Months Of Rifampicin Research Articles

Safety and Tolerability of Six Months of Isoniazid Plus Pyridoxine or Three Months of Rifampicin for Tuberculosis among Subjects with Diabetes Mellitus: A Randomized Trial.

Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.

Factors associated with non-completion of TB preventive treatment in Brazil.

BACKGROUND: Among Brazilian initiatives to scale up TB preventive therapy (TPT) are the adoption of the 3HP regimen (12 weekly doses of rifapentine and isoniazid [INH]) in 2021 and the implementation in 2018 of the TPT surveillance information system. Since then, 63% of the 76,000 eligible individuals notified completed TPT. Recommended regimens in this period were 6H, 9H (6 or 9 months of INH) and 4R (4 months of rifampicin).OBJECTIVE: To analyse the factors associated with TPT non-completion.METHODS: We analysed the cohort of TPT notifications from 2018 to 2020. Robust variance Poisson regression model was used to verify the association of TPT non-completion with sociodemographic, clinical and epidemiological variables.RESULTS: Of the 39,973 TPT notified in the study period, 8,534 (21.5%) were non-completed, of which 7,858 (92.1%) were lost to follow-up. Age 15-60 years (relative risk [RR] 1.27, 95% confidence interval [95% CI] 1.20-1.35), TPT with isoniazid (RR 1.40, 95% CI 1.19-1.64) and Black/mixed race (RR 1.17, 95% CI 1.09-1.25) were associated with a higher risk of non-completion.CONCLUSION: Individuals in situations of social and financial vulnerability such as being Black/pardo race, younger and on longer TPT regimens were more likely to be associated with TPT incompletion.

Four months of rifampicin monotherapy for latent tuberculosis infection in children.

Diagnosing and treating latent tuberculosis infection (LTBI) is an important part of efforts to combat tuberculosis (TB). The Korean guidelines for TB published in 2020 recommend 2 LTBI regimens for children and adolescents: 9 months of daily isoniazid (9H) and 3 months of daily isoniazid plus rifampicin. Isoniazid for 6–12 months has been used to effectively treat LTBI in children for over 50 years. However, a long treatment period results in poor patient compliance. This review summarizes pediatric data on the treatment completion rate, safety, and efficacy of 4 months of daily rifampicin (4R) and evaluates the pharmacokinetics and pharmacodynamics of rifampicin in children. The 4R regimen has a higher treatment completion rate than the 9H regimen and equivalent safety in children. The efficacy of preventing TB is also consistent with that of 9H when summarizing reports published to date. A shorter treatment period could increase patient compliance and, therefore, prevent TB in more patients. By using an effective, safe, and highly compliant regimen for the treatment of children with LTBI, we would become one step closer to our goal of eradicating TB.

Treatment of latent tuberculous infection among health care workers at a tertiary hospital in Korea.

To evaluate the acceptance of, adherence to, and outcomes of latent tuberculous infection (LTBI) treatment among health care workers (HCWs). This was a retrospective study in a tertiary hospital in Korea. From May to August 2017, 2190 HCWs simultaneously underwent a tuberculin skin test (TST) and interferon-gamma release assay (IGRA). LTBI was diagnosed if the TST induration was 10 mm or IGRA results were positive. Of 2190 HCWs tested, 1006 (45.9%) were diagnosed with LTBI. Of these, 655 (65.1%) HCWs visited out-patient clinics, 234 (35.7%) of whom were advised treatment by physicians. Among these, 120 (51.3%) accepted the physicians' recommendations. In general, HCWs who were older, male and smoked were less likely to visit out-patient clinics. Sixty (50%) HCWs received 3 months of isoniazid plus rifampicin (3HR) and 57 (47.5%) HCWs received 4 months of rifampicin (4R). The proportion of HCWs with 2 side effects (3HR 20% vs. 4R 7.0%, P = 0.041) and drug stoppage rate (3HR 20% vs. 4R 5.3%, P = 0.017) were higher in the 3HR group than in the 4R group. Of the 120 HCWs, 78 (65%) completed LTBI treatment. Overall, the acceptance and completion rate for LTBI treatment was not adequate. For effective LTBI management in HCWs, further programmatic strategies are needed.

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis

Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. World Health Organization and Canadian Institutes of Health Research.

Drug-related hepatitis in patients treated with standard anti-tuberculosis chemotherapy over a 30-year period.

Drug-induced hepatitis is known to occur in a proportion of patients on treatment for active tuberculosis (TB). We prospectively examined the incidence of drug-induced hepatitis in 2070 patients treated for TB with the standard regimen based on 6 months of rifampicin (R, RMP) and isoniazid (H, INH), with 2 months of initial pyrazinamide (Z, PZA) and ethambutol (E, EMB), over a 30-year period from 1981 to 2010, in Blackburn, UK. Of the 1031 (49.8%) males and 1039 (50.2%) females studied, 451 (21.8%) were White and 1585 (76.6%) were of South Asian origin. Only 34 (1.6%) were of African or other origins. Of the total number of patients treated, 63 (3.0%) had drug-related hepatitis, 26 (5.8%) of whom were White, 37 (2.33%) Asians and 0 other. Incidence was significantly higher in Whites than Asians (OR 2.13, P = 0.008). Incidence increased with increasing age (OR 1.16, P = 0.02). The presumed causative drug was PZA 57%, RMP 32%, INH 11%, EMB 0%. There was no trend of increased hepatitis rates over time. Rates of drug-induced hepatitis where change of treatment is required are low in patients treated with standard RHZE-based therapy (3%). Caucasians and older patients were more likely to develop hepatitis than their counterparts.

Baseline abnormal liver function tests are more important than age in the development of isoniazid-induced hepatoxicity for patients receiving preventive therapy for latent tuberculosis infection.

One of the cornerstones of Australia's public health programmes to eliminate tuberculosis (TB) is the identification and treatment of latent tuberculosis infection (LTBI). The main aim of this study is to determine the demographics, compliance, completion rates and adverse events of patients on preventive therapy (PT) for LTBI at our institution. The secondary aim is to determine the rates of isoniazid (INH) hepatotoxicity and identify any contributory factors. The method used was an audit using medical records of 100 consecutive patients (2010-2014) treated with PT for LTBI. Seventy-two patients with confirmed LTBI started 9 months of INH and 22 started 4 months of rifampicin (RIF). The median age was 30 years. Half the patients were born in high TB-prevalence countries. Fifty-six per cent were contacts of index cases with confirmed TB, and 26% were pre-immunosuppression. Seventy-seven per cent completed PT with adequate compliance. Thirty-three per cent on INH and 23% on RIF experienced some liver function test (LFT) abnormality while on treatment. INH was ceased in 3% due to asymptomatic hepatic dysfunction (transaminases >5x upper limit of normal). No patients had permanent liver damage. Significant risk factors for liver dysfunction during PT were risk factors for liver disease (χ(3)(2) = 8.7; P = 0.03) or abnormal pre-therapy LFT (χ(3)(2)= 22.4; P < 0.001). No patients developed active TB. The completion rate of 77% and rate of INH-induced hepatic dysfunction of 3% is comparable with the literature. We found no age association with the risk of INH-induced hepatic dysfunction; however, there was a significant and linear association with the degree of liver function abnormality during INH therapy and the presence of abnormal baseline LFT. Routine LFT monitoring allowed early cessation of INH in those with significant but asymptomatic hepatitis who did not meet criteria for ATS/CDC LFT monitoring.

Comparative Study of Laparoscopic Abdominopelvic and Fallopian Tube Findings Before and After Antitubercular Therapy in Female Genital Tuberculosis With Infertility

Study ObjectiveTo study the effect of antitubercular treatment (ATT) on the laparoscopic abdominopelvic and fallopian tube findings in female genital tuberculosis (FGBT). DesignProspective cohort (Canadian Task Force classification II2). SettingTertiary referral center in northern India. PatientsFifty women with infertility and diagnosed with FGTB on laparoscopy, histopathology findings, or endometrial sampling (acid-fast bacilli culture, granuloma on histopathology, positive polymerase chain reaction). InterventionsDiagnostic laparoscopy in all women diagnosed with FGTB before and after a 6-month course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid). All procedures were performed by the same surgeon between June 2012 and May 2014. Measurements and Main ResultsThe mean patient age was 28.7 years, mean parity was 0.9, and mean body mass index was 23.6 kg/m2. Infertility was seen in all 50 women (66% primary infertility, 34% secondary infertility), with a mean duration of 6.06 years. Abnormal laparoscopic findings of FGTB included tubercles in the pelvic peritoneum, fallopian tube, and ovary in 27 women (54%) before ATT and in only 1 (2.04%) woman after ATT (p < .001). Caseous nodules and encysted ascites were seen in 4 women (8%) before ATT, and in no women after ATT (p < .001); however, there was no change from before ATT to after ATT in the rate of pelvic adhesions (42% vs 42.5%) and perihepatic adhesions (56% vs 58%). Laparoscopic findings in fallopian tubes included hydrosalpinx (32%), pyosalpinx (4%), beaded tubes (12%), nonvisualization of tube (20%), and tubal blockage on the right side (56%), left side (50%), and both sides (38%) before ATT. Hydrosalpinx, beaded tubes, and nonvisualized tube were seen in 33.4%, 4.1%, and 20.8% cases, respectively, after ATT; however, free spill increased to 52% on the right side and 50% on left side after ATT. ConclusionATT improves laparoscopic findings in FGTB with infertility. However, advanced fibrotic lesions (eg, pelvic and perihepatic adhesions, bilateral blocked tubes) do not improve with ATT.

Mediastinal and peripheral lymphadenopathy

A 32-year-old man, with no history of cigarette smoking, had four weeks history of non productive cough, chest pain and myalgias. Physical examination revealed a painless bilateral cervical lymphadenopathy, the respiratory examination was normal. Chest radiography showed an enlarged upper and middle mediastinum (A). Computed tomography (CT) of the thorax showed a large and non homogeneous mass in the anterior and middle mediastinum and a small pericardial effusion, with displacement of vascular structures (B). Laboratory analysis revealed an elevated lactate dehydrogenase level of 690 IU per liter. The exicional biopsy of the left cervical lymph node revealed a caseating and necrotizing granulomatous lesions and confirmed a diagnosis of lymph node tuberculosis. The biopsy of the right cervical lymph node established a B-cell non-Hodgkin lymphoma, and so a rare association with tuberculosis. The patient received anti-tuberculosis therapy. The regimen was based on two months of ethambutol, rifampicin, pyrazinamide and isoniazid, followed by four months of rifampicin and isoniazid. He received also chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. The patient presented, two months later with clinical and radiographic improvement.

Paraclinical, Therapeutic and Evolutionary Profile of Osteoarticular Tuberculosis: A Report about 550 Cases in Abidjan

Objective: To describe paraclinical, therapeutic and evolutionary aspects of osteoarticular tuberculosis in Abidjan. Materials and Method: We realized a descriptive retrospective study carried out in the Rheumatology Department of the University Hospital Center of Cocody in Abidjan about 550 patients over a period of 10 years from January 2004 to December 2013. The paraclinical, therapeutic and evolutionary data had interested us. Results: Osteoarticular tuberculosis represented 12.13% of 4531 rheumatic diseases identified during the study period. The tuberculin skin test was positive in 78.49% of cases. An inflammatory syndrome was present with erythrocyte sedimentation rate and C-reactive protein respectively into 69.45% and 76.54% of cases. The research of Mycobacterium tuberculosis was realized into 176 of cases which 50% was positive. Polymerase chain reaction and biopsy of tissue were performed respectively in 8 and 6 cases. Plain radiography (89.82%) and computed tomography (83.63%) were the most realized imaging. Computed tomography has contributed for the diagnostic in 99.78% of cases. The majority of our patients (82.91%) received anti-tuberculous treatment which consisted of two months of combination of rifampicin (R), isoniazid (H), pyrazinamide (Z) and Ethambutol (E) (2RHZE), followed by 10 months of rifampicin (R) and isoniazid (H) (10 RH). The outcome in patients on this treatment was favorable in 528 cases (96%). Conclusion: This study revealed that the research of Mycobacterium tuberculosis was often realized and positive. On the contrary, polymerase chain reaction and biopsy of tissue were rarely performed. The main imaging is computed tomography. Our protocol of treatment is effective.

P187 The Use Of Moxifloxacin For The Treatment Of Ophthalmic Tuberculosis

Background The number of patients we are treating for ophthalmic tuberculosis (TB) have increased year on year, from two in 2009 to twenty in 2013. A recent global review of the strategies used in the diagnosis and treatment of ophthalmic TB showed a wide disparity of diagnostic and treatment strategies. We present a review of our current practice and justification for out treatment regimens. Methods We identified all the cases in our hospital treated for ophthalmic TB between 2009 and 2013. Age, gender, ophthalmic examination findings, blood tests, treatment regimens, including durations and outcomes, and adverse drug reactions were collected and analysed. Results A total of 60 cases were identified. Mean age was 45.0 +/- 14.4 years. 61.7% were male. The most commonly used regimen was 2 months rifampicin, isoniazid, pyrazinamide and moxifloxacin followed by 10 months of rifampicin, isoniazid and moxifloxacin. A response to treatment, with no evidence of disease recurrence on cessation of therapy, was seen in 78.3% of cases. 5% experienced hepatotoxicity requiring a change in treatment. There was no significant difference in either the success of treatment (p = 0.102) or the risk of hepatotoxicity (p = 0.264) between regimens with moxifloxacin (n = 43) or without it (n = 17). 32 patients on moxifloxacin had ECGs of which 6 (18.8%) newly developed a raised QTc. This resulted in moxifloxacin being stopped during the step-down phase of treatment in two patients. Maximum QTc was never found to be above 500 milliseconds and there were no episodes of documented arrhythmias or syncope. Conclusions We recommend a treatment regimen including moxifloxacin in place of ethambutol so that any reported visual change is unlikely to be related to treatment, and we propose continuing moxifloxacin beyond the intensive phase, if tolerated, when culture is unavailable. We treat ophthalmic TB for the same duration as central nervous system TB. Our data shows that this is a safe and effective regimen but more evidence is required before recommending definitive guidelines.

P192 Aside From Age, Do Other Factors Increase The Risk Of Hepatotoxicity In Patients Treated For Latent Tb Infection?

Background Reactivation of latent tuberculosis infection (LTBI) occurs in a number of at-risk groups including: tuberculosis (TB) contacts, migrants from high prevalence countries and those who are immunosuppressed. The risk of hepatotoxicity in treating LTBI is thought to be low but much of this evidence is in patients treated with 6 months of isoniazid (6H) rather than 3 months of rifampicin and isoniazid (3RH). Equally, other than age, there is limited data on other factors which may contribute to the risk of developing hepatotoxicity. Methods A retrospective study was performed at our centre. We analysed all patients treated with chemoprophylaxis, regardless of indication, between 2009 and 2013. Demographic data, treatment regimens and adverse drug reactions, including hepatotoxicity, were recorded. Severe hepatotoxicity was defined as either a rise in ALT five times greater than the upper limit of normal, or as any change in liver function that required an interruption or alteration in treatment. Liver function tests (LFTs) were routinely measured at baseline and then again at two weeks. Results 290 cases were identified. 84.5% of patients were treated with 3RH, 12.1% were treated with 6H. 2.1% experienced severe hepatotoxicity 2 weeks into treatment. None had symptoms which prompted blood tests prior to our standard 2 week LFTs. Gender, age, documented co-existing liver disease, regimen choice, concomitant use of hepatotoxic drugs and reason for giving chemoprophylaxis were not significantly associated with an increased risk of hepatotoxicity. LTBI treatment was case managed by TB nurses with 91.7% of patients successfully completing treatment. There was no significant difference in treatment completion or adherence rates in those who developed hepatotoxicity compared with those who did not. Conclusions Our review demonstrates a low incidence of hepatotoxicity associated with treatment of LTBI and highlights the difficulty in predicting those in whom it will occur. If management of LTBI moves from primary to secondary care it will remain important to perform LFTs at two weeks.

Safety and completion of a 4-month course of rifampicin for latent tuberculous infection in children

Children's Tuberculosis Clinic, Houston, Texas. To describe adherence to and tolerability of 4 months of rifampicin (4RMP) compared to 9 months of isoniazid (9INH) in children with latent tuberculous infection (LTBI). Retrospective descriptive case series of children treated for LTBI from 2010 to 2013 by self-administered therapy or directly observed preventive therapy (DOPT) administered by the local health department. Four hundred and four children were treated, 324 (80%) with 9INH and 80 with 4RMP: the mean age was 7.3 years, and 47% were girls. Of these, 37% were identified during contact investigations. DOPT was used in 51% and self-administered therapy in 49%; 81% completed therapy. Completion of self-administered 4RMP therapy was not significantly different from completion rates for children receiving 9INH administered as DOPT (93% vs. 88%, OR 0.6, 95%CI 0.2-1.7), but was significantly higher than in the 9INH self-administration group (OR 7.9, 95%CI 2.7-23.2). Adverse events were rare: 20 (6%) in the 9INH group and 2 (3%) in the 4RMP group, and none was serious. Completion rates for 4RMP surpassed those of 9INH for all methods of delivery, except for DOPT, where completion rates were similar. 4RMP was well tolerated. The increased cost of 4RMP over 9INH may be offset by increased effectiveness, as gauged by completion rates.

Diagnosis and Treatment of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Diseases due to Initiation of Anti-Tumor Necrosis Factor Therapy.

Patients with intractable inflammatory bowel diseases (IBD) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IBD due to the initiation of anti-TNF therapy. The traditional LTBI treatment regimen has consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin have been used increasingly to improve treatment completion rates. In this review, the incidence of TB and the prevalence of LTBI in patients with IBD will be briefly described, as well as methods for diagnosing latent and active TB before anti-TNF therapy, current LTBI treatment regimens, recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

Diagnosis and Treatment of Latent Tuberculosis Infection due to Initiation of Anti-TNF Therapy.

Patients with immune-mediated inflammatory diseases (IMIDs) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in these patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IMIDs. The traditional LTBI treatment regimen consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin are increasingly being used to improve treatment completion rates. In this review, the screening methods for diagnosing latent and active TB before anti-TNF therapy in patients with IMIDs will be briefly described, as well as the current LTBI treatment regimens, the recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

Rifampicin compared to isoniazid for preventing active TB in HIV-negative people at risk of developing active TB: Implications for public health

A Cochrane systematic review summarized the evidence for the effects of four regimens containing short courses of rifampicin or rifamycin-combinations compared to isoniazid (INH) given for six to nine months on the development of active tuberculosis (TB), adherence, treatment-limiting adverse events, and hepatotoxicity in HIV-negative people with latent TB infection (LTBI) or at risk of developing active TB. The review included 10 randomized controlled trials that enrolled 10,717 HIV-negative (2% HIV-positive) adults and children (older than two years) that were conducted in Brazil, Canada, Germany, Hong Kong, Saudi Arabia, Spain, Taiwan, and USA. Participants were recruited from clinics in general hospitals or university-affiliated hospitals, pneumoconiosis clinics, homeless shelters, or in prison. The regimens compared were: rifampicin mono-therapy (three to four months) versus isoniazid (INH) mono-therapy (six months); rifampicin plus INH (three months) versus INH (six months); rifampicin plus pyrazinamide (two months) versus INH (six months); and rifapentine (900 mg) plus INH (900 mg) combination therapy, once-weekly, directly-observed (DOT) for three months versus self-administered INH (300 mg) for nine months. Follow-up ranged from two to five years.The review concluded that four months of rifampicin and the standard INH treatment for six or nine months may not differ in the incidence of active TB in HIV-negative people at risk of active TB. Rifampicin probably increases treatment completion compared to INH in adults. While it is uncertain if treatment-limiting adverse events are any different, rifampicin probably results in significantly less hepatotoxicity in adults than INH. No instances of rifampicin resistance were observed in people who developed active TB while on rifampicin in the included trials. The review also concluded that two months of rifampicin plus INH may offer no advantage over longer INH treatment, and rifampicin combined with pyrazinamide is associated with more liver toxicity and treatment-limiting adverse events with uncertain benefits for TB incidence, or adherence compared to INH. A weekly regimen of supervised rifapentine plus INH for three months has higher completion rates, is probably as effective and a safer option than nine months of self-administered INH, though more data on its effects in adults in high TB burden countries, and in children are needed.

Changes in QuantiFERON®-TB Gold In-Tube results during treatment for tuberculous infection

Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil. To compare QuantiFERON®-TB Gold In-Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens. Participants in the trial were invited to undergo serial QFT-GIT. Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points. Of 215 participants, 118 completed treatment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant difference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non-adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment. Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions.

Management of latent tuberculous infection in Norway in 2009: a descriptive cross-sectional study.

Despite a steep increase in the number of individuals treated for latent tuberculous infection (LTBI), few data are available on how treatment is implemented. To obtain baseline information on initiation and completion of treatment for LTBI in Norway in 2009. A descriptive cross-sectional study. All 721 patients treated for LTBI in 2009 in Norway were included, of whom 607 (84%) completed treatment. The treatment regimen generally consisted of 3 months of rifampicin and isoniazid. The three main reasons for starting treatment were: 1) countries of origin with high tuberculosis (TB) prevalence, 2) a positive tuberculin skin test, and 3) a positive interferon gamma release assay. The use of directly observed treatment varied by health region and age. The majority of the 34 medical specialists interviewed saw a need for new national guidelines to improve the selection of high-risk patients with LTBI. Management of LTBI is in accordance with current guidelines, with a high completion rate. More targeted selection of which patients should be offered preventive treatment is required, and new guidelines and tools to enhance risk assessment are necessary.

Problems of multidrug- and extensively drug-resistant TB

Worldwide, it is thought that in 2010 around 9 million people developed tuberculosis (TB) and around 1.5 million people died from the disease.1 Standard therapy (6 months of rifampicin and...

Effectiveness of 3 months of rifampicin and isoniazid chemoprophylaxis for the treatment of latent tuberculosis infection in children

Background/settingTreatment for 3 months with rifampicin (R) and isoniazid (H) (3RH) for latent tuberculosis infection (LTBI), defined as an inappropriately positive tuberculin skin test with no clinical or x-ray evidence...