scholarly journals Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

2016 ◽  
Vol 54 (3) ◽  
pp. 727-733 ◽  
Author(s):  
Maha R. Farhat ◽  
Karen R. Jacobson ◽  
Molly F. Franke ◽  
Devinder Kaur ◽  
Alex Sloutsky ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Fluoroquinolone Resistance ◽  
Test Results ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Disease Mutations ◽  
The Individual ◽  
Selection Of

Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in thegyrgenes are known to confer most fluoroquinolone resistance, but knowledge about the effects ofgyrmutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the fullgyrAandgyrBopen reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found thatgyrBmutations contribute to fluoroquinolone resistance both individually and through interactions withgyrAmutations. These effects were statistically significant. In these clinical isolates, severalgyrAandgyrBmutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration ofgyrmutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects ofgyrmutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment.

Lung Resection for Multidrug-Resistant Tuberculosis

2005 ◽  
Vol 13 (2) ◽  
pp. 172-174 ◽  
Author(s):  
Rishen Naidoo ◽  
Anu Reddi
Keyword(s):  
Lung Resection ◽  
Postoperative Mortality ◽  
Multidrug Resistant ◽  
Cure Rate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Traditional Drug ◽  
Localized Disease ◽  
Cure Rates

The emergence of multidrug-resistant tuberculosis poses a serious challenge to traditional drug therapy. In view of the relapse rate of up to 50% following medical management, there has been renewed interest in the role of surgery for this problem. We report our experience with lung resection for this condition. Over a 5-year period, resection was performed in 23 patients who were diagnosed with multidrug resistance after completing a course of standard chemotherapy and at least 3 months of second-line therapy. Pneumonectomy was performed in 17 patients and lobectomy in 6. There was no operative or postoperative mortality. Major complications developed in 4 patients (17.4%): 2 had post-pneumonectomy empyema and 2 underwent rethoracotomy for bleeding. Ten patients were sputum positive preoperatively, and only 1 remained positive after surgery. The patients were put on appropriate chemotherapy and followed up for 18 months. The cure rate was 95.6%. Pulmonary resection can be considered as an important adjunct to medical therapy in carefully selected patients: those who have localized disease with adequate pulmonary reserve, or who have multiple previous relapses, or whose sputum remains positive after 4 to 6 months of appropriate medical treatment. Surgery offers high cure rates with acceptable morbidity and mortality.

scholarly journals Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Amber Arnold ◽  
Graham S. Cooke ◽  
Onn Min Kon ◽  
Martin Dedicoat ◽  
Marc Lipman ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Adverse Effects ◽  
Total Duration ◽  
Multidrug Resistant ◽  
World Health ◽  
Fluoroquinolone Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Number Of Patients ◽  
Mdr Tb

ABSTRACT The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.

Role of Treatment Cost on Transmission of Multidrug-Resistant Tuberculosis Into Iran

2015 ◽  
Vol 61 (6) ◽  
pp. 1029-1030 ◽  
Author(s):  
Abed Zahedi Bialvaei ◽  
Hossein Samadi Kafil ◽  
Mohammad Asgharzadeh
Keyword(s):  
Treatment Cost ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Modeling treatment effect modification in multidrug-resistant tuberculosis in an individual patientdata meta-analysis

2021 ◽  
pp. 096228022110463
Author(s):  
Yan Liu ◽  
Mireille E Schnitzer ◽  
Guanbo Wang ◽  
Edward Kennedy ◽  
Piret Viiklepp ◽  
...  
Keyword(s):  
Structural Model ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Multidrug Resistant ◽  
Effect Modification ◽  
Marginal Structural Model ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
The Individual

Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data from multiple studies to estimate these treatment effect models. Our data arise from a systematic review of observational studies contrasting different treatments for multidrug-resistant tuberculosis, where multiple antimicrobial agents are taken concurrently to cure the infection. We propose a marginal structural model for effect modification by different patient characteristics and co-medications in a meta-analysis of observational individual patient data. We develop, evaluate, and apply a targeted maximum likelihood estimator for the doubly robust estimation of the parameters of the proposed marginal structural model in this context. In particular, we allow for differential availability of treatments across studies, measured confounding within and across studies, and random effects by study.

scholarly journals Patients’ Perception of a Community Pharmacist-Managed Multidrug-Resistant Tuberculosis Program in Peru: A Public Health Perspective

2017 ◽  
Vol 8 (3) ◽  
pp. 11 ◽  
Author(s):  
Sean O'Brien ◽  
Jacy Downey
Keyword(s):  
Public Health ◽  
Community Pharmacist ◽  
Community Pharmacists ◽  
Multidrug Resistant ◽  
Perceived Barriers ◽  
The Public ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Objectives: The primary objective is to investigate the public’s perception about the role of the community pharmacist in Peru’s directly observed treatment, short course (DOTS) program. The secondary objective is to assess perceived barriers that would prevent the public from utilizing community pharmacists in order to identify future opportunities for community pharmacists to increase adherence to multidrug-resistant tuberculosis (MDR-TB) therapy. Design: Qualitative study comprised of an 8 close-ended survey questionnaire. Setting: Healthcare clinics established by a medical mission group in Lima and surrounding communities, Peru, from July 13 to July 27, 2015. Participants: Patients 15 years of age and over who sought healthcare at the clinics. Main outcome measures: Public’s perception about the role of the community pharmacist in Peru and barriers that would prevent the public from seeking a community pharmacist. Results: Out of the 445 patients approached, 438 patients completed the survey, resulting in a 98% response rate. More than half (52%) of the respondents were likely to seek a community pharmacist to assist them in completing a MDR-TB medication regimen. Almost half (48%) of the respondents felt comfortable with assistance of a community pharmacist in completing an MDR-TB regimen. The physician was the first health care professional that was contacted for all medical situations, including drug-related questions (61%). Lack of privacy in the pharmacy (53%) and busyness of the pharmacists (52%) were the top perceived barriers for asking community pharmacists questions. Conclusion: This study highlights the need for pharmacist participation in Peru’s DOTS program. Furthermore, this investigation has identified several issues of concern related to current community pharmacy practice in Peru. Therefore, future efforts may be necessary to address these identified areas of opportunity to promote the community pharmacist’s role in health screening, drug therapy monitoring, and counseling to decrease the public health burden of MDR-TB. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents or royalties.   Type: Original Research

scholarly journals STUDI FENOMENOLOGI : DUKUNGAN TERHADAP KEPATUHAN MINUM OBAT PADA PENDERITA TUBERCULOSIS DENGAN MULTIDRUG-RESISTANT

2021 ◽  
Vol 8 (1) ◽  
pp. 12-20
Author(s):  
Murwanti Murwanti
Keyword(s):  
Health Services ◽  
Community Involvement ◽  
Sampling Technique ◽  
Phenomenological Approach ◽  
Multidrug Resistant ◽  
Spiritual Support ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Background: Tuberculosis is an infectious disease if the patient does not complete therapeutic treatment can cause multidrug-resistant tuberculosis (MDR-TB). The role of the environment is needed to support treatment.The study aims to explore more deeply the family's support for medication adherence in patients with multidrug-resistant tuberculosis (TBC-MDR). Method: This type of research is qualitative using a descriptive phenomenological approach, in-depth interviews of 5 participants based on purposive sampling technique. Results: The results of the study found the role of the family towards TB-MDR patients manifested in emotional, physical, instrumental, and spiritual support. emotional support consists of positive and negative emotional. Community involvement after counseling was supportive but there were some who could not accept even families of MDR-TB sufferers were also shunned. The role of health services is to convey information, prepare medicines, supervise, motivate treatment, remind check schedules, refer to more complete facilities when needed, visit homes and ensure patients take medication if unable to come to the public health service. Conclusion: This study found 3 main themes, namely the role of comprehensive family, community involvement and the role of health services in mentoring TB-MDR patients.

scholarly journals Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1132
Author(s):  
Antonella Obinu ◽  
Elena Piera Porcu ◽  
Sandra Piras ◽  
Roberta Ibba ◽  
Antonio Carta ◽  
...  
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Oral Absorption ◽  
Antitubercular Activity ◽  
Multidrug Resistant ◽  
Lipid Nanoparticles ◽  
Particle Size Range ◽  
Solid Lipid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.

scholarly journals Deciphering Tuberactinomycin Biosynthesis: Isolation, Sequencing, and Annotation of the Viomycin Biosynthetic Gene Cluster

2003 ◽  
Vol 47 (9) ◽  
pp. 2823-2830 ◽  
Author(s):  
Michael G. Thomas ◽  
Yolande A. Chan ◽  
Sarah G. Ozanick
Keyword(s):  
Gene Cluster ◽  
Bacterial Infections ◽  
Biosynthetic Gene Cluster ◽  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Combinatorial Biosynthesis ◽  
Biosynthetic Gene ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Essential Components

ABSTRACT The tuberactinomycin antibiotics are essential components in the drug arsenal against Mycobacterium tuberculosis infections and are specifically used for the treatment of multidrug-resistant tuberculosis. These antibiotics are also being investigated for their targeting of the catalytic RNAs involved in viral replication and for the treatment of bacterial infections caused by methicillin-resistant Staphylococcus aureus strains and vancomycin-resistant enterococci. We report on the isolation, sequencing, and annotation of the biosynthetic gene cluster for one member of this antibiotic family, viomycin, from Streptomyces sp. strain ATCC 11861. This is the first gene cluster for a member of the tuberactinomycin family of antibiotics sequenced, and the information gained can be extrapolated to all members of this family. The gene cluster covers 36.3 kb of DNA and encodes 20 open reading frames that we propose are involved in the biosynthesis, regulation, export, and activation of viomycin, in addition to self-resistance to the antibiotic. These results enable us to predict the metabolic logic of tuberactinomycin production and begin steps toward the combinatorial biosynthesis of these antibiotics to complement existing chemical modification techniques to produce novel tuberactinomycin derivatives.

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