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Faheem Jan, Shahid Wali, Sadia Sadia, Muhammad Taj Akbar, Hafiz Sajid Akbar, Waqas Ahmad, Manzoor Ahmad, Anwar Khalid
Introduction: Multidrug resistant TB (MDR-TB), defined as resistance to at least rifampicin and isoniazid together, has been rapidly spreading in recent years. In new pulmonary tuberculosis patients, rapid spread of MDR-TB and XDR-TB challenging the effectiveness of national TB control programs especially in many low-income countries. This study was aimed to determine the resistance pattern of Mycobacterium tuberculosis among new cases, cured, failure, relapse, defaulted, treatment completed, treatment not evaluated and suspect to be resistant to first line antitubercular drugs of pulmonary tuberculosis (PTB)...
March 2018: Tüberküloz Ve Toraks
Imran Rizvi, Hardeep Singh Malhotra, Ravindra Kumar Garg, Neeraj Kumar, Ravi Uniyal, Shweta Pandey
OBJECTIVES: Tuberculous meningitis carries high rate of mortality and morbidity despite adequate treatment. Newer agents are being searched to improve outcome of these patients. Fluoroquinolones might be useful in the management of tuberculous meningitis in view of good cerebrospinal fluid penetration and good in-vitro activity against mycobacterium. This review summarizes the effects of fluoroquinolone in first line regimens in tuberculous meningitis. METHODS: A systematic search of literature was performed using PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and LILACS for articles published till march 2017...
July 12, 2018: Journal of Infection
Md Masud Parvez, Nazia Kaisar, Ho Jung Shin, Yoon Jae Lee, Jae-Gook Shin
Substrate potential of antituberculosis drugs on SLC transporters are not well characterized to date, despite a well-established understanding of their drug dispositions and pharmacokinetics. In this study, we investigated comprehensively the substrate potentials of the 22 currently available antituberculosis drugs for solute carrier (SLC) family transporter-mediated uptake, using Xenopus laevis oocytes and stably transfected HEK-293 cells in vitro The result suggested that, ethambutol, isoniazid, amoxicillin, and prothionamide act as novel substrates for the SLC transporters...
July 16, 2018: Antimicrobial Agents and Chemotherapy
Byoung Soo Kwon, Mi-Na Kim, Heungsup Sung, Younsuck Koh, Woo-Sung Kim, Jin-Woo Song, Yeon-Mok Oh, Sang-Do Lee, Sei Won Lee, Jae-Seung Lee, Chae-Man Lim, Chang-Min Choi, Jin-Won Huh, Sang-Bum Hong, Sojung Park, Tae Sun Shim, Yong Pil Chong, Kyung-Wook Jo
Although it is known that in vitro minimal inhibitory concentrations (MICs) of rifampin and ethambutol are poorly correlated with clinical response in Mycobacterium avium complex lung disease (MAC-LD), its evidence is limited. This study investigated the association between treatment outcome and in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea...
July 16, 2018: Antimicrobial Agents and Chemotherapy
Conor D Tweed, Angela M Crook, Evans I Amukoye, Rodney Dawson, Andreas H Diacon, Madeline Hanekom, Timothy D McHugh, Carl M Mendel, Sarah K Meredith, Michael E Murphy, Saraswathi E Murthy, Andrew J Nunn, Patrick P J Phillips, Kasha P Singh, Melvin Spigelman, Genevieve H Wills, Stephen H Gillespie
BACKGROUND: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. METHODS: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded...
July 11, 2018: BMC Infectious Diseases
S Q Wang, G L Jiang, G M Wei, F M Huo, L L Dong, L P Zhao, H R Huang, G R Wang
Objective: To investigate the antimicrobial susceptibility and genotyping of Mycobacterium intracellulare . Methods: A total of 150 M . intracellulare isolates were collected. The susceptibility against 15 antimicrobial agents widely used for treatment of non-tuberculosis mycobacteria (NTM) infections, was tested by broth microdilution assay. Variable number of tandem repeats (VNTR) assay was also performed using the 16-loci genotyping method. Results: The drug susceptibility test revealed that clarithromycin (97...
July 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
Clara Aguilar-Pérez, Begoña Gracia, Liliana Rodrigues, Asunción Vitoria, Rubén Cebrián, Nathalie Deboosère, Ok-Ryul Song, Priscille Brodin, Mercedes Maqueda, José A Aínsa
The increasing incidence of multi-drug resistant Mycobacterium tuberculosis and the very few drugs available for treatment is promoting the discovery and development of new molecules that could help in the control of this disease. Bacteriocin AS-48 is an antibacterial peptide produced by Enterococcus faecalis , active against several Gram-positive bacteria. We have found that AS-48 was active against Mycobacterium tuberculosis , including H37Rv and other reference and clinical strains, and also against some non-tuberculous clinical mycobacterial species...
July 9, 2018: Antimicrobial Agents and Chemotherapy
Pureepat Arttawejkul, Napplika Kongpolprom
A 56-year-old previously healthy female presented with chronic productive cough and fever. Chest X-ray revealed right middle lung opacities. Sputum acid fast bacilli smear was positive, however polymerase chain reaction was negative for Mycobacterium tuberculosis . Further investigations were pursued, which identified Mycobacterium asiaticum. Appropriate therapy with isoniazid, rifampin and clarithromycin for total 18 months (including pyrazinamide and ethambutol for first 4 months) resulted in clinical and radiographic improvement...
2018: Respiratory Medicine Case Reports
Hannah Kavookjian, Joel W Jones, Sweeti Shah, Hugo Escobar, Douglas Swanson, Pamela Nicklaus
OBJECTIVES: To describe a safe and effective treatment for endobronchial Mycobacterium avium complex. METHODS: Case report and literature review. RESULTS: We present a case of endobronchial M. avium complex in a healthy child treated with serial carbon-dioxide laser excisions and antibiotic triple therapy using azithromycin, rifampin, and ethambutol. No current guideline for the treatment of these lesions in the pediatric population exists...
June 1, 2018: Annals of Otology, Rhinology, and Laryngology
Joana M Andrade, Luísa Custódio, Alessandra Romagnoli, Catarina P Reis, Maria J Rodrigues, Catarina Garcia, Elisa Petruccioli, Delia Goletti, Célia Faustino, Gian M Fimia, Patrícia Rijo
AIM:  Confirm the use of Plectanthus spp. plants in traditional medicine, particularly as anti-inflammatory and anti-infective agents. MATERIALS & METHODS:  Compounds previously isolated from Plectranthus spp. were studied for their anti-inflammatory activity using the SNAP assay and RAW 264.7 cells, by the quantification of nitric oxide. An halimane diterpene and its derivatives were tested in infected macrophages with M. tuberculosis H37Rv, using CFU counts assay, at their minimum inhibitory concentration values...
June 29, 2018: Future Medicinal Chemistry
Willy Ssengooba, Germine Nakayita, Carolyn C Namaganda, Moses L Joloba
INTRODUCTION: Although Sensititre Mycobacterium tuberculosis (MYCOTB) plate offers both drug susceptibility testing (DST) and minimum inhibitory concentration (MIC) results, it has not been evaluated against both Lowenstein Jensen (LJ) and Middlebrook 7H10 (MB7H10) DST methods at standard critical concentrations. MATERIALS AND METHODS: We analyzed 76 M. tuberculosis isolates consisting of 54 isolates from the Uganda National TB drug resistance survey done December 2009-February 2011 and 22 isolates from the World Health Organization External Quality Assessment panel for the year 2011...
2018: PloS One
Sonia Rebollo Ramirez, Sina Krokowski, Damian Lobato-Márquez, Michael Thomson, Ivana Pennisi, Serge Mostowy, Gerald Larrouy-Maumus
Antimicrobial resistance is a major threat the world is currently facing. Development of new antibiotics and the assessment of their toxicity represents an important challenge. Current methods to address antibiotic toxicity rely on measuring mitochondrial damage using ATP and/or membrane potential as a read-out. In this study, we propose an alternative read-out looking at changes in the lipidome on intact and unprocessed cells by MALDI mass spectrometry. As proof-of-principle, we evaluated the impact of known antibiotics (levofloxacin, ethambutol, and kanamycin) on the lipidome of HELA cells and mouse bone marrow-derived macrophages...
June 27, 2018: Chemical Research in Toxicology
Carolien Ruesen, Anca Lelia Riza, Adriana Florescu, Lidya Chaidir, Cornelia Editoiu, Nicole Aalders, Dragos Nicolosu, Victor Grecu, Mihai Ioana, Reinout van Crevel, Jakko van Ingen
Mycobacterium tuberculosis drug resistance poses a major threat to tuberculosis control. Current phenotypic tests for drug susceptibility are time-consuming, technically complex, and expensive. Whole genome sequencing is a promising alternative, though the impact of different drug resistance mutations on the minimum inhibitory concentration (MIC) remains to be investigated. We examined the genomes of 72 phenotypically drug-resistant Mycobacterium tuberculosis isolates from 72 Romanian patients for drug resistance mutations...
June 26, 2018: Scientific Reports
Margit Drapal, Paul R Wheeler, Paul D Fraser
Mycobacterium species can cause a range of nontuberculous infections of healthy and immunocompromised people as well as infect people during and after surgical procedures. The similarity of nontuberculous mycobacteria (NTM) to the tuberculosis bacilli (TB) could ultimately enable the use of anti-TB drugs for the genus. Hence, three NTM (M. smegmatis, M. phlei and M. avium) were cultured under different lab conditions, causing two mycobacterial phenotypes (active and dormant), and treated with isoniazid (INH) and ethambutol (EMB) independently or in combination...
June 26, 2018: FEMS Microbiology Letters
Fatma Kamer Varıcı Balcı, Cengiz Çavuşoğlu
Tuberculosis is still one of the most important public health problems worldwide. Due to the increase of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis cases, fast, practical and standardized methods need to be developed for the determination of drug resistance in Mycobacterium tuberculosis complex. The aim of this study was to compare the Sensititre MycoTB plate method with the gold standard agar proportion method (APM); in order to determine if the Sensititre MycoTB plate method is effective enough to be used instead of the APM...
April 2018: Mikrobiyoloji Bülteni
Elin M Svensson, Robin J Svensson, Lindsey H M Te Brake, Martin J Boeree, Norbert Heinrich, Sarah Konsten, Gavin Churchyard, Rodney Dawson, Andreas H Diacon, Gibson S Kibiki, Lilian T Minja, Nyanda E Ntingiya, Ian Sanne, Stephen H Gillespie, Michael Hoelscher, Patrick P J Phillips, Ulrika S H Simonsson, Rob Aarnoutse
Background: Tuberculosis remains a huge public health problem and the prolonged treatment duration obstructs effective tuberculosis control. Higher rifampicin doses have been associated with better bactericidal activity, but optimal dosing is uncertain. This analysis aimed to characterize the relationship between rifampicin plasma exposure and treatment response over 6 months in a recent study investigating the potential for treatment shortening with high-dose rifampicin. Methods: Data were analyzed from 336 patients with pulmonary tuberculosis (97 with pharmacokinetic data) treated with rifampicin doses of 10, 20, or 35 mg/kg...
June 18, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Syed Beenish Rufai, Jitendra Singh, Parveen Kumar, Purva Mathur, Sarman Singh
There is limited data on the use of Genotype MTBDRslVersion 1 (MTBDRsl V1) as an initial rapid screening test to rule out XDR-TB and most importantly its performance in various genotypes of Mycobacterium tuberculosis is scarcely studied. A total of 359 MDR-TB isolates were tested for gene mutations representing second line drug resistance, using the MTBDRsl_V.1 and the results were compared with phenotypic method (Bactec MGIT-960 system) for second-line drug (SLD) susceptibility testing. Genetic lineages of all these isolates were also determined using spoligotyping and SITVIT2 WEB database...
June 18, 2018: Scientific Reports
Yasuhiro Horita, Abdullah Alsultan, Awewura Kwara, Sampson Antwi, Antony Enimil, Antoinette Orstin, Albert Dompreh, Hongmei Yang, Lubbe Wiesner, Charles A Peloquin
Optimal doses for anti-tuberculosis (TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosages ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) for at least 4 weeks had blood samples collected at pre-dose, 1, 2, 4, and 8-hours post-dose...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Bernice J Klotoe, Barbara Molina-Moya, Harrison Magdinier Gomes, Michel K Gomgnimbou, Lorenna Oliveira Suzarte, Maria H Féres Saad, Sajid Ali, José Dominguez, Edita Pimkina, Elena Zholdybayeva, Christophe Sola, Guislaine Refrégier
Several diagnostic tests are being developed to detect drug resistance in tuberculosis. In line with previous developments detecting rifampicin and isoniazid resistance using microbead-based systems (spoligoriftyping and TB-SPRINT), we present here an assay called TB-EFI detecting mutations involved in resistance to ethambutol, fluoroquinolones and the three classical injectable drugs (kanamycin, amikacin and capreomycin) in Mycobacterium tuberculosis. The proposed test includes both wild-type and mutant probes for each targeted locus...
June 15, 2018: Journal of Microbiological Methods
Florian P Maurer, Philipp Pohle, Margrit Kernbach, Daniela Sievert, Doris Hillemann, Jan Rupp, Michael Hombach, Katharina Kranzer
OBJECTIVES: To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cutoff (ECOFF) values. METHODS: 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare; n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid...
June 12, 2018: Clinical Microbiology and Infection
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