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https://www.readbyqxmd.com/read/28438933/pyrazinoic-acid-inhibits-a-bifunctional-enzyme-in-mycobacterium-tuberculosis
#1
Moses Njire, Na Wang, Bangxing Wang, Yaoju Tan, Xingshan Cai, Yanwen Liu, Julius Mugweru, Jintao Guo, H M Adnan Hameed, Shouyong Tan, Jianxiong Liu, Wing Wai Yew, Eric Nuermberger, Gyanu Lamichhane, Jinsong Liu, Tianyu Zhang
Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug by Mycobacterium tuberculosis into pyrazinoic acid (POA) has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report a new PZA resistance determinant: Asp67Asn substitution in Rv2783 confers M. tuberculosis resistance to PZA. Expression of the mutant but not the wild-type allele in M...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438924/analysis-of-the-effects-on-the-qt-interval-of-a-gatifloxacin-containing-regimen-versus-standard-treatment-of-pulmonary-tuberculosis
#2
Piero L Olliaro, Corinne Merle, Thuli Mthiyane, Boubacar Bah, Ferdinand Kassa, Evans Amukoye, Alimatou N' Diaye, Christian Perronne, Christian Lienhardt, Helen Mcilleron, Katherine Fielding
Background: The effects on ventricular repolarisation - recorded on the ECG as lengthening of the QT interval - of acute tuberculosis and those of standard and alternative anti-tuberculosis regimens are under-documented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero.Methods: ECGs were performed pre- and 1-5 hours post-dosing (month 1, 2, end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampicin and isoniazid for 6 months, pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampicin and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28427917/application-of-the-isoniazid-assay-in-dried-blood-spots-using-the-ultra-performance-liquid-chromatography-tandem-mass-spectrometry
#3
Kyunghoon Lee, Sun-Hee Jun, Moon-Suk Choi, Sang Hoon Song, Jong Sun Park, Jae Ho Lee, Kyoung Un Park, Junghan Song
OBJECTIVES: Therapeutic drug monitoring (TDM) of anti-tuberculosis (TB) drugs is important for proper treatment of TB. Dried blood spots (DBSs) are widely used for TDM because of their several advantages. Rifampicin and pyrazinamide assays with DBSs have already been developed. However, isoniazid (INH) assay for capillary DBSs have not been reported because of INH instability. We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measuring INH concentrations in venous and capillary DBSs...
April 17, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28425484/mycobacterium-tuberculosis-resistance-prediction-and-lineage-classification-from-genome-sequencing-comparison-of-automated-analysis-tools
#4
Viola Schleusener, Claudio U Köser, Patrick Beckert, Stefan Niemann, Silke Feuerriegel
Whole-genome sequencing (WGS) has the potential to accelerate drug-susceptibility testing (DST) to design appropriate regimens for drug-resistant tuberculosis (TB). Several recently developed automated software tools promise to standardize the analysis and interpretation of WGS data. We assessed five tools (CASTB, KvarQ, Mykrobe Predictor TB, PhyResSE, and TBProfiler) with regards to DST and phylogenetic lineage classification, which we compared with phenotypic DST, Sanger sequencing, and traditional typing results for a collection of 91 strains...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425350/metabolomics-approach-discriminates-toxicity-index-of-pyrazinamide-and-its-metabolic-products-pyrazinoic-acid-and-5-hydroxy-pyrazinoic-acid
#5
A Rawat, S Chaturvedi, A K Singh, A Guleria, D Dubey, A K Keshari, V Raj, A Rai, A Prakash, U Kumar, D Kumar, S Saha
Pyrazinamide (PYZ)-an essential component of primary drug regimen used for the treatment and management of multidrug resistant or latent tuberculosis-is well known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity is still unknown to researchers. Studies have shown that the drug is metabolized in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which individually may cause different degrees of hepatotoxicity. To evaluate this hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally (respectively, at 250, 125, and 125 mg kg(-1) for 28 days)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28411185/detection-of-pyrazinamide-resistance-of-mycobacterium-tuberculosis-using-nicotinamide-as-a-surrogate
#6
Yanjie Hu, Xiaoguang Wu, Jingjing Luo, Yuhong Fu, Liping Zhao, Yifeng Ma, Yunxu Li, Qian Liang, Yuanyuan Shang, Hairong Huang
OBJECTIVES: Despite the importance of pyrazinamide (PZA) in tuberculosis treatment, PZA susceptibility testing is not routinely performed because of acid pH requirement. The aim of our assay was to evaluate the Microplate Alamar Blue assay (MABA) to detect resistance to PZA using nicotinamide (NIC) as a surrogate in neutral pH, and identify the appropriate cutoff point for the assay. METHODS: The NIC minimal inhibition concentrations (MICs) for 125 Mycobacterium tuberculosis clinical isolates were tested by MABA at nine different concentrations (from 8 to 2000μg/ml)...
April 11, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28410699/anaphylaxis-to-rifampicin-and-pyrazinamide-in-a-child-with-tuberculous-meningitis-a-case-report
#7
Gulnaz Nadri, Sunil Taneja, Varinder Singh, Purvi Mittal
Rifampicin (RFP) and pyrazinamide (PZA) are the primary anti-tubercular drugs with a considerably safe profile. However, none of the drugs are without adverse reactions. They both can lead to a variety of adverse effects including life-threatening anaphylaxis. We report an interesting and possibly the first case of concurrent hypersensitivity to two primary anti-tubercular treatment (ATT) drugs. Hypersensitivity to RFP and PZA was confirmed in this patient by drug provocation and intradermal skin testing. He improved on alternative ATT regime withdrawing RFP and PZA...
April 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28404681/non-pnca-gene-mutated-but-pyrazinamide-resistant-m-tuberculosis-why-is-that
#8
Jim Werngren, Erik Alm, Mikael Mansjö
Pyrazinamide (PZA) is a key component for the effective treatment of drug susceptible and PZA-susceptible MDR (MDR(PZA-S)) tuberculosis. pncA gene mutations are usually detected in a clear majority (>90%) of the PZA resistant strains but obviously not in all. Rapid and reliable PZA DST is critical whenever PZA will be used in the regimen, not least for the treatment of MDR(PZA-S) TB. In this study, we selected 26 PZA resistant isolates reported to carry a wildtype pncA gene. To confirm resistance, susceptibility testing was repeated to 100 mg/L and 200 mg/L PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant...
April 12, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28374540/antibacterial-and-anti-tubercular-evaluation-of-dihydronaphthalenone-indole-hybrid-analogues
#9
V Praveen Kumar, J Renjitha, Ct Fathimath Salfeena, K T Ashitha, Rangappa S Keri, Sunil Varughese, B S Sasidhar
A new series of indole appended dihydronaphthalenone hybrid analogues (5a-t) have been synthesized through the Lewis acid catalyzed Michael addition of indoles to the arylidene/hetero arylidene ketones. All the synthesized derivatives are well characterized through the (1) H-NMR, (13) C-NMR, HRMS spectroscopic techniques, compound 5r was further confirmed through single crystal X-ray analysis and screened for antibacterial and anti-tubercular activities. Among the synthesized compounds, the minimum inhibition concentration of 5l (against E...
April 4, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28373198/lung-tissue-concentrations-of-pyrazinamide-among-patients-with-drug-resistant-pulmonary-tuberculosis
#10
Russell R Kempker, Marc Tobias Heinrichs, Ketino Nikolaishvili, Irina Sabulua, Nino Bablishvili, Shota Gogishvili, Zaza Avaliani, Nestani Tukvadze, Brent Little, Adam Bernheim, Timothy D Read, Jeannette Guarner, Hartmut Derendorf, Charles A Peloquin, Henry M Blumberg, Sergo Vashakidze
Background: Improved knowledge regarding tissue penetration of anti-tuberculosis drugs may help optimize drug management.Methods: Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide drug concentrations.Results: Among ten patients, the median pyrazinamide dose was 24.7 mg/kg. Imaging revealed predominant lung lesions as cavitary (6), mass-like (3), or consolidative (1)...
April 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28373190/delamanid-kills-dormant-mycobacteria-in-vitro-and-in-the-guinea-pig-model-of-tuberculosis
#11
Xiuhao Chen, Hiroyuki Hashizume, Tatsuo Tomishige, Izuru Nakamura, Miki Matsuba, Mamoru Fujiwara, Ryuki Kitamoto, Erina Hanaki, Yoshio Ooba, Makoto Matsumoto
TB treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug-susceptibility. Drugs with broad activity are urgently needed. The study aimed to evaluate delamanid's activity against growing or dormant bacilli in vitro as well as in vivo Culture of Mycobacterium bovis BCG Tokyo under aerobic and anaerobic condition was used to study delamanid's activity against growing and dormant bacilli, respectively. Delamanid exhibited significant bactericidal activity against replicating and dormant bacilli at or above the concentrations of 0...
April 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28361737/therapy-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis
#12
Barbara J Seaworth, David E Griffith
The global epidemic of multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. Extensively drug-resistant tuberculosis (XDR-TB), MDR-TB with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of MDR cases globally. Cases in India, China, and the Russian Federation account for >45% of the cases of MDR-TB...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28357124/antibiotic-associated-suspected-adverse-drug-reactions-among-hospitalized-patients-in-uganda-a-prospective-cohort-study
#13
Ronald Kiguba, Charles Karamagi, Sheila M Bird
We sought to determine the prevalence at admission and incidence during hospitalization of antibiotic-associated suspected adverse drug reactions (aa-ADRs) among Ugandan inpatients; and to characterize these aa-ADRs. We conducted a prospective cohort study of 762 consented adults admitted on medical and gynecological wards of the 1790-bed Mulago National Referral Hospital. Thirty percent were known HIV-seropositive (232/762). Nineteen percent (148/762; 95% CI: 17-22%) of inpatients experienced at least one aa-ADR...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28346018/antiretroviral-treatment-in-hiv-infected-children-who-require-a-rifamycin-containing-regimen-for-tuberculosis
#14
REVIEW
Helena Rabie, Eric H Decloedt, Anthony J Garcia-Prats, Mark F Cotton, Lisa Frigati, Marc Lallemant, Anneke Hesseling, H Simon Schaaf
In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy. Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28331797/paradoxical-response-with-increased-tumor-necrosis-factor-%C3%AE-levels-to-anti-tuberculosis-treatment-in-a-patient-with-disseminated-tuberculosis
#15
Sho Watanabe, Yugo Kaneko, Hironori Kawamoto, Tomoki Maehara, Yuri Baba, Ikumi Fujisaki, Nayuta Saito, Kai Ryu, Aya Seki, Tsugumi Horikiri, Akira Kinoshita, Hiroshi Takeda, Keisuke Saito, Kazuyosi Kuwano
It has been reported that tuberculosis (TB) worsens after cessation of tumor necrosis factor-α inhibitors and starting anti-TB treatment. Little is known about the immunological pathogenesis of this paradoxical response (PR). We report the first case of a TB patient in whom PR occurred concurrently with elevation of circulating tumor necrosis factor-α (TNFα) levels. A 75-year-old woman, who had been treated with adalimumab for SAPHO syndrome, developed disseminated TB. Soon after administration of anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol), and after discontinuation of adalimumab, a PR occurred...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28331796/an-unexpected-finding-in-a-man-with-multiple-pulmonary-nodules-a-pleural-effusion-and-respiratory-failure
#16
Yik Lam Pang, Quentin Jones
We report the case of a 47-year old Caucasian man with a history of depression and high alcohol intake who presented with a one-month history of weight loss, dry cough and abdominal pain. He had no smoking history of note. The patient was treated for a suspected chest infection, however developed respiratory failure and was intubated. A CT showed multiple pulmonary nodules, left pleural thickening extending to the mediastinum and bilateral pleural effusions-larger on the left, suggestive of disseminated malignancy...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28331044/effectiveness-and-safety-of-clofazimine-in%C3%A2-multidrug-resistant-tuberculosis-a%C3%A2-nationwide-report-from-brazil
#17
Margareth Dalcolmo, Regina Gayoso, Giovanni Sotgiu, Lia D'Ambrosio, Jorge L Rocha, Liamar Borga, Fatima Fandinho, Jose U Braga, Vera M N Galesi, Draurio Barreira, Denise A Sanchez, Fernanda Dockhorn, Rosella Centis, Jose A Caminero, Giovanni B Migliori
Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day(-1) (body weight ≥45 kg) as part of a standardised MDR-TB treatment regimen until 2006 (thereafter pyrazinamide was used).All MDR-TB patients included in the Sistema de Informação de Tratamentos Especiais da Tuberculose (SITETB) individual electronic register were analysed...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28329197/systematic-review-meta-analysis-and-cost-effectiveness-of-treatment-of-latent-tuberculosis-infection-to-reduce-progression-to-multidrug-resistant-tuberculosis
#18
Suzanne M Marks, Sundari R Mase, Sapna Bamrah Morris
Background: Evidence-based recommendations for treating persons having presumed latent tuberculosis infection (LTBI) after contact to infectious multidrug-resistant tuberculosis (MDR TB) are lacking because published data consist of small observational studies. TB incidence in persons treated for latent multidrug-resistant-TB infection (MDR LTBI) is unknown. Methods: We conducted a systematic review of studies published (1/1/1994-12/31/2014) to analyze TB incidence, treatment completion and discontinuation, and cost effectiveness...
March 14, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28327117/preliminary-evaluation-of-anti-tuberculosis-potential-of-siderophores-against-drug-resistant-mycobacterium-tuberculosis-by-mycobacteria-growth-indicator-tube-drug-sensitivity-test
#19
Karuna Gokarn, Ramprasad B Pal
BACKGROUND: Alternative treatment strategies have become essential in overcoming the problem of drug-resistant Mycobacterium tuberculosis (Mtb). In this preliminary in vitro study, the anti-tuberculosis (anti-TB) activity of exogenous iron chelators (xenosiderophores) such as Exochelin-MS (Exo-MS) and Deferoxamine-B (DFO-B) was evaluated against ten multi-drug-resistant (MDR) and seven pyrazinamide-resistant (PZA (R) ) Mtb isolates. METHODS: Mycobacteria Growth Indicator Tube-Drug Susceptibility Test was used to assess the anti-TB effect of Exo-MS or DFO-B individually and their combinations with isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA)...
March 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28318196/-paradoxical-reaction-to-antituberculosis-treatment-in-an-immunocompetent-girl-with-pulmonary-tuberculosis
#20
Ignacio Ruiz Del Olmo Izuzquiza, Claudia Orden Rueda, Laura Ochoa Gómez, Nuria Clavero Montañés, Enrique Berdún Chéliz, Carmelo Guerrero Laleona
Paradoxical reaction to antituberculosis treatment is rare in paediatric population. We report a 9-year-old girl with high fever and productive cough for the last three weeks. Tuberculine test and Quantiferon were positive, erythrocyte sedimentation rate was 64 mm/h, culture and polymerase chain reaction for M. tuberculosis negative, and chest X ray showed a widened right mediastinum. Tuberculosis was diagnosed, therefore treatment with standard doses of rifampicin, isoniazid, pyrazinamide and ethambutol was started...
April 1, 2017: Archivos Argentinos de Pediatría
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