The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis

Somoskövi, Ákos; Parsons, Linda M.; Salfinger, Max

doi:10.1186/rr54

Cited by 279 publications

(104 citation statements)

References 37 publications

(54 reference statements)

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“…Although, rifampicin resistance occurs most often in strains that are also resistant to isoniazid, no simultaneous resistance to isoniazid and rifampcin was observed in this study. It has been noted that mono resistance to isoniazid is common but monoresistance to rifampicin is quite rare [33]- [35]. Moreover, detection of polyresistance in the present study indicates the chance of occurrence of MDR-TB.…”

Section: Discussionmentioning

confidence: 52%

Drug Susceptibility Testing of Mycobacteria Isolated from Humans and Cattle from Selected Sites of Ethiopia

Tadesse¹,

Ameni²,

Desta³

2014

JTR

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Background: The effectiveness of a standard anti-tuberculosis (TB) treatment regimen correlates with in vitro drug susceptibility pattern of the infecting tubercle bacilli. The results of the drug susceptibility tests help select a proper treatment regimen or modify treatment regimen for a better management of patients and surveillance and timely control of the spread of the drug resistant TB in the community. Treatment of drug resistant TB is costly, and the outcomes, including survivorship, can be poor. As the result, the drug susceptibility test has become more important than ever. Objective: To determine the drug-susceptibility pattern of M. tuberculosis and M. bovis isolated from selected sites of Ethiopia. Methods: The conventional indirect Löwenstein-Jensen (L-J) proportion method was used to detect the drug susceptibility pattern of 29 isolates of M. tuberculosis and 21 isolates of M. bovis to four anti-TB drugs (streptomycin, rifampicin, isoniazid and ethambutol). Results: Resistance was observed only in M. tuberculosis isolates while all isolates of M. bovis were fully susceptible to the four drugs. Thus, the overall resistance of M. tubeculosis isolates to any of the four drugs was 51.7%. As such, any type of drug resistance was most frequent to streptomycin (41.3%) followed by isoniazid (20.6%) while it was minimal to rifampicin (6.8%) and ethambutol (3.4%). Multidrug resistant TB (MDR-TB) was not detected in the study. Conclusion: This preliminary study showed high level of resistance in M. tuberculosis isolates warranting appropriate use of anti-TB drugs in those sites from where the isolates were obtained.

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Section: Discussionmentioning

confidence: 52%

Drug Susceptibility Testing of Mycobacteria Isolated from Humans and Cattle from Selected Sites of Ethiopia

Tadesse¹,

Ameni²,

Desta³

2014

JTR

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“…Resistance to one fluoroquinolone, particularly if of high level, generally confers cross-resistance to all other members of this class. With the increasing use of fluoroquinolones for a variety of infections, including respiratory tract infections, fluoroquinolone resistance has emerged among strains of Streptococcus pneumonia [143][144][145][146][147][148][149][150].…”

Section: Discussionmentioning

confidence: 99%

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

Asif

2015

IJSW

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The need of new chemotherapeutic drugs to improve tuberculosis control and treatment particularly against multidrugresistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium. The atitubercular drugs are used in current chemotherapy have different chemical moieties. In this review, we provide an overview of the quinolone drugs as an antitubercular drug. Generally quinolone drugs are mainly used against many gram-positive and gram-negative bacterial infections including resistance strains also. Various quinolones are being used to control and treatment of tubercular infections including MDR, XDR and atypical Mycobacterium strains. Fluoroquinolones are an important quinolones, especially for strains that are resistant to first-line agents.

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“…If INH can be continued, one could even argue that we should not label these patients as having MDR-TB at this level of INH resistance, since their clinical outcome is different than those of highly INHand RIF-resistant patients (6). The presence of an inhA mutation may also alert the clinician not to include ethionamide or prothionamide in the MDR-TB treatment regimen due to potential crossresistance to these agents with this genetic mechanism in the background (3,4). Recent studies of programmatic selection of ethionamide-resistant MDR-TB strains in South Africa in the absence of this information clearly underlines the importance of the clinical impact of this question (7).…”

Section: Is Rapid Confirmation Of the Fact That The Patient Has Mdr-omentioning

confidence: 99%

“…These molecular markers may provide such important additional information as to significantly influence the care of the patient and ultimately, enable us to cure the patient (3,4). Keeping this in mind, we need to address the following questions: In the presence of inhA mutations, a low level of phenotypic isoniazid (INH) mutation, which can usually be successfully controlled with high-dose INH therapy, can be expected (4,5).…”

Section: Is Rapid Confirmation Of the Fact That The Patient Has Mdr-omentioning

confidence: 99%

Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

Somoskövi

2015

J Clin Microbiol

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A ccording to the World Health Organization (WHO), there are many hot spots of multidrug-resistant tuberculosis (MDR-TB), defined as resistance to rifampin (RIF) and isoniazid (INH), in the world. In one of the hot spots, the Russian Federation, a total of 142,500 TB cases, including an estimated 41,000 MDR-TB pulmonary cases in 2013, were reported. Of all new TB cases, 19% were MDR-TB, and among retreated cases, 49% were MDR-TB cases (1). In contrast, the U.S. Centers for Disease Control and Prevention (CDC) reported 9,582 TB cases, including 96 MDR-TB cases in 2014, resulting in 1.3% of all TB cases with available antimicrobial susceptibility test (AST) results (2). The time has come to screen all TB cases in the United States for MDR-TB either at the time a sputum specimen tests positive with a nucleic acid amplification test (NAAT) or when the culture yields a positive result for Mycobacterium tuberculosis complex.The faster turnaround time for diagnosing MDR-TB, enabled by current molecular assays which yield results within hours compared to weeks and months with conventional testing, is needed in order to make up for lost time because of patient and/or health care system delays. An earlier diagnosis of MDR-TB facilitates earlier prescription of an adequate regimen benefiting patients and public health. However, in addition to screening all patients rapidly for MDR-TB, additional information is necessary from molecular assays for the successful management of MDR-TB patients.Besides the presence or absence of M. tuberculosis, the next additional answer from a routine rapid molecular test is whether the patient's specimen contains MDR-TB. In cases where MDR-TB is confirmed, the second question that such an assay will need to rapidly confirm is the presence of extensively drug-resistant tuberculosis (XDR-TB), which is defined as MDR-TB plus resistance to quinolones and second-line injectable drugs. IS RAPID CONFIRMATION OF THE FACT THAT THE PATIENT HAS MDR-OR XDR-TB ENOUGH OR DO WE NEED TO GO BEYOND WITH RAPID MOLECULAR SCREENING?In light of the accumulating evidence on the meaning of molecular mechanisms of different first-and second-line antituberculosis drugs, by appropriate characterization of known and newly identified resistance-associated mutations with quantitative phenotypic susceptibility testing, it is time to raise the question " is rapid detection of MDR and XDR-TB alone enough to successfully win the war on TB or MDR-TB?" Can we extract and utilize more meaningful diagnostic information from currently used molecular tests for our patients?In order to settle this question, we need to keep in mind that molecular markers cannot only rapidly confirm the presence of MDR-TB, they may also provide additional valuable information that can help to predict the level of phenotypic resistance or even cross-resistance to certain first-and second-line antituberculosis drugs. These molecular markers may provide such important additional information as to significantly influence the care of the patient and ultim...

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The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis

Cited by 279 publications

References 37 publications

Drug Susceptibility Testing of Mycobacteria Isolated from Humans and Cattle from Selected Sites of Ethiopia

Drug Susceptibility Testing of Mycobacteria Isolated from Humans and Cattle from Selected Sites of Ethiopia

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

Commentary: The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug-Resistant Tuberculosis

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