Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey

Early diagnosis and appropriate treatment for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infection is a big challenge for clinicians due to its high mortality. Every effort has been made to improve its clinical outcomes. However, treatment according to synergy susceptibility testing has never been reported in the literature. We reported a 29-year-old systemic lupus erythematosus female with CR-Kp blood stream infection. We highlighted the identification by next generation sequencing and treatment according to synergy susceptibility testing in the case.

Download Full-text

TB Elimination Requires Discovery and Development of Transformational Agents

Applied Sciences ◽

10.3390/app10072605 ◽

2020 ◽

Vol 10 (7) ◽

pp. 2605 ◽

Cited By ~ 1

Author(s):

Christian Lienhardt ◽

Mario C. Raviglione

Keyword(s):

Rapid Detection ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

New Drugs ◽

World Health ◽

Drug Resistant ◽

The World ◽

Health Organization ◽

Combination Regimens

The World Health Organization (WHO) End Tuberculosis (TB) Strategy has set ambitious targets to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. Given the current rate of TB incidence decline (about 2% per year annually), reaching these targets will require new transformational tools and innovative ways to deliver them. In addition to improved tests for early and rapid detection of TB and universal drug-susceptibility testing, as well as novel vaccines for improved prevention, better, safer, shorter and more efficacious treatments for all forms of TB are needed. Only a handful of new drugs are currently in phase II or III clinical trials, and a few combination regimens are being tested, mainly for drug-resistant TB. In this article, capitalising on an increasingly rich medicine pipeline and taking advantage of new methodological designs with great potential, the main areas where progress is needed for a transformational improvement of treatment of all forms of TB are described.

Download Full-text

Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

Epidemiology and Infection ◽

10.1017/s0950268819001006 ◽

2019 ◽

Vol 147 ◽

Cited By ~ 5

Author(s):

R. S. Salvato ◽

S. Schiefelbein ◽

R. B. Barcellos ◽

B. M. Praetzel ◽

I. S. Anusca ◽

...

Keyword(s):

Susceptibility Testing ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Molecular Characterisation ◽

Drug Resistant ◽

Isoniazid Resistance ◽

High Burden ◽

Brics Countries ◽

Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

Download Full-text

Susceptibility Testing of Extensively Drug-Resistant and Pre-Extensively Drug-Resistant Mycobacterium tuberculosis against Levofloxacin, Linezolid, and Amoxicillin-Clavulanate

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02020-12 ◽

2013 ◽

Vol 57 (6) ◽

pp. 2522-2525 ◽

Cited By ~ 20

Author(s):

Imran Ahmed ◽

Kauser Jabeen ◽

Raunaq Inayat ◽

Rumina Hasan

Keyword(s):

Mycobacterium Tuberculosis ◽

Susceptibility Testing ◽

Critical Concentration ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Fluoroquinolone Resistance ◽

Drug Resistant ◽

Content Type ◽

Extensively Drug Resistant ◽

Amoxicillin Clavulanate

ABSTRACTPakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR)Mycobacterium tuberculosisagainst LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC.M. tuberculosisH37Rv was used as a control strain. A total of 102M. tuberculosisisolates (XDR,n= 59; pre-XDR,n= 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases.

Download Full-text

Integration of Mycobacterium tuberculosis Drug Susceptibility Testing and Genotyping with Epidemiological Data Analysis To Gain Insight into the Epidemiology of Drug-Resistant Tuberculosis in Malatya, Turkey

Journal of Clinical Microbiology ◽

10.1128/jcm.02459-09 ◽

2010 ◽

Vol 48 (9) ◽

pp. 3301-3305 ◽

Cited By ~ 4

Author(s):

M. Agarwal ◽

S. Gunal ◽

R. Durmaz ◽

Z. Yang

Keyword(s):

Mycobacterium Tuberculosis ◽

Data Analysis ◽

Susceptibility Testing ◽

Epidemiological Data ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Insight Into

Download Full-text

Simple, direct drug susceptibility testing technique for diagnosis of drug-resistant tuberculosis in resource-poor settings

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.12.1009 ◽

2013 ◽

Vol 17 (9) ◽

pp. 1212-1216 ◽

Cited By ~ 4

Author(s):

C-K. Kim ◽

Y-T. Joo ◽

E. P. Lee ◽

Y. K. Park ◽

H-J. Kim ◽

...

Keyword(s):

Susceptibility Testing ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Drug Resistant ◽

Testing Technique ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Resource Poor

Download Full-text

Sensititre MycoTB Plate Compared to Bactec MGIT 960 for First- and Second-Line Antituberculosis Drug Susceptibility Testing in Tanzania: a Call To Operationalize MICs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01117-15 ◽

2015 ◽

Vol 59 (11) ◽

pp. 7104-7108 ◽

Cited By ~ 29

Author(s):

Scott K. Heysell ◽

Suporn Pholwat ◽

Stellah G. Mpagama ◽

Saumu J. Pazia ◽

Happy Kumburu ◽

...

Keyword(s):

Susceptibility Testing ◽

Acquired Resistance ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Drug Resistant ◽

Second Line ◽

Drug Resistant Tuberculosis ◽

Content Type ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant

ABSTRACTMIC testing forMycobacterium tuberculosisis now commercially available. Drug susceptibility testing by the MycoTB MIC plate has not been directly compared to that by the Bactec MGIT 960. We describe a case of extensively drug-resistant tuberculosis (XDR-TB) in Tanzania where initial MIC testing may have prevented acquired resistance. From testing on archived isolates, the accuracy with the MycoTB plate was >90% for important first- and second-line drugs compared to that with the MGIT 960, and clinically useful quantitative interpretation was also provided.

Download Full-text

A standardised method for interpreting the association between mutations and phenotypic drug resistance inMycobacterium tuberculosis

European Respiratory Journal ◽

10.1183/13993003.01354-2017 ◽

2017 ◽

Vol 50 (6) ◽

pp. 1701354 ◽

Cited By ~ 135

Author(s):

Paolo Miotto ◽

Belay Tessema ◽

Elisa Tagliani ◽

Leonid Chindelevitch ◽

Angela M. Starks ◽

...

Keyword(s):

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Clear Understanding ◽

Drug Resistant ◽

Resistant Tuberculosis ◽

Statistical Measures ◽

Correlation Data ◽

Phenotypic Methods ◽

Generation Sequencing ◽

Phenotypic Drug Resistance

A clear understanding of the genetic basis of antibiotic resistance inMycobacterium tuberculosisis required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6–90.9%), while for isoniazid it was 78.2% (77.4–79.0%) and their specificities were 96.3% (95.7–96.8%) and 94.4% (93.1–95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1–70.6%) for capreomycin to 88.2% (85.1–90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1–92.5%) for moxifloxacin to 99.5% (99.0–99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors ofM. tuberculosisdrug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.

Download Full-text