scholarly journals Distribution of Linezolid in Tuberculosis Lesions in Patients with Spinal Multidrug-Resistant Tuberculosis

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Yuan Li ◽  
Weijie Dong ◽  
Tinglong Lan ◽  
Jun Fan ◽  
Shibing Qin ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Granulation Tissue ◽  
High Performance ◽  
Multidrug Resistant ◽  
Sample Collection ◽  
Tissue Samples ◽  
Content Type ◽  
Mdr Tb ◽  
The Mean ◽  
The Difference

ABSTRACT Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study was to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples, and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography-tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, and 14.08 ± 10.61 mg/liter, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t = −2.810, P = 0.015; t = −4.901, P = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB-infected tissues in patients with spinal MDR-TB.

scholarly journals A study to know the various causes of pleural effusion and role of pleural fluid adenosine deaminase enzyme in tuberculous pleural effusion

2020 ◽  
Vol 8 (4) ◽  
pp. 1231
Author(s):  
Avdhesh Kumar ◽  
Brijesh Kumar ◽  
Sanjay Kumar Verma ◽  
Anand Kumar ◽  
R. K. Mathur ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Common Cause ◽  
Tuberculous Pleural Effusion ◽  
Mdr Tb ◽  
The Mean ◽  
The Difference

Background: India has the maximum burden of both non MDR tuberculosis (TB) and Multidrug-Resistant (MDR) TB, as per data reported in Global TB Report 2018 and tuberculosis is remains one of the most common cause of pleural effusions.Methods: This was a cross-sectional study conducted in Department of Respiratory Diseases and a total of 110 patients with pleural effusion were included in the study, which were enrolled for treatment from July 2018 to June 2019.Results: One hundred and ten patients with pleural effusion were enrolled during the study period. There were 65 males (59%) and 45 (40.9%) females.  The overall mean age for males and females were 44.4±18.84 years (35-87 years) and 38.28±17.66 years (35-87 years) respectively. Tuberculous Pleural Effusion group (TPE) seen in 82 patients. Right sided pleural effusion (69.5 %) were more common than left sided (30.4 %). In TPE group the mean pleural fluid ADA level were 86.41±38.08 IU/L (range: 14-195 IU/L). The Malignant Pleural Effusion (MPE) group included 21 patients. In MPE group the mean pleural fluid ADA level were 34.10±32.88 IU/L (range: 8-144 IU/L). The difference in pleural fluid ADA levels between TPE and MPE group was statistically highly significant.Conclusions: Tuberculous pleural effusion was the most common cause of pleural effusion in present study and observed in 74.5% cases.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Cost of illness of non-multidrug-resistant tuberculosis in Germany: an update

2020 ◽  
Vol 6 (4) ◽  
pp. 00329-2020
Author(s):  
Roland Diel ◽  
Albert Nienhaus
Keyword(s):  
Central Committee ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Current Therapy ◽  
Productivity Losses ◽  
Public Health Screening ◽  
Mdr Tb ◽  
The Mean ◽  
Mean Cost

BackgroundA total of 5429 new cases of tuberculosis (TB) were reported in Germany in 2018; out of the 3780 TB cases for whom drug susceptibility testing was available, the proportion of multidrug-resistant TB (MDR-TB) cases was only 3.1% (118 cases).MethodsOn the basis of the current therapy guidelines of the German Central Committee against Tuberculosis, this study estimates the mean direct outpatient and combined in- and outpatient costs per non-MDR-TB patient from the perspective of the German statutory health insurance (SHI) system, together with costs arising from productivity losses and costs due to public health screening for TB in close contacts.ResultsFrom the insurance perspective, the mean outpatient costs (rounded) per case were €1628 for adults and €1179 for children for standard therapy; the mean cost of inpatient treatment amounted to €8626. The mean combined inpatient/outpatient cost was €8756 for adults and €8512 for children. As 95% of all TB patients were adults, the weighted treatment cost per patient in Germany in 2018 was €8746. These are in addition to the mean cost arising from productivity losses (€1839) and, weighted by pulmonary infectivity, cost of contact investigations (€368), coming to a total of €10 953.ConclusionGiven the clear increase in the number of non-MDR-TB cases since 2015, TB is still a disease of significant economic impact in Germany.

scholarly journals Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Agibothu Kupparam Hemanth Kumar ◽  
Alok Kumar ◽  
Thiruvengadam Kannan ◽  
Rakesh Bhatia ◽  
Dipti Agarwal ◽  
...  
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Second Line ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

scholarly journals Imipenem/Cilastatin/Relebactam Alone and in Combination against Pseudomonas aeruginosa in the In Vitro Pharmacodynamic Model

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Iris H. Chen ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Pharmacodynamic Model ◽  
Resistance Development ◽  
Content Type ◽  
Combination Studies ◽  
The Mean ◽  
Combined Drugs

ABSTRACT Combination therapy may enhance imipenem/cilastatin/relebactam’s (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible P. aeruginosa isolates in an in vitro pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were −2.52 ± 0.49, −1.49 ± 0.49, −1.15 ± 0.67, and −0.61 ± 0.10 log10 CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic (n = 1) or additive (n = 2) interactions against three isolates with 24-h CFU reductions ranging from −2.62 to −4.67 log10 CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving −0.51- to −3.33-log10 CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant P. aeruginosa, I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some P. aeruginosa, whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.

Pressure in the sagittal sinus during intracranial hypertension in man

1974 ◽  
Vol 40 (5) ◽  
pp. 603-608 ◽  
Author(s):  
Albert N. Martins ◽  
Arthur I. Kobrine ◽  
Douglas F. Larsen
Keyword(s):  
Brain Tumors ◽  
Intracranial Hypertension ◽  
Cerebral Blood Volume ◽  
Content Type ◽  
Sagittal Sinus ◽  
Sagittal Sinus Pressure ◽  
The Mean ◽  
The Difference ◽  
Spatial Compensation ◽  
Sinus Pressure

✓ Intracranial pressure (ICP) and sagittal sinus pressure (SSP) were measured simultaneously in 12 patients with brain tumors and secondary intracranial hypertension (ICH). In nine, the mean SSP was largely unaffected by changes in ICP. In three, SSP changed with the ICP. In all but one patient, the ICP remained higher than SSP and, as the ICP increased, the difference between the two also increased. Sinograms performed during ICH demonstrated partial collapse of the sinuses in some patients and not in others. The mean SSP in adults with brain tumors appears to respond unpredictably to changes in ICP. Since the rate of cerebrospinal fluid drainage depends upon the gradient between ICP and SSP, intracranial spatial compensation is probably influenced by the response of SSP to ICP. Individuals with gradients that rapidly increase because their sinuses do not collapse probably compensate more rapidly than those whose sinuses do collapse. This assumed difference in the rate of spatial compensation may account for some of the variability of the ICP response to an enlarging intracranial mass or a change in cerebral blood volume.

scholarly journals Mutations ingyrAandgyrBamong Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates

2016 ◽  
Vol 60 (4) ◽  
pp. 2090-2096 ◽  
Author(s):  
Jung-Yien Chien ◽  
Wei-Yih Chiu ◽  
Shun-Tien Chien ◽  
Chia-Jung Chiang ◽  
Chong-Jen Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
East Asian ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Content Type ◽  
Low Level ◽  
High Prevalence ◽  
Mdr Tb ◽  
High Level

ABSTRACTIn order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.

scholarly journals Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

2015 ◽  
Vol 59 (12) ◽  
pp. 7805-7810 ◽  
Author(s):  
Johana Rueda ◽  
Teresa Realpe ◽  
Gloria Isabel Mejia ◽  
Elsa Zapata ◽  
Juan Carlos Rozo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Content Type ◽  
Genotypic Analysis ◽  
Mdr Tb ◽  
Proportion Method ◽  
Emergence Of Resistance ◽  
Phenotypic Susceptibility

ABSTRACTEthionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in theMycobacterium tuberculosispopulation. ETH resistance inM. tuberculosisis phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in theinhApromoter and in the following genes:katG,ethA,ethR,mshA,ndh, andinhA. We sequenced the above genes in 64M. tuberculosisisolates (n= 57 ETH-resistant MDR-TB isolates;n= 3 ETH-susceptible MDR-TB isolates; andn= 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% inkatG, 72% inethA, 45.6% inmshA, 8.7% inndh, and 33.3% ininhAor its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations inkatG; one had a mutation inethA, and another, inmshAandinhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations inmshAgene unrelated to the resistance. Mutations not previously reported were found in theethA,mshA,katG, andndhgenes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in theM. tuberculosisisolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

scholarly journals Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Kingsley King-Gee Tam ◽  
Kenneth Siu-Sing Leung ◽  
Gilman Kit-Hang Siu ◽  
Kwok-Chiu Chang ◽  
Samson Sai-Yin Wong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Direct Detection ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Activity Data ◽  
Content Type ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Respiratory Specimens

ABSTRACT An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

scholarly journals Simple Assay for Detection of the Central Asia Outbreak Clade of theMycobacterium tuberculosisBeijing Genotype

2019 ◽  
Vol 57 (7) ◽  
Author(s):  
Egor Shitikov ◽  
Anna Vyazovaya ◽  
Maja Malakhova ◽  
Andrei Guliaev ◽  
Julia Bespyatykh ◽  
...  
Keyword(s):  
Soviet Union ◽  
Molecular Marker ◽  
Central Asia ◽  
Former Soviet Union ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Beijing Genotype ◽  
Data Set ◽  
Content Type ◽  
Mdr Tb

ABSTRACTThe Central Asia outbreak (CAO) clade is a branch of theMycobacterium tuberculosisBeijing genotype that is associated with multidrug resistance, increased transmissibility, and epidemic spread in parts of the former Soviet Union. Furthermore, migration flows bring these strains far beyond their areas of origin. We aimed to find a specific molecular marker of the Beijing CAO clade and develop a simple and affordable method for its detection. Based on the bioinformatics analysis of the largeM. tuberculosiswhole-genome sequencing (WGS) data set (n = 1,398), we identified an IS6110insertion in theRv1359-Rv1360intergenic region as a specific molecular marker of the CAO clade. We further designed and optimized a multiplex PCR method to detect this insertion. The method was validatedin silicowith the recently published WGS data set from Central Asia (n = 277) and experimentally withM. tuberculosisisolates from European and Asian parts of Russia, the former Soviet Union, and East Asia (n = 319). The developed molecular assay may be recommended for rapid screening of retrospective collections and for prospective surveillance when comprehensive but expensive WGS is not available or practical. The assay may be especially useful in high multidrug-resistant tuberculosis (MDR-TB) burden countries of the former Soviet Union and in countries with respective immigrant communities.

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