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PubMed1994

Clinically significant drug interactions with antituberculosis agents.

Standard short-course regimens for tuberculosis are used worldwide with very few problems. Unfortunately, the emergence of multiple drug-resistant tuberculosis in many parts of the world is leading to a diversification of drug regimens and to the use of drugs that are more toxic per se and more likely to interact with others. In addition, the treatment of HIV/AIDS patients with tuberculosis or disease due to Mycobacterium avium-intracellulare complex (MAC) infection with new drugs and multidrug regimens has added to the problem of drug interactions, especially as such patients may often be receiving concomitant treatment for a range of bacterial, fungal and viral infections. In general, there are very few clinically significant interactions between the first-line antituberculosis drugs themselves, although problems of bioavailability, notably of rifampicin (rifampin), have been encountered in the manufacture of combination tablets. Of the first-line drugs used to treat tuberculosis, i.e. rifampicin, isoniazid and pyrazinamide, rifampicin is particularly likely to cause clinically significant drug interactions as it is a potent inducer of the cytochrome P450 enzyme group, which is involved in the metabolism of many drugs, in particular oral contraceptives, corticosteroids, oral anticoagulants and cyclosproin. The use of quinolones to treat multiple drug-resistant tuberculosis and AIDS-related MAC disease raises further problems of drug interactions as, in contrast to rifampicin, these drugs inhibit some cytochrome isoenzymes, leading to reduced metabolism of certain drugs.

Absorption↗
PubMed2001

Drug treatment for tuberculosis during pregnancy: safety considerations.

Untreated tuberculosis in pregnancy poses a significant threat to the mother, fetus and family. Adherence to treatment is especially difficult in pregnancy because of the general fear of any medication and pregnancy-related nausea. Supervised treatment is especially helpful in encouraging adherence. All 4 first line drugs [isoniazid, rifampicin (rifampin), ethambutol and pyrazinamide] have an excellent safety record in pregnancy and are not associated with human fetal malformations. Drug-induced hepatitis, especially with isoniazid, is a significant problem in treating tuberculosis, not peculiar to pregnancy; close monitoring of liver function is recommended. Liver enzyme induction by rifampicin alters the metabolism of other drugs, e.g. methadone doses will need to be increased. Streptomycin should not be used in pregnancy, as perhaps 1 in 6 babies will have problems with hearing and/or balance. Ciprofloxacin has the best safety profile of second line drugs in the treatment of drug-resistant tuberculosis. Preventive treatment with isoniazid can be undertaken safely during pregnancy. Pyridoxine (vitamin B6) should be added to the drug treatment of tuberculosis in all pregnant women taking isoniazid. Neither tuberculin nor the bacille Calmette Guérin (BCG) vaccine are treatments for tuberculosis, but they play an important role in the management of the disease. Tuberculin testing is safe, but BCG vaccination should be avoided in pregnancy and instead given earlier in life.

Animals↗
PubMed1996

Tuberculosis in the elderly. Epidemiology and optimal management.

The problem with the emergence of HIV-associated tuberculosis (which usually occurs in young adults) is that attention has been diverted away from the fact that, in the developed world, the elderly represent the biggest pool of tubercular disease and therefore the greatest pool of infection within the community. Although the incidence rate of tuberculosis continues to decline in most countries, there is evidence from parts of the developing world that rates may be beginning to increase. The presentation of the disease in the elderly is often uncharacteristic, e.g. disease tending to be more insidious in onset, pyrexia often absent and haemoptysis less common. Chest x-ray changes may also mislead the clinician in that disease is frequently present in the mid or lower zones. The elderly are probably at greater risk of extrapulmonary tuberculosis, which also presents in uncharacteristic ways. The diagnosis remains based on clinical presentation and the presence of smear and culture positivity, although some patients may be treated in the absence of microbiological proof. Standard treatment is with a combination of isoniazid, rifampicin and pyrazinamide, with or without a fourth drug such as ethambutol. The incidence of adverse effects in the elderly is much greater than that in younger patients, often resulting in the need to change the medication to drugs which are better tolerated. This may require changing to regimens which are less effective and therefore have to be taken for a longer period of time. The presence of concomitant disease such as liver or renal failure may also necessitate the administration of a suboptimal regimen. Mortality in elderly patients with tuberculosis is considerably higher than that in younger patients, even when treatment appears to have been started on time; even in the developed world mortality exceeds 30% in those patients over 70 years of age.

Age Distribution↗
PubMedDate not supplied

Clinical pharmacokinetics of the antituberculosis drugs.

The quantitative aspects of the disposition in man of 12 antituberculosis drugs [isoniazid, rifampicin, (rifampin), ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone] are reviewed. Isoniazid appears to be the only agent for which plasma concentrations and clearance are related to hereditary differences in acetylator status and for which there is an appreciable 'first-pass' effect. Recent data cast doubt on the suggestion that isoniazid may be more hepatotoxic for rapid as opposed to slow acetylators. Continuous administration of rifampicin leads to induction of enzymes in the liver with a concomitant decrease in maximum plasma concentrations, the time required to achieve this level, elimination half-life, and area under the plasma concentration-time curve (AUC). Coadministration of para-aminosalicylic acid leads to increases in the serum concentrations and elimination half-life of isoniazid. With a few exceptions, the metabolites of the antituberculosis drugs are devoid of antimicrobial activity; the exceptions are 25-desacetylrifampicin which accounts for approximately 80% of the drug's antimicrobial activity in human bile, the acetylated and glycylated metabolites of para-aminosalicylic acid, and the sulphoxide metabolites of ethionamide. The effect of renal impairment is relatively unimportant for the excretion of isoniazid, rifampicin and para-aminosalicylic acid, but the elimination half-life of streptomycin increases to 100 hours when the blood urea nitrogen level is greater than 100mg/100ml, and ototoxicity is strikingly more frequent. In states of malnutrition, such as kwashiorkor, the protein binding of para-aminosalicylic acid decreases from 15% to essentially zero and in the case of ethionamide and streptomycin binding decreases by 6% and 16% respectively. Of the data concerning age-related effects, most notable are the prolonged elimination half-life of isoniazid in neonates (up to 19.8 hours), and the lower peak serum concentrations of rifampicin in children of one-third to one-tenth those of adults following a similar dose on a weight basis. For kanamycin, the maximum plasma concentration varies inversely with age but is not influenced by birthweight; however, the clearance is directly dependent upon birthweight and postnatal age. For the elderly, age is an insignificant factor for the elimination of isoniazid when compared with young adults of similar acetylator status, and the metabolism of rifampicin may be considered globally unaltered in this age group.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1989

Clinical pharmacokinetic considerations in the treatment of patients with leprosy.

On the basis of the efficacy of the available agents, the World Health Organization has recommended only 4 drugs for combined chemotherapy of leprosy: rifampicin, dapsone, clofazimine and ethionamide/prothionamide. Thiacetazone and isoniazid are also used to a lesser extent by some physicians. Pyrazinamide may find a place in treating 'persister' bacilli. Dapsone is absorbed slowly after oral administration. Peak plasma drug concentration is reached at about 4 hours; absorption half-life is 1.1 hours; elimination half-life is about 30 hours. Oral availability is around 90%. Dapsone is approximately 70% protein-bound, while its monoacetylated metabolite is almost entirely bound. Dapsone crosses the placenta and is excreted into breast milk. It is metabolised via acetylation and N-hydroxylation, but acetylation polymorphism has no effect on dapsone handling by leprosy patients. Dapsone penetrates into sciatic nerves of experimental animals but its presence has not been demonstrated in Schwann cells. Oral doses of rifampicin are rapidly and completely absorbed. The bioavailability is greater when the drug is given before meals; peak concentrations occur at 1 to 2 hours. 80 to 90% of rifampicin is bound to plasma proteins, and the drug is found in saliva, cerebrospinal fluid and breast milk. Its main metabolite, desacetyl rifampicin, also exhibits antimycobacterial activity in tuberculosis. Rifampicin induces its own metabolism, as well as that of dapsone and steroids. Absorption of dapsone and rifampicin is reported to be reduced in leprosy patients. Clofazimine has been in use in leprosy treatment since 1960. In higher doses it exerts an anti-inflammatory action which is useful in treating leprosy patients in reaction. Oral absorption of the drug is slow and dose-dependent; faecal excretion also increases with dose. Single- and multiple-dose studies have shown a plasma half-life of around 10 days. Bioavailability of the drug is higher when given with food than when fasting; the peak plasma concentration occurs at 4 to 8 hours when the drug is administered with breakfast. After absorption, the drug is thought to circulate in protein-bound form, accounting for the fact that it is deposited in various tissues. Uneven distribution and prolonged retention in the tissues are special features of clofazimine metabolism. One unconjugated and 2 conjugated metabolites have been detected in urine, and the urinary excretion of both the parent compound and its metabolites is around 1% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed2001

The role of fluoroquinolones in tuberculosis today.

Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today. The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease. Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml. Resistance in TB to fluoroquinolones may occur spontaneously or may be acquired, especially when these agents are used inappropriately. Cross-resistance among the fluoroquinolones has been shown in TB. The fluoroquinolones offer a favourable pharmacokinetic profile for the treatment of TB. Most demonstrate excellent oral bioavailability and achieve maximum (peak) serum concentrations well above the MIC. They are also distributed widely, including intracellularly. The fluoroquinolones are cleared renally and/or hepatically, with varying serum half-lives. Fluoroquinolones are most effective when the peak concentration (Cmax) to MIC ratio is maximised. Fluoroquinolones such as ciprofloxacin and ofloxacin have been used in regimens for the prevention of TB, but have been poorly tolerated when used in combination with pyrazinamide. Favourable responses with fluoroquinolones in regimens used in the treatment of clinical TB disease have been seen. They, however, are not to be considered as equal replacements for isoniazid or rifampicin (rifampin) and should be used with at least 2 other antituberculous agents. Therapeutic drug monitoring of fluoroquinolones is beneficial in assuring that maximum Cmax to MIC ratios are being achieved, especially in patients at risk for malabsorption, such as those infected with HIV. Higher, once-daily doses of most fluoroquinolones are becoming more common in treating TB. Fluoroquinolones are generally well tolerated with long term use in treating TB, but rare, serious adverse effects have been reported with general fluoroquinolone use. The most common drug interactions with fluoroquinolones in TB therapy include the malabsorption interactions associated with multivalent cations and cytochrome P450 interactions with ciprofloxacin. An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically. When using fluoroquinolones to treat TB, careful consideration of individual susceptibility patterns, pharmacokinetic and toxicity profiles should be taken. The aid of a TB expert may also be warranted. The exact role of the fluoroquinolones in treating TB remains to be determined.

Animals↗
PubMed2006

Safety, efficacy and pharmacokinetics of ritonavir 400mg/saquinavir 400mg twice daily plus rifampicin combined therapy in HIV patients with tuberculosis.

OBJECTIVE: To assess the drug concentrations, efficacy and safety of concomitant use of rifampicin and regimens containing ritonavir/saquinavir (400mg/400mg twice daily) in tuberculosis-HIV treatment-naive patients. DESIGN AND METHODS: This was an open-label, non-randomised, multiple-dose study. On study day (D)1, tuberculosis treatment (rifampicin 600mg/isoniazid 400mg per day fasting plus pyrazinamide 2 g/day) was introduced in 30 patients. On D31, highly active antiretroviral therapy (HAART) consisting of two nucleoside analogues plus ritonavir/saquinavir 400mg/400mg twice daily was initiated (n = 20). The pharmacokinetics were assayed with a validated reversed-phase HPLC method before the introduction of HAART on D30 (for rifampicin), after 30 days of HAART at D60 (for rifampicin plus ritonavir/saquinavir), and at the end of the study (without rifampicin) on D210 (for ritonavir/saquinavir). Clinical evaluations were performed on a monthly basis. CD4 counts and viral load were collected on D30, D60 and D180. Genotyping test for HIV was collected at baseline and at D180. Primary endpoints were drug concentration and viral load at D180 (<80 copies/mL). Secondary endpoints were presence of grade 3 and serious adverse events, clinical improvement, CD4 count and genotypic resistance to ritonavir/saquinavir. RESULTS: Ten patients dropped out of the study during tuberculosis therapy alone. Mean (+/- SD) baseline CD4 count (on D30) was 151.89 (+/- 146.77) cells/mm(3) and viral load was 5.34 (+/- 0.4) log. During the antiretroviral therapy, 15 patients dropped out, 14 because of adverse events. One patient (of five) presented a viral load of <80 copies/mL at D180. All but one patient increased CD4 counts from baseline. No genotypic resistance was detected. Clinical improvement was evident in all five patients who tolerated the therapy. Serum concentrations of ritonavir/saquinavir and rifampicin remained within the therapeutic range. CONCLUSIONS: Therapeutic concentrations of the studied drugs and reduction of viral load were achieved; adverse events are the main limitation of use of a ritonavir/saquinavir regimen in treatment-naive patients, but its clinical benefits were evident.

AIDS-Related Opportunistic Infections↗
PubMed2005

Influence of silymarin administration on hepatic glutathione-conjugating enzyme system in rats treated with antitubercular drugs.

OBJECTIVE: This study evaluated the influence of simultaneous administration of silymarin (SIL), a hepatoprotective and antioxidant agent, on the status of glutathione (GSH) and its metabolising enzymes in the liver tissue of rats treated with antitubercular drugs, i.e. isoniazid (INH), rifampicin (RIF) and pyrazinamide (PYR). METHODS: Male Wistar albino rats (n = 24) were randomly divided into four groups. Group I received saline as they served as controls. Group II rats were administered antitubercular drugs (INH 25 mg/kg + RIF 50 mg/kg + PYR 140 mg/kg orally) daily for 45 days. Group III animals were treated with SIL (50 mg/kg orally) simultaneously with the antitubercular drugs for the same period. Group IV animals were treated with SIL alone. The status of GSH, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-s-transferase (GST) in liver tissue was evaluated at the end of the study. RESULTS: Administration of antitubercular drugs caused a significant decrease (p < 0.001) in the status of GPx, GST and GR and of non-enzymic (GSH) antioxidants in liver tissue when compared with saline-treated control rats. Simultaneous treatment of SIL with antitubercular drugs completely prevented decreases in the levels of all the above parameters. Treatment with SIL alone enhanced the activities of GST (p < 0.001) and GPx (p < 0.05) and did not alter glutathione levels compared with control. CONCLUSION: A fall in the status of glutathione and its conjugating enzymes upon administration of antitubercular drugs denotes an impairment of the antioxidant defence mechanism. Simultaneous administration of SIL afforded complete protection of the liver against this abnormality, an effect that could have been due to the strong antioxidant properties of SIL.

Animals↗
PubMed2005

Bacterial pericarditis: diagnosis and management.

Bacterial pericarditis occurs by direct infection during trauma, thoracic surgery, or catheter drainage, by spread from an intrathoracic, myocardial, or subdiaphragmatic focus, and by hematogenous dissemination. The frequent causes are Staphylococcus and Streptococcus (rheumatic pancarditis), Haemophilus, and M. tuberculosis. In AIDS pericarditis, the incidence of bacterial infection is much higher than in the general population, with a high proportion of Mycobacterium avium-intracellulare infection. Purulent pericarditis is the most serious manifestation of bacterial pericarditis, characterized by gross pus in the pericardium or microscopically purulent effusion. It is an acute, fulminant illness with fever in virtually all patients. Chest pain is uncommon. Purulent pericarditis is always fatal if untreated. The mortality rate in treated patients is 40%, and death is mostly due to cardiac tamponade, systemic toxicity, cardiac decompensation, and constriction. Tuberculous infection may present as acute pericarditis, cardiac tamponade, silent (often large) relapsing pericardial effusion, effusive-constrictive pericarditis, toxic symptoms with persistent fever, and acute, subacute, or chronic constriction. The mortality in untreated patients approaches 85%. Urgent pericardial drainage, combined with intravenous antibacterial therapy (e.g. vancomycin 1g twice daily, ceftriaxone 1-2g twice daily, and ciprofloxacin 400 mg/day) is mandatory in purulent pericarditis. Irrigation with urokinase or streptokinase, using large catheters, may liquify the purulent exudate, but open surgical drainage is preferable. The initial treatment of tuberculous pericarditis should include isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25 mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential. Pericardiectomy is reserved for recurrent effusions or continued elevation of central venous pressure after 4-6 weeks of antituberculous and corticosteroid therapy.

Anti-Bacterial Agents↗
PubMed1994

Sjögren's syndrome in one of two sisters with idiopathic renal hypouricemia.

Concomitance of idiopathic hypouricemia and Sjögren's syndrome is reported. A 37-year-old Japanese woman with Sjögren's syndrome and her 39-year-old sister without this syndrome both had extremely low levels of serum uric acid. Markedly increased urinary excretion of uric acid and poor response to the pyrazinamide suppression test revealed that the hypouricemia in these sisters was caused by a defect in the pre-secretory reabsorption of uric acid. It is categorized as idiopathic renal hypouricemia than hypouricemia rather secondary to Sjögren's syndrome. Thus, idiopathic renal hypouricemia should be considered even in cases with autoimmune diseases.

Adult↗
PubMed2004

Fluoroquinolones as chemotherapeutics against mycobacterial infections.

The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in >95% cure in uncomplicated tuberculosis infection. Drug resistance greatly complicates treatment of this disease. Treatment of tuberculosis caused by multiply drug-resistant strains with "second-line" drugs remains complex, and is generally tailored to the individual patient and strain. Several of the fluoroquinolones have shown promise as second line drugs for treatment of active disease and, in combination with clarithromycin or azithromycin, ethambutol, and other agents, for treatment of Mycobacterium avium complex infection. While large clinical trials are not possible with second line drugs, clinical treatment data are available and suggest that the quinolones have various degrees of promise in treatment of these infections. Bacterial type II DNA topoisomerases, DNA gyrase and topoisomerase IV, are the targets of quinolones, and provide the genetic basis for quinolone activity in mycobacteria. Mutations in these enzymes results in resistance, and characterization of resistant mutants allows correlation of genotype with susceptibility phenotype. Structure-activity relationship studies have provided further insight into optimal use of quinolones in mycobacterial infections. Care should be taken in treating pneumonia with fluoroquinolones if there is a degree of suspicion of tuberculosis, since quinolone monotherapy may rapidly select for quinolone resistance, thereby removing that class of antibiotic from the small range of treatment options.

Animals↗
PubMed2002

Drugs that inhibit mycolic acid biosynthesis in Mycobacterium tuberculosis.

Tuberculosis resurged in the late 1980s and now kills more than 2 million people a year. The reemergence of tuberculosis as a potential public health threat, the high susceptibility of human immunodeficiency virus-infected persons to the disease, and the proliferation of multi-drug-resistant (MDR) strains have created much scientific interest in developing new antimycobacterial agents to both treat Mycobacterium tuberculosis strains resistant to existing drugs, and shorten the duration of short-course treatment to improve patient compliance. Bacterial cell-wall biosynthesis is a proven target for new antibacterial drugs. Mycolic acids, which are key components of the mycobacterial cell wall, are alpha-alkyl, beta-hydroxy fatty acids, with a species-dependent saturated "short" arm of 20-26 carbon atoms and a "long" meromycolic acid arm of 50-60 carbon atoms. The latter arm is functionalized at regular intervals by cyclopropyl, alpha-methyl ketone, or alpha-methyl methylethers groups. The mycolic acid biosynthetic pathway has been proposed to involve five distinct stages: (i) synthesis of C20 to C26 straight-chain saturated fatty acids to provide the alpha-alkyl branch; (ii) synthesis of the meromycolic acid chain to provide the main carbon backbone, (iii) modification of this backbone to introduce other functional groups; (iv) the final Claisen-type condensation step followed by reduction; and (v) various mycolyltransferase processes to cellular lipids. The drugs shown to inhibit mycolic acid biosynthesis are isoniazid, ethionamide, isoxyl, thiolactomycin, and triclosan. In addition, pyrazinamide was shown to inhibit fatty acid synthase type I which, in turn, provides precursors for fatty acid elongation to long-chain mycolic acids by fatty acid synthase II. Here we review the biosynthesis of mycolic acids and the mechanism of action of antimicrobial agents that act upon this pathway. In addition, we describe molecular modeling studies on InhA, the bona-fide target for isoniazid, which should improve our understanding of the amino acid residues involved in the enzyme's mechanism of action and, accordingly, provide a rational approach to the design of new drugs.

Antitubercular Agents↗
PubMed1995

Treatment of tuberculous meningitis in Turkey.

A prospective study was performed on 72 cases of tuberculous meningitis studying various treatments. 37 patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and streptomycin for 2 months, followed by a combination of isoniazid and rifampicin for 6 months. 35 patients were treated with various combinations of antituberculous drugs for 12-16 months. Disappearance of symptoms took (mean) 17 days. Mean duration of therapy for the hospitalized patients was 36 +/- 4 days. Seven (9.7%) patients died, 5 in the short-course therapy group and 2 in the long-course therapy group. Sequelae persisted in 18 (31%) cases, 8 of which cases were in the short-course therapy group and 10 in the long-course therapy group. No relapse was observed in either of the groups.

Adolescent↗
PubMed1996

High proportion of multi-drug resistant Mycobacterium tuberculosis in Saudi Arabia.

289 patients with TB, presented to a single tertiary care unit in Saudi Arabia between 1989 and 1994. The isolate from each patient was tested for in vitro susceptibility to rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin. 25 patients (8.7%) had isolates resistant to at least 1 anti-tuberculous drug. Single drug resistance (SDR)-mainly isoniazid-occurred in 14, and resistance to at least 2 drugs (multi-drug resistance-MDR) in 11, of which 8 were due to both isoniazid and rifampicin. Previous drug treatment occurred significantly more often in patients with MDR (8/11), than SDR (1/14) (p = 0.0021). A literature review of another 5571 patients from Saudi Arabia with TB revealed an incidence of resistance of M. tuberculosis isolates to at least 1 anti-tuberculous drug tested, of between 5.9% and 44%. The overall percentage of patients with resistant tuberculosis (including our own patients) was 14.9%. Resistance to streptomycin (8.9%), isoniazid (6.6%), and rifampicin (6.1%) were the commonest reported. There were as many patients with MDR as there were SDR. A history of previous anti-tuberculous treatment was found in over 40%. The high rate of anti-tuberculous resistance in Saudi Arabia may be due to poor supervision of anti-TB treatment, the embryonic healthcare system, over-the-counter antibiotic availability, treatment of endemic diseases such as brucella with rifampicin etc., a large migrant work force, and possibly increased toxicity of anti-tuberculous drugs secondary to the high incidence of chronic liver disease in the country.

Adolescent↗
PubMed2004

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2003. A report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2003. A total of 784 cases were identified by bacteriology, representing an annual reporting rate of 3.9 cases of laboratory confirmed tuberculosis per 100,000 population. The most commonly encountered culture-positive specimens were sputum (n = 351), lymph node (n = 176) and from bronchoscopy (n = 97). Smears containing acid fast bacilli were present in sputum (53.0%), bronchoscopy (32.0%) and lymph node (23.3%). Five children (female n = 3, male n = 2) under 10 years of age had bacteriologically confirmed tuberculosis. Eighty isolates of M. tuberculosis and one of Mycobacterium africanum (10.3%) were resistant to at least one of the standard anti-tuberculosis agents. Mono-resistance to isoniazid, ethambutol, rifampicin, and pyrazinamide was detected in 45, three, two, and one isolates respectively. Multidrug-resistance (MDRTB) defined as resistance to both isoniazid and rifampcin was observed in seven (0.9%) isolates. Of the seven MDRTB isolates, six were from the respiratory tract and four were from smear positive specimens. Of the 81 patients with drug resistant isolates, 78 (96.3%) were classified as having initial resistance; two had acquired resistance and no information was available for one isolate; five were Australian-born; and 76 (93.8%) had migrated from a total of 30 countries.

Adolescent↗
PubMed2006

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2004: a report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on new cases of disease caused by Mycobacterium tuberculosis complex in the year 2004. A total of 787 cases were identified by bacteriology, representing an annual reporting rate of 3.9 cases per 100,000 population. Almost all isolates were identified as M. tuberculosis (n = 785), the remaining isolates being one each of Mycobacterium africanum and Mycobacterium canettii. Seven children under 10 years of age (female n = 5, male n = 2) had bacteriologically confirmed tuberculosis (gastric aspirate n = 4, lymph node n = 1, pleural n = 1, thigh wound n = 1). Results of in vitro drug susceptibility testing were available for all 787 isolates for isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of 71 (9.0%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least both H and R (defined as multidrug resistance) was detected in 12 (1.5%) isolates; 10 were from the respiratory tract (sputum n = 7, bronchoscopy n = 3). The country of birth was known for 68/71 (95.8%) cases with a drug resistant strain; eight were Australian, 60 were overseas born, and three were unknown. Of the 60 migrants with drug resistant disease, 37 (61.7%) were from three countries; Viet Nam (n = 20), China (n = 9) and India (n = 8).

Adolescent↗
PubMed1994

A case of extra-hepatic portal hypertension caused by periportal tuberculous lymphadenitis.

This report describes a case of portal hypertension caused by periportal tuberculous lymphadenitis. There were a few reports of portal hypertension associated with tuberculosis. A 27-year-old man was admitted to the hospital because of recurrent hematemesis for 7 days. There was a history of mediastinal tuberculous lymphadenitis 3 years earlier that was treated with isoniazide, rifampin, ethambutol, and pyrazinamide for 2 years. Clinical evaluation revealed esophageal variceal bleeding and main portal vein obstruction by enlarged periportal lymph nodes. The patient underwent distal splenorenal shunt. Pathologic examination of the excised periportal lymph node revealed chronic granulomatous inflammation with central caseous necrosis. Thereafter the patient took antituberculous medication for 12 months. The patient has not re-bled 3 years since the shunt operation.

Adult↗
PubMed2004

A case of pseudomembranous colitis associated with rifampin.

Pseudomembranous colitis is known to develop with long-term antibiotic administration, but antitubercular agents are rarely reported as a cause of this disease. We experienced a case of pseudomembranous colitis associated with rifampin. The patient was twice admitted to our hospital for the management of frequent bloody, mucoid, jelly-like diarrhea and lower abdominal pain that developed after antituberculosis therapy that included rifampin. Sigmoidoscopic appearance of the rectum and sigmoid colon and mucosal biopsy were compatible with pseudomembranous colitis. The antitubercular agents were discontinued and metronidazole was administered orally. The patient's symptoms were resolved within several days. The antituberculosis therapy was changed to isoniazid, ethambutol and pyrazinamide after a second bout of colitis. The patient had no further recurrence of diarrhea and abdominal pain. We report here on a case of pseudomembranous colitis associated with rifampin.

Aged↗