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PubMed2002

Risk factors for antituberculous chemotherapy-induced hepatotoxicity in Japanese pediatric patients.

OBJECTIVE: Our objective was to clarify risk factors associated with the development of severe hepatotoxicity during antituberculosis chemotherapy in Japanese children. METHODS: In a retrospective analysis in a 350-bed referral children's hospital in a metropolitan area, the medical charts of all pediatric patients who received antituberculosis chemotherapy between January 1995 and November 1999 were surveyed. Univariate and multivariate analyses were performed to find any demographic parameters (ie, sex, age, height, and body weight), clinical characteristics (ie, nutritional or developmental status, co-infection with hepatitis viruses [B or C] or human immunodeficiency virus, presence of extrapulmonary tuberculosis, or medical history of liver disease), or individual antituberculosis agents used that would be associated with the likelihood of development of severe hepatotoxicity during antituberculous chemotherapy. Severe hepatotoxicity (defined as an elevation of ALT and AST levels that were greater than 5 times the respective reference values) was attributed to the chemotherapy when it developed in children with normal pretreatment values for these parameters and no other potential causes were identified. Those who had abnormal ALT or AST values before treatment were excluded from analysis. RESULTS: Among the 117 patients surveyed (58 males and 59 females; age range, 0 to 16 years), 18 were excluded from the analysis because of abnormal baseline ALT and AST values. Severe hepatotoxicity developed in 8 of the 99 eligible children, and all 8 of those children were younger than 5 years old. The univariate analysis revealed that the children in whom hepatotoxicity developed were significantly (P <.05) younger, were predominantly male, had extrapulmonary tuberculosis, and were given pyrazinamide more often than those who had no hepatotoxicity. However, the multivariate logistic regression analysis revealed that only age and the administration of pyrazinamide would have a significant contribution (P <.05) to the development of severe hepatotoxicity, with odds ratios of 143 (95% confidence interval, 4.2 to 4934.9) and 0.60 (95% confidence interval, 0.39 to 0.90), respectively: the estimated probability of development of hepatotoxicity in a typical pediatric patient at 1, 5, and 10 years receiving pyrazinamide with rifampin (INN, rifampicin) and isoniazid would be 0.95, 0.72, and 0.16, respectively. CONCLUSIONS: This study indicated that intensive monitoring of hepatotoxicity should be performed for younger children (<5 years) receiving pyrazinamide for antituberculosis chemotherapy.

Adolescent↗

PubMed2002

An ex vivo culture model for screening drug activity against in vivo phenotypes of Mycobacterium tuberculosis.

Since the activity of drugs against Mycobacterium tuberculosis grown in microbiological culture can differ from their activity against bacteria present in infected tissues, compounds with optimal activity against in vivo phenotypes may be overlooked in drug-discovery programmes that rely on in vitro screens. The authors have investigated the use of an ex vivo cell-culture model to assess the action of drugs on M. tuberculosis in an environment resembling that encountered during infection. Mycobacterial viability in the ex vivo model was shown to be regulated by the cell-mediated immune system, with growth inhibited by CD4(+) T cells at an early stage of infection in BCG-vaccinated mice, and at a later stage after infection in naive mice. Screening of drugs in the ex vivo model demonstrated a window of pyrazinamide susceptibility that coincides with the onset of the T-cell-mediated immune response in naive or vaccinated mice. It is proposed that pyrazinamide acts on a population of bacteria that are exposed to an acidic environment as a result of immune activation. Clinically, administration of pyrazinamide during the initial phase of treatment reduces the risk of relapse after 6 months, suggesting that the early pyrazinamide-susceptible population may contribute to the later pool of mycobacteria that persist during prolonged chemotherapy.

Animals↗

PubMed1981

Controlled clinical trial of five short-course (4-month) chemotherapy regimens in pulmonary tuberculosis. Second report of the 4th study. East African/British Medical Research Councils Study.

We compared the bacteriologic relapse between 5 and 28 months for five 4-month chemotherapeutic regimens for pulmonary tuberculosis. The regimens were: (1) streptomycin plus isoniazid plus rifampin plus pyrazinamide daily for 8 wk followed by isoniazid plus rifampin plus pyrazinamide daily for 9 wk; (2) the same 4 initial drugs for 8 wk followed by isoniazid plus rifampin daily for 9 wk; (3) the same 4 initial drugs for 8 wk followed by isoniazid plus pyrazinamide daily for 9 wk; (4) the same 4 drugs for 8 wk followed by isoniazid daily for 9 wk; (5) the same as regimen 4; but without streptomycin for the first 8 wk. The first 2 regimens, in which rifampin was given for 4 months, had relapse rates of 16 and 11%, respectively, but the rates were much higher for the regimens in which rifampin was given for only 2 months (32 and 30 %, respectively). The addition of pyrazinamide in the continuation phase had no effect on relapse rate. Removal of the streptomycin (regimen 5) resulted in a relapse rate of 40%, but this was not significantly higher than that (30%) after regimen 4 (p = 0.2).

Adolescent↗

PubMed1996

Low antituberculosis drug concentrations in patients with AIDS.

OBJECTIVE: To determine the frequency and magnitude of below normal apparent peak serum concentrations for antituberculosis drugs in patients with AIDS and CD4 cell counts less than 200 cells/mm3. We also explored the data for potential relationships between response variables and patient characteristics. DESIGN: Prospective study of consecutive patients seen in tuberculosis clinics. SETTING: Five urban tuberculosis clinics in four major metropolitan areas. PARTICIPANTS: Twenty-six patients diagnosed with HIV infection and receiving treatment for active tuberculosis were eligible. MAIN OUTCOME MEASURES: After 2 weeks or more of therapy, blood was collected 2 hours after observed doses of the antituberculosis drugs. Serum samples were frozen, shipped to National Jewish Center in Denver, and analyzed by HPLC or GC. Serum concentrations were compared with the proposed normal ranges. Data were analyzed to determine correlations between antituberculosis drug serum concentrations and patient characteristics. RESULTS: Low-2-hour serum concentrations were common for antituberculosis drugs, particularly rifampin and ethambutol. Absorption of isoniazid was generally high. Potential drug-drug interactions were found between rifampin and fluconazole (fluconazole appears to increase rifampin concentrations) and between pyrazinamide and zidovudine (zidovudine may lower pyrazinamide concentrations). Patients receiving pyrazinamide had lower rifampin concentrations than those not receiving pyrazinamide. CONCLUSIONS: Low antituberculosis drug serum concentrations occur frequently during the treatment of tuberculosis in patients with AIDS. Additional research is required for patients with drug-resistant tuberculosis, and to clarify the nature of the potential drug-drug interactions.

Adult↗

PubMed2005

Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy.

STUDY OBJECTIVES: To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide. DESIGN: Retrospective case-control study. SETTING: Tertiary university medical center. PATIENTS: One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects. RESULTS: The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects). CONCLUSIONS: Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

Adult↗

PubMed1999

The colorimetric analysis of anti-tuberculosis fixed-dose combination tablets and capsules.

SETTING: The perceived need to demonstrate whether or not the actual amounts of rifampicin, isoniazid and pyrazinamide in fixed-dose combination tablets or capsules correspond to their stated drug contents. OBJECTIVE: To adapt specific, robust and simple colorimetric methods that have been previously applied to measuring plasma and urinary rifampicin, isoniazid, pyrazinamide and ethambutol concentrations to estimate tablet and capsule drug contents. DESIGN: The methods were applied to the analysis of 14 commercially manufactured fixed-dose combinations: two capsule and three tablet formulations containing rifampicin and isoniazid; seven tablet formulations containing rifampicin, isoniazid and pyrazinamide; and two tablet formulations containing rifampicin, isoniazid, pyrazinamide and ethambutol. RESULTS: All the combined formulations contained near to their stated drug contents. Replicate analyses confirmed the excellent precision of the drug analyses. CONCLUSION: Such methods are not only rapid to perform but should be practical in many Third World situations with relatively modest laboratory facilities.

Antitubercular Agents↗

PubMed2000

[Studies on pncA gene mutations in M. tuberculosis isolates].

OBJECTIVE: To understand the mutations of pncA gene in M. tuberculosis isolates, and to evaluate their clinical value. METHODS: Analyzing the pncA genes in 74 M. tuberculosis clinical isolates with PCR-SSCP and PCR-AS. M. tuberculosis strain H37Rv was used as control. RESULTS: 32 drug-sensitive isolates all displayed normal pncA SSCP profile. Of 20 non-pyrazinamide-resistant isolates, 4 had abnormal pncA SSCP profile, in which 2 isolates were sequenced, one was TTC-->TTA mutation at codon 58, another was TGG-->CGG mutation at codon 68. Of 22 pyrazinamide-resistant isolates, 10 displayed abnormal pncA SSCP profile, in which 2 isolates sequenced had TTC-->TTA mutation at codon 58. CONCLUSIONS: The mutation of pncA gene is a pyrazinamide-resistant molecular mechanism in M. tuberculosis. Detecting the mutations of pncA genes might diagnose pyrazinamide resistance rapidly in some M. tuberculosis isolates.

Amidohydrolases↗

PubMed2000

Drugs for preventing tuberculosis in HIV infected persons.

BACKGROUND: People with HIV have a increased risk of developing tuberculosis. Preventive therapy may help prevent progression of tuberculosis infection to disease. OBJECTIVES: The objective of this review was to assess the effects of preventive therapy with anti-tuberculosis drugs in people with HIV infection. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Researchers in the field were contacted. SELECTION CRITERIA: Randomised trials of anti-tuberculosis drugs in people with HIV infection but without evidence of active tuberculosis. DATA COLLECTION AND ANALYSIS: One reviewer assessed eligibility and trial quality. Study authors were contacted for additional information. MAIN RESULTS: Six trials were included. Compared to placebo, preventive therapy was associated with a lower incidence of active tuberculosis (relative risk 0.54, 95% confidence interval 0.39 to 0.76). Risk of death (relative risk 0.96, 95% confidence interval 0.82 to 1.13) was not significantly different in the two groups. Incidence of tuberculosis was reduced in people with a positive tuberculin skin test (relative risk 0.24, 95% confidence interval 0.14 to 0.40), but was not significantly lower in those with a negative skin test (relative risk 0.87, 95% confidence interval 0.56 to 1.36). Similarly death was less frequent in those with a positive skin test who received preventive therapy (relative risk 0.77, 95% confidence interval 0.58 to 1.03), but this difference was not observed among those with a negative skin test (relative risk 1.07, 95% confidence interval 0.88 to 1.30). Each regimen (isoniazid alone, isoniazid plus rifampicin, isoniazid plus rifampicin plus pyrazinamide, rifampicin plus pyrazinamide) had similar protective effects against active tuberculosis for people with positive skin tests. REVIEWER'S CONCLUSIONS: Preventive therapy appears to be effective in reducing incidence of tuberculosis, and death from tuberculosis in HIV infected adults with a positive tuberculin skin test, at least in the short to medium term.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Anti-tuberculosis drug consumption as an indicator of the epidemiological situation of tuberculosis in Spain].

OBJECTIVES: To describe anti-tuberculosis drug consumption in Spain for the period, 1985-1995, compare the associated time trend and geographical pattern against case reports of tuberculosis (TB), and estimate the number of persons undergoing anti-tuberculosis therapy in 1995. METHODS: The official Drug Database was used to ascertain consumption of anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) in Spain during the period, 1985-1995. The technical units of measurement used for comparison purposes were daily defined dose (DDD) and DDD rate per day per 100,000 population. Annual trends and geographical patterns of consumption were plotted. The respective numbers of persons treated in 1995 with each of the four drugs were first estimated and then compared against TB case reports. RESULTS: There was an overall decline in the consumption of isoniazid, rifampicin and ethambutol over the period, 1985-1995, though the former two registered rises in 1991 and 1992. Pyrazinamide consumption showed growth throughout the study period. The highest 1995 consumption rates were registered by Galicia, Cantabria, Asturias, the Basque Country, Ceuta and Melilla, and the lowest by the Canary Islands and Navarre. Comparisons run against TB case reports revealed a greater degree of underreporting in certain provinces. In 1995, approximately 18,858 persons (48 per 100,000 population) must be assumed to have undergone pyrazinamide therapy in Spain, indicating that the reported TB rate of 22 per 100,000 population could well represent underreporting in excess of 100%. CONCLUSIONS: The trend in anti-tuberculosis drug consumption reflects shifts in treatment guidelines and is compatible with a rise in TB incidence in recent years. Major underreporting of TB marked by wide inter-regional and -provincial differences was in evidence. Pyrazinamide consumption is probably the best indicator for estimating minimum TB incidence.

Antitubercular Agents↗

PubMed2004

Multicenter evaluation of the MB/BACT system for susceptibility testing of Mycobacterium tuberculosis.

The reliability of the MB/BACT system for susceptibility testing of Mycobacterium tuberculosis to pyrazinamide, rifampin, isoniazid, streptomycin, and ethambutol was compared to the BACTEC 460TB system. The proportion method was used to resolve discrepant results by an independent arbiter. Two interpretative methods were used, with an undiluted control (direct control) and a diluted control (10(-1) control). As no significant difference was observed between the two controls, the method with the direct control was adopted as the most accurate one. One hundred sixty-six strains were tested, with an overall agreement of 98.3%. After resolution of the 18 discrepant results by the proportion method, the sensitivity and specificity of the MB/BACT system were 100% for rifampin, isoniazid, and pyrazinamide. For ethambutol, sensitivity was 92.3% at the critical concentration and 33% at the high concentration, and specificity was 100% at both concentrations. For streptomycin, sensitivity was 100% at the critical concentration and 80% at the high concentration, and specificity was 98.6% at the critical concentration and 100% at the high concentration. The rifampin, isoniazid, streptomycin, and ethambutol susceptibility test results were obtained in 6.6 days with the MB/BACT versus 5 days with the BACTEC 460TB. The pyrazinamide susceptibility test results were obtained in 7.8 days with the MB/BACT, versus 6.7 days with the BACTEC 460TB. These data demonstrate that the fully automated MB/BACT system is a very reliable method for rapid susceptibility testing of M. tuberculosis against rifampin, isoniazid, and pyrazinamide. Sensitivity results have to be improved for ethambutol and streptomycin, especially at the high concentration.

Antitubercular Agents↗

PubMed2001

[New recommendations and perspectives for the control of tuberculosis].

This report summarises the ATC/CDC recommendations on the diagnosis and treatment of latent tuberculosis infection. Based on the sensitivity and specificity of the tuberculin skin test and the prevalence of TB in different groups, 3 cut-off levels have been proposed for defining a positive tuberculin reaction: > or =5 mm, >/=10 mm and > or =15 mm of induration. Treatment can be carried out mainly with Isoniazid, but there are alternatives such as Rifampin plus Pyrazinamide in the following cases: when Isoniazid-resistant M. tuberculosis appears and when the treatment is to be shortened; Rifampin alone for persons who cannot tolerate Pyrazinamide. Rifabutin can be substituted for Rifampin in HIV+ patients taking some protease inhibitors and non-nucleoside reverse transcriptase inhibitors. In persons who have been infected with multidrug resistant strains, Ethambutol and Pyrazinamide or Pyrazinamide and a fluoroquinolone can be prescribed. On the other hand, for a general prophylaxis BCG vaccination is not usually recommended due to its variable effectiveness, except in children and health care workers exposed continually to an untreated patient or to one with multidrug resistant M. tuberculosis strains. In order to achieve a new vaccine, a programme is currently being developed in the European Union called "The cluster for Tuberculosis vaccine development", which involves four main projects: optimisation and preclinical evaluation of TB vaccines, development of new live attenuated vaccines, non-protein antigens for TB vaccine and identification of mechanisms and indicators of protective immunity.

English Abstract↗

PubMed1996

[Fulminant, rapidly reversible hepatitis and life-threatening anaphylaxis following rifampicin in an HIV-positive female patient with latent adrenal cortex insufficiency].

We report the case of a 28-year-old-prostitute from Thailand with HIV infection stage B2 associated with retroperitoneal lymph node tuberculosis. 6 days after the beginning of anti-tuberculous therapy (isoniazid, rifampicin, pyrazinamid and ethambutol) the temperature rose to 40.5 degrees C, diarrhea, vomiting, and tachycardia developed and systolic blood pressure fell to 80 mm Hg. Liver function tests revealed acute hepatic failure (ALT 800 IU/l rising to 1500; serum bilirubin 89 mumol/l rising to 238.0; alkaline phosphatase 199 IU/l; glucose 1.8 mmol/l; prothrombin time 20%). Isoniazid, rifampicin, and pyrazinamid were replaced by streptomycin and PAS. A few days after withdrawal the liver profile returned to normal. Hours after the reintroduction of rifampicin total body erythema, pruritus, vomiting and severe hypotension developed, requiring saline methylprednisolone and epinephrine administration. The next reexposure to intravenous rifampicin produced a rash and was rapidly discontinued. Liver function tests remained normal. Later mild adverse reactions to streptomycin and pyrazinamid occurred, two drugs which had been well tolerated before. Subsequently the diagnosis of adrenal insufficiency was established. After initiation of steroid replacement (50 mg prednisolone) the antituberculous therapy with isoniazid, pyrazinamid and ethambutol was well tolerated. We conclude that the shock in this HIV-infected patient was either due to severe anaphylaxis to rifampicin or acute adrenal insufficiency ensuing on this drug. The reversible fulminant acute hepatic failure represents either an adverse effect of antituberculous drugs, especially hepatotoxic interactions of drug combinations, or an ischemic liver injury during hypotension caused by anaphylaxis. The case illustrates the complex nature of side effects of antituberculous drugs in HIV patients and their aggravation by adrenal insufficiency.

Adrenal Insufficiency↗

PubMed1975

Hyperuricosuria and increased tubular secretion of urate in sickle cell anemia.

Seven young adults with uric acid overproduction due to sickle cell anemia were normouricemic with a mean serum uric acid level of 4.9 mg/100 ml. Urate clearance was greater in these patients than in normal subjects or in patients with primary hyperuricemia due to uric acid overproduction. The increase in urate clearance was entirely accounted for by increased pyrazinamide suppressible urate clearance. Pyrazinamide administration abolished the uricosuric response to ribonucleic acid (RNA) feeding in these patients with sickle cell anemia, and maximal uricosuric response to the administration of probenecid was similar in the patients with sickle cell anemia and in normal subjects suggesting that reabsorption of both filtered and secreted urate was not impaired in sickle cell disease. Pyrazinamide suppressible urate clearance at maximal uricosuric response to probenecid was increased in patients with sickle cell disease suggesting increased tubular secretion of urate. This increase in urate secretion permits most young adults with urate overproduction due to sickle cell anemia to remain normouricemic and may account for the low frequency of secondary gout in this disease.

Adolescent↗

PubMed1976

Renal transport of urate during diuretic-induced hypouricemia.

The effect of two weeks administration of a uricosuric diuretic (SKF-62698) on renal urate handling has been examined in 11 normal men. Plasma urate concentrations had declined by more than 60 per cent after two weeks. Urate excretion per unit of glomerular filtration rate and urate clearance (Curate) per unit of glomerular filtration rate were increased after the administration of SKF-62698. The importance of intact tubular secretion of urate in producing these changes was assessed by administering pyrazinamide, an agent that curtails urate secretion, to each participant. The decrements in urate excretion and clearance produced by pyrazinamide both increased significantly, whereas the residual urate excretion rates and clearances not suppressible by pyrazinamide were only minimally altered by SKF-62698 treatment. These results suggest that the excretion of secreted urate was enhanced by prolonged administration of SKF-62698, probably secondary to the inhibition of postsecretory urate reabsorption. In addition, because the nonsuppressible urate excretion did not decline despite a 63 per cent reduction in the plasma urate, it is likely that the reabsorption of filtered urate also was impaired by SKF-62698.

Adult↗

PubMed1980

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↗

PubMed1983

Controlled clinical trial of 4 short-couse regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis.

Four daily short-course chemotherapy regimens (three 6-month and one 8-month) for pulmonary tuberculosis have been compared. All four had the same initial 2-month intensive phase of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ). The continuation phase of the 6-month regimens was: 1) isoniazid and rifampicin (4HR), or 2) isoniazid and pyrazinamide (4HZ), or 3) isoniazid alone (4H) and of the 8-month regimen 4) isoniazid alone (6H). All patients have been followed up for 12 months after stopping chemotherapy. In patients with fully sensitive strains pretreatment the 6-month regimen with rifampicin throughout (4 HR) was highly effective with a bacteriological relapse rate of 2% of 167 patients, significantly better (P less than 0.01) than the rate of 9% of 158 patients in the 6-month regimen with isoniazid alone in the continuation phase (4H). The 8-month regimen (6H) was also highly effective, with a relapse rate of 3% of 119 patients but was not significantly better (p greater than 0.1) than the 6-month isoniazid regimen (4H). The regimen with pyrazinamide throughout (4HZ) had a relapse rate of 4% of 165 patients, not significantly different from any of the other regimens. An important finding in the two regimens with isoniazid alone in the continuation phase (4H and 6H) was that 1 of the 2 failures during chemotherapy and 17 of the 18 bacteriological relapses after stopping occurred with strains still sensitive to isoniazid. In patients with strains resistant to isoniazid pretreatment, 8 of 19 patients on the 4H or 6H regimens had an unfavourable response during chemotherapy compared with none of 26 on the HR or HZ regimens (P less than 0.005). Of the 851 patients who started treatment, 24 developed possible adverse reactions but only 6 required modification of their chemotherapy.

Adolescent↗

PubMed1985

Hereditary renal hypouricemia in children.

The renal handling of urate was investigated in four children with hereditary renal hypouricemia and in their parents. The urate/creatinine clearance ratios in the four patients were 1.02 +/- 0.28, 0.93 +/- 0.11, 1.03 +/- 0.24, and 1.46 +/- 0.26, markedly higher than those in control subjects. Except for a partial response to pyrazinamide (change in clearance ratio from 1.46 to 1.07) in one patient, pyrazinamide and benzbromarone did not affect the clearance ratios in our patients. In the parents, the urate/creatinine clearance ratios were intermediate between those of the patients and control subjects, but responses to pyrazinamide and benzbromarone were normal. These data indicate that our patients have a combined defect in renal urate reabsorption, and that one of them might be subclassified as having the hypersecretion of defect. Results also show that heterozygotes can be identified by testing their urate/creatinine clearance ratio.

Benzbromarone↗

PubMed1986

Controlled clinical trial of three short-course regimens of chemotherapy for pulmonary tuberculosis in Nigeria--a preliminary report.

A controlled clinical trial of daily short course (6-month) chemotherapy in newly diagnosed cases of pulmonary tuberculosis in Nigerians was carried out. The three regimens used contained streptomycin, isoniazid, rifampicin and pyrazinamide in the initial phase; and isoniazid plus rifampicin or isoniazid plus rifampicin and/or pyrazinamide in the continuation phase. Sputum culture conversion was satisfactory after 2 and 6 months of treatment and no positive cultures were found one year after treatment had been completed. Side effects were few and consisted mainly of arthralgia, possibly associated with pyrazinamide.

Adolescent↗