SEARCH · PubMed Health

Results for “Pyrazinamide”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed1998

Short-course prophylaxis against tuberculosis in HIV-infected persons. A decision and cost-effectiveness analysis.

BACKGROUND: Isoniazid prophylaxis for 12 months effectively prevents tuberculosis in HIV-infected persons and may decrease the incidence of other HIV-related disease and mortality. Recent clinical trials have found that some short-course regimens also effectively prevent tuberculosis. OBJECTIVE: To compare the benefits, risks, and cost-effectiveness of isoniazid prophylaxis and short-course prophylaxis regimens. DESIGN: Decision and cost-effectiveness analysis. SETTING: United States. PATIENTS: Hypothetical patients who are HIV-infected and have CD4 counts of 200 cells/mm3 or less and positive results on tuberculin skin tests. INTERVENTIONS: Isoniazid prophylaxis lasting 12 months and six short-course prophylaxis regimens of isoniazid, rifampin, and pyrazinamide alone or in combination. MEASUREMENTS: 5-year survival rate, life expectancy, lifetime incidence of tuberculosis, and cost per quality-adjusted life-year saved. RESULTS: Compared with no prophylaxis, the 12-month isoniazid regimen increased 5-year survival rates by 9% and life expectancy by 8.7 months, decreased incidence of tuberculosis by 27%, and saved 4 medical care dollars for every 1 spent on prophylaxis. Regimens of isoniazid for 6 months, isoniazid and rifampin for 3 months, and rifampin and pyrazinamide for 2 months had similar results: 6.2- to 8.6-month increases in life expectancy, 19% to 26% reductions in incidence of tuberculosis, and 1 to 7 medical care dollars saved for every 1 spent on prophylaxis. A 3-month regimen of isoniazid, rifampin, and pyrazinamide resulted in fewer clinical benefits and was the only regimen tested that did not save medical care dollars. CONCLUSIONS: Prophylaxis decreases the incidence of tuberculosis and increases life expectancy for HIV-infected patients. Some regimens save medical care dollars, and some short-course regimens have clinical and economic benefits similar to those of the 12-month isoniazid regimen. Short-course prophylaxis is a reasonable alternative to the 12-month isoniazid regimen.

AIDS-Related Opportunistic Infections↗

PubMed1979

Hypouricemia by defect in the tubular reabsorption.

Two patients with hypouricemia with high levels of uric acid in their urine were given pyrazinamide and probenecid. The uric acid clearance decreased to low or normal values after pyrazinamide administration. In both cases, probenecid produced a slight increment in the uric acid excretion. This type of response suggests a defect in the reabsorption component. It is tempting to speculate on a postsecretory reabsorption defect based on the results of pyrazinamide and probenecid tests.

Absorption↗

PubMed1993

[Disseminated tuberculosis with a multiresistant strain of Mycobacterium tuberculosis in an HIV-infected Swiss male].

Multidrug-resistant M. tuberculosis in HIV-infected people has not yet been reported in Switzerland, and there have been no nosocomial epidemics as they have recently occurred in the USA. We present the case of a 38-ear-old HIV-infected man who developed disseminated tuberculosis as AIDS-defining disease. Initially he was treated with isoniazid, pyrazinamide and rifampin. Due to the emergence of resistance to isoniazid and streptomycin, ethambutol was added for one month. Later the therapy was changed back to the initial three drugs. The patient responded well to this therapy, but five months later developed a relapse. In addition to the originally diagnosed double-drug resistance, a reduced susceptibility to rifampin appeared. Ethambutol, ciprofloxacin and amikacin were added to the original three-drug regimen. This resulted in rapid clinical improvement, although sputum cultures remained positive for M. tuberculosis two months later. This isolate was resistant to pyrazinamide. For that reason pyrazinamide was replaced by clofazimine. 14 months after diagnosis the patient died of hepatic failure. Because there was a delay in isolation of one week, 37 potentially exposed health care workers were tested by the Mantoux skin test. No conversions were observed. This case report demonstrates that tuberculosis in HIV-infected patients in Switzerland may be caused by multidrug-resistant M. tuberculosis. We propose that until the results of a susceptibility assay are known, a four-drug combination should be used initially in this patient group.

AIDS-Related Opportunistic Infections↗

PubMed2000

[Drug resistance in Mycobacterium tuberculosis. A multicenter study of the Barcelona area. Grupo de Trabajo sobre Resistencias en Tuberculosis].

BACKGROUND: The aims of this multicenter study was to establish the level of primary and acquired drug resistance of M. Tuberculosis strains isolated in Barcelona and to identify possible risk groups using clinical data. PATIENTS AND METHODS: All tuberculosis patients with isolation and identification of M. tuberculosis strains from October 1995 to September 1997 were included. Susceptibility tests isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were performed using the Bactec 460 system and the proportions method on solid medium. Logistic progression was used for statistical analysis. RESULTS: The total number of patients included was 1,749 (1,535 non-treated and 214 previously treated). Primary drug resistance was 5.7% (isoniazid 3.8%; rifampin 1.0%, streptomycin 2.1%, ethambutol 0.3% and pyrazinamide 1.0%). Acquired drug resistance was 20.5% (isoniazid 17.3%, rifampin 9.8%, ethambutol 1.9%, streptomycin 4.7% and pyrazinamide 6.5%). Primary drug resistance was associated with people over 60 years old and women. CONCLUSIONS: The low level of drug resistance enables antituberculosis treatment of non-treated patients to start with the standardised three-drug regimes except in the case of foreign people from countries with a high level of drug resistance. Susceptibility tests are recommended on all M. tuberculosis strains isolated, together with controlled studies of drug resistance surveillance.

Adolescent↗

PubMed1999

[Congenital tuberculosis: difficulties in early diagnosis].

BACKGROUND: Neonatal and/or congenital tuberculosis is insufficiently understood. CASE REPORTS: Case 1. A premature hypotrophic neonate presented at the age of 45 days, without any maternal contact, a bilateral bronchopneumopathy. Whilst the pregnancy and birth had not been affected by any noteworthy problem, the mother died from miliary tuberculosis despite rifampin, isoniazid and pyrazinamide treatment. Her baby also died on day 52 from multivisceral failure. Culture of tracheal secretions confirmed a few weeks later the diagnosis of tuberculosis. Case 2. A premature, hypotrophic neonate presented on day 22 signs of respiratory distress (miliary), icterus and hepatosplenomegaly. Whilst the pregnancy and birth had not been affected by any particular problem, the mother, 18 days after giving birth, presented miliary and pleural tuberculosis. Despite treatment with rifampin, isoniazid and pyrazinamid started on day 22, the baby died on day 27 from multivisceral failure. The post-mortem liver biopsy confirmed the diagnosis of tuberculosis. Case 3. A baby born at term was hospitalized on day 4 for jaundice. Whilst the pregnancy and birth had not presented any problem, the mother developed a pleural tuberculosis on day 10. Breast-feeding was stopped. Due to the presence of opacities at the top of the right lung, the child was given rifampin, isioniazid, and pyrazinamide. The course was marked by the appearance of hepatomegaly and poor weight gain up to day 25, followed by an improvement. CONCLUSION: The frequency of congenital tuberculosis is probably under-estimated. Its early diagnosis is essential but often difficult as the initial manifestations are delayed. Improved screening of women at risk and sensitization of the medical community are necessary.

Antitubercular Agents↗

PubMed2006

In vitro inhibitory effect of antituberculosis drugs on clinical and environmental strains of Coccidioides posadasii.

OBJECTIVES: The aim of the present study was to evaluate the in vitro effect of the first-line antimicrobial drugs for pulmonary tuberculosis against the fungal pathogen Coccidioides posadasii. METHODS: The in vitro activities of rifampicin, isoniazid, pyrazinamide and ethambutol against clinical and environmental strains of C. posadasii were determined in accordance with the CSLI M38-A macrodilution method. The antimicrobials were tested alone or in combinations of two or more drugs. RESULTS: With the exception of pyrazinamide, all of the tested drugs interfered with the in vitro growth of C. posadasii. The 2 day MIC ranges of the tested drugs were as follows: rifampicin 1,060-4,250 mg/L; isoniazid < or =250 mg/L; ethambutol < or =620 mg/L. Pronounced in vitro synergism was demonstrated for combined antituberculosis drugs. The combination of rifampicin plus pyrazinamide was the only one that did not inhibit fungal growth. CONCLUSIONS: The present study showed that the first-line antituberculosis drugs, alone or in combinations, interfered with the vegetative growth of C. posadasii strains in vitro. Further studies in a murine model will need to be conducted in order to evaluate the in vivo effect of antituberculosis drugs on Coccidioides spp.

Antifungal Agents↗

PubMed2004

Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.

Renal hypouricemia is an inherited and heterogeneous disorder characterized by increased urate clearance (CUA). The authors recently established that urate was reabsorbed via URAT1 on the tubular apical membrane and that mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to elucidate and correlate clinical and genetic features of renal hypouricemia. The SLC22A12 gene was sequenced in 32 unrelated idiopathic renal hypouricemia patients, and the relationships of serum urate levels, and CUA/creatinine clearance (Ccr) to SLC22A12 genotype were examined. Uricosuric (probenecid and benzbromarone) and anti-uricosuric drug (pyrazinamide) loading tests were also performed in some patients. Three patients had exercise-induced acute renal failure (9.4%), and four patients had urolithiasis (12.5%). The authors identified eight new mutations and two previously reported mutations that result in loss of function. Thirty patients had SLC22A12 mutations; 24 homozygotes and compound heterozygotes, and 6 heterozygotes. Mutation G774A dominated SLC22A12 mutations (74.1% in 54 alleles). Serum urate levels were significantly lower and CUA/Ccr was significantly higher in heterozygotes compared with healthy subjects; these changes were even more significant in homozygotes and compound heterozygotes. These CUA/Ccr relations demonstrated a gene dosage effect that corresponds with the difference in serum urate levels. In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid. The findings indicate that SLC22A12 was responsible for most renal hypouricemia and that URAT1 is the primary reabsorptive urate transporter, targeted by pyrazinamide, benzbromarone, and probenecid in vivo.

Carrier Proteins↗

PubMed2003

Fluoroquinolone-containing third-line regimen against Mycobacterium tuberculosis in vivo.

The objective of the present study was to compare the activities of a third-line regimen recommended by the World Health Organization (WHO) and two derivatives of that regimen with the activity of the standard combination of isoniazid, rifampin, and pyrazinamide as a positive control against Mycobacterium tuberculosis in a murine model. The WHO regimen combines ofloxacin (OFX), ethionamide, amikacin, and pyrazinamide; in the two derivatives of this regimen, OFX was replaced by levofloxacin (LVX) or moxifloxacin (MXF). The four drugs, a fluoroquinolone (either OFX, LVX, or MXF), ethionamide, pyrazinamide, and amikacin, were administered for the first 2 months (initial phase); and two drugs, a fluoroquinolone (either OFX, LVX, or MXF) and ethionamide, were administered for the following 10 months (continuation phase). After 6 months of treatment, only the spleens and lungs of mice treated with the standard regimen became culture negative. From 9 months onward, all of the organs of mice treated with the MXF-containing third-line regimen were culture negative. The majority of organs from mice treated with the OFX-containing regimen continued to be culture positive, and the mean CFU counts remained unchanged for as long as 12 months. The results for mice treated with the LVX-containing regimen fell between those for the groups receiving the MXF- and OFX-containing regimens. In conclusion, the activity of the OFX-containing third-line regimen against M. tuberculosis was rather weak in vivo, whereas when OFX was replaced by MXF, 9 months of treatment with a modified third-line regimen displayed bactericidal activity comparable to that of 6 months of treatment with the standard regimen in mice. The MXF-containing third-line regimen seems to be a powerful alternative for the treatment of tuberculosis (TB) when isoniazid and rifampin cannot be used, which is the main feature of multidrug-resistant TB.

Animals↗

PubMed2026

First-line drug-resistant tuberculosis among children under 15 years in Ethiopia: insights from phenotypic and whole-genome sequencing approaches.

BACKGROUND: Childhood drug-resistant tuberculosis is often underdiagnosed and inadequately characterized due to the paucibacillary nature of the disease. This study aimed to assess resistance to first-line anti-tuberculosis drugs in children using phenotypic drug susceptibility testing and whole-genome sequencing. METHODS: A retrospective-prospective study was conducted on culture-confirmed childhood tuberculosis cases in Ethiopia (2017–2023). Phenotypic drug susceptibility testing was performed on 110 Mycobacterium tuberculosis complex isolates. Whole-genome sequencing was completed for 85 of these isolates, which were analyzed using the TB-Profiler and MTBSeq pipelines. We assessed the sensitivity, specificity, predictive values, and kappa agreement of whole-genome sequencing compared with phenotypic drug susceptibility testing. RESULTS: Phenotypic resistance to at least one first-line anti-TB drug was observed in 26/110 (23.6%) of the examined isolates, with isoniazid resistance being the most frequent, 23/110 (20.9%), followed by rifampicin resistance, 18/110 (16.4%). TB-Profiler showed almost perfect agreement with phenotypic drug susceptibility testing for rifampicin (sensitivity 94.4%, kappa = 0.96) and isoniazid (sensitivity 91.3%, kappa = 0.91), whereas MTBSeq showed slightly lower performance. Both pipelines demonstrated moderate to weak agreement with phenotypic drug susceptibility testing for detecting resistance to ethambutol, pyrazinamide, and streptomycin. The most frequently observed resistance mutations among phenotypically resistant isolates were rpoB (Ser450Leu), katG (S315Thr), embB (Met306Ile), and pncA (C-11 A > G) for rifampicin, isoniazid, ethambutol, and pyrazinamide, respectively. Discrepancies between genotypic and phenotypic drug susceptibility testing were observed across all first-line anti-TB drug-resistant isolates, particularly for ethambutol and pyrazinamide. CONCLUSION: We found a high prevalence of isoniazid resistance, along with rifampicin resistance, underscoring the need for early detection in vulnerable groups. Whole-genome sequencing showed good accuracy for these drugs, with TB-Profiler performing best. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗

PubMed2004

Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.

The potential for drug-drug interactions mediated by the inhibition of cytochrome P-450 (CYP) were concerned during antituberculosis therapy. However, the information regarding human CYP inhibition by antituberculosis drugs is limited to isoniazid. In the current study, we examined the inhibitory effects of pyrazinamide and ethionamide, both of which are chemically related to isoniazid, on the CYP-mediated activities in human liver microsomes and compared them to that of isoniazid. No remarkable effects on any CYP activities were observed by pyrazinamide and ethionamide. In contrast, in addition to the reported inhibitory effect of isoniazid on CYP1A2, CYP2A6, CYP2C19, and CYP3A activities, our results newly showed its effect on CYP2C9 and CYP2E1 activities. Isoniazid showed potent direct inhibitory effect on S-warfarin 7-hydroxylation, while a preincubation step in the presence of NADPH was needed to inhibit chlorzoxazone 6-hydroxylation. Furthermore, irreversible inhibition of CYP2C19 activity by isoniazid was also observed in the dilution study. These results suggested that pyrazinamide and ethionamide did not seem to cause drug interactions mediated by the inhibition of CYP. In contrast, isoniazid might contribute to the severe drug interactions by a different inhibitory mechanism depending on each of the CYP isozymes, in addition to the reported observations.

Antitubercular Agents↗

PubMed1992

Drug treatment of tuberculosis--1992.

The impact of the acquired immunodeficiency syndrome (AIDS) pandemic has made tuberculosis an increasing worldwide problem, and the effectiveness of modern chemotherapy has been blunted by the high incidence of primary drug resistance, especially in developing countries. The prospect of finding new and highly effective drugs similar to isoniazid or rifampicin is dim, yet the maximum benefits from the existing drugs which are highly effective have not been received. A 6-month regimen of isoniazid plus rifampicin, supplemented by pyrazinamide during the first 2 months, for treatment of uncomplicated tuberculosis is highly effective and the regimen of choice. Ethambutol should be added if the risk of isoniazid resistance is increased. A regimen of isoniazid, rifampicin, pyrazinamide and streptomycin for 4 months provides effective defence against smear-negative pulmonary tuberculosis. Re-treatment of multiple drug-resistant tuberculosis remains a difficult therapeutic problem. At least 3 drugs that the patient has never previously received, and that are effective according to laboratory susceptibility testing, must be used. Preventive therapy against tuberculosis is accomplished with isoniazid for 6 to 12 months, although rifampicin plus isoniazid for 3 months has been used in the United Kingdom with success. In a mouse model, rifampicin plus pyrazinamide for 2 months is more effective than isoniazid for 6 months as preventive treatment. Patient noncompliance with medication remains the biggest problem in tuberculosis control, and is a complex issue. It can only be resolved by multiple approaches. Intermittent directly observed short course chemotherapy is a major, but not the only, possible solution.

Animals↗

PubMedDate not supplied

Treatment of tuberculous infection and disease in children: the North American perspective.

The standard preventive therapy for paediatric patients with tuberculous infection centres on isoniazid therapy. The chosen regimen of isoniazid therapy is based on individual patient factors. In the case of known or suspected resistance, combination therapy [e.g. isoniazid and rifampicin (rifampin)] or alternative therapies (e.g. pyrazinamide, a fluoroquinolone and/or ethambutol) should be employed. The goal of treatment of tuberculous disease is to achieve sterilisation in the shortest possible time. More intensive multiple drug combination regimens (e.g. isoniazid, rifampicin and pyrazinamide) have resulted in successful 6- and 9-month treatment regimens in children. If drug resistance is suspected then a fourth drug is added to the initial treatment regimen and the length of therapy may be extended to 18 months. The paediatric information available on the commonly used antituberculous agents (e.g. isoniazid, rifampicin, pyrazinamide and ethambutol) is reviewed in this article. Agents are described with an emphasis on their formulation availability, mechanism of action, pharmacokinetic properties (e.g. absorption, distribution, metabolism and elimination), adverse effects, and interactions (e.g. drug-drug, drug-food and drug-disease).

Antitubercular Agents↗

PubMed1999

Rifampicin bioavailability: a review of its pharmacology and the chemotherapeutic necessity for ensuring optimal absorption.

The World Health Organization encourages the use of fixed dose combinations (FDCs) of rifampicin (RMP) and isoniazid together with pyrazinamide or pyrazinamide plus ethambutol for the treatment of tuberculosis. The main advantages of such FDCs are the simplification of procurement and prescribing practices and the protection they afford against the potential selection of RMP-resistant strains of Mycobacterium tuberculosis. There is convincing evidence, however, that the rifampicin absorption from FDCs manufactured under suboptimal conditions may be significantly impaired, and this appears to be especially problematic with combined formulations of rifampicin, isoniazid and pyrazinamide. In view of the marked dose-dependence of rifampicin's bacterial sterilizing action, it is therefore essential that tuberculosis control programmes only use rifampicin-containing FDCs with proven rifampicin bioavailability. The comprehensive literature on the pharmacology of rifampicin is reviewed, together with the methods employed for determining it and its most important metabolite, desacetyl-rifampicin, in either serum or urine. By contrast, published information concerning the absorption of rifampicin from currently marketed combined formulations and on laboratory methods for precisely assessing their bioavailability is very sparse. There is therefore a crucial need to establish the quality of currently marketed rifampicin-containing FDCs in studies using adequate numbers of volunteers, precise analytical techniques and sophisticated statistical techniques.

Absorption↗

PubMed2001

The management of anti-tuberculosis drug-induced hepatotoxicity.

SETTING: A tuberculosis ward in a chest disease teaching hospital. OBJECTIVE: To compare the efficacy of two different retreatment protocols on hepatotoxicity recurrence in tuberculosis treatment. DESIGN: In a prospective, randomised study, 45 patients with new tuberculosis developed hepatotoxicity after anti-tuberculosis treatment. Patients in Group I (n = 20) were retreated with a drug regimen consisting of isoniazid, rifampicin, ethambutol and streptomycin administered by gradually increasing the number and dosage of the drugs. Patients in Group II (n = 25) were retreated with the same regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) in the same dosages throughout. RESULTS: Hepatotoxicity recurred in respectively zero and six (24%) patients in Groups I and II (P = 0.021). Of the six patients with recurrence of hepatitis, one could not be followed up. The other five received the same retreatment protocol as Group I. By the end of retreatment, all patients were cured. CONCLUSION: The recurrence rate of hepatotoxicity in the retreatment of tuberculosis is higher in the reintroduction of a full-dose regimen including pyrazinamide, which causes more hepatotoxicity than gradual reintroduction of a regimen without pyrazinamide.

Adolescent↗

PubMed2006

API TB Consensus Guidelines 2006: Management of pulmonary tuberculosis, extra-pulmonary tuberculosis and tuberculosis in special situations.

INTRODUCTION: The World Health Organization (WHO) has declared Tuberculosis (TB) a global emergency in 1993. Prevalence of TB and Human Immunodeficiency Virus (HIV) co-infection worldwide is 0.18% and about 8% TB cases have HIV infection. Effective chemotherapy has been available for treatment of TB for over 50 years now. In World Health Organization (WHO)-International Union Against Tuberculosis and Lung Disease (IUATLD) Working Group Global Anti-Tuberculosis Drug Resistance Surveillance (1994-1997), the incidence of MDR TB in Delhi was found to be 14%, of which primary multi-drug resistance was only 1.4%, indicating that most of MDR TB is acquired as a result of poor chemotherapy. DIAGNOSIS OF TB: Since TB is an infectious disease caused by Mycobacterium (M) tuberculosis the diagnosis of TB should (as far as possible) be by demonstration of M. tuberculosis on culture or acid-fast bacilli (AFB) on smear examination. The World Health Organization (WHO) has strongly recommended sputum smear examination as the preferred screening test and suggests examination of 3 deeply coughed out sputum samples - spot sample on day 1, overnight sample and a spot sample in the morning on day 2. Recently it has been shown that sputum smear positivity is greater than 90% where greater than 5 ml of sputum is used for smear diagnosis of pulmonary TB. Culture of M. tuberculosis is the gold standard for diagnosis of TB. Culture of mycobacteria is a much more sensitive test than smear examination and has been estimated to detect 10-100 viable mycobacteria per ml of sample and in case of active disease they are found to be 81% sensitive and 98.5% specific. Culture methods are also required for further drug sensitivity testing in cases of suspected drug resistant cases. Isoniazid and rifampicin resistance can be reliably measured; resistance to pyrazinamide, ethambutol, and streptomycin is more difficult due to limitations of technique. The therapeutic index for a given drug is low for certain second-line drugs such as ethionamide, cycloserine, viomycin and para amino salicylic acid (PAS) and it leads to misinterpretation of results due to failure to distinguish between sensitive and resistant strains. Misdiagnosis of MDR-TB due to laboratory related errors has been reported recently. MANAGEMENT OF TB: Chemotherapy of TB consists of prevention of infection, also called primary chemoprophylaxis, when isoniazid 5 mg/kg is given to prevent infection in newborn infants of infectious mothers till mother is sputum smear positive (2-3months). Treatment of latent tuberculosis, also called secondary chemoprophylaxis, when isoniazid 5 mg/kg is given for 6 months to prevent disease in infected persons (asymptomatic MT positive individuals) and treatment of disease with Short Course Chemotherapy (SCC), as per WHO categories. Essential anti-tuberculosis (ATT) drugs Isoniazid (H), Rifampicin (R), Ethambutol (E), Pyrazinamide (Z) and Streptomycin (S) are the essential first line anti-tuberculosis drugs. Anti TB regimen consists of two phases: an initial intensive phase (IIP) and a continuation phase (CP). Best effective SCC for treatment of TB, for adults and children, for pregnant and lactating females, for cases associated with diabetes mellitus and HIV infection, for cases with pre-existing liver diseases (but normal liver functions) and mild renal failure is 2EHRZ, 4HR given daily or thrice weekly. Higher dose SCC intermittent therapy given in thrice weekly (2E3H3R3Z3, 4H3R3) has now been advocated by WHO and implemented by the Revised National TB Control Programme. DOTS, directly observed therapy short course, where the patient takes the drugs under the direct observation (DO) of a health worker to ensure regularity of consumption of drugs. Fixed dose combinations (FDCs) drugs consisting of two or three antituberculosis medications, provide a realistic and welcome alternative to DO that minimizes the opportunity for a patient to selectively take only a single medication. MANAGEMENT OF TB IN SPECIAL SITUATIONS: Pregnancy: All drugs, that is, rifampicin, isoniazid, ethambutol, and pyrazinamide can be used during pregnancy. Streptomycin is not given due to ototoxicity to the fetus. Prophylactic pyridoxine in the dose of 10mg/day is recommended along with ATT. Diabetes mellitus: The drug regimen is same as in nondiabetic. Strict control of blood glucose is mandatory. Also, doses of oral hypoglycemic agents may have to be increased due to interaction with Rifampicin. Prophylactic pyridoxine is indicated. Renal failure: Dosages may have to be adjusted according to the creatinine clearance especially for streptomycin, ethambutol and isoniazid. In acute renal failure, ethambutol should be given 8 hours before hemodialysis. In post renal transplant patients: Rifampicin-containing regimens are avoided as rifampicin causes increased clearance of cyclosporin. Pre-existing liver disease: In stable disease with normal liver enzymes, all anti-tuberculous drugs may be used but frequent monitoring of liver function tests is required. Treatment in unconscious patient (patients unable to swallow): If patients are fed by Ryle's tube or gastrostomy tube, usual doses and drugs may be powdered and administered avoiding feeds 2-3 hours before and after the dose. In cases where enterostomy has been performed or parenteral nutrition is being used, intramuscular streptomycin and isoniazid and intravenous quinolones may be used and switch to oral therapy once oral feed resume. Treatment of TB with HIV co-infection: In early stages the presentations of TB in TB-HIV co-infection is the same as HIV negative but in late stages extra-pulmonary and dissemination are common. The usual short course chemotherapy is indicated in HIV positive patients. The response is usually good but relapse is frequent. After initiating ATT or anti-retroviral therapy (ART) worsening of preexisting lesions or appearance of new lesions is seen, "paradoxical response" or "immune reconstitution phenomenon". Multidrug resistant TB can occur due to poor compliance to ATT due to behavioural pattern, increased incidence of side effects and malabsorption of drugs due to associated diarrhea. ART for HIV, containing protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) cannot be used along with R, as R induces metabolism of PI and reduces the efficacy. The various options are i) to postpone anti-retroviral therapy ii) to use no PI or NNRTI containing anti-retroviral combinations iii) to use certain PI/ and/or NNRTIs with modification in doses iv) Efavirenz (EFZ) or Saquinavir with Ritonavir, without the need to adjust the doses v) to use non R regimens e.g. 2SHEZ+10HE MANAGEMENT OF MDR TB: As far as possible treatment of MDR TB should be referred to specialized units with facilities for quality controlled DST and experienced in handling such cases. If such referrals are not possible, one must remember that while initiating or revising therapy for MDR-TB, drugs selection must rely on prior treatment history, results of susceptibility testing and an evaluation of the patient's adherence.

Algorithms↗

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↗

PubMed1995

Correlation between steady-state plasma concentration of antituberculous drugs and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters.

A regional hospital in Hong Kong examined the correlation between plasma concentrations of rifampicin, pyrazinamide, isoniazid and its metabolite hydrazine and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters. One hundred eighty subjects with tuberculosis were admitted consecutively to the medical wards of the Prince of Wales Hospital over a one and a half year period. Elderly patients > 65 years were randomized into one of two treatments with and without rifampicin in addition to isoniazid, pyrazinamide and ethambutol; younger patients received all four drugs. Plasma antituberculous drug concentrations were determined using high performance liquid chromatography. Elderly patients taking rifampicin had a higher mean steady-state concentration of isoniazid, together with a higher incidence of adverse effects compared with those not taking rifampicin. No age related differences were observed for the other drugs. For the whole group, higher mean concentrations of hydrazine, rifampicin and pyrazinamide were associated with a higher incidence of adverse effects and the presence of coexisting diseases. It is concluded that in sick elderly patients with coexisting diseases, use of rifampicin in the antituberculous regimen should be accompanied by close monitoring for side effects, and that there may be an indication for use of lower dosages of antituberculous drugs in such patients.

Adult↗

PubMedDate not supplied

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↗