Drug-resistant tuberculosis: the rise of the monos

Variava, Ebrahim; Martinson, Neil

doi:10.1016/s1473-3099(18)30247-0

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…The spread of drug-resistant strains of TB (mono-resistant, multidrug-resistant, extensively drug-resistant and totally drug-resistant) is alarmingly high and accounted for 490,000 cases of multidrug-resistant TB (MDR-TB) in 2016. Around 47% of the MDR-TB cases are reported in Southeast Asia [15]. Increase in isoniazid-susceptible rifampin resistance was also noted in 2016, with 110,000 cases globally.…”

Section: Mycobacteria: the Global Disease Burdenmentioning

confidence: 99%

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery

Waman

Vedithi

Thomas

et al. 2019

Emerging Microbes & Infections

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Of the more than 190 distinct species of Mycobacterium genus, many are economically and clinically important pathogens of humans or animals. Among those mycobacteria that infect humans, three species namely Mycobacterium tuberculosis (causative agent of tuberculosis), Mycobacterium leprae (causative agent of leprosy) and Mycobacterium abscessus (causative agent of chronic pulmonary infections) pose concern to global public health. Although antibiotics have been successfully developed to combat each of these, the emergence of drug-resistant strains is an increasing challenge for treatment and drug discovery. Here we describe the impact of the rapid expansion of genome sequencing and genome/pathway annotations that have greatly improved the progress of structure-guided drug discovery. We focus on the applications of comparative genomics, metabolomics, evolutionary bioinformatics and structural proteomics to identify potential drug targets. The opportunities and challenges for the design of drugs for M. tuberculosis, M. leprae and M. abscessus to combat resistance are discussed.

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Section: Mycobacteria: the Global Disease Burdenmentioning

confidence: 99%

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery

Waman

Vedithi

Thomas

et al. 2019

Emerging Microbes & Infections

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“…Currently available agents for drug resistant TB, classified into groups A-C are shown in Box 1. Monoresistance to rifampicin or isoniazid is also a growing problem in TB endemic regions (Variava and Martinson, 2018). In 2020, 71% (2.1 of 3.0 million) of people diagnosed with bacteriologically confirmed pulmonary TB were also tested for rifampicin resistance (RR).…”

Section: Introductionmentioning

confidence: 99%

Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management

Liebenberg

Gordhan

Kana

2022

Front. Cell. Infect. Microbiol.

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Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms. Global control of tuberculosis will require interventions that effectively address these and related aspects. Interrupting tuberculosis transmission is dependent on the availability of novel rapid diagnostics which provide accurate results, as near-patient as is possible, together with appropriate linkage to care. Contact tracing, longitudinal follow-up for symptoms and active mapping of social contacts are essential elements to curb further community-wide spread of drug resistant strains. Appropriate prophylaxis for contacts of drug resistant index cases is imperative to limit disease progression and subsequent transmission. Preventing the evolution of drug resistant strains will require the development of shorter regimens that rapidly eliminate all populations of mycobacteria, whilst concurrently limiting bacterial metabolic processes that drive drug tolerance, mutagenesis and the ultimate emergence of resistance. Drug discovery programs that specifically target bacterial genetic determinants associated with these processes will be paramount to tuberculosis eradication. In addition, the development of appropriate clinical endpoints that quantify drug tolerant organisms in sputum, such as differentially culturable/detectable tubercle bacteria is necessary to accurately assess the potential of new therapies to effectively shorten treatment duration. When combined, this holistic approach to addressing the critical problems associated with drug resistance will support delivery of quality care to patients suffering from tuberculosis and bolster efforts to eradicate this disease.

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“…The combination of infectious pathogens ( 15 - 17 ) has negative effects on the prognosis and the possibility of clinical recovery ( 18 , 19 ). Secondary infections, occurring in the form of exacerbation of nonspecific bronchitis and pneumonia and complicating the course of fibrous-cavernous TB, infiltrative TB, TB, et cetera, are diverse and are not caused by a specific pathogen ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…Secondary infections, occurring in the form of exacerbation of nonspecific bronchitis and pneumonia and complicating the course of fibrous-cavernous TB, infiltrative TB, TB, et cetera, are diverse and are not caused by a specific pathogen ( 20 , 21 ). The rates of combination of TB with nonspecific respiratory diseases and other non-TBinfections vary from 7% to 49% ( 16 - 19 ). In patients with recurrent pulmonary TB, chronic nonspecific respiratory diseases occur in 17.5-63.2% of cases ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of secondary infections on the multidrug-resistant Tuberculosis: A cohort study

Tabriz

Nurtazina

Кожамуратов

et al. 2021

Med. J. Islam. Republ. Iran

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Background: Tuberculosis (TB) causes over a million deaths annually and is still one of the most important public health problems worldwide. According to the World Health Organization estimates, the highest rates of TB in the European Region are in Tajikistan, Kazakhstan, Moldova, Kyrgyzstan, Romania, and Uzbekistan. The purpose of this study was to investigate the spectrum of nonspecific microorganisms isolated in patients with multidrug-resistant TB in Central Kazakhstan and to assess their susceptibility to antimicrobial drugs. Methods: The patients were divided into 2 groups: group 1 with multidrug-resistant forms of pulmonary TB (n = 107 patients); group 2 with sensitive forms of pulmonary TB (n = 122 patients). Gender, age, and social status of the patients were studied. Microorganisms were identified using the MALDI-TOF method. The statistical significance of different values for binary and nominal parameters was determined using the chi-square test. Changes in binary variables were analyzed using the McNeimer test. Results: During the study, an expectedly high proportion of tetracycline-resistant pneumococcal strains (66.7% and 60%, respectively) was isolated, which was a consequence of a long-term and practically uncontrolled use of these drugs in Kazakhstan. Fluoroquinolones showed low activity. The results showed that beta-lactam antibacterial drugs maintained their high activity against the causative agents of pneumococcal infection. Conclusion: It was concluded that secondary microorganisms isolated in patients with multidrug-resistant TB were represented by the strains that were resistant to modern antibacterial drugs. Therefore, for appropriate antibiotic prescription, it is necessary to study materials from the respiratory system in all patients admitted for TB treatment to study the spectrum of nonspecific microorganisms and assess their susceptibility to antimicrobial drugs.

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Drug-resistant tuberculosis: the rise of the monos

Cited by 5 publications

References 7 publications

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery

Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management

Effects of secondary infections on the multidrug-resistant Tuberculosis: A cohort study

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