Clinical Characteristics and Treatment Outcomes of Patients with Isoniazid‐Monoresistant Tuberculosis

Cattamanchi, Adithya; Dantes, Raymund; Metcalfe, John; Jarlsberg, Leah G.; Grinsdale, Jennifer; Kawamura, L. Masae; Osmond, Dennis; Hopewell, Philip C.; Nahid, Payam

doi:10.1086/595689

Cited by 98 publications

(109 citation statements)

References 16 publications

(9 reference statements)

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“…The prevalence of isoniazidresistant TB among newly diagnosed cases ranges geographically from 5 to 25% (16). Although the treatment outcomes for such cases remain unclear, several retrospective studies suggest that further drug resistance is promoted in the community when isoniazid resistance is not recognized and standard treatment is provided (17)(18)(19)(20). Interestingly, the CϪ15T mutation, which is significantly less common than the katG S315T mutation in isoniazid-resistant isolates worldwide (21) and in Panama, was present in all 3 cases in our study, suggesting the possibility of recent transmission.…”

Section: Discussionmentioning

confidence: 59%

First Evaluation of GenoType MTBDR plus 2.0 Performed Directly on Respiratory Specimens in Central America

et al. 2016

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dThe turnaround times for conventional methods used to detect Mycobacterium tuberculosis in sputum samples and to obtain drug susceptibility information are long in many developing countries, including Panama, leading to delays in appropriate treatment initiation and continued transmission in the community. We evaluated the performance of a molecular line probe assay, the Genotype MTBDRplus version 2.0 assay, in detecting M. tuberculosis complex directly in respiratory specimens from smearpositive tuberculosis cases from four different regions in Panama, as well as the most frequent mutations in genes conferring resistance to isoniazid (katG and inhA) and rifampin (rpoB). Our results were confirmed with the nitrate reductase assay and genomic sequencing. M. tuberculosis complex was detected by the Genotype MTBDRplus 2.0 assay with 100% sensitivity and specificity. The sensitivity and specificity for rifampin resistance were 100% and 100%, respectively, and those for isoniazid resistance were 90.7% and 100%. Isoniazid monoresistance was detected in 5.2% of new cases. Genotype MTBDRplus 2.0 is highly accurate in detecting M. tuberculosis complex in respiratory specimens and is able to discriminate isoniazid-monoresistant cases from multidrug-resistant cases within 2 days.

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Section: Discussionmentioning

confidence: 59%

First Evaluation of GenoType MTBDR plus 2.0 Performed Directly on Respiratory Specimens in Central America

et al. 2016

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“…probes can facilitate trial conduction and help ensure inclusion of appropriate participants. In clinical care, there has been debate about the significance of INH monoresistance and effects on TB treatment outcomes (24)(25)(26)(27). However, a South African study (27) and a meta-analysis (26) have both demonstrated poor TB outcomes with INH monoresistance, and two studies suggest that early detection of INH resistance with modification of treatment led to better outcomes (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…In clinical care, there has been debate about the significance of INH monoresistance and effects on TB treatment outcomes (24)(25)(26)(27). However, a South African study (27) and a meta-analysis (26) have both demonstrated poor TB outcomes with INH monoresistance, and two studies suggest that early detection of INH resistance with modification of treatment led to better outcomes (24,25). Further, the presence of rifampin resistance alone cannot be relied upon to predict INH resistance; INH susceptibility ranges from Յ11% to Ͼ40% of RIF-resistant isolates, depending on the setting (28,29).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Two Line Probe Assays for Rapid Detection of Mycobacterium tuberculosis, Tuberculosis (TB) Drug Resistance, and Non-TB Mycobacteria in HIV-Infected Individuals with Suspected TB

Luetkemeyer

Kendall

et al. 2014

J Clin Microbiol

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R apid laboratory identification of tuberculosis (TB) and Mycobacterium tuberculosis drug resistance are critical to ensure timely initiation of therapy, to inform appropriate TB therapy, and to facilitate infection control. Early diagnosis of TB and drugresistant disease is of particular importance in human immunodeficiency virus (HIV)-infected individuals, as delay of therapy (1, 2) and drug-resistant TB (3) can be devastating in those with compromised immune systems. Diagnosis of TB in HIV can be a particular challenge, as 24% to 61% of HIV coinfected individuals with pulmonary TB have acid-fast bacillus (AFB)-smear-negative sputum (2). Culture-based testing for M. tuberculosis and M. tuberculosis drug resistance requires an unacceptably long turnaround for results, is limited by contamination rates, and requires considerable infrastructure and human resources.Molecular line probe assays (LPA) permit rapid diagnosis of TB, isoniazid and rifampin resistance, and clinically relevant non-M. tuberculosis mycobacteria. In these assays, DNA or RNA is isolated from culture or direct (i.e., sputum) respiratory samples and then amplified and reverse hybridized onto a nitrocellulose strip with immobilized probes for different mycobacteria or for mutations that confer resistance. These strips can be quickly interpreted using a template, with the entire testing process taking a day or less in most cases. In 2008, the World Health Organization endorsed the use of line probe assays for detection of M. tuberculosis drug resistance; however, use was recommended on culture specimens and AFB-positive (AFB ϩ ) sputum specimens only, given the lack of data for use in AFB-negative sputum (4). Given the prevalence of paucibacillary disease in HIV-TB coinfection, it is important to understand line probe performance across the spectrum of bacillary loads in HIV-infected persons, in whom there are limited data to inform use of line probe assays.The GenoType MTBDRplus (MTBDR-Plus) (Hain Lifesciences GmBH, Nehren, Germany) identifies rifampin (RIF) and isoniazid (INH) resistance by detecting the most common mutations of the rpoB gene and the katG and inhA genes, respectively, and can be used on both cultured and direct specimens. MTBDR-Plus LPA

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“…However, treatment failures are frequently reported, suggesting inadequate eradication of chlamydiae from the sites of infection (21). C. trachomatis treatment failure has been observed in up to 14% of patients, whereas only 2% of patients seem to fail initial treatment in Mycobacterium tuberculosis infections (1,4). In addition, the propensity of C. trachomatis to induce persistent infections when subinhibitory antibiotic concentrations are applied is of major concern.…”

Section: Discussionmentioning

confidence: 99%

Impact of a Low-Oxygen Environment on the Efficacy of Antimicrobials against Intracellular Chlamydia trachomatis

Shima

Szaszák

Solbach

et al. 2011

Antimicrob Agents Chemother

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Emergence of chronic inflammation in the urogenital tract induced by Chlamydia trachomatis infection in females is a long-standing concern. To avoid the severe sequelae of C. trachomatis infection, such as pelvic inflammatory diseases (PID), ectopic pregnancies, and tubal infertility, antibiotic strategies aim to eradicate the pathogen even in asymptomatic and uncomplicated infections. Although first-line antimicrobials have proven successful for the treatment of C. trachomatis infection, treatment failures have been observed in a notable number of cases. Due to the obligate intracellular growth of C. trachomatis, reliable antimicrobial susceptibility assays have to consider environmental conditions and host cell-specific factors. Oxygen concentrations in the female urogenital tract are physiologically low and decrease further during an inflammatory process. We compared MIC testing and time-kill curves (TKC) for doxycycline, azithromycin, rifampin, and moxifloxacin under hypoxia (2% O 2 ) and normoxia (20% O 2 ). While low oxygen availability only moderately decreased the antichlamydial activity of azithromycin in conventional MIC testing (0.08 g/ml versus 0.04 g/ml; P < 0.05), TKC analyses revealed profound divergences for antibiotic efficacies between the two conditions. Thus, C. trachomatis was significantly less rapidly killed by doxycycline and azithromycin under hypoxia, whereas the efficacies of moxifloxacin and rifampin remained unaffected using concentrations at therapeutic serum levels. Chemical inhibition of multidrug resistance protein 1 (MDR-1), but not multidrug resistance-associated protein 1 (MRP-1), restored doxycycline activity against intracellular C. trachomatis under hypoxia. We suggest careful consideration of tissue-specific characteristics, including oxygen availability, when testing antimicrobial activities of antibiotics against intracellular bacteria.

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Clinical Characteristics and Treatment Outcomes of Patients with Isoniazid‐Monoresistant Tuberculosis

Cited by 98 publications

References 16 publications

First Evaluation of GenoType MTBDR plus 2.0 Performed Directly on Respiratory Specimens in Central America

First Evaluation of GenoType MTBDR plus 2.0 Performed Directly on Respiratory Specimens in Central America

Evaluation of Two Line Probe Assays for Rapid Detection of Mycobacterium tuberculosis, Tuberculosis (TB) Drug Resistance, and Non-TB Mycobacteria in HIV-Infected Individuals with Suspected TB

Impact of a Low-Oxygen Environment on the Efficacy of Antimicrobials against Intracellular Chlamydia trachomatis

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