rifapentine and Tuberculosis--Multidrug-Resistant

Children were often the forgotten victims of the global tuberculosis (TB) epidemic, neglected by traditional TB services as well as maternal and child health initiatives. Luckily this is changing with a greater focus on children and the issues regarding their optimal management. A common misconception is that children with TB are always difficult to diagnose and treat. New diagnostic tools are urgently needed, but most children with TB in high-burden settings can be diagnosed with available approaches and treatment outcomes are generally excellent. Increased TB awareness, appropriate training of health care workers and inclusion in integrated management of childhood illness strategies will improve the access and quality of care that children receive. This review highlights what needs to be done to ensure that no child unnecessarily dies from TB and provides a brief overview of new advances in the field.

Topics: Antitubercular Agents; BCG Vaccine; Child; Global Health; Health Knowledge, Attitudes, Practice; Humans; Isoniazid; Mycobacterium tuberculosis; Rifampin; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Vaccination

Topics: Antitubercular Agents; Aza Compounds; Cross-Sectional Studies; Diagnosis, Differential; Diarylquinolines; Fluoroquinolones; Germany; Humans; Moxifloxacin; Nitroimidazoles; Oxazoles; Prognosis; Quinolines; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another-both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoniazid; Latent Tuberculosis; Male; Rifampin; Time Factors; Treatment Outcome; Tuberculin Test; Tuberculosis, Multidrug-Resistant

The World Health Organization estimates that up to 50 million persons worldwide may be infected with drug resistant strains of TB. The fatality rate of MDR-TB is 20-80%. Drug resistant tuberculosis cases are on the rise in Pakistan. The reasons for this menace are multiple including improper prescription, compliance and over the counter sale of anti-TB drugs. The treatment cost of drug-resistant TB is high, both to the individual patient and society. This article is written to create awareness about the available second line drugs and those in the pipeline. Considering the fact that resistant tuberculosis is difficult to manage, it is suggested that these drugs should only be used after consultation with a physician experienced in the treatment of drug resistant TB. The most frequent mistake made by treating physicians is addition of one drug in the failing regimen. At present, 27 potential anti-TB drugs are at various stages of development. The aim is that by 2010 at least one of these molecules completes the journey and should come in the market.

Topics: Antitubercular Agents; Fluoroquinolones; Humans; Rifabutin; Rifampin; Treatment Failure; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: Antibiotics, Antitubercular; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment.. We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival.. The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine-isoniazid group, 2.9 per 100 person-years in the rifampin-isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance.. On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00057122.).

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antitubercular Agents; Cause of Death; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Isoniazid; Kaplan-Meier Estimate; Male; Mycobacterium tuberculosis; Patient Compliance; Proportional Hazards Models; Rifampin; Risk; Tuberculosis; Tuberculosis, Multidrug-Resistant

To evaluate the curative effect and safety of a long course regimen containing Chinese-made rifabutin as compared to the regimen containing rifapentine in the treatment of multi-drug resistant pulmonary tuberculosis.. During 18 month treatment, 130 patients with multi-drug resistant pulmonary tuberculosis were divided into a treatment group (rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide, amikacin for 3 months, rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide for 6 months, rifabutin, pasiniazide, levofloxacin, ethambutol for 9 months), and a control group (rifapentine, pasiniazide, levofloxacin, ethambutol, ethionamide, amikacin for 3 months, rifabutin, pasiniazide, levofloxacin, ethambutol, ethionamide for 6 months, rifabutin, pasiniazide, levofloxacin, ethambutol for 9 months) with proportion 1:1 random, and parallel compared method.. After intensive phase, the sputum negative conversion rates (smear negative, culture negative) of the treatment group and the control group were 41.54% (27/65) and 35.94% (23/65), chi(2) = 2.42, P > 0.05, respectively. The remarkable effective rates in chest X-ray of the two groups were all 10.77% (7/65), chi(2) = 0.01, P > 0.05, and the effective rates were 67.69% (44/65) and 56.92% (37/65), chi(2) = 1.44, P > 0.05, respectively. At the end of the treatment, the sputum negative conversion rate (smear negative, culture negative) of the treatment group was 75.0% (48/65), and of the control group was 65.08% (41/65), chi(2) = 1.88, P > 0.05. The remarkable effective rates in chest X-ray of the two groups were 46.15% (30/65) and 44.62% (29/65), chi(2) = 0.02, P > 0.05, and the effective rates were 76.92% (50/65) and 73.85% (48/65), chi(2) = 0.19, P > 0.05, respectively. The cavity closure rates were 23.64% (13/55) and 33.33% (17/51), chi(2) = 0.00, P > 0.05, respectively.. Regimens containing rifabutin or rifapentine. are very effective in sputum negative conversion rate, lesion absorption and cavity closing for the treatment of multi-drug resistant pulmonary tuberculosis, with good safety and tolerance.

Topics: Adult; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

In order to detect the in vitro synergistic effect of 4 drugs-pasiniazid (PA), moxifloxacin, rifabutin and rifapentini on multidrug-resistant mycobacterium tuberculosis (MDR-MTB) and extensively drug-resistant mycobacterium tuberculosis(XDR-MTB), which were core drugs of"The program of retreatment research of tuberculosis".. The checkerboard method was used to detect the minimum inhibitory concentration (MIC) of antituberculosis drug combination schemes (moxifloxacin-PA, moxifloxacin-PA-rifabutin and moxifloxacin-PA-rifapentini) to 40 strains of clinical drug resistant MTB(20 strains of MDR-MTB and 20 XDR-MTB) and the standard strain H37Rv, by calculating the fractional inhibitory concentration index of joint action in vitro to judge the combined effect, with fractional inhibitory concentration index(FICI)≤0.5 and FICI≤0.75 as the basis of 2 drugs and 3 drugs showing synergy.. The FICI of moxifloxacin-PA scheme for DR-MTB was 0.125 to 1.000, only 5 strains with a FICI ≤0.5, showing synergistic effect. The FICI of moxifloxacin-Pa-rifabutin scheme with 20 strains of MDR-MTB ranged from 0.310 to 1.260, 10 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifabutin scheme with 20 strains of XDR-MTB ranged from 0.215 to 1.250, 11 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of MDR-MTB ranged from 0.150 to 0.780, 19 strains with a FICI≤0.75, showing synergistic effect. The FICI of moxifloxacin-PA-rifapentini scheme with 20 strains of XDR-MTB ranged from 0.200 to 1.280, 16 strains with a FICI≤0.75, showing synergistic effect.. The synergistic effect of moxifloxacin-PA scheme was poor, but showing better synergy when further combined with rifabutin or rifapentini. Rifabutin showed better effect than rifapentini, but the synergistic effect of moxifloxacin-PA-rifabutin combination scheme was poor than that of moxifloxacin-PA-rifapentini combination scheme.

Topics: Aminosalicylic Acids; Antibiotics, Antitubercular; Drug Synergism; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Fluoroquinolones; Isoniazid; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium tuberculosis; Retreatment; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant

Novel oral regimens composed of new drugs with potent activity against Mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new agents currently in phase 2/3 trials (TMC207 [bedaquiline], PA-824 and PNU-100480 [sutezolid], and/or clofazimine) proved superior to the first-line regimen of rifampin, pyrazinamide, and isoniazid. TMC207 plus PNU-100480 was the most effective drug pair. In the second experiment, in which 3- and 4-drug combinations composed of TMC207 and pyrazinamide plus rifapentine, clofazimine, PNU-100480, or both rifapentine and clofazimine were evaluated, the rank order of drugs improving the sterilizing activity of TMC207 and pyrazinamide was as follows: rifapentine plus clofazimine ≥ clofazimine ≥ rifapentine > PNU-100480. The results revealed potential new building blocks for universally active short-course regimens for drug-resistant tuberculosis. The inclusion of pyrazinamide against susceptible isolates may shorten the duration of treatment further.

Topics: Animals; Antitubercular Agents; Drug Therapy, Combination; Female; Isoniazid; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Nitroimidazoles; Oxazolidinones; Pyrazinamide; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant

We report a case of rifampicin (RMP) dependent/enhanced multidrug-resistant (MDR-TB) from a patient who had been treated with the World Health Organization optional thrice-weekly treatment and document the clinical and bacteriological features. RMP-enhanced tubercle bacilli that grew poorly without RMP but grew better in its presence were isolated from the patient with treatment failure. The bacteria grown without RMP consisted of mixed morphologies of short rod-shaped acid-fast bacteria and poorly stained coccoid bacteria, but stained normally as acid-fast rods when grown in the presence of RMP. The isolated RMP-enhanced bacteria harbored the common S531L mutation and a novel mutation F584S in the rpoB gene. Treatment containing RMP or replacement of RMP with more powerful rifapentine paradoxically aggravated the disease, but its removal led to successful cure of the patient. This study highlights the potential dangers of continued treatment of MDR-TB with rifamycins that can occur due to delayed or absent drug susceptibility results and calls for timely detection of RMP-dependent/-enhanced bacteria in treatment failure patients by including RMP in culture media and removal of RMP from treatment regimen upon detection.

Topics: Adult; Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Humans; Male; Mutation; Mycobacterium tuberculosis; Rifampin; Treatment Failure; Tuberculosis, Multidrug-Resistant

Topics: Antitubercular Agents; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Pyrazinamide; Rifampin; Streptomycin; Thioacetazone; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; World Health Organization

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Clinical Trials as Topic; Drug Approval; Drug Industry; Fluoroquinolones; Humans; Mycobacterium avium-intracellulare Infection; Rifampin; Technology, Pharmaceutical; Tuberculosis, Multidrug-Resistant; United States