu" is the best suitable model for drug evaluation against M. leprae, there is, however, nothing in the presented results which is against this model, especially as the actions of DDS and PTH or RAMP is concerned. A new combination of DDS with trimethoprim (TMP) or TMP derivatives has also been studied and seems to be a promising candidate. In addition, a technique is described to differentiate between bacteriostatic and bactericidal action of the tested inhibitors against "M. lufu."

Animals↗
PubMed1982

[Photometry of Mycobacteria and its application in sensitivity-testing of chemotherapeutic agents (author's transl)].

Using photometry in measuring the growth of mycobacteria in liquid medium 7 H 9 Middlebrook slightly modified, we could achieve a 5 to 8 fold increase of extinction values within 8 days. The reproducibility of these results were investigated by tenfold assay of the laboratory mycobacterial strain H37Rv and about 10 strains recently isolated from patients. As antituberculous chemotherapeutic agents require different pH for their optimal activity, the experiments were performed at pH 5.5, pH 6.8 and pH 7.3. By daily measuring the extinction values of all strains showed less growth at pH 5.5 compared to their behaviour at pH 6.8 and 7.3. Yet growth at pH 5.5 was sufficient to estimate the inhibitory effect of Pyrazinamide as later experiments could show. The variation coefficient at pH 5.5 revealed to be significantly lower than at pH 6.8 and pH 7.3. Isoniazid, Prothionamid and Rifampicin were tested at pH 6.8, Streptomycin, Ethambutol and Tetracyclin at pH 7.3 and Pyrazinamide at pH 5.5. The results of our calculations were expressed as growth percentages in relation to growth in the control tubes. Usüally the measurements of the last day of incubation were chosen for this evaluation. Inhibition of growth in 50% or more of the extinction values of the control tubes was the criterion for regarding a strain as sensitive to a given drug. All drugs were tested in two concentrations. In case of only one concentration effecting inhibition of growth in 50% ore more, the strain was reported to give a borderline result. Sensitivity testing with photometry was compared to conventionally performed tests on Loewenstein-Jensen-Medium which were in good agreement between 80 and 100%. Results being available within 8 days in an advantage of the photometric method of sensitivity testing. Furthermore Pyrazinamide and Tetracyclin can be tested without difficulties while these drugs give unsatisfactory results when tested on Loewenstein-Jensen-medium.

Antitubercular Agents↗
PubMed2003

Longitudinal study of tuberculosis outcomes among immunologically naive Aché natives of Paraguay.

This study documents the course of a tuberculosis epidemic in an immunologically naive group of South American Indians within fewer than 20 years after first sustained contact with outsiders. Groups of Northern Aché (ah-CHAY) of eastern Paraguay were contacted and settled on reservations between 1971-1979. Not surprisingly, the Aché are very susceptible to tuberculosis, and the epidemiological characteristics of the disease are quite different from those of populations that have had tuberculosis for centuries. Within 6 years of the first detected case of tuberculosis among the Aché, the prevalence rate of active tuberculosis cases reached 18.2%, and of infected cases among adults, 64.6%, some of the highest rates ever reported for any human group. Remarkably, males and females are equally likely to have been diagnosed with active tuberculosis, Aché children between birth and 5 years of age are least vulnerable to tuberculosis, high nutritional and socioeconomic status do not decrease the risk of disease or infection, and children immunized with BCG are less responsive to tuberculin challenge than are other children. Moreover, similar to the Yanomamö, but unlike populations of European or African descent, a high percentage of Aché with active disease test negative on tuberculin challenge tests (purified protein derivative; PPD). These differences may be due to a high prevalence of diminished cell-mediated immunity, and T-helper 2 dominance. We also hypothesize that these immunological characteristics, low genetic diversity, hostile intergroup interactions, and behavioral noncompliance to treatment protocols together contribute to the high rates of active disease observed. Existing tuberculosis control programs are poorly equipped to handle the impact of these causal complexities on the course of recent tuberculosis epidemics that have quickly spread throughout native communities of Latin America during the last decade.

Adolescent↗
PubMed2001

[Chemotherapy-induced erythema nodosum leprosum: successful treatment with thalidomide].

The severity and outcome of a chronic granulomatous infection caused by M. leprae depend on the cell-mediated immunity towards the pathogen. The disease classification is based on the host's response to M. leprae ranging from high to low resistance (polar tuberculoid leprosy to polar lepromatous leprosy). The host's position in the spectrum is not stable; leprosy reactions reflecting changed immune status may occur spontaneously or during chemotherapy. The type II reaction or erythema nodosum leprosum can most often be seen in patients with lepromatous leprosy, a multiorgan disease characterized by an unrestricted bacillary replication. Clinically, this reaction is characterized by crops of painful bright pink, dermal and subcutaneous nodules arising in clinically normal skin, in association with fever, malaise, glomerulonephritis and arthralgias. Therefore, prompt institution of immunosuppressive therapy with corticosteroids or thalidomide is recommended. This case report describes the development of erythema nodosum leprosum during chemotherapy treated successfully with thalidomide. Furthermore, immunologic effects and potential side effects of this drug are discussed.

Adult↗