pyrazinamide and Pulmonary Consumption studies

pyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis.

Research Excerpts

Excerpt	Relevance	Reference
" The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status."	9.15	Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. ( Donald, PR; Hesseling, AC; Magdorf, K; Roll, S; Rosenkranz, B; Schaaf, HS; Seddon, JA; Seifart, HI; Thee, S; Werely, CJ, 2011)
"To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and minimal inhibitory concentration (MIC)."	9.11	Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess. ( Jutte, PC; Rutgers, SR; Uges, DR; Van Altena, R; Van Horn, JR, 2004)
"A case of isoniazid induced gynecomastia is being reported in an 18-year old male, who received a re-treatment regimen for the relapse of pulmonary tuberculosis (TB)."	8.87	Unilateral and painless development of isoniazid induced gynecomastia during re-treatment of pulmonary tuberculosis. ( Behera, D; Gupta, R; Jaiswal, A; Kumar, L; Murar, A; Puri, MM, 2011)
"Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children."	7.88	Pharmacokinetics and Drug-Drug Interactions of Lopinavir-Ritonavir Administered with First- and Second-Line Antituberculosis Drugs in HIV-Infected Children Treated for Multidrug-Resistant Tuberculosis. ( de Kock, M; Denti, P; Garcia-Prats, AJ; Hesseling, AC; McIlleron, H; Norman, J; Schaaf, HS; Tikiso, T; van der Laan, LE; Wiesner, L; Winckler, J, 2018)
"We report the case of a 35-year-old man treated by RHEZ for a first episode of a smear positive pulmonary tuberculosis and who developed a DRESS syndrome due to pyrazinamide after twenty days of treatment, associated with a viral reactivation to Human Herpes Virus 6 (HHV6)."	7.88	[DRESS syndrome secondary to pyrazinamide: An uncommon complication of tuberculosis treatment]. ( Dia Kane, Y; Diouf, NF; Fall, L; Ka, W; Kombila, UD; Koutonin, ANE; Mbaye, FBR; Ouedraogo, P; Oumar Toure Badiane, N, 2018)
"Rifampin (RIF) mono-resistant tuberculosis (RMR-TB) is a rare disease."	7.85	Treatment outcomes of rifampin-sparing treatment in patients with pulmonary tuberculosis with rifampin-mono-resistance or rifampin adverse events: A retrospective cohort analysis. ( Jo, KW; Kim, WS; Lee, SD; Park, S; Shim, TS, 2017)
"Pyrazinamide (PZA) has been in use for almost 50 years as a first-line drug for short-course chemotherapy against Mycobacterium tuberculosis."	7.76	Molecular epidemiological study of pyrazinamide-resistance in clinical isolates of mycobacterium tuberculosis from South India. ( Ayalusamy, N; Jagadeesan, S; Muthaiah, M; Muthuraj, U; Prabhu, SS; Senthilkumar, K; Sreenivasan, M; Veerappan, S, 2010)
"In this study we investigated whether leptin and TNFalpha levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients."	7.70	Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis. ( Aral, Y; Cakir, B; Demirbaş, B; Güler, S; Gürsoy, G; Odabaşi, E; Yönem, A, 1999)
"We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid, rifampin, and other agents."	7.69	Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. ( Nelson, SD; Nolan, CM; Sandblom, RE; Slattery, JT; Thummel, KE, 1994)
"Noncaseating granulomatous hepatitis may be caused by a variety of drugs, but we have not found, by computer search of the literature, a previous describe of granulomatous hepatitis associated with pyrazinamide."	7.69	Pyrazinamide-induced granulomatous hepatitis. ( Buyanowsky, G; Dan, M; Knobel, B; Zaidel, L, 1997)
"A case of thrombocytopenia caused by pyrazinamide is reported in a patient receiving chemotherapy for pulmonary tuberculosis."	7.67	Pyrazinamide induced thrombocytopenia. ( Jain, VK; Prakash, OM; Vardhan, H, 1988)
"Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide."	7.67	Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide. ( Janardhanam, B; Parthasarathy, R; Ramachandran, P; Santha, T; Sarma, GR; Sivasubramanian, S; Somasundaram, PR; Tripathy, SP, 1986)
" PZA dosage was less than 1."	6.69	[Hyperuricemia and arthralgia during pyrazinamide treatment]. ( Ikeda, N; Ikeda, T; Inoue, T; Kurasawa, T; Nakatani, K; Sato, A; Yoshimatsu, H, 1999)
" One hundred patients with pulmonary tuberculosis (65% coinfected with HIV-1) were intensively sampled to determine rifampin, isoniazid, and pyrazinamide plasma concentrations after 7 to 8 weeks of a daily quadruple-therapy regimen dosed according to World Health Organization (WHO) weight bands."	5.43	HIV-1 Coinfection Does Not Reduce Exposure to Rifampin, Isoniazid, and Pyrazinamide in South African Tuberculosis Outpatients. ( Chirehwa, M; Denti, P; McIlleron, H; Meintjes, G; Rockwood, N; Wiesner, L; Wilkinson, RJ, 2016)
"Rosacea is a common chronic inflammatory cutaneous disease of unknown etiology, characterized by remissions and exacerbations, presenting with centrofacial erythema and telangiectasias."	5.42	Pyridoxine induced rosacea-like dermatitis. ( Mokos, ZB; Paštar, Z; Rezaković, S, 2015)
"Pyrazinamide is an antituberculous drug that is administered as a two-month course during treatment of pulmonary tuberculosis."	5.35	Epidemiological survey of hyperuricemia as an adverse reaction to antituberculous therapy with pyrazinamide. ( Murakami, T; Nikai, T; Ogawa, K; Taki, H, 2008)
"The isoniazid was discontinued, and the gynecomastia was partially resolved by the end of treatment."	5.35	Gynecomastia: a rare adverse effect of isoniazid. ( Braz, AG; Maia, JA; Morrone Junior, N; Morrone, N, 2008)
"Pyrazinamide therapy has been associated with dose-dependent hepatotoxicity, hyperuricaemia, arthralgia and arthritis."	5.28	Tubulointerstitial nephritis associated with pyrazinamide. ( Kauffmann, RH; Sanwikarja, S; Serlie, J; te Velde, J, 1989)
" The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status."	5.15	Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. ( Donald, PR; Hesseling, AC; Magdorf, K; Roll, S; Rosenkranz, B; Schaaf, HS; Seddon, JA; Seifart, HI; Thee, S; Werely, CJ, 2011)
"To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and minimal inhibitory concentration (MIC)."	5.11	Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess. ( Jutte, PC; Rutgers, SR; Uges, DR; Van Altena, R; Van Horn, JR, 2004)
"A case of isoniazid induced gynecomastia is being reported in an 18-year old male, who received a re-treatment regimen for the relapse of pulmonary tuberculosis (TB)."	4.87	Unilateral and painless development of isoniazid induced gynecomastia during re-treatment of pulmonary tuberculosis. ( Behera, D; Gupta, R; Jaiswal, A; Kumar, L; Murar, A; Puri, MM, 2011)
"Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children."	3.88	Pharmacokinetics and Drug-Drug Interactions of Lopinavir-Ritonavir Administered with First- and Second-Line Antituberculosis Drugs in HIV-Infected Children Treated for Multidrug-Resistant Tuberculosis. ( de Kock, M; Denti, P; Garcia-Prats, AJ; Hesseling, AC; McIlleron, H; Norman, J; Schaaf, HS; Tikiso, T; van der Laan, LE; Wiesner, L; Winckler, J, 2018)
"We report the case of a 35-year-old man treated by RHEZ for a first episode of a smear positive pulmonary tuberculosis and who developed a DRESS syndrome due to pyrazinamide after twenty days of treatment, associated with a viral reactivation to Human Herpes Virus 6 (HHV6)."	3.88	[DRESS syndrome secondary to pyrazinamide: An uncommon complication of tuberculosis treatment]. ( Dia Kane, Y; Diouf, NF; Fall, L; Ka, W; Kombila, UD; Koutonin, ANE; Mbaye, FBR; Ouedraogo, P; Oumar Toure Badiane, N, 2018)
"Rifampin (RIF) mono-resistant tuberculosis (RMR-TB) is a rare disease."	3.85	Treatment outcomes of rifampin-sparing treatment in patients with pulmonary tuberculosis with rifampin-mono-resistance or rifampin adverse events: A retrospective cohort analysis. ( Jo, KW; Kim, WS; Lee, SD; Park, S; Shim, TS, 2017)
"A 26-year-old man, who had started treatment for pulmonary tuberculosis, developed polyarthralgia, generalised myalgia, weakness, and elevated uric acid and creatine kinase levels."	3.81	Drug-induced myopathy in a patient with pulmonary tuberculosis. ( Shah, R; Venkatesan, P, 2015)
" The objectives of this investigation were to evaluate the impact of body weight on the overall systemic exposure to pyrazinamide (PZA) and to assess whether the use of one fixed dose, without adjustment according to weight, would ensure target exposure and safety requirements across the overall patient population."	3.78	Feasibility of a fixed-dose regimen of pyrazinamide and its impact on systemic drug exposure and liver safety in patients with tuberculosis. ( Della Pasqua, O; Sahota, T, 2012)
"Pyrazinamide (PZA) has been in use for almost 50 years as a first-line drug for short-course chemotherapy against Mycobacterium tuberculosis."	3.76	Molecular epidemiological study of pyrazinamide-resistance in clinical isolates of mycobacterium tuberculosis from South India. ( Ayalusamy, N; Jagadeesan, S; Muthaiah, M; Muthuraj, U; Prabhu, SS; Senthilkumar, K; Sreenivasan, M; Veerappan, S, 2010)
"We present the case of an elderly patient who died of fulminant hepatic failure in the course of receiving 2 months of treatment with pyrazinamide and rifampin for his latent tuberculosis."	3.71	Death associated with rifampin and pyrazinamide 2-month treatment of latent mycobacterium tuberculosis. ( Medinger, A, 2002)
"In this study we investigated whether leptin and TNFalpha levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients."	3.70	Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis. ( Aral, Y; Cakir, B; Demirbaş, B; Güler, S; Gürsoy, G; Odabaşi, E; Yönem, A, 1999)
"We report three patients who experienced hepatotoxic reactions in association with acetaminophen ingestion while undergoing treatment for active tuberculosis with isoniazid, rifampin, and other agents."	3.69	Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. ( Nelson, SD; Nolan, CM; Sandblom, RE; Slattery, JT; Thummel, KE, 1994)
"To test the efficacy of a short-course regimen of 6 months rifampicin and isoniazid supplemented by 2 months initial pyrazinamide (2HRZ-4HR), in the treatment of smear and culture-negative pulmonary tuberculosis and tuberculous pleural effusion in routine clinical practice."	3.69	Short-course chemotherapy for tuberculous pleural effusion and culture-negative pulmonary tuberculosis. ( Horsfield, N; McCarthy, OR; Ormerod, LP; Rudd, RM, 1995)
"Noncaseating granulomatous hepatitis may be caused by a variety of drugs, but we have not found, by computer search of the literature, a previous describe of granulomatous hepatitis associated with pyrazinamide."	3.69	Pyrazinamide-induced granulomatous hepatitis. ( Buyanowsky, G; Dan, M; Knobel, B; Zaidel, L, 1997)
"A case of thrombocytopenia caused by pyrazinamide is reported in a patient receiving chemotherapy for pulmonary tuberculosis."	3.67	Pyrazinamide induced thrombocytopenia. ( Jain, VK; Prakash, OM; Vardhan, H, 1988)
"Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide."	3.67	Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide. ( Janardhanam, B; Parthasarathy, R; Ramachandran, P; Santha, T; Sarma, GR; Sivasubramanian, S; Somasundaram, PR; Tripathy, SP, 1986)
"An analysis carried out on the dosage schemes adopted in several controlled clinical trials in tuberculosis has indicated that preestablishing the daily doses of isoniazid, rifampicin, and pyrazinamide in the initial intensive phase results in large deviations of the doses administered from those considered appropriate in mg/kg body weight."	3.67	Short-course chemotherapy of pulmonary tuberculosis: a new approach to drug dosage in the initial intensive phase. ( Acocella, G; Angel, JH, 1986)
" Secondary outcomes were clinical signs and symptoms of pulmonary TB and adverse drug reactions (ADRs) related to anti-TB agents."	3.01	Efficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis: A randomized controlled trial. ( Kawkitinarong, K; Laohapojanart, N; Ratanajamit, C; Srichana, T, 2021)
"Linezolid is increasingly used for the treatment of tuberculosis resistant to first-line agents, but the most effective dosing strategy is yet unknown."	2.94	Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis. ( Burger, DA; Dawson, R; De Jager, VR; Diacon, AH; Everitt, D; Mendel, CM; Narunsky, K; Nedelman, J; Pappas, F; Vanker, N, 2020)
" We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial."	2.90	Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status. ( Crook, AM; Dawson, R; Diacon, AH; Gillespie, SH; McHugh, TD; Mendel, CM; Meredith, SK; Mohapi, L; Murphy, ME; Nunn, AJ; Phillips, PPJ; Singh, KP; Spigelman, M; Tweed, CD, 2019)
"Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially."	2.90	Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial. ( Ahn, H; Cho, YJ; Choi, HS; Choi, SM; Hahn, S; Han, J; Heo, EY; Hwang, YR; Jeong, I; Jo, YS; Joh, JS; Ki, J; Kim, DK; Kim, H; Kim, HS; Kim, J; Kim, SJ; Kwak, N; Lee, CH; Lee, J; Lee, JH; Lee, JK; Lee, JY; Lee, M; Lee, SH; Lee, SM; Lee, YJ; Lim, JN; Park, JH; Park, JS; Park, SS; Park, YS; Song, T; Yim, JJ; Yoon, HI, 2019)
"Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) remain unsatisfactory, and long-term use of second-line anti-TB drugs is accompanied by the frequent occurrence of adverse events, low treatment compliance, and high costs."	2.90	Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, m ( Ahn, H; Ahn, JH; Cho, SN; Hahn, S; Jang, JY; Jeon, D; Jhun, BW; Jo, KW; Kang, YA; Kim, CK; Kim, DK; Kim, JS; Kim, SY; Kim, YR; Koh, WJ; Lee, JH; Lee, JY; Lee, M; Lee, SH; Lee, T; Mok, J; Park, JS; Shim, TS; Shin, S; Shin, SJ; Song, T; Won, HJ; Yim, JJ, 2019)
" Incidence rate of adverse effects was 19."	2.90	Efficacy and safety of cholecalciferol-augmented anti-tuberculosis therapy for treatment of naïve patients with pulmonary tuberculosis: A randomized, controlled, clinical study. ( Abd-Ellatief, RB; Hasanain, AFA; Nafee, AMA; Zayed, AAH, 2019)
" In conclusion, regimen including PZA seems to be safe for late elderly patients with pulmonary TB."	2.90	Safety of pyrazinamide-including regimen in late elderly patients with pulmonary tuberculosis: A prospective randomized open-label study. ( Asaoka, M; Baba, T; Hagiwara, E; Katano, T; Kitamura, H; Komatsu, S; Ogura, T; Okuda, R; Sekine, A; Suido, Y, 2019)
" Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed."	2.84	Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis. ( Aarnoutse, RE; Boeree, MJ; Colbers, A; Gillespie, SH; Haraka, F; Hoelscher, M; Kibiki, GS; Logger, JGM; Magis-Escurra, C; Mpagama, SG; Mtabho, CM; Phillips, PPJ; Plemper van Balen, G; Reither, K; Semvua, HH; Sumari-de Boer, IM; Te Brake, LHM; van den Boogaard, J; Wattenberg, M, 2017)
" Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of SLCO1B1 rs1104581 (previously associated with low rifampin concentrations)."	2.82	Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis. ( Egan, D; Hennig, S; Kellerman, T; McIlleron, H; Naiker, S; Owen, A; Pym, A; Reddy, T; Wiesner, L, 2016)
"There are limited pharmacokinetic data for use of the first-line antituberculosis drugs during infancy (<12 months of age), when drug disposition may differ."	2.82	Pharmacokinetics of Rifampin, Isoniazid, Pyrazinamide, and Ethambutol in Infants Dosed According to Revised WHO-Recommended Treatment Guidelines. ( Bekker, A; Donald, PR; Draper, HR; Hesseling, AC; McIlleron, HM; Murray, S; Schaaf, HS; van der Laan, L; Wiesner, L, 2016)
"To assess whether increasing the dose of rifampicin (RMP) from 10 mg/kg to 15 or 20 mg/kg results in an increase in grade 3 or 4 hepatic adverse events and/or serious adverse events (SAE)."	2.82	A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis. ( Atwine, D; Bonnet, M; Borgulya, G; Burgos, M; Checkley, AM; de Fernandes, RA; de Patiño, IW; Dubash, F; Gonzales, T; Harrison, TS; Jindani, A; Mitchison, D; Patel, N; Shrestha, B, 2016)
" Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily."	2.82	A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis. ( Armstrong, DT; Barnes, GL; Cavalcante, SC; Chaisson, RE; Cohn, S; Conde, MB; Dalcolmo, M; Dooley, KE; Dorman, SE; Duarte, RS; Durovni, B; Efron, A; Loredo, C; Marzinke, MA; Mello, FC; Moulton, LH; Rolla, V; Savic, RM, 2016)
" There was a nonlinear increase in exposure to rifampin without an apparent ceiling effect and a greater estimated fall in bacterial load in the higher dosing groups."	2.80	A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. ( Aarnoutse, RE; Boeree, MJ; Burger, D; Dawson, R; Diacon, AH; du Bois, J; Gillespie, SH; Heinrich, N; Hoelscher, M; Magis-Escurra, C; McHugh, TD; Narunsky, K; Phillips, PP; Plemper van Balen, G; Rehal, S; van Ingen, J; van Soolingen, D; Venter, A, 2015)
" We also assessed safety and tolerability by monitoring adverse events."	2.80	Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pul ( Burger, DA; Conradie, A; Dawson, R; Diacon, AH; Donald, PR; Eisenach, K; Everitt, D; Ive, P; Mendel, CM; Ntinginya, NE; Page-Shipp, L; Pym, A; Reither, K; Schall, R; Spigelman, M; van Niekerk, C; Variava, E; Venter, A; von Groote-Bidlingmaier, F, 2015)
"3%] in the RPT 450 mg, RPT 600 mg and RMP groups), as were ⩾grade 3 adverse events (0/54 [0%], 1/51 [2."	2.80	Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis. ( Barnes, GL; Carman, D; Chaisson, RE; Dawson, R; Dorman, SE; Efron, A; Gupte, N; Hoffman, J; McIlleron, H; Narunsky, K; Whitelaw, A, 2015)
"To observe the clinical effect on type 2 diabetes mellitus (T2DM) complicated with pulmonary tuberculosis (TB) of insulin, isoniazid, rifampicin, pyrazinamide and ethambutol (conventional medication) administered together with Qi-boosting and Yin-nourishing decoction derived from Traditional Chinese Medicine (TCM)."	2.80	Effects on type 2 diabetes complicated with pulmonary tuberculosis: regiment of insulin, isoniazid, rifampicin, pyrazinamide and ethambutol versus the regiment plus Qi-boosting and Yin-nourishing decoction of Traditional Chinese Medicine. ( Shi, G; Zhang, L, 2015)
" Data was analysed using population pharmacokinetic modelling."	2.80	Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania. ( Andersen, AB; Castel, S; Changalucha, J; Chigutsa, E; Christiansen, M; Denti, P; Faurholt-Jepsen, D; Friis, H; Hagen, CM; Jeremiah, K; McIlleron, H; PrayGod, G; Range, N; Wiesner, L, 2015)
"The pyrazinamide MIC range was 12."	2.79	The pyrazinamide susceptibility breakpoint above which combination therapy fails. ( Chigutsa, E; Gumbo, T; McIlleron, H; Pasipanodya, J; Sirgel, FA; van Helden, PD; Visser, M, 2014)
" Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported."	2.78	Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study. ( Aarnoutse, RE; Boeree, MJ; Burger, DM; Fillekes, Q; Kibiki, GS; Kisanga, ER; Kisonga, RM; Mleoh, L; Mtabho, CM; Ndaro, A; Semvua, HH; van den Boogaard, J; van der Ven, A, 2013)
" Noninferiority was dependent on consistent results from a per-protocol and modified intention-to-treat analysis, using 2 different models for the latter, classifying all changes of treatment or refusal to continue treatment (eg, bacteriological failure/relapse, adverse event, default, drug resistance) as unfavorable (model 1) and classifying changes of treatment for reasons other than therapeutic outcomes according to their 18-month bacteriological outcome if available (post hoc model 2)."	2.76	Efficacy and safety of a 4-drug fixed-dose combination regimen compared with separate drugs for treatment of pulmonary tuberculosis: the Study C randomized controlled trial. ( Anyo, G; Burgos, M; Cook, SV; Enarson, DA; Jindani, A; Kim, SJ; Lienhardt, C; Nunn, AJ; Rigouts, L; Yorke-Edwards, V, 2011)
"Rifampin is a key drug for tuberculosis (TB) treatment."	2.73	Pharmacokinetics and tolerability of a higher rifampin dose versus the standard dose in pulmonary tuberculosis patients. ( Aarnoutse, RE; Alisjahbana, B; Nijland, HM; Parwati, I; Ruslami, R; van Crevel, R, 2007)
"The patients with drug susceptible pulmonary tuberculosis treated with 2HRZE/4H2R2 under the supervision by the pharmacists or the patients treated with 2HRZE/4HR by self-administration were followed-up for two years after completion of chemotherapy."	2.73	[Relapse rate of pulmonary tuberculosis within two years following completion of twice weekly intermittent chemotherapy]. ( Hoshino, H; Mitarai, S; Ogata, H; Ohmori, M; Okumura, M; Uchimura, K; Wada, M; Yoshiyama, T, 2008)
" With a dosage of 30 mg/kg PZA, efficient serum levels were reached."	2.73	Pyrazinamide serum levels in childhood tuberculosis. ( Detjen, A; Magdorf, K; Thee, S; Wahn, U, 2008)
"Patients were treated in a controlled clinical trial with 2HRZE3/6HE with thrice-weekly direct dosing in the intensive phase and once-weekly with six doses self-administered in the continuation phase."	2.73	Evaluation of a non-rifampicin continuation phase (6HE) following thrice-weekly intensive phase for the treatment of new sputum positive pulmonary tuberculosis. ( , 2007)
" The occurrence of adverse effects was also monitored."	2.73	Clinical evaluation and monitoring of adverse effects for fixed multidose combination against single drug therapy in pulmonary tuberculosis patients. ( Chaudhry, A; Jamshaid, M; Zaka-Ur-Rehman, Z, 2008)
"The concentration and half-life of theophylline was decreased and its clearance was increased significantly at days 5-7 after administration of antituberculosis agents compared to before the therapy was started."	2.71	The clearance of theophylline is increased during the initial period of tuberculosis treatment. ( Ahn, HC; Lee, YC, 2003)
"Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months."	2.71	Use of Rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial. ( Badaró, R; Bandeira, AC; Barberin, MG; Brites, C; Guerra, C; Netto, EM; Pedral-Sampaio, DB, 2003)
" There was no significant difference in the pharmacokinetic parameters of rifampicin as a component of Mairin-P and in combination with antitubercuous agents as free dosage forms."	2.71	[Assessment of the use of a multicomponent drug in the treatment of new cases of pulmonary tuberculosis]. ( Semenova, OV, 2003)
"Fifty patients with drug-resistant pulmonary tuberculosis were managed by withdrawing all anti-tuberculosis drugs until the results of a drug sensitivity test were obtained (approximately 3 months), and then a 12-month self-administered regimen with four to six anti-tuberculosis drugs at full daily doses was initiated, based primarily on the sensitivity test and secondarily on the history of previous treatment."	2.70	Results of a 12-month regimen for drug-resistant pulmonary tuberculosis. ( Martínez-Rossier, LA; Pérez-Guzmán, C; Torres-Cruz, A; Vargas, MH; Villarreal-Velarde, H, 2002)
" Group II also registered; the maximum cost and highest incidence of adverse effects."	2.70	Comparative evaluation of efficacy and safety profile of three anti-tuberculous regimens in Mangalore. ( Beena, S; Pai, MR; Rao, KN, 2002)
" Further studies with increased rifapentine dosage are necessary."	2.70	Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Final report at 5 years: prognostic value of various measures. ( Chan, SL; Goodall, RL; Kam, KM; Mitchison, DA; Tam, CM, 2002)
" Because of poor bioavailability of the rifapentine used (produced in China), its dose size was increased from 600 mg initially to about 750 mg in the last third of patients to obtain serum concentrations similar to those with rifapentine of Western origin; all doses were given after a meal promoting absorption."	2.69	Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report. ( Chan, SL; Kam, KM; Lam, CW; Leung, CC; Mitchison, DA; Morris, JS; Tam, CM, 1998)
" PZA dosage was less than 1."	2.69	[Hyperuricemia and arthralgia during pyrazinamide treatment]. ( Ikeda, N; Ikeda, T; Inoue, T; Kurasawa, T; Nakatani, K; Sato, A; Yoshimatsu, H, 1999)
"Ethambutol (E) was sometimes substituted for streptomycin."	2.69	Modified short-course chemotherapy of pulmonary tuberculosis in Ibadan, Nigeria--a preliminary report. ( Bakare, NA; Ige, OM; Onadeko, BO, 2000)
"Three hundred eight new smear positive pulmonary tuberculosis patients were randomly allocated with a ratio of 2 to 1 into treatment group (227 cases, receiving 2RIFATER/4RIFINAH regimen) and controls (81 cases, 2HRZ/4HR) for observation."	2.69	[Controlled clinical study on efficacy of fixed-dose compounds rifater/rifinah in antituberculous chemotherapy]. ( Ma, W; Yan, B; Zhu, L, 1998)
"The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven."	2.68	[Clinical trial of a combination of three drugs in fixed proportions in the treatment of tuberculosis. Groupe de Travail sur la Chimiothérapie de la Tuberculose]. ( Boulahbal, F; Chaulet, P, 1995)
" Food may however decrease the oral bioavailability of rifampicin and isoniazid."	2.68	Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. ( Smith, P; Zent, C, 1995)
"To compare the pharmacokinetic parameters and the clinical efficacy of isoniazid, administered in 10 mg/kg or 5 mg/kg to children suffering from pulmonary tuberculosis."	2.68	Pharmacokinetics of isoniazid in pulmonary tuberculosis--a comparative study at two dose levels. ( Chopra, K; Roy, V; Tekur, U, 1996)
"310 patients with pulmonary tuberculosis disseminating bacteria received isoniazid, rifampicin, streptomycin (ethambutol) and pirazinamid in different regimens and dosage forms."	2.67	[Combined chemotherapy of patients with tuberculosis - new regimens and dosage forms]. ( Elistratova, NA; Khalbaeva, IV; Koriakin, VA; Sokolova, GB; Ziia, AV, 1993)
" The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide."	2.67	Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy. ( Acocella, G; Grassi, C; Grassi, GG; Luisetti, M; Peona, V; Pozzi, E, 1993)
"250 patients suffering from pulmonary tuberculosis who were smear positive received a chemotherapy regime for 6 months combining Rifampicin and Isoniazid every day with a daily supplement of Pyrazinamide for the first 8 weeks."	2.67	[A therapeutic trial of a combination of 3 essential drugs in a short course of chemotherapy in tuberculosis. Results 6 months after the end of treatment]. ( Agounitestane, D; Ait Khaled, N; Boulahbal, F; Chaulet, P; Chiheb, M; Khaled, S, 1990)
"7%]); had similar rates of adverse drug reactions (7."	2.67	USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results. ( Combs, DL; Geiter, LJ; O'Brien, RJ, 1990)
" New data on optimal drug selection and dosing are emerging with the inclusion of children in clinical trials and ongoing research on age-related pharmacokinetics and pharmacodynamics."	2.66	Tuberculosis treatment in children: The changing landscape. ( Huynh, J; Marais, BJ; Schaaf, HS; Thwaites, G, 2020)
"Intracranial tuberculomas are rare yet lethal forms of tuberculosis."	2.66	Multiple tuberculomas in an immunocompetent patient and their diagnostic challenge in a high prevalence country: Case report and literature review. ( Alva-Diaz, C; Esteban-Arias, D; López-Saavedra, A; Metcalf, T; Orellana-Tovar, I; Pacheco-Barrios, K; Rodriguez-López, E; Velásquez-Rimachi, V, 2020)
" The dosage of each drug was very similar whether it was given combined or separately."	2.66	Acceptability, compliance, and adverse reactions when isoniazid, rifampin, and pyrazinamide are given as a combined formulation or separately during three-times-weekly antituberculosis chemotherapy. ( , 1989)
"Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months."	2.66	Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis. ( Aluoch, JA; Babu Swai, O; Darbyshire, JH; Edwards, EA; Githui, WA; Nunn, AJ; Thiong'o, R, 1988)
"To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981."	2.66	Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru. ( Baron, RB; Ganter, B; Hopewell, PC; Sanchez-Hernandez, M, 1985)
" tuberculosis were treated in the initial phase as inpatients for 2-3 months at random with either pyrazinamide (Z) or ethambutol (E) in combination with isoniazid (H) and rifampicin (R)."	2.66	[Which is the best drug combination for the short-term therapy of tuberculosis? A prospective randomized study with 190 patients]. ( Bezel, R; Brändli, O; Häcki, M; Karrer, W; Röthlisberger, K; Rubin, S, 1985)
"When pyrazinamide was omitted in the first 2 months the relapse rates were 18% for the 6-month and 6% for the 8-month series."	2.65	Controlled clinical trial of four short-course regimens of chemotherapy for two durations in the treatment of pulmonary tuberculosis. Second report. Third East African/British Medical Research Council Study. ( , 1980)
"A cooperative french trial in the treatment of pulmonary tuberculosis has compared the efficacy and the tolerance of daily antituberculous regimes, one of short duration of 18 weeks (HRSZ/HRZ), the other of standard duration of 9 months (HRE)."	2.65	[Short-term chemotherapy of tuberculosis. Cooperative French trial]. ( Pretet, S, 1983)
"Relapses have occurred in two of 119 SHRZ6 patients, four of 127 EHRZ6 patients and two of 127 EHR9 patients."	2.65	A controlled trial of 6 months' chemotherapy in pulmonary tuberculosis. Final report: results during the 36 months after the end of chemotherapy and beyond. British Thoracic Society. ( , 1984)
" In a controlled study of culture-positive advanced pulmonary tuberculosis we have compared treatment regimens with PZA in a dosage of less than 2 g and with ethambutol (EMB)."	2.65	[Pyrazinamide versus ethambutol in short-term therapy of lung tuberculosis. A randomized study]. ( Brändli, O; Fiala, W; Häcki, MA, 1983)
"Relapse has occurred in 1 of 125 SHRZ6 patients, 3 of 132 EHRZ6, and 2 of 136 EHR9 patients."	2.65	A controlled trial of six months chemotherapy in pulmonary tuberculosis. Second report: results during the 24 months after the end of chemotherapy. British Thoracic Association. ( , 1982)
" It is concluded that the arthralgia was often self-limiting, that aspirin had a small beneficial effect, that allopurinol, in the dosage studied, may have had a slightly deleterious effect, but that it would be worth studying larger dosages of allopurinol because the dosage studied did not affect the serum uric acid concentration."	2.65	Double blind controlled comparison of aspirin, allopurinol and placebo in the management of arthralgia during pyrazinamide administration. ( Allan, WG; Fox, W; Girling, DJ; Horsfall, PA; Nunn, AJ; Plummer, J, 1979)
"All 33 relapses were with strains sensitive to isoniazid and streptomycin, and 76 per cent of them occurred in the first 3 months after the end of chemotherapy."	2.64	Controlled trial of 6- and 9-month regimens of daily and intermittent streptomycin plus isoniazid plus pyrazinamide for pulmonary tuberculosis in Hong Kong. ( , 1975)
" The results confirm that the twice-weekly regimen is highly effective and demonstrate that its efficacy is not influenced by the rate of inactivation of isoniazid or by a reduction (by one-fourth) in the dosage of streptomycin."	2.63	A controlled comparison of a twice-weekly and three once-weekly regimens in the initial treatment of pulmonary tuberculosis. ( , 1970)
"To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens."	2.52	Clinical research in the treatment of tuberculosis: current status and future prospects. ( Chang, KC; Sotgiu, G; Yew, WW, 2015)
"This review will introduce pharmacokinetic parameters for key anti-TB drugs, as well as the indications and limitations of measuring these parameters in clinical practice."	2.50	Understanding pharmacokinetics to improve tuberculosis treatment outcome. ( Heysell, SK; Reynolds, J, 2014)
"Pyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy."	2.48	Pyrazinamide pharmacokinetics and efficacy in adults and children. ( Diacon, AH; Donald, PR; Maritz, JS, 2012)
" The rifamycin activity could be improved by increasing the dose size of rifampicin or by daily dosing with long acting rifapentine."	2.46	The near future: improving the activity of rifamycins and pyrazinamide. ( Fourie, PB; Mitchison, DA, 2010)
"About 97% of patients with pulmonary tuberculosis became bacteriologically quiescent by the 12 months of streptomycin, para-aminosalicylate and isoniazid."	2.41	[Effectiveness and problems of PZA-containing 6-month regimen for the treatment of new pulmonary tuberculosis patients]. ( Wada, M, 2001)
"Treatment of tuberculosis has three major goals: healing the patient, preventing selection of resistant strains and control transmission of tuberculosis."	2.40	[Antitubercular chemotherapy]. ( Dautzenberg, B; Jouveshomme, S, 1997)
"appearance of a bilateral bacillary pulmonary tuberculosis with a severe involvement of the right lung."	2.40	[Sharp syndrome complicating pulmonary tuberculosis: apropos of a case]. ( Ba, O; Cissokho, S; Diatta, A; Dieng, MT; Hane, AA; Kandji, M; Ndiaye, B; Ndiaye, M; Ndir, M; Niang, A, 1999)
"The here described investigations show correspondingly that the administration of isoniazid, rifampicin and pyrazinamide in a fixed combination of the administration of the individual substances is bioequivalent under pharmacokinetic aspects."	2.38	[Pharmacokinetic aspects of tuberculosis therapy with a fixed combination of rifampicin, isoniazide and pyrazinamide]. ( Lode, H; Schaberg, T, 1991)
"Pyrazinamide is an antituberculosis drug synthesized in the 1950s and formerly used only as salvage therapy."	2.37	The role of pyrazinamide in tuberculosis chemotherapy. ( Des Prez, RM; Steele, MA, 1988)
" Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks."	1.72	High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis. ( Chasweka, M; Chirambo, AP; Chitani, A; Corbett, EL; Davies, GR; Ghany, JF; Gordon, SB; Khoo, SH; Malamba, R; Mallewa, JE; McCallum, AD; Meghji, JZ; Mwandumba, HC; Pertinez, HE; Shani, D; Sheha, I; Sloan, DJ, 2022)
" The effect of CART-derived thresholds for individualized dosing on treatment outcome should be studied in a randomized controlled trial."	1.62	Drug Exposure and Minimum Inhibitory Concentration Predict Pulmonary Tuberculosis Treatment Response. ( Alffenaar, JW; Bao, Z; Bruchfeld, J; Forsman, LD; Gao, Y; Hoffner, S; Hu, Y; Li, X; Ren, W; Zheng, X, 2021)
"This features mimic Gitelman's syndrome which is an autosomal recessive disorder affecting kidneys causing electrolyte disturbances."	1.56	Gitelman-like syndrome: A rare complication of using aminoglycosides in tuberculosis - A case report. ( E R, V; Keny, S; Lawande, D; Parrikar, A, 2020)
" Blood sampling was also performed 120 minutes after dosing for the detection of Cmax purpose."	1.56	Effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti-tuberculosis drugs in Chinese population. ( Chu, N; Du, Y; Guo, R; Han, X; Pang, Y; Wang, J; Wang, Q, 2020)
"There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM."	1.51	Effect of diabetes mellitus on TB drug concentrations in Tanzanian patients. ( Aarnoutse, RE; Boeree, MJ; Burger, DM; Colbers, A; Irongo, CF; Kibiki, GS; Mtabho, CM; Semvua, HH; Tostmann, A; van Crevel, R; van den Boogaard, J; van der Ven, AJAM, 2019)
" Stochastic PK/pharmacodynamic (PD) simulations were carried out to evaluate current regimen combinations and dosing guidelines in distinct patient strata."	1.51	Tuberculosis drugs' distribution and emergence of resistance in patient's lung lesions: A mechanistic model and tool for regimen and dose optimization. ( Bang, H; Barry, CE; Dartois, V; Eum, S; Fox, WS; Gupta, SV; Lee, M; Savic, RM; Shim, T; Strydom, N; Via, LE; Zimmerman, M, 2019)
"Treatment of isoniazid, rifampicin, pyrazinamide with the diagnosis of epituberculosis was started by taking a sample of gastric aspirate culture sample."	1.48	[Management and treatment difficulties of multi-drug resistant pulmonary tuberculosis in a pediatric case]. ( Acar, EM; Bayramoğlu, Z; Çalışkan, E; Erköse, G; Hançerli Törün, S; Kılıçaslan, Z; Şatana, D; Somer, A, 2018)
"Ulcerative skin tuberculosis (TB) is a rare form of extrapulmonary TB."	1.48	Perianal ulcerative skin tuberculosis: A case report. ( Chen, H; Song, X; Wang, W; Wu, S; Xiong, W; Yu, X, 2018)
"Pyrazinamide (PZA) is a critical component of current first-line TB therapy."	1.48	Efficacy of pyrazinoic acid dry powder aerosols in resolving necrotic and non-necrotic granulomas in a guinea pig model of tuberculosis. ( Braunstein, M; Durham, PG; Hayden, JD; Hickey, AJ; Lin, FC; Miller, BK; Montgomery, SA; Rank, L; Welch, JT; Young, EF; Zulauf, KE, 2018)
" Pyrazinamide pharmacokinetic (PK) data from 61 HIV/TB-coinfected patients in South Africa were used in the analysis."	1.46	Pharmacokinetics of Pyrazinamide and Optimal Dosing Regimens for Drug-Sensitive and -Resistant Tuberculosis. ( Chirehwa, MT; Denti, P; McIlleron, H; Mthiyane, T; Onyebujoh, P; Rustomjee, R; Smith, P, 2017)
"Upon diagnosis, Pulmonary Tuberculosis patients are treated for TB for a period of 6-9 months."	1.46	Serum levels of soluble urokinase plasminogen activator receptor (suPAR) as a marker of tuberculosis treatment efficacy. ( Indumati, V; Krishnaswamy, D; Rajeshwari, V; Ramesh, A; Shantala, D; Shilpa, A; Vijay, V, 2017)
" As irrational use and inadequate dosing of anti-TB drugs may contribute to the epidemic of drug-resistant TB, we assessed the drug types and dosages prescribed in the treatment of TB cases in a representative sample of health care facilities in Yunnan."	1.46	Prescription practice of anti-tuberculosis drugs in Yunnan, China: A clinical audit. ( Chen, J; Chiang, CY; Innes, AL; Li, L; Xu, L, 2017)
"The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC)."	1.46	Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar. ( Al-Shaer, MH; Elewa, H; Iqbal, F; Mansour, H; Salameh, P, 2017)
"If isoniazid Cmax was <4."	1.46	Concentration-Dependent Antagonism and Culture Conversion in Pulmonary Tuberculosis. ( Denti, P; Gumbo, T; Lesosky, M; McIlleron, H; Meintjes, G; Pasipanodya, JG; Rockwood, N; Sirgel, F; Wilkinson, RJ, 2017)
"Seventeen (4."	1.43	Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome. ( Cho, YJ; Kim, SJ; Lee, CT; Lee, JH; Lee, JY; Lee, YJ; Park, JS; Song, J; Yoon, HI, 2016)
"Pyrazinamide (PZA) is a key sterilizing drug in first-line tuberculosis (TB) regimens and exerts its activity entirely during the first 2 months in human infections."	1.43	Sterilizing Activity of Pyrazinamide in Combination with First-Line Drugs in a C3HeB/FeJ Mouse Model of Tuberculosis. ( Betoudji, F; Lanoix, JP; Nuermberger, E, 2016)
"Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on PZA resistant (PZA-R) rate in China."	1.43	Prevalence and transmission of pyrazinamide resistant Mycobacterium tuberculosis in China. ( Gao, Q; Gicquel, B; Luo, T; Nsofor, CA; Shen, X; Wu, J; Xu, P; Yang, C; Zhang, Y; Zhu, G, 2016)
"A population-based multicenter study of pulmonary tuberculosis (TB) cases was carried out from 2011 to 2013 in four Chinese districts/counties with different geographic and socioeconomic features."	1.43	Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China. ( Drobniewski, F; Hoffner, S; Hu, Y; Li, D; Mansjö, M; Werngren, J; Xu, B; Zheng, X, 2016)
"Pyrazinamide resistance was assessed in 4972 patients."	1.43	Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project. ( Alikhanova, N; Andres, S; Cabibbe, AM; Cirillo, DM; Dadu, A; Dean, AS; Dreyer, A; Driesen, M; Floyd, K; Gilpin, C; Hasan, R; Hasan, Z; Hoffner, S; Husain, A; Hussain, A; Ismail, N; Kamal, M; Kimerling, M; Mansjö, M; Mukadi, YD; Mvusi, L; Niemann, S; Omar, SV; Qadeer, E; Raviglione, MC; Rigouts, L; Ruesch-Gerdes, S; Schito, M; Seyfaddinova, M; Skrahina, A; Tahseen, S; Wells, WA; Weyer, K; Zignol, M, 2016)
" One hundred patients with pulmonary tuberculosis (65% coinfected with HIV-1) were intensively sampled to determine rifampin, isoniazid, and pyrazinamide plasma concentrations after 7 to 8 weeks of a daily quadruple-therapy regimen dosed according to World Health Organization (WHO) weight bands."	1.43	HIV-1 Coinfection Does Not Reduce Exposure to Rifampin, Isoniazid, and Pyrazinamide in South African Tuberculosis Outpatients. ( Chirehwa, M; Denti, P; McIlleron, H; Meintjes, G; Rockwood, N; Wiesner, L; Wilkinson, RJ, 2016)
"Pirfenidone is a recently approved antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF)."	1.43	The antifibrotic drug pirfenidone promotes pulmonary cavitation and drug resistance in a mouse model of chronic tuberculosis. ( Ahidjo, BA; Andrade, BB; Beck, S; Bishai, WR; Cheung, LS; Ihms, EA; Jain, S; Maiga, M; Maiga, MC; Ordonez, AA, 2016)
"Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment."	1.43	Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study. ( He, JQ; Ji, GY; Liu, QQ; Sandford, AJ; Wang, Y; Wu, JC; Wu, SQ; Zhang, MM, 2016)
"33 patients with pulmonary tuberculosis were treated with one Risorine kit, daily consisting of one capsule of Risorine, one tablet of ethambutol (800 mg) and two tablets of Pyrazinamide 750 mg each, for first two months of therapy."	1.43	Role of Risorine in the Treatment of Drug - Susceptible Pulmonary Tuberculosis: A Pilot Study. ( Patel, K; Patel, S; Vora, A, 2016)
"The available pharmacokinetic data on anti-tubercular drugs in children raises the concern of suboptimal plasma concentrations attained when doses extrapolated from adult studies are used."	1.42	Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in Indian children. ( Kabra, SK; Kanhiya, K; Lodha, R; Mukherjee, A; Singla, M; Velpandian, T, 2015)
"Rosacea is a common chronic inflammatory cutaneous disease of unknown etiology, characterized by remissions and exacerbations, presenting with centrofacial erythema and telangiectasias."	1.42	Pyridoxine induced rosacea-like dermatitis. ( Mokos, ZB; Paštar, Z; Rezaković, S, 2015)
"Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug that is generally administered with isoniazid, rifampicin, ethambutol and streptomycin."	1.40	Characterisation of pyrazinamide-resistant Mycobacterium tuberculosis strains isolated in Poland and Germany. ( Augustynowicz-Kopeć, E; Hillemann, D; Napiórkowska, A; Richter, E; Rüsch-Gerdes, S, 2014)
" In this study, we sought to investigate the sterilizing activity of human-equivalent doses of thioridazine when given in combination with the "Denver regimen" against acute murine tuberculosis."	1.40	Sterilizing activity of thioridazine in combination with the first-line regimen against acute murine tuberculosis. ( Dutta, NK; Karakousis, PC; Pinn, ML, 2014)
"Seventy-five male patients with pulmonary tuberculosis (mean age, 40."	1.40	Association of serum levels of iron, copper, and zinc, and inflammatory markers with bacteriological sputum conversion during tuberculosis treatment. ( de Melo Guedes de Oliveira, HM; de Oliveira, MM; Delogo, KN; Dos Anjos, MJ; Kritski, AL; Mesquita, ED; Miranda, PF; Moraes, ML; Netto, AR; Ramalho, DM, 2014)
"Gastrointestinal events, hepatitis, hearing impairment, arthralgia, psychosis, hypothyroidism, visual disturbances, giddiness, peripheral neuropathy, skin reactions, swelling or pain at injection site, anorexia and sleep disturbances were important amongst these."	1.40	Profile of adverse drug reactions in drug resistant tuberculosis from Punjab. ( Bharti, H; Bhushan, B; Chander, R; Gupta, A; Kajal, NC; Ranga, V, 2014)
" We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling."	1.39	Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients. ( Aarnoutse, RE; Boeree, MJ; Kibiki, GS; Mtabho, CM; Semvua, HH; Tostmann, A; van den Boogaard, J, 2013)
"[Methods] Thirty-six patients with pulmonary tuberculosis, who were admitted to Yokohama City University Hospital between June 2011 and March 2012 were included."	1.39	[Comparison of drug-induced hepatitis occurring in elderly and younger patients during anti-tuberculosis treatment with a regimen including pyrazinamide]. ( Horita, N; Ishigatsubo, Y; Miyazawa, N; Sasaki, M; Takahashi, R; Tomaru, K; Tsukahara, T, 2013)
"The isoniazid C2 h was noticeably lower in fast versus slow acetylators (0."	1.39	Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients. ( Aarnoutse, R; Ascobat, P; Burhan, E; Donders, R; Ginanjar, A; Mangunnegoro, H; Ruesen, C; Ruslami, R; van Crevel, R, 2013)
" Serum concentration-time profiles, maximum serum concentrations, time to achieve maximum serum concentrations, the half-life and the areas under the serum concentration-time curve for each of the four drugs were determined."	1.39	Pharmacokinetics and serum concentrations of antimycobacterial drugs in adult Turkish patients. ( Arpag, H; Babalık, A; Bakirci, N; Çarpaner, E; Dagyildiz, L; Kuyucu, T; Ulus, IH, 2013)
"The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran."	1.39	Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis. ( Bozorg, BD; Dastan, F; Emami, S; Fahimi, F; Goodarzi, A; Habibi, M; Kobarfard, F; Salamzadeh, J; Shahsavari, N; Tabarsi, P, 2013)
" This is despite the availability of antibiotics that have good activity against Mycobacterium tuberculosis in vitro and favorable pharmacokinetic profiles in plasma."	1.38	Pharmacokinetic evaluation of the penetration of antituberculosis agents in rabbit pulmonary lesions. ( Barry, CE; Dartois, V; Goh, A; Kern, S; Kjellsson, MC; Low, KM; Pillai, G; Via, LE; Weiner, D, 2012)
"Pyrazinamide (PZA) is an important drug in the treatment of tuberculosis."	1.38	A new approach for pyrazinamide susceptibility testing in Mycobacterium tuberculosis. ( Cotrina, M; Fuentes, P; Gilman, RH; Gutierrez, A; Kirwan, D; Loli, S; Sheen, P; Zimic, M, 2012)
"Pyrazinamide was omitted in 15 cases while rifampicin only in one patient."	1.38	Management of and risk factors related to hepatotoxicity during tuberculosis treatment. ( Ağca, S; Arda, H; Babalık, A; Bakırcı, N; Calışır, HC; Cetintaş, G; Kızıltaş, S; Oruç, K, 2012)
"Rifampin-treated BALB/c mice remained culture positive at 3 months."	1.37	Treatment of tuberculosis with rifamycin-containing regimens in immune-deficient mice. ( Ahmad, Z; Almeida, DV; Converse, PJ; Grosset, JH; Li, SY; Nuermberger, EL; Peloquin, CA; Rosenthal, IM; Zhang, M, 2011)
"Paragonimiasis is a food-borne zoonosis caused by a trematode of the genus Paragonimus(1,2)."	1.37	[Pulmonary paragonimiasis]. ( Fortes-Alen, J; Gómez-Escolar, PF; Gómez-Seco, J; Presa-Abos, T; Rodríguez-Guzmán, MJ; Rodríguez-Nieto, MJ, 2011)
"Thirteen patients with pulmonary tuberculosis detected."	1.37	Pulmonary tuberculosis in infants less than one year old: implications for early diagnosis. ( Bayhan, GI; Ekşioğlu, AS; Kitiş Çelik, B; Tanır, G, 2011)
"The frequency of late recurrences following treatment completion has not been well-studied."	1.37	When tuberculosis comes back: who develops recurrent tuberculosis in california? ( Deriemer, K; Flood, JM; Pascopella, L; Watt, JP, 2011)
" Intensive pharmacokinetic sampling was performed for rifampin, pyrazinamide, and ethambutol at steady state."	1.36	Pharmacokinetics of antituberculosis drugs in pulmonary tuberculosis patients with type 2 diabetes. ( Aarnoutse, RE; Adhiarta, IG; Alisjahbana, B; Kariadi, SH; Nijland, HM; Ruslami, R; van Crevel, R, 2010)
"Pyrazinamide sensitivity was carried out using the BACTEC 7H12 medium."	1.36	Drug resistance pattern in multidrug resistance pulmonary tuberculosis patients. ( Irfan, M; Mehfooz, Z; Rao, NA; Soomro, MM, 2010)
"Pyrazinamide (PZA) is an important first-line antituberculous drug, which is applied together with INH, RMP, EMB and SM."	1.36	[Phenotypic characterization of pyrazinamide-resistant Mycobacterium tuberculosis isolated in Poland]. ( Augustynowicz-Kopeć, E; Napiórkowska, A; Zwolska, Z, 2010)
"Metronidazole treatment (for 6 weeks at 100 mg/kg of body weight) resulted in no reduction in the bacillary burden and significantly worsened lesion inflammation."	1.35	Metronidazole lacks antibacterial activity in guinea pigs infected with Mycobacterium tuberculosis. ( Basaraba, RJ; Brooks, EJ; Caraway, ML; Driver, ER; Hoff, DR; Lenaerts, AJ; Orme, IM; Peloquin, CA; Ryan, GJ, 2008)
"Pyrazinamide was the most sensitive drug i."	1.35	Primary drug resistance against Mycobacterium tuberculosis in Karachi. ( Hussain, SJ; Irfan, M; Rao, NA, 2008)
"Treatment with rifampin and pyrazinamide was more effective than treatment with rifampin, isoniazid, and pyrazinamide at reducing the lung CFU count, consistent with past evidence of isoniazid's antagonism in this model."	1.35	Enhanced bactericidal activity of rifampin and/or pyrazinamide when combined with PA-824 in a murine model of tuberculosis. ( Grosset, J; Nuermberger, E; Tasneen, R; Tyagi, S; Williams, K, 2008)
"Pyrazinamide is an antituberculous drug that is administered as a two-month course during treatment of pulmonary tuberculosis."	1.35	Epidemiological survey of hyperuricemia as an adverse reaction to antituberculous therapy with pyrazinamide. ( Murakami, T; Nikai, T; Ogawa, K; Taki, H, 2008)
"tuberculosis isolates from pulmonary tuberculosis patients."	1.35	Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates. ( Fourie, PB; Grewal, HM; Mannsåker, T; Mphahlele, M; Muthivhi, T; Stavrum, R; Syre, H; Valvatne, H; Weyer, K, 2008)
"Temozolomide (TMZ) is a cytotoxic agent of the imidazotetrazine class, chemically related to dacarbazine."	1.35	Tuberculosis in a patient on temozolomide: a case report. ( de Barros e Silva, MJ; de Paiva, TF; Fanelli, MF; Gimenes, DL; Rinck, JA, 2009)
"The isoniazid was discontinued, and the gynecomastia was partially resolved by the end of treatment."	1.35	Gynecomastia: a rare adverse effect of isoniazid. ( Braz, AG; Maia, JA; Morrone Junior, N; Morrone, N, 2008)
" Therefore, lowering of pyrazinamide dosage is suggested in children for better patient compliance along with reduction in cost, side-effects and toxicity without compromising its efficacy."	1.35	Pharmacokinetics of pyrazinamide in children with primary progressive disease of lungs. ( Arya, DS; Nandave, M; Ojha, SK; Semwal, OP, 2008)
" Therapy was performed according to regimens 3 and 1, by using individual dosage regimens depending on the extent and severity of a specific process, the presence of complications, and age-related features."	1.35	[Optimization of chemotherapy regimens in children with primary pulmonary tuberculosis]. ( Dovgaliuk, IF; Ovchinnikova, IuE; Starshinova, AA, 2009)
"Isoniazid was stopped and patient was continued on R & E till completion of the treatment up to nine months."	1.35	Isoniazid induced gynaecomastia: a case report. ( Garg, R; Mehra, S; Prasad, R, 2009)
"In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs."	1.34	Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. ( Andries, K; Chauffour, A; Ibrahim, M; Jarlier, V; Lounis, N; Truffot-Pernot, C; Veziris, N, 2007)
"He was diagnosed as pulmonary tuberculosis, and started treatment with INH, RFP, EB, and PZA."	1.34	[A case of tuberculosis showing immune reconstitution syndrome after the initiation of antiretroviral therapy for HIV infection]. ( Izumi, S; Taniguchi, H, 2007)
"A 65-year-old woman developed a confusional syndrome one week after starting treatment for pulmonary military tuberculosis."	1.34	[Aseptic cerebral venous thrombosis and multiple cerebral tuberculomas associated with pulmonary miliary tuberculosis]. ( Amara, B; Belahsen, MF; Benjelloun, FZ; Benjelloun, MC; Messouak, O; Tizniti, S, 2007)
"Types and frequency of drug-related adverse events and outcomes of treatment."	1.33	Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons. ( Bock, NN; Grabau, JC; Jasmer, RM; Lobato, MN; Reves, RR; Shang, N, 2005)
"89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions."	1.33	Population pharmacokinetics of pyrazinamide in elephants. ( Dunker, F; Isaza, R; Maslow, JN; Mikota, SK; Peloquin, CA; Riddle, H; Zhu, M, 2005)
"MDR-TB can be successfully treated during pregnancy by using a regimen including effective second-line anti-tuberculosis drugs."	1.33	[Treatment outcome of patients with multidrug-resistant pulmonary tuberculosis during pregnancy]. ( Ano, H; Danno, K; Han, Y; Kawahara, K; Matsumoto, T; Nagai, T; Takashima, T; Tamura, Y; Tsuyuguchi, I; Yoshida, H, 2006)
"All cases had evidence of pulmonary tuberculosis."	1.33	Ocular tuberculosis in acquired immunodeficiency syndrome. ( Babu, RB; Biswas, J; Kumarasamy, N; Sudharshan, S; Therese, L, 2006)
"Major adverse reactions to antituberculosis drugs can cause significant morbidity, and compromise treatment regimens for tuberculosis (TB)."	1.32	Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. ( Menzies, D; Parisien, I; Pelletier, M; Rocher, I; Valiquette, C; Yee, D, 2003)
"A healthy 57 year-old woman with past untreated pulmonary tuberculosis, disclosed a bilateral uveitic syndrome characte rized by iritis, vitreitis, multiple peripheral retinal punched-out lesions, and cystoid macular edema."	1.32	[Tuberculous peripheral multifocal choroiditis]. ( González Guijarro, J; Pérez Alvarez, MJ; Santos Gil, I, 2003)
"In total, 45 children with pulmonary tuberculosis participated."	1.32	Follow-up of compliance with tuberculosis treatment in children: monitoring by urine tests. ( Gultekin, D; Kayaalp, N; Palanduz, A, 2003)
" Relative bioavailability of encapsulated drugs was greater than that of free drugs."	1.32	Chemotherapeutic potential of orally administered poly(lactide-co-glycolide) microparticles containing isoniazid, rifampin, and pyrazinamide against experimental tuberculosis. ( Khuller, GK; Sharma, S; Ul-Ain, Q, 2003)
"All 44 non-private hospitals in Malawi treating pulmonary tuberculosis (PTB) patients with an oral regimen (0."	1.32	Prescriptions and dosages of anti-tuberculosis drugs in the National Tuberculosis Control Programme of Malawi. ( Gausi, F; Harries, AD; Salaniponi, FM, 2004)
"A hundred new cases of active pulmonary tuberculosis whose age was 60 to 87 years were treated by the intensive chemotherapy regimen recommended by the WHO."	1.32	[Efficiency of an intensive stage of chemotherapy for tuberculosis in elderly and senile patients]. ( Karachunskiĭ, MA; Uvarova, TE, 2004)
" Severe adverse reactions included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome (seven), and four deaths."	1.32	Efficacy and safety of Efavirenz in HIV patients on Rifampin for tuberculosis. ( Alves, CR; Badaro, R; Brites, C; Netto, EM; Oliveira, AS; Pedral-Sampaio, DB, 2004)
"A case of Pulmonary Alveolar Proteinosis (PAP), in association with tuberculosis, is described in a 35-year-old diabetic patient."	1.31	Pulmonary alveolar proteinosis and tuberculosis in a diabetic patient: a rare or a seldom diagnosed association? ( Coelho JC, JC; Marinho, MM; Pereira-Silva, JL; Veloso, TV, 2002)
"Lupus vulgaris is the most common cutaneous manifestation of tuberculosis in industrialised countries, but nevertheless it remains rare and it is a very unusual presenting feature of underlying pulmonary tuberculosis."	1.31	[Pulmonary tuberculosis presenting as tubercular lupus]. ( Barbaud, A; Fays, S; Martin, S; Schmutz, JL, 2002)
"Intracranial tuberculomas are a rare manifestation of neurotuberculosis and are due to hematogenous dissemination of distant focuses of Mycobacterium tuberculosis infection."	1.31	[Intracranial tuberculomas developing during treatment of pulmonary tuberculosis: case report]. ( Alves, SM; Belo Neto, E; Brandão, RZ; Novis, SA; Pimentel, ML, 2000)
"Hyponatremia is seen in 40% to 60% of hospitalized acquired immune deficiency syndrome (AIDS) patients."	1.31	Normouricemia in the syndrome of inappropriate antidiuretic hormone secretion. ( Akalin, E; Chandrakantan, A; Hamburger, RJ; Keane, J, 2001)
"Pyrazinamide was not used in the intensive phase in the control group (n = 73)."	1.31	[Effectiveness of chemotherapy of intrathoracic tuberculosis in children: late follow-up data]. ( Iukhimenko, NV, 2001)
"Pericardial effusion was shown by echocardiography and subsequently removed by pericardiocentesis."	1.31	Tuberculous pericarditis in an infant evolving during triple chemotherapy. ( Bettendorf, M; Meyburg, J; Nützenadel, W; Schmidt, KG, 2002)
"Pyrazinamide (PZA) is a first-line drug for short-course tuberculosis therapy."	1.30	Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. ( Cynamon, M; Gilman, R; Heifets, L; Lindholm-Levy, P; Scorpio, A; Siddiqi, S; Zhang, Y, 1997)
"The re-treatment pulmonary tuberculosis with positive spits represent 13."	1.30	[The results of retreatment of pulmonary tuberculosis using a short 6-month protocol 1985-1991 in the pneumo-phthisiology department of the Point G hospital in Bamako]. ( Kayantao, D; Keïta, B; Sangaré, S, 1997)
"Two patients with multidrug-resistant pulmonary tuberculosis were surgically treated after 3 and 7 years of unsuccessful chemotherapy."	1.30	[Surgical treatment of patients with multi-resistant pulmonary tuberculosis--case reports]. ( Kuś, J; Michałowska-Mitczuk, D, 1997)
"Although relapse was more frequent in patients with positive smears than those with negative smears (9."	1.30	Should we take a history of prior treatment, and check sputum status at 2-3 months when treating patients for tuberculosis? ( Bechan, S; Connolly, C; Short, GM; Standing, E; Wilkinson, D, 1998)
"Pyrazinamide, which was readministered last (at the full dose in one case and at progressive doses in the two others), induced a recurrence in two of them."	1.30	[Eruption after the 1st dose of standard antitubercular chemotherapy. Thoughts on pyrazinamide]. ( Autret, E; Carré, P; Jonville-Bera, AP; Lemarié, E; Radal, M; Van-Egroo, C, 1998)
"The management of pulmonary tuberculosis (TB) in Scotland in 1993 was studied by asking the physicians responsible for all 321 adult cases of the disease notified that year to complete a standardized questionnaire relating to drug treatment and bacteriology."	1.30	The management of pulmonary tuberculosis in adults notified in Scotland in 1993. ( Heald, SH; Leitch, AG; Simpson, AJ; Sudlow, MF; Watt, B, 1998)
"Pyrazinamide, which was re-administered last, induced a recurrence."	1.30	-Skin eruption after the first dose of antitubercular quadri-therapy: consideration of pyrazinamide-. ( Autret, E; Jonville-Béra, AP; Martel, C; Mazaud, S; Olivier, C; Radal, M, 1998)
"Out of 1128 new pulmonary tuberculosis patients, six-hundred twenty started treatment with six-month (2HRZS or E/4HRE) in Fukujuji Hospital, JATA, in Tokyo from January 1991 to December 1996."	1.30	[Six-months chemotherapy (2HRZS or E/4HRE) of new cases of pulmonary tuberculosis--six year experiences on its effectiveness, toxicity, and acceptability]. ( Ito, K; Mizutani, S; Ogata, H; Sugita, H; Wada, M; Yoshiyama, T, 1999)
"Seventy-seven patients had pulmonary tuberculosis, 23 extrapulmonary and three had both."	1.30	The spectrum of mycobacterial disease in a Dublin teaching hospital. ( McDonnell, T; O'Reilly, P, 1999)
"Isoniazid resistance was more likely in HIV seronegative patients with M."	1.30	Tuberculosis chemotherapy and sputum conversion among HIV-seropositive and HIV-seronegative patients in south-eastern Uganda. ( Borgdorff, MW; Bretzel, G; Bwire, R; Kawuma, HJ; Rieder, HL; Rüsch-Gerdes, S; Sticht-Groh, V, 1999)
"The frequency of chromosomal aberrations and sister-chromatid exchanges (SCEs) did not show any statistically significant differences in the patients before treatment and after exposure to combined HRZ therapy as compared to controls (p > 0."	1.29	Cytogenetic study of tuberculosis patients before and after tuberculostatic drug treatment. ( Ekmekçi, A; Sayli, A, 1995)
"Fourteen (30%) infants had extrapulmonary tuberculosis (11 central nervous system disease, 2 disseminated disease, and 1 cervical adenitis)."	1.29	Clinical features, diagnosis, and treatment of tuberculosis in infants. ( Ong, LT; Starke, JR; Vallejo, JG, 1994)
"There are few reports of children with AIDS and TB."	1.29	Clinical manifestation and outcome of tuberculosis in children with acquired immunodeficiency syndrome. ( Birnbaum, J; Chan, SP; Rao, M; Steiner, P, 1996)
"Patients with cavitating pulmonary tuberculosis continue to excrete viable tubercle bacilli for approximately 6 weeks despite supervised treatment."	1.29	The duration of excretion of viable bacilli in elderly patients on treatment for cavitating pulmonary tuberculosis. ( Morris, CD, 1996)
"They are enlarged in acute pulmonary tuberculosis."	1.29	Changes in the size of adrenal glands in acute pulmonary tuberculosis with therapy. ( Durak, AC; Gülmez, I; Keleştimur, F; Ozesmi, M, 1996)
"1,350 smear positive pulmonary tuberculosis cases in the ten research pilot counties of Liaoning province from 1992 to 1993 were selected to receive short-course intermittent chemotherapies under full-course supervision."	1.29	[Analysis of short-term effects of short-course intermittent chemotherapies of the World Bank Loaned Project]. ( Su, Y; Wen, S; Zhang, F, 1996)
"Twenty-nine patients with extensive pulmonary tuberculosis and drug-induced hepatitis were treated with ofloxacin along with other relatively non-hepatotoxic drugs, either during the interim phase to await recovery of liver function in some, or as definitive therapy as required by the compromised hepatic status of others."	1.28	Tolerance of ofloxacin in the treatment of pulmonary tuberculosis in presence of hepatic dysfunction. ( Kwan, SY; Lee, J; Wong, PC; Yew, WW, 1992)
"Patients with direct smear positive pulmonary tuberculosis were admitted to hospital during the initial phase of treatment for two months."	1.28	Fixed dose combination short course chemotherapy in the treatment of pulmonary tuberculosis. ( Abdi, A; Lema, E; Roscigno, G; Wolde, K, 1992)
"Pyrazinamide (PZN) was administered to 10 patients of pulmonary tuberculosis (for 7 consecutive days) each day after an overnight fast."	1.28	Effect of simultaneous isoniazid administration on pharmacokinetic parameters of pyrazinamide. ( Singhal, KC; Varshney, MK, 1991)
"Forty-one of our patients had pulmonary tuberculosis, 38 had extra pulmonary and in 61 it was disseminated."	1.28	AIDS and tuberculosis in Spain. A report of 140 cases. ( Adrados, M; Díaz, F; García Aguado, C; González Lahoz, JM; Laguna, F; Martínez, R; Puente, S, 1991)
"Seven patients received no treatment because tuberculosis was first diagnosed after death."	1.28	Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection. ( Chaisson, RE; Goodman, PC; Hopewell, PC; Sande, MA; Schecter, GF; Small, PM, 1991)
"Pyrazinamide was prescribed to 80%, which represents a substantial increase on the 19% recorded in a similar survey of patients notified in 1983."	1.28	The management of pulmonary tuberculosis in adults notified in England and Wales in 1988. The British Thoracic Society Research Committee and the Medical Research Council Cardiothoracic Epidemiology Group. ( , 1991)
"0, 12 experimental groups, each containing 10 mice, were treated for 8 weeks with pyrazinamide (PZA) given in mean daily dosages of 100, 200 or 400 mg/kg/day, with the interval between the doses within each dosage group being 1, 2, 4 or 8 days."	1.28	Efficacy of intermittent pyrazinamide in experimental murine tuberculosis. ( Dickinson, JM; Mitchison, DA, 1991)
" Elderly patients are more sensitive to antituberculous (anti-TB) drugs; therefore, a modification in the dosage for this patient group should be considered."	1.28	The disposition of antituberculous drugs in plasma of elderly patients. II. Isoniazid, rifampicin and pyrazinamide. ( Chan, HS; Chan, K; Walubo, A; Wong, CL; Woo, J, 1991)
"In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A)."	1.28	Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population. ( Kusema, T; Mhonda, M; Neill, P; Nhachi, CF; Pringle, D, 1990)
"No relapse was noted among patients with extrapulmonary tuberculosis."	1.28	[Treatment of tuberculosis. Drug combinations, therapeutic problems and results in a 10-year case load]. ( Morland, L, 1990)
"We investigated the pharmacokinetic interaction of RMP (administered from the first day of treatment onwards), PZA (given from the second day onwards), and INH (day 17 onwards) in ten, previously untreated patients with pulmonary tuberculosis (five slow acetylators and five fast acetylators)."	1.28	[Clinico-pharmacokinetic interactions of rifampicin, pyrazinamide and isoniazide]. ( Loos, U; Musch, E; Schwabe, HK, 1990)
"Pyrazinamide therapy has been associated with dose-dependent hepatotoxicity, hyperuricaemia, arthralgia and arthritis."	1.28	Tubulointerstitial nephritis associated with pyrazinamide. ( Kauffmann, RH; Sanwikarja, S; Serlie, J; te Velde, J, 1989)
"The good results gotten employing short-term (6 months) medication regimes with rifampin, isoniazid and an initial supplement (2 months) of streptomycin and pyrazinamide, gave an impulse to pharmacodynamic research."	1.27	[Pharmacokinetics of antitubercular agents in man]. ( Acocella, G, 1984)
" The therapeutic advantage of using these two drugs in combination should be more readily appreciated."	1.27	A comparative evaluation of drug combinations used in the treatment of pulmonary tuberculosis. ( Miller, SD, 1983)
" Bioavailability of pyrazinamide was only slightly increased in patients, its dialysis extraction coefficient being 55."	1.27	Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure. ( Farinotti, R; Fessi, H; Kenouch, S; Méry, JP; Montes, C; Stamatakis, G; Trouvin, JH, 1988)
"Due to these findings systemic lupus erythematosus (SLE) was suspected."	1.27	[Tuberculostatics-induced systemic lupus erythematosus]. ( Engelhard, M; Layer, P, 1986)
" Minor adverse reactions occurred with similar frequencies during daily (5%) and intermittent (5%) treatment but in no case was modification of rifampicin dosage required."	1.27	Safety of thrice-weekly rifampicin for tuberculosis in South-East Asian refugees. ( McKenzie, DK; Mukerjee, CM, 1985)
"The adverse effects of drugs which caused changes in therapeutic regimens have been studied in 511 patients with pulmonary tuberculosis, at the Pavilion Koch of Buenos Aires University."	1.26	Adverse effects of antituberculosis drugs causing changes in treatment. ( Dambrosi, A; Dambrosi, VM; Gonzalez Montaner, LJ; Manassero, M, 1982)
"Pyrazinamide was found to be capable of significantly inducing amino-levulinic acid synthetase activity; the other antituberculous drugs caused either slight or no induction of amino-levulinic acid synthetase."	1.26	Exacerbation of porphyria during treatment of pulmonary tuberculosis. ( Magnussen, CR; Patterson, JR; Treece, GL; Tschudy, DP, 1976)

Research

Studies (1,055)

Authors

Clinical Trials (47)

Trial Overview

Trial Outcomes

Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).

Timeframe	Studies, this research(%)	All Research%
pre-1990	481 (45.59)	18.7374
1990's	168 (15.92)	18.2507
2000's	165 (15.64)	29.6817
2010's	208 (19.72)	24.3611
2020's	33 (3.13)	2.80

Authors	Studies
Ibrahim, M	2
Andries, K	3
Lounis, N	2
Chauffour, A	1
Truffot-Pernot, C	3
Jarlier, V	2
Veziris, N	2
Ruslami, R	5
Nijland, HM	2
Alisjahbana, B	2
Parwati, I	1
van Crevel, R	5
Aarnoutse, RE	7
Hoff, DR	1
Caraway, ML	2
Brooks, EJ	1
Driver, ER	1
Ryan, GJ	1
Peloquin, CA	13
Orme, IM	3
Basaraba, RJ	2
Lenaerts, AJ	3
Adhiarta, IG	1
Kariadi, SH	1
Rullas, J	1
García, JI	1
Beltrán, M	1
Cardona, PJ	1
Cáceres, N	1
García-Bustos, JF	1
Angulo-Barturen, I	1
Shaikh, A	1
Sriraman, K	1
Vaswani, S	1
Oswal, V	1
Rao, S	1
Mistry, N	1
Kim, JS	2
Kim, YH	3
Lee, SH	4
Kim, JW	1
Kang, JY	1
Kim, SK	1
Kim, SJ	7
Kang, YS	1
Kim, TH	1
Mok, J	3
Byun, MK	1
Park, HJ	1
Joh, JS	2
Park, YB	1
Lim, HS	1
Choi, H	1
Kim, H	4
Yang, J	1
Shen, X	2
Alsultan, A	2
Cho, I	1
Geiter, L	2
Shim, TS	3
Carr, W	1
Kurbatova, E	1
Starks, A	1
Goswami, N	1
Allen, L	1
Winston, C	1
McCallum, AD	1
Pertinez, HE	1
Chirambo, AP	1
Sheha, I	1
Chasweka, M	1
Malamba, R	1
Shani, D	1
Chitani, A	1
Mallewa, JE	1
Meghji, JZ	1
Ghany, JF	1
Corbett, EL	1
Gordon, SB	1
Davies, GR	3
Khoo, SH	2
Sloan, DJ	1
Mwandumba, HC	1
Lopez-Varela, E	1
Abulfathi, AA	1
Strydom, N	2
Goussard, P	1
van Wyk, AC	1
Demers, AM	1
Deventer, AV	1
Garcia-Prats, AJ	2
van der Merwe, J	1
Zimmerman, M	2
Carter, CL	1
Janson, J	1
Morrison, J	1
Reuter, H	1
Decloedt, EH	1
Seddon, JA	2
Svensson, EM	1
Warren, R	1
Savic, RM	3
Dartois, V	5
Hesseling, AC	4
Heysell, SK	3
Mpagama, SG	4
Ogarkov, OB	1
Conaway, M	1
Ahmed, S	1
Zhdanova, S	1
Pholwat, S	1
Alshaer, MH	1
Chongolo, AM	1
Mujaga, B	1
Sariko, M	1
Saba, S	1
Rahman, SMM	1
Uddin, MKM	1
Suzdalnitsky, A	1
Moiseeva, E	1
Zorkaltseva, E	1
Koshcheyev, M	1
Vitko, S	1
Mmbaga, BT	1
Kibiki, GS	8
Pasipanodya, JG	4
Banu, S	1
Houpt, ER	2
Kwak, N	2
Jeon, D	2
Park, Y	1
Kang, YA	2
Kim, KJ	1
Kim, YR	2
Kwon, BS	1
Kwon, YS	1
Kim, HJ	2
Lee, JH	5
Lee, JY	4
Lee, JK	3
Cheon, M	1
Park, J	1
Hahn, S	3
Yim, JJ	3
Lyons, MA	1
Dooley, KE	5
Hendricks, B	3
Gupte, N	5
Barnes, G	3
Narunsky, K	8
Whitelaw, C	3
Smit, T	3
Ignatius, EH	4
Friedman, A	3
Dorman, SE	5
Dawson, R	13
Paton, NI	1
Cousins, C	1
Suresh, C	1
Burhan, E	3
Chew, KL	1
Dalay, VB	1
Lu, Q	1
Kusmiati, T	1
Balanag, VM	1
Lee, SL	1
Pokharkar, Y	1
Djaharuddin, I	1
Sugiri, JJR	1
Veto, RS	1
Sekaggya-Wiltshire, C	2
Avihingsanon, A	1
Sarin, R	1
Papineni, P	1
Nunn, AJ	13
Crook, AM	3
Tweed, CD	1
Diacon, AH	9
McHugh, TD	6
Mendel, CM	6
Meredith, SK	3
Mohapi, L	1
Murphy, ME	1
Phillips, PPJ	3
Singh, KP	1
Spigelman, M	2
Gillespie, SH	9
Esmail, H	1
Lipman, MC	2
Nunn, A	2
Walker, TM	1
Mtabho, CM	4
Semvua, HH	5
van den Boogaard, J	4
Irongo, CF	1
Boeree, MJ	6
Colbers, A	3
Burger, DM	2
van der Ven, AJAM	1
Tostmann, A	2
Peetluk, LS	1
Rebeiro, PF	1
Cordeiro-Santos, M	1
Kritski, A	1
Andrade, BB	2
Durovni, B	2
Calvacante, S	1
Arriaga, MB	1
Turner, MM	1
Figueiredo, MC	1
Rolla, VC	1
Sterling, TR	1
McKenna, L	1
Furin, J	1
Filipenko, ML	1
Dymova, MA	1
Cherednichenko, AG	1
Khrapov, EA	1
Mishukova, OV	1
Schwartz, YS	1
De Jager, VR	2
Vanker, N	2
Burger, DA	2
Everitt, D	3
Pappas, F	2
Nedelman, J	1
Genestet, C	1
Hodille, E	1
Berland, JL	1
Ginevra, C	1
Bryant, JE	1
Ader, F	1
Lina, G	1
Dumitrescu, O	1
Cho, HJ	1
Lim, YJ	1
Kim, J	3
Koh, WJ	3
Song, CH	1
Kang, MW	1
Decroo, T	1
de Jong, BC	5
Piubello, A	1
Lynen, L	1
Van Deun, A	2
Rahimi, BA	1
Rahimy, N	1
Ahmadi, Q	1
Hayat, MS	1
Wasiq, AW	1
van Niekerk, C	4
Hutchings, J	1
van der Merwe, L	1
Choi, J	1
Nam, K	1
Huynh, J	1
Thwaites, G	1
Marais, BJ	1
Schaaf, HS	5
Manyazewal, T	1
Woldeamanuel, Y	1
Holland, DP	1
Fekadu, A	1
Blumberg, HM	1
Marconi, VC	1
Naluyange, R	1
Mboowa, G	1
Komakech, K	1
Semugenze, D	1
Kateete, DP	1
Ssengooba, W	1
Dean, P	1
Berger, T	1
Matt, M	1
Schlaudecker, E	1
Riney, L	1
Velásquez-Rimachi, V	1
Orellana-Tovar, I	1
Rodriguez-López, E	1
López-Saavedra, A	1
Esteban-Arias, D	1
Pacheco-Barrios, K	1
Metcalf, T	1
Alva-Diaz, C	1
Saroha, D	1
Garg, D	1
Singh, AK	1
Dhamija, RK	1
E R, V	1
Parrikar, A	1
Keny, S	1
Lawande, D	1
Swindells, S	1
Zheng, X	3
Bao, Z	1
Forsman, LD	2
Hu, Y	4
Ren, W	1
Gao, Y	1
Li, X	3
Hoffner, S	4
Bruchfeld, J	1
Alffenaar, JW	2
Wang, J	4
Du, Y	1
Guo, R	1
Han, X	1
Wang, Q	4
Pang, Y	1
Chu, N	2
Fernandez Do Porto, DA	1
Monteserin, J	1
Campos, J	1
Sosa, EJ	1
Matteo, M	1
Serral, F	1
Yokobori, N	1
Benevento, AF	1
Poklepovich, T	1
Pardo, A	1
Wainmayer, I	1
Simboli, N	1
Castello, F	1
Paul, R	2
Martí, M	1
López, B	1
Turjanski, A	1
Ritacco, V	1
Xu, X	1
Hu, X	1
Hase, I	1
Toren, KG	1
Hirano, H	1
Sakurai, K	1
Horne, DJ	2
Saito, T	1
Narita, M	3
Laohapojanart, N	1
Ratanajamit, C	1
Kawkitinarong, K	1
Srichana, T	1
Chiwala, G	1
Liu, Z	1
Mugweru, JN	1
Wang, B	1
Khan, SA	1
Bate, PNN	1
Yusuf, B	1
Hameed, HMA	1
Fang, C	1
Tan, Y	1
Guan, P	1
Hu, J	1
Tan, S	2
Liu, J	1
Zhong, N	1
Zhang, T	1
Wang, Y	4
Xiang, X	1
Wu, SQ	3
Chen, G	2
Zhang, MM	3
Wang, MG	1
Wang, FJ	1
Sandford, AJ	2
He, JQ	3
Dutta, NK	3
Pinn, ML	4
Karakousis, PC	5
Driesen, M	2
Kondo, Y	1
Torrea, G	2
Asnong, S	1
Desmaretz, C	1
Mostofa, KSM	1
Tahseen, S	2
Whitfield, MG	1
Cirillo, DM	2
Miotto, P	1
Cabibbe, AM	2
Rigouts, L	5
Omonge, E	1
Otieno, F	1
Kubo, M	1
Shiruli, B	1
Chirehwa, MT	1
McIlleron, H	13
Rustomjee, R	4
Mthiyane, T	3
Onyebujoh, P	1
Smith, P	4
Denti, P	7
de Knegt, GJ	2
Dickinson, L	1
Pertinez, H	2
Evangelopoulos, D	2
Bakker-Woudenberg, IAJM	1
de Steenwinkel, JEM	2
Li, SY	3
Tasneen, R	6
Tyagi, S	7
Soni, H	1
Converse, PJ	3
Mdluli, K	1
Nuermberger, EL	6
Namasivayam, S	1
Maiga, M	2
Yuan, W	1
Thovarai, V	1
Costa, DL	1
Mittereder, LR	1
Wipperman, MF	1
Glickman, MS	1
Dzutsev, A	1
Trinchieri, G	1
Sher, A	1
Goel, N	1
Kumar, V	1
Arora, S	1
Ghosh, B	1
Indumati, V	1
Vijay, V	1
Krishnaswamy, D	1
Rajeshwari, V	1
Ramesh, A	1
Shantala, D	1
Shilpa, A	1
Mourik, BC	1
Verbon, A	1
Mouton, JW	1
Bax, HI	1
Calderón, RI	1
Velásquez, GE	1
Becerra, MC	2
Zhang, Z	3
Contreras, CC	1
Yataco, RM	1
Galea, JT	1
Lecca, LW	1
Kritski, AL	3
Murray, MB	1
Mitnick, CD	3
Reither, K	3
Haraka, F	1
Sumari-de Boer, IM	1
Magis-Escurra, C	2
Wattenberg, M	1
Logger, JGM	1
Te Brake, LHM	1
Hoelscher, M	3
Plemper van Balen, G	2
Díaz, A	1
Bongiovanni, B	1
D'Attilio, L	1
Santucci, N	1
Dídoli, G	1
Fernández, RDV	1
Kovalevski, L	1
Lioi, S	1
Gardeñez, W	1
Brandan, N	1
Nannini, LJ	1
Besedovsky, H	1
Del Rey, A	1
Bottasso, O	1
Bay, ML	1
Castelnuovo, B	1
von Braun, A	1
Musaazi, J	1
Muller, D	1
Buzibye, A	1
Gutteck, U	1
Henning, L	1
Ledergerber, B	1
Corti, N	1
Lamorde, M	1
Fehr, J	1
Kambugu, A	1
Feng, M	1
Wu, JC	2
Ji, GY	2
Liu, QQ	2
Park, S	1
Jo, KW	2
Lee, SD	1
Kim, WS	1
Xu, L	1
Chen, J	2
Innes, AL	1
Li, L	2
Chiang, CY	3
Ngabonziza, JCS	1
Diallo, AB	1
Tagliani, E	1
Diarra, B	1
Kadanga, AE	1
Togo, ACG	1
Thiam, A	1
de Rijk, WB	1
Alagna, R	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
2R2: Higher Dose Rifampin for 2 Months vs Standard Dose Rifampin for Latent TB: a 3-arm Randomized Trial.[NCT03988933]	Phase 2	1,368 participants (Actual)	Interventional	2019-09-20	Active, not recruiting
Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.[NCT00760149]	Phase 2	150 participants (Actual)	Interventional	2010-07-31	Completed
A Prospective, Randomized, Open, Active-controlled, Interventional, Exploratory, Phase II Trial to Evaluate the EBA, Safety and PK of Orally Administered LCB01-0371 in Adult Patients With Smear-positive Pulmonary Tuberculosis[NCT02836483]	Phase 2	79 participants (Actual)	Interventional	2016-12-10	Completed
Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin to 3 Months After Culture Conversion (Hi-DoRi-3): A Phase 3, Multicenter, Randomized, Open-label, Clinical Trial[NCT04485156]	Phase 3	926 participants (Anticipated)	Interventional	2020-09-30	Not yet recruiting
A Phase 2 Dose-ranging Trial to Evaluate the Bactericidal Activity, Safety, Tolerability and Pharmacokinetics of Linezolid in Adult Subjects With Newly Diagnosed Drug-Sensitive, Smear-Positive Pulmonary Tuberculosis.[NCT02279875]	Phase 2	113 participants (Actual)	Interventional	2014-11-30	Completed
Electronic Pillbox-enabled Self-administered Therapy Versus Standard Directly Observed Therapy for Tuberculosis Medication Adherence and Treatment Outcomes in Ethiopia: a Multicenter Randomized Controlled Trial[NCT04216420]		114 participants (Actual)	Interventional	2020-06-01	Completed
Evaluation of the Pharmacokinetics of Antituberculosis Drugs and Tuberculosis Treatment Outcomes in HIV-tuberculosis Co-infected Ugandan Adults[NCT01782950]	Phase 4	400 participants (Anticipated)	Interventional	2013-02-28	Recruiting
Substitution of Ethambutol With Linezolid During the Intensive Phase of Treatment of Pulmonary Tuberculosis: A Prospective, Multicenter, Randomized, Open-label Phase II Trial[NCT01994460]	Phase 2	429 participants (Anticipated)	Interventional	2014-01-31	Recruiting
A Randomised Open-Label Controlled Trial of a 4-Month Gatifloxacin-Containing Regimen Versus Standard Regimen for the Treatment of Adult Patients With Pulmonary Tuberculosis[NCT00216385]	Phase 3	2,070 participants	Interventional	2005-01-31	Recruiting
Delamanid, Linezolid, Levofloxacin, and Pyrazinamide for the Treatment of Patients With Fluoroquinolone-sensitive MDR-TB: A Phase 2/3, Multicenter, Randomized, Open-label, Clinical Trial[NCT02619994]	Phase 2	238 participants (Anticipated)	Interventional	2016-01-31	Recruiting
A Prospective, Randomized Open-Label Phase II Study of the Safety and Tolerability of Metformin in Combination With Standard Antimicrobial Treatment of Pulmonary Tuberculosis in People With TB and Co-infected With HIV[NCT04930744]	Phase 2	112 participants (Anticipated)	Interventional	2021-08-03	Recruiting
Metformin as Adjunctive Therapy in Overweight and Obese Patients With Dengue: an Open-label Safety and Tolerability Trial[NCT04377451]	Phase 1/Phase 2	120 participants (Actual)	Interventional	2020-07-27	Completed
Pharmacokinetics of Standard First and Second Line Anti-TB Drugs in the Lung and Lesions of Subjects Elected for Resection Surgery[NCT00816426]	Phase 1	19 participants (Actual)	Interventional	2008-12-29	Completed
A Phase II Trial to Describe the Pharmacokinetics, Safety and Efficacy of Pharmacogenetics-guided Dosing of Isoniazid in Patients With HIV-associated TB[NCT05124678]	Phase 2	40 participants (Anticipated)	Interventional	2021-12-07	Recruiting
A Randomized, Four-arm Open Label Phase Two-b Clinical Trial to Evaluate the Pharmacokinetics, Safety/Tolerability and Efficacy of High Dose Rifampicin in TB-HIV Co-infected Patients on Efavirenz- or Dolutegravir-based Antiretroviral Therapy[NCT03982277]	Phase 2	130 participants (Actual)	Interventional	2019-04-30	Completed
Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis[NCT03827811]		625 participants (Anticipated)	Observational	2020-01-30	Recruiting
A Randomized Clinical Trial of Early Empiric Anti-Mycobacterium Tuberculosis Therapy for Sepsis in Sub-Saharan Africa[NCT04618198]	Phase 3	436 participants (Anticipated)	Interventional	2021-12-10	Recruiting
A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening[NCT00864383]	Phase 3	1,931 participants (Actual)	Interventional	2008-01-31	Completed
Using Biomarkers to Predict TB Treatment Duration[NCT02821832]	Phase 2	946 participants (Actual)	Interventional	2017-06-21	Active, not recruiting
A Prospective, Randomized Controlled Study for the Efficacy and Safety of the Substitution of Pyrazinamide and Ethambutol With Moxifloxacin During the Intensive Phase of Treatment of Pulmonary Tuberculosis[NCT04187469]		286 participants (Anticipated)	Interventional	2020-03-01	Not yet recruiting
Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4][NCT05169554]	Phase 2	140 participants (Anticipated)	Interventional	2021-12-01	Recruiting
A Pragmatic Trial With Optimized Dose of Rifampicin and Moxifloxacin for the Treatment of Drug Susceptible Pulmonary Tuberculosis[NCT05575518]	Phase 3	414 participants (Anticipated)	Interventional	2023-08-11	Recruiting
Rifampin to Reduce Elevated Levels of Blood and Urine Calcium in Patients With Idiopathic Infantile Hypercalcemia[NCT03384121]	Phase 1	5 participants (Anticipated)	Interventional	2018-02-22	Recruiting
A Phase IIA Dose Ranging Trial to Evaluate the Safety, Tolerability, Extended Early Bactericidal Activity and Pharmacokinetics of Higher Doses of Rifampicin in Adult Subjects With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis[NCT01392911]	Phase 2	128 participants (Anticipated)	Interventional	2011-06-30	Completed
A Phase II Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 8 Weeks of Treatment in Adult Patients With Newly Diagnosed Drug-Sensitive or Multi D[NCT01498419]	Phase 2	207 participants (Actual)	Interventional	2012-03-31	Completed
Pharmacokinetics of Rifabutin Combined With Antiretroviral Therapy in the Treatment of Tuberculosis Patient With HIV Infection in South Africa: A Phase II Trial[NCT00640887]	Phase 2	48 participants (Anticipated)	Interventional	2009-02-28	Completed
Optimal Dosing of 1st Line Antituberculosis and Antiretroviral Drugs in Children (a Pharmacokinetic Study)[NCT01637558]	Phase 4	200 participants (Actual)	Interventional	2012-11-30	Completed
A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis[NCT00728507]	Phase 2	121 participants (Actual)	Interventional	2009-11-30	Terminated (stopped due to Funding withdrawn)
A Multiple Arm, Multiple Stage, Phase 2, OL, Randomized, Controlled Trial to Evaluate 4 Treatment Regimens of SQ109, Increased Doses of Rifampicin, and Moxifloxacin in Adults With Newly Diagnosed, Smear-positive Pulmonary Tuberculosis[NCT01785186]	Phase 2	365 participants (Actual)	Interventional	2013-04-30	Completed
A Pharmacokinetics Study Comparing Lopinavir Plasma Exposure When Given as Lopinavir/Ritonavir (1:1) in the Presence of Rifampicin and Lopinavir/Ritonavir (4:1) Without Rifampicin in HIV and TB Co-infected Children in South Africa.[NCT02348177]	Phase 4	96 participants (Actual)	Interventional	2013-01-31	Completed
TBTC Study 31 PK/PD: Population Pharmacokinetic and Pharmacodynamic Study of Efficacy and Safety of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis in the Study 31 Treatment Trial: Intensive PK Sampling[NCT02563327]	Phase 3	60 participants (Anticipated)	Interventional	2016-05-30	Recruiting
Phase 2 Randomized Trial of a Moxifloxacin-Containing Regimen For Treatment of Smear-Positive Pulmonary Tuberculosis in Adults With and Without HIV Infection[NCT00082173]	Phase 2	170 participants (Actual)	Interventional	2004-10-31	Completed
DNA Sequencing of MDR TB in Eastern Siberia[NCT02508610]		630 participants (Anticipated)	Observational	2013-11-30	Recruiting
A Prospective Study of Shortening the Duration of Standard Short Course Chemotherapy From 6 Months to 4 Months in HIV-non-infected Patients With Fully Drug-Susceptible, Non-cavitary Pulmonary Tuberculosis With Negative Sputum Cultures After 2 Months of An[NCT00130247]	Phase 3	394 participants (Actual)	Interventional	2002-04-08	Completed
Prophylactic Use of Entecavir to Reduce Hepatitis Flare in Highly Viremic HBV Patients With Active Tuberculosis Receiving Anti-tuberculous Treatment[NCT01724723]	Phase 4	50 participants (Anticipated)	Interventional	2012-12-31	Not yet recruiting
International Multicenter Trial for the Evaluation of a Four-Drug Fixed Dose Combined Tablet Daily in the Initial Intensive Phase of Chemotherapy Followed by a Two-Drug Fixed Dose Combined Tablet Three Times a Week in the Continuation Phase for the Treatm[NCT00216333]	Phase 4	1,500 participants	Interventional	2003-12-31	Recruiting
A Phase II Dose Ranging Trial to Evaluate the Extended Early Bactericidal Activity, Safety, Tolerability, and Pharmacokinetics of PA-824 in Adult Participants With Newly Diagnosed, Uncomplicated, Smear-Positive, Pulmonary Tuberculosis[NCT00944021]	Phase 2	69 participants (Actual)	Interventional	2009-08-31	Completed
Early Bactericidal Activity of Standard Drugs Used to Treat Mycobacterium Avium Complex: a Pilot Study[NCT04287049]	Phase 2	30 participants (Anticipated)	Interventional	2020-02-24	Recruiting
A Phase II Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of the Following: TMC207 Alone, TMC207 Plus Pyrazinamide,TMC207 Plus PA-824,PA-824 Plus Pyrazinamide and PA-824 Plus Pyrazinamide and Moxifloxacin, in Adult Patients Wit[NCT01215851]	Phase 2	85 participants (Actual)	Interventional	2010-10-31	Completed
NexGen EBA Radiologic and Immunologic Biomarkers of Sterilizing Drug Activity in Tuberculosis[NCT02371681]	Phase 2	262 participants (Actual)	Interventional	2015-02-25	Completed
A Phase 2 Randomized, Open-label Trial of Daily Rifapentine 450mg or 600mg in Place of Rifampicin 600mg for Intensive Phase Treatment of Smear-positive Pulmonary Tuberculosis[NCT00814671]	Phase 2	153 participants (Actual)	Interventional	2010-04-30	Completed
Randomized Clinical Trial to Assess the Efficacy of Short Course Intermittent Regimens for the Treatment of HIV-Associated Tuberculosis[NCT00376012]	Phase 3	300 participants (Actual)	Interventional	2001-02-28	Active, not recruiting
Evaluation of Two Different Preventive Therapy Regimens for Tuberculosis in HIV Infected Persons[NCT00351702]	Phase 3	650 participants (Actual)	Interventional	2001-02-28	Completed
URBAN ARCH (3/5) Uganda Cohort TB Preventive Therapy for HIV-infected Alcohol Users in Uganda: an Evaluation of Safety Tolerability and Adherence[NCT03302299]	Phase 4	302 participants (Actual)	Interventional	2017-04-07	Completed
TB Treatment Support Tools: Refinement and Evaluation of an Interactive Mobile App and Direct Adherence Monitoring on TB Treatment Outcomes[NCT04221789]		555 participants (Actual)	Interventional	2020-11-17	Active, not recruiting
The Treatment of Pulmonary Mycobacterium Tuberculosis in HIV Infection[NCT00001033]	Phase 3	650 participants	Interventional		Completed
Efficacy of Simultaneous Versus Sequential Antiretroviral Therapy and Antituberculosis Treatment in Patients With AIDS and Active Tuberculosis. Open, Randomized and Controlled, Multisite Clinical Trial.[NCT00737724]		63 participants (Actual)	Interventional	2008-03-31	Terminated (stopped due to Other published trials showed definitive expected superiority of Group 1)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. (NCT00864383)
Timeframe: 18 months (within one year of completion of therapy)

Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).

Intervention	participants with failure or relapse (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	65
Regimen 2 - 2MHRZ/2MHR	98
Regimen 3 - 2EMRZ/2MR	131

The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results. (NCT00864383)
Timeframe: 18 months (within one year of completion of therapy)

Number of Patients Who Are Culture Negative (Liquid MGIT Culture)

Intervention	participants with failure or relapse (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	43
Regimen 2 - 2MHRZ/2MHR	78
Regimen 3 - 2EMRZ/2MR	105

Number of patients who are TB MGIT culture negative at 8 weeks. (NCT00864383)
Timeframe: 8 weeks

Number of Patients Who Are Culture Negative (Solid LJ Culture)

Intervention	participants who are culture negative (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	235
Regimen 2 - 2MHRZ/2MHR	274
Regimen 3 - 2EMRZ/2MR	260

Number of patients who are TB LJ culture negative at 8 weeks. (NCT00864383)
Timeframe: 8 weeks

Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting)

Intervention	participants who are culture negative (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	352
Regimen 2 - 2MHRZ/2MHR	394
Regimen 3 - 2EMRZ/2MR	401

The number of participants includes all patients who had at least one grade 3 or 4 adverse event. (NCT00864383)
Timeframe: 18 months (within one year of completion of therapy)

Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.

Intervention	participants with Grade 3 or 4 AEs (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	123
Regimen 2 - 2MHRZ/2MHR	127
Regimen 3 - 2EMRZ/2MR	111

"Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result (isolated positive culture) was followed by at least two negative culture results." (NCT00864383)
Timeframe: 18 months

Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.

Intervention	participants with unfavorable outcome (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	87
Regimen 2 - 2MHRZ/2MHR	132
Regimen 3 - 2EMRZ/2MR	132

"Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result (isolated positive culture) was followed by at least two negative culture results." (NCT00864383)
Timeframe: 18 months

Time to First Culture Negative Sputum Sample (LJ Solid Media)

Time to First Culture Negative Sputum Sample (MGIT Liquid Media)

Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C

Intervention	participants with unfavorable outcome (Number)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	172
Regimen 2 - 2MHRZ/2MHR	219
Regimen 3 - 2EMRZ/2MR	217

Intervention	Time to culture negative status / weeks (Median)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	6.0
Regimen 2 - 2MHRZ/2MHR	6.0
Regimen 3 - 2EMRZ/2MR	6.0

Intervention	Time to culture negative status / weeks (Median)
Regimen 1 - 2EHRZ/4HR (Control Regimen)	11.9
Regimen 2 - 2MHRZ/2MHR	8.0
Regimen 3 - 2EMRZ/2MR	8.0

Estimation of the lower bound of a one-sided 95% confidence interval of the difference in success rates between arms B and C. If the lower bound is greater than -7%, this will be evidence that the treatment-shortening arm is not inferior to the standard duration arm. (NCT02821832)
Timeframe: 18 months

Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.

Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media

Intervention	Participants (Count of Participants)
	Cured	Confirmed relapses	Late withdrawal, lost to follow-up	Probable relapses	Treatment Failure
Arm A	217	5	13	1	1
Arm B	121	1	9	1	0
Arm C	117	9	6	3	4

Intervention	percentage of participants (Number)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	13
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	19
Drug Sensitive: Rifafour	12
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	12

Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. This was measured at visit 24(Day 57). (NCT01498419)
Timeframe: Day 57 after eight weeks of daily treatment

Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media

Intervention	percentage of patients (Number)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	65.7
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	71.4
Drug Sensitive: Rifafour	37.8
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	50.0

Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. (Day 57) (NCT01498419)
Timeframe: Day 57 after eight weeks of daily treatment

The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment.

Intervention	percentage of participants (Number)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	82.9
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	94.3
Drug Sensitive: Rifafour	87.5
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	62.5

The primary efficacy endpoint was bactericidal activity characterized by the daily rate of change in mean log10CFU counts during 8 weeks of treatment (bactericidal activity assessed by CFU on solid media for days 0-56). (NCT01498419)
Timeframe: 8 weeks

The Rate of Change in Time to Sputum Culture Positivity (TTP) Through 8 Weeks in the MGIT System in Sputum Over 8 Weeks in Participants as Derived From a Non-linear Regression Model.

Intervention	log10CFU/ml/day (Mean)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	0.133
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	0.155
Drug Sensitive: Rifafour	0.112
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	0.117

Measurement of TTP in liquid culture media Mycobacteria growth indicator tube (MGIT) using standard procedures (NCT01498419)
Timeframe: 8 weeks

Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media

Intervention	log10hours/day (Mean)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	0.020
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	0.020
Drug Sensitive: Rifafour	0.017
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	0.015

liquid culture = Mycobacteria growth indicator tube (MGIT) Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB (NCT01498419)
Timeframe: 8 weeks

Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media

Intervention	days (Median)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	42.0
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	49.0
Drug Sensitive: Rifafour	56.0
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	56.0

To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.

Pharmacokinetics Including AUC, Cl, t1/2, Vd, and Protein Binding

Intervention	days (Median)
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)	28.0
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)	28.0
Drug Sensitive: Rifafour	35.0
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)	35.0

Intervention	percentage of participants (Number)
HPZM	78.3
HRZE	84.3

"Pharmacokinetic parameters will be assessed for rifampicin, moxifloxacin and SQ109:~area under the plasma concentration curve from dosing to the end of the dosing interval (AUC 0-24) (in h*ng/mL)~the observed maximum concentration (Cmax( (in ng/mL)~time to reach Cmax (Tmax)(in hours)~the minimum observed plasma concentration 24 hours following the last dose (Cmin) (in hours),~clearance (Cl) (in mL/minute),~volume of distribution (Vd) (in L),~elimination half-life (T1/2,) (in hours)~free (protein-unbound) fraction (for rifampicin only) (in percent)." (NCT01785186)
Timeframe: 0 - 12 weeks

Sputum Culture Conversion (2 Negative Cultures) Using Liquid Media

Intervention	Rifampicin AUC(mg*h/l) (Geometric Mean)
HRZQ	17.4
Arm 1 (R35)	170
HR20ZQ	68.3
HR20ZM	57.8
HRZE	24.2

From enrollment, the time to stable culture conversion (2 consecutive negative weekly cultures) in liquid media. (NCT01785186)
Timeframe: 0 - 12 weeks

Frequency of Adverse Events

Intervention	days (Median)
Arm 1 (R35)	48
HRZQ	63
HR20ZQ	66
HR20ZM	55
HRZE	62

All Adverse Events (AE), and AEs considered to be drug-related will coded using standard AE dictionaries. (NCT01785186)
Timeframe: 0 - 12 weeks

Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications

Intervention	participants (Number)
	Number of Patients with at least 1 AE	Number of patients with at least 1 SAE
Arm 1 (R35)	53	4
HR20ZM	49	4
HR20ZQ	42	5
HRZE	92	6
HRZQ	49	4

Proportion of patients with Grade 3 or 4 adverse reactions attributable to study medications (NCT00082173)
Timeframe: 8 weeks

Proportion of Patients With Sterile Sputum Cultures

Intervention	Participants (Number)
Experimental Arm	0
Control Arm	0

Proportion of patients with sterile sputum cultures (NCT00082173)
Timeframe: 8 weeks

Acquired Drug Resistance in Patients Who Relapsed

Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol

Intervention	Participants (Number)
Experimental Arm	59
Control Arm	45

Intervention	Participants (Number)
4-Month Arm	0
6-Month Arm	0

Patients who presented with TB after completion of study phase treatment but before the end of follow-up were classified as relapses. A bacteriologic relapse was defined as a patient who became consistently culture-positive [defined as at least 1 of the following]: (a) at least 1 sputum mycobacterial culture growing at least 10 colonies of MTB on solid medium; (b) 2 or more respiratory secretion cultures that are positive for MTB in liquid media; or (c) any culture from an extrapulmonary site that is positive for MTB during follow-up after successful completion of initial anti-TB treatment. (NCT00130247)
Timeframe: 30 months

Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat

Intervention	Participants (Number)
4-Month Arm	13
6-Month Arm	3

Relapses at 1 and 2 Years

Intervention	Participants (Number)
4-Month Arm	13
6-Month Arm	3

(NCT00130247)
Timeframe: 1 and 2 years after successful completion of initial anti-TB treatment

Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat

Intervention	Participants (Number)
	Relapses at 1 year	Relapses at 2 years
4-Month Arm	10	13
6-Month Arm	3	3

A culture-positive treatment failure was defined as initial culture conversion but subsequent reversion to culture positivity. A clinical treatment failure was defined as a patient with clinical and/or radiographic evidence of progressive tuberculosis not confirmed by a positive culture after 4 or more months of anti-TB treatment while still receiving treatment. Patients who defaulted before completing study treatment and returned later with culture-positive tuberculosis were termed failures after non-adherence. (NCT00130247)
Timeframe: 2 years

Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol

Intervention	Participants (Number)
	Treatment Failures	Relapses
4-Month Arm	0	13
6-Month Arm	0	3

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1).

Intervention	Participants (Number)
	Treatment Failures	Relapses
4-Month Arm	0	13
6-Month Arm	0	3

Intervention	log10CFU/ml/day (Mean)
PA-824 50 mg/qd	0.063
PA-824 100mg/qd	0.091
PA-824 150mg/qd	0.078
PA-824 200mg/qd	0.112
Rifafour e-275mg	0.177

Intervention	log10CFU/ml/day (Mean)
PA-824 50 mg/qd	0.093
PA-824 100mg/qd	0.111
PA-824 150mg/qd	-0.009
PA-824 200mg/qd	0.160
Rifafour e-275mg	0.470

Intervention	log10CFU/ml/day (Mean)
PA-824 50 mg/qd	0.059
PA-824 100mg/qd	0.088
PA-824 150mg/qd	0.096
PA-824 200mg/qd	0.104
Rifafour e-275mg	0.128

(NCT00944021)
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1).

Intervention	ng * hour/mL (Mean)
PA-824 50 mg/qd	11923.94
PA-824 100mg/qd	18408.59
PA-824 150mg/qd	28654.83
PA-824 200mg/qd	38485.04

(NCT00944021)
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1).

Intervention	ng/mL (Mean)
PA-824 50 mg/qd	465.3
PA-824 100mg/qd	662.3
PA-824 150mg/qd	994.7
PA-824 200mg/qd	1183.0

(NCT00944021)
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, and 24 hours post-dose on Day 1 of treatment

Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14).

Intervention	hours (Mean)
PA-824 50 mg/qd	16.142
PA-824 100mg/qd	18.597
PA-824 150mg/qd	19.005
PA-824 200mg/qd	21.092

(NCT00944021)
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 24 and 30 hours post-dose on Day 14 of 14 consecutive days of treatment

Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14).

Intervention	hour (Mean)
PA-824 50 mg/qd	18.645
PA-824 100mg/qd	19.274
PA-824 150mg/qd	20.207
PA-824 200mg/qd	23.811

(NCT00944021)
Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12,16, 24, and 30 hours post-dose on Day 14 of 14 consecutive days of treatment

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

Intervention	ng/mL (Mean)
PA-824 50 mg/qd	777.3
PA-824 100mg/qd	1116.5
PA-824 150mg/qd	1543.9
PA-824 200mg/qd	2223.8

Intervention	hours/day (Mean)
PA-824 50 mg/qd	2.621
PA-824 100mg/qd	4.969
PA-824 150mg/qd	4.633
PA-824 200mg/qd	4.640
Rifafour e-275mg	13.364

Intervention	hours/day (Mean)
PA-824 50 mg/qd	1.483
PA-824 100mg/qd	-1.345
PA-824 150mg/qd	4.867
PA-824 200mg/qd	3.096
Rifafour e-275mg	37.016

Intervention	hours/day (Mean)
PA-824 50 mg/qd	2.958
PA-824 100mg/qd	5.744
PA-824 150mg/qd	4.594
PA-824 200mg/qd	5.391
Rifafour e-275mg	9.422

Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline. (NCT01215851)
Timeframe: 14 consecutive days of treatment

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

Intervention	log10CFU/ml/day (Mean)
TMC207	0.061
TMC207 and Pyrazinamide	0.131
PA-824 and Pyrazinamide	0.154
PA-824 and Moxifloxacin and Pyrazinamide	0.233
Rifafour e-275 mg	0.140
TMC207 and PA-824	0.114

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

Intervention	log10CFU/ml/day (Mean)
TMC207	-0.022
TMC207 and Pyrazinamide	0.079
PA-824 and Pyrazinamide	0.170
PA-824 and Moxifloxacin and Pyrazinamide	0.315
Rifafour e-275 mg	0.177
TMC207 and PA-824	0.114

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).

Intervention	log10CFU/ml/day (Mean)
TMC207	0.076
TMC207 and Pyrazinamide	0.143
PA-824 and Pyrazinamide	0.148
PA-824 and Moxifloxacin and Pyrazinamide	0.222
Rifafour e-275 mg	0.135
TMC207 and PA-824	0.114

Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)

Intervention	log10CFU/ml/day (Mean)
TMC207	0.123
TMC207 and Pyrazinamide	0.152
PA-824 and Pyrazinamide	0.124
PA-824 and Moxifloxacin and Pyrazinamide	0.175
Rifafour e-275 mg	0.136
TMC207 and PA-824	0.114

The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (TTP versus Day). (NCT01215851)
Timeframe: 14 Days

Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8

Pharmacokinetics of Rifapentine

Intervention	time (h) to positive per day (Mean)
TMC207	5.414
TMC207 and Pyrazinamide	9.970
PA-824 and Pyrazinamide	8.805
PA-824 and Moxifloxacin and Pyrazinamide	18.482
Rifafour e-275 mg	11.841
TMC207 and PA-824	5.855

Intervention	percentage of participants w/LJ cx con (Number)
RPT450	85
RIF 600	94
RPT 600	96

area under the concentration time curve (AUC[0-24]) for rifapentine administered once daily at doses of 450 mg or 600 mg in the context of multi drug intensive phase TB treatment (NCT00814671)
Timeframe: 8 weeks

Time to Stable Culture Conversion on Liquid MGIT Media

Time (in days) to stable culture conversion on liquid MGIT media (NCT00814671)
Timeframe: 12 weeks

Time to Stable Culture Conversion on Solid Medium

Time to stable culture conversion (in days) on Lowenstein Jensen solid medium (NCT00814671)
Timeframe: 12 weeks

Tolerability

percentage of participants discontinuing assigned treatment (NCT00814671)
Timeframe: 10 weeks

Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity

Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period. (NCT03302299)
Timeframe: Hepatotoxicity occurring during the six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.

Number of Participants Who Discontinued Treatment

Lack of tolerability will be defined as any isoniazid (INH) treatment discontinuation prior to completion of the prescribed course (6 months of INH taken over a maximum period of 9 months) due to side effects or alanine transaminase (ALT)/aspartate transaminase (AST) elevations. (NCT03302299)
Timeframe: Six month course (180 pills) of isoniazid (INH), which may be taken over a maximum of 9 months.

Number of Participants With Alanine Transaminase (ALT) or Aspartate Transaminase (AST) Elevations at Study Screening

Alanine transaminase (ALT) or aspartate transaminase (AST) elevations (>2x the upper limit of normal) at study screening (NCT03302299)
Timeframe: Study screening visit

Number of Participants With Latent Tuberculosis at Study Screening.

Latent tuberculosis assessed at screening via tuberculin skin testing (TST). A TST induration >=5mm was considered positive for latent tuberculosis. (NCT03302299)
Timeframe: Study screening visit

INH Concentration in Hair: (INH Pmol + Acetyl INH Pmol) Per mg of Hair

INH concentration in hair (pmol/mg) will be measured at 3- and 6- months during INH therapy. (NCT03302299)
Timeframe: Measured at 3- and 6- months after INH initiation

Percentage of Participants With Suboptimal INH Medication Adherence

Suboptimal INH adherence was defined as <90% of days with at least 1 electronic medication management (EMM) pill cap opening in the previous 90 days, at 3- and 6-months. (NCT03302299)
Timeframe: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter)

Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days

"Participants were asked In the past 30 days, how many days in total have you not taken your pill? and were presented with a visual analog scale (VAS) to indicate the percentage of INH taken in the past 30 days. We converted the VAS percentage into number of days out of 30 to match the first question. Our final self-report measure was the minimum number of the 2 self-reported measurements." (NCT03302299)
Timeframe: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INH

Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale

The Self Rating Single Item (SRSI) adherence scale asks participants to rate their ability to take their medications as prescribed over the past 30 days. Participants reporting INH use in the prior 30 days at the 3- or 6-month interview are included here, and reported their INH adherence in the prior 30 days as excellent, very good, good, fair, poor, or very poor. (NCT03302299)
Timeframe: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INH

Intervention	ug x h/ml (Median)
Rifapentine 450 mg	330
Rifapentine 600 mg	435

Intervention	Participants (Count of Participants)
	At 3 months72558043						At 6 months72558043
	Excellent	Very good	Good	Fair	Poor	Very poor
INH and Vitamin B6	160
INH and Vitamin B6	79
INH and Vitamin B6	38
INH and Vitamin B6	2
INH and Vitamin B6	124
INH and Vitamin B6	90
INH and Vitamin B6	41
INH and Vitamin B6	4
INH and Vitamin B6	0
INH and Vitamin B6	1

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Tuberculosis treatment in children: The changing landscape. Paediatric respiratory reviews, 2020, Volume: 36 Topics: Antitubercular Agents; Child; Drug Therapy, Combination; Duration of Therapy; Ethambutol; Humans; Is	2020
Multiple tuberculomas in an immunocompetent patient and their diagnostic challenge in a high prevalence country: Case report and literature review. The Indian journal of tuberculosis, 2020, Volume: 67, Issue:3 Topics: Antitubercular Agents; Blindness; Brain; Brain Diseases; Cerebellar Ataxia; Dexamethasone; Drug Ther	2020
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The Biology and Epidemiology of Mycobacterium africanum. Advances in experimental medicine and biology, 2017, Volume: 1019 Topics: Africa, Western; Animals; Antitubercular Agents; Bacterial Typing Techniques; Genetic Variation; Gen	2017
Severe disseminated tuberculosis in HIV-negative refugees. The Lancet. Infectious diseases, 2019, Volume: 19, Issue:10 Topics: Adolescent; Adult; Antibiotics, Antitubercular; Ethambutol; Fluorine Radioisotopes; HIV Infections;	2019
PA-824 , moxifloxacin and pyrazinamide combination therapy for tuberculosis. Expert opinion on investigational drugs, 2013, Volume: 22, Issue:7 Topics: Animals; Antitubercular Agents; Aza Compounds; Clinical Trials as Topic; Drug Combinations; Drug Res	2013
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Newer and second-line drugs in the treatment of drug-resistant tuberculosis in children. The Medical clinics of North America, 1967, Volume: 51, Issue:5 Topics: Anti-Bacterial Agents; Antitubercular Agents; Child, Preschool; Cycloserine; Drug Resistance, Microb	1967
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Tuberculosis in Hong Kong ten years later. Tubercle, 1973, Volume: 54, Issue:3 Topics: Aminosalicylic Acids; BCG Vaccine; Child, Preschool; China; Cycloserine; Drug Resistance, Microbial;	1973
[Results of 2 or 3 secondary drug combinations in the retreatment of chronic pulmonary tuberculosis]. Revista clinica espanola, 1968, Apr-30, Volume: 109, Issue:2 Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; Cycloserine; Drug Synergism; Ethambutol;	1968
Chemotherapy of pulmonary tuberculosis. Annals of internal medicine, 1969, Volume: 70, Issue:2 Topics: Aminosalicylic Acids; Antitubercular Agents; Drug Resistance, Microbial; Ethambutol; Hospitalization	1969

Authors	Studies
Ibrahim, M	2
Andries, K	3
Lounis, N	2
Chauffour, A	1
Truffot-Pernot, C	3
Jarlier, V	2
Veziris, N	2
Ruslami, R	5
Nijland, HM	2
Alisjahbana, B	2
Parwati, I	1
van Crevel, R	5
Aarnoutse, RE	7
Hoff, DR	1
Caraway, ML	2
Brooks, EJ	1
Driver, ER	1
Ryan, GJ	1
Peloquin, CA	13
Orme, IM	3
Basaraba, RJ	2
Lenaerts, AJ	3
Adhiarta, IG	1
Kariadi, SH	1
Rullas, J	1
García, JI	1
Beltrán, M	1
Cardona, PJ	1
Cáceres, N	1
García-Bustos, JF	1
Angulo-Barturen, I	1
Shaikh, A	1
Sriraman, K	1
Vaswani, S	1
Oswal, V	1
Rao, S	1
Mistry, N	1
Kim, JS	2
Kim, YH	3
Lee, SH	4

pyrazinamide and Pulmonary Consumption

Research Excerpts

Research

Studies (1,055)

Authors

Clinical Trials (47)

Trial Overview

Trial Outcomes

Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).

Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).

Number of Patients Who Are Culture Negative (Liquid MGIT Culture)

Number of Patients Who Are Culture Negative (Solid LJ Culture)

Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting)

Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.

Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.

Time to First Culture Negative Sputum Sample (LJ Solid Media)

Time to First Culture Negative Sputum Sample (MGIT Liquid Media)

Comparison of the Rate of Treatment Success at 18 Months (After Treatment Initiation) Between Arms B and C

Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.

Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media

Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media

The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment.

The Rate of Change in Time to Sputum Culture Positivity (TTP) Through 8 Weeks in the MGIT System in Sputum Over 8 Weeks in Participants as Derived From a Non-linear Regression Model.

Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media

Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media

To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.

Pharmacokinetics Including AUC, Cl, t1/2, Vd, and Protein Binding

Sputum Culture Conversion (2 Negative Cultures) Using Liquid Media

Frequency of Adverse Events

Proportion of Patients With Grade 3 or 4 Adverse Reactions Attributable to Study Medications

Proportion of Patients With Sterile Sputum Cultures

Acquired Drug Resistance in Patients Who Relapsed

Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol

Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat

Relapses at 1 and 2 Years

Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat

Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Reduction of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

Pharmacokinetics- Area Under the Plasma Concentration Time Curve From Zero to Infinity (AUC 0 to Infinity) (Day 1).

Pharmacokinetics- Maximum Observed Plasma Concentration (Cmax) (Day 1).

Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 1).

Pharmacokinetics- Terminal Elimination Phase Half-life (t1/2) (Day 14).

Pharmacokinetics-Maximum Observed Plasma Concentration (Cmax) (Day 14).

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14).

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-2).

Rate of Change in Increased Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 2-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).

Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).

Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)

Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8

Pharmacokinetics of Rifapentine

Time to Stable Culture Conversion on Liquid MGIT Media

Time to Stable Culture Conversion on Solid Medium

Tolerability

Cumulative Incidence of Participants Experiencing a Grade 3/4 Hepatotoxicity

Number of Participants Who Discontinued Treatment

Number of Participants With Alanine Transaminase (ALT) or Aspartate Transaminase (AST) Elevations at Study Screening

Number of Participants With Latent Tuberculosis at Study Screening.

INH Concentration in Hair: (INH Pmol + Acetyl INH Pmol) Per mg of Hair

Percentage of Participants With Suboptimal INH Medication Adherence

Self-reported INH Medication Adherence: Number of Days Taking INH in the Past 30 Days

Self-reported INH Medication Adherence by the Self Rating Single Item (SRSI) Scale

Reviews

Trials

Other Studies