International Journal of Mycobacteriology最新文献

Background: Information on genotypic with comparison of phenotypic drug sensitivity test of anti-tuberculosis (TB) has been reported in several studies, which have variable results. The present study aimed to assess the Genotype MTBDRsl version 2.0/Line probe assay (LPA) for the detection of fluoroquinolones (FQ) and aminoglycosides (AMGs) resistance mutations among drug-resistant Mycobacterium TB (MTB) strains and also to compare the patterns of genotypic mutations of gyrA/B, rrs, and eis with mycobacteria growth indicator tube (MGIT 960).

Methods: A total of 1416 samples were subjected to Genotype MTBDRsl version 2.0 assay. One hundred and twenty sputum smear positive MTB isolates and 37 sputum smear negative MTB isolates confirmed multiple drug resistance resistant to FQ and AMG by the Genotype MTBDRsl version 2.0 were subjected to phenotypic drug susceptibility testing (DST) were analyzed.

Results: The association sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the resistance detection between MGIT (DST) and the Genotype MTBDRsl version 2.0 assay was significant (P < 0.01) of moxifloxacin (MFX) concentration. Sensitivity and specificity value for kanamycin (KAN) resistance was 76% and 89%; 47% and 94% for capreomycin (CAP); and 60% and 76% for low-level KAN, respectively.

Conclusion: Our results indicate that MFX (0.25and 1 μg/mL), KAN (2.5 μg/mL), and CAP (2.5 μg/mL) significantly (P < 0.01) and support the World Health Organization guidance to test FQ and AMG by genotypic test.

Background: Mycobacterium tuberculosis is a bacterium that has historically had a substantial impact on human health. Despite advances in understanding and management of tuberculosis (TB), the disease remains a crucial problem that necessitates ongoing work to discover effective drugs, minimize transmission, and improve global health outcomes.

Methods: The purpose of this study is to use molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses to explore the molecular interactions of different proteins that are involved in mycolic acid biosynthesis (HadAB, InhA, KasA, FabD, and beta-ketoacyl-acyl carrier protein synthase III) of M. tuberculosis with Demospongiae metabolites. The docking findings were evaluated using the glide gscore, and the top 10 compounds docked against each protein receptor were chosen. Furthermore, the selected compounds underwent ADMET analysis, indicating that they have the potential for therapeutic development.

Results: Among the selected compounds, makaluvamine G showed the highest binding affinity against HadAB, psammaplysin E showed highest binding affinity against InhA, pseudotheonamide D showed the highest binding affinity against KasA protein, dinordehydrobatzelladine B showed the highest binding affinity against FabD, and nagelamide X showed the highest binding affinity against beta-ketoacyl-acyl carrier protein synthase III. Additionally, molecular mechanics generalized born surface area (MM-GBSA) binding free energy and molecular dynamics simulations were used to support the docking investigations.

Conclusion: The results of the study suggest that these compounds may eventually be used to treat TB. However, computer validations were included in this study, and more in vitro research is required to turn these prospective inhibitors into clinical drugs.

An 84-year-old man visited our hospital with a high fever. He had cut his right index finger 7 days previously. Blood culture became positive on day 3. Gram staining was negative, and acid-fast staining was positive. The organism was subsequently identified as Mycobacterium obuense using a MALDI Biotyper. M. obuense was also detected in the soil at the patient's house, suggesting that it had entered his bloodstream through the cut on his finger. He was treated with a combination of imipenem/cilastatin, amikacin, and clarithromycin for 2 weeks. His clinical condition improved, and he was discharged after 2 weeks and was prescribed clarithromycin and levofloxacin therapy. Only two cases of human infection with M. obuense have been reported previously.

Background: Fluoroquinolones (FQs) have substantial activity against the Mycobacterium tuberculosis complex (MTBc) by preventing bacterial DNA synthesis through DNA gyrase inhibition. The reference standard for FQ-resistance testing is phenotypic drug-susceptibility testing (pDST) based on growth inhibition of MTBc in drug-containing Mycobacteria Growth Indicator Tube system (MGIT) media at a critical concentration (CC) that differentiates phenotypically wild-type from nonwild-type MTBc and at a clinical breakpoint that identifies strains that will likely still respond to treatment at higher doses. Despite the recent introduction of powerful new TB drugs, highly sensitive detection of clinically defined FQ resistance remains key.

Method: In this study, we re-evaluated the current WHO-recommended CCs of Lfx (1.0 mg/ml), Mfx (0.25 mg/ml), Gfx (0.25 μg/ml), and the nowadays, obsolete CC of Ofx (2.0 mg/ml) for MGIT, using 147 MTBc isolates with known gyrA and gyrB sequences including both high-and low-level FQ resistance-conferring mutants. We tested a wide range of drug concentrations covering the current and former/obsolete WHO-recommended CCs for FQs and some intermediate concentrations to challenge the current WHO-recommended CCs.

Results: The specificity of all four CCs was 100%. The sensitivities varied: 92.4% for Ofx and Lfx, 85.7% for Mfx, and 83.2% for Gfx. Lowering the CC of Mfx to 0.125 mg/ml would allow to correctly classify all wild-type and mutant isolates while lowering the CC of Gfx to 0.125 mg/ml would still misclassify some gyrA/gyrB mutants as susceptible.

Conclusion: Based on our findings, a minimal inhibitory concentration of 0.125 mg/ml on MGIT medium is a more appropriate CC for Mfx and probably also as a surrogate for overall FQ resistance in the MTBc.

We present the case of a drug reaction with eosinophilia and systemic symptoms (DRESS) manifesting multi-organ dysfunction syndrome (MODS) that led to death in an elderly patient during the intensive phase of antitubercular therapy (ATT). A 74-year-old male developed skin rash (morbilliform), patchy erythematous macules, pustular-purpuric nonblanching spots, fever, lymphadenopathy, liver dysfunction, leukocytosis, and eosinophilia during intensive phase of ATT (ATT: day 45). Laboratory tests revealed hypereosinophilia (eosinophils; 10500/μL), hyperacute fulminant hepatic failure (aspartate transaminase/alanine transaminase; 1444/1375 IU/L, total bilirubin; 11.3 mg/dL), hepatic encephalopathy (Child-Pugh score: 15), coagulopathy (international normalized ratio; 3.0 and activated partial thromboplastin time; 52 s), and acute renal failure (serum creatinine; 2.6 mg/dL). The patient was diagnosed with DRESS with a RegiSCAR score of 7 (definite). ATT was discontinued. Despite immediate treatment with pulse methylprednisolone, N-acetylcysteine and sustained low-efficiency dialysis, the patient's clinical condition evolved to shock due to MODS (sequential organ failure Assessment: 15 points), and on day 51, he succumbed. Concluding, an elderly patient with high-dose antitubercular drugs needs a clinical management review. Clinical symptoms pertaining to DRESS may paradoxically worsen after 3-4 days of discontinuation of the offending drug.

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown.

Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991-2021).

Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations.

Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting.

Background: The purpose of this meta-analysis is to verify that rs1861494 and rs2069718, two polymorphisms in the IFN-gene, are associated with tuberculosis (TB) infection in Asian populations.

Methods: To find appropriate case-control studies, a search was done from the databases, including Google Scholar, Science Direct, Embase, and PubMed. With the aid of MetaGenyo software, statistical analyses were performed. Case and control studies from the available database were used to investigate the relationship between IFN-γ gene polymorphisms and TB infection risk. The protocol for the present meta-analysis was registered using PROSPERO (ID Number: 443605).

Results: Information obtained through examining two different variants of the IFN-γ gene showed associations with recessive, allelic, overdominant, and dominant models. This indicates that the statistical value obtained was found to be statistically significant at P = 0.05. The findings of the IFN-γ rs1861494 gene polymorphisms for allelic, dominant, and overdominant models were statistically significant with P > 0.05, whereas the recessive model exhibited a statistically insignificant value (P = 0.25). The IFN-γ rs2069718 gene polymorphism demonstrated statistically significant value for overdominant, recessive, and allelic models (P > 0.05). However, the dominant model shows a statistically insignificant value P = 0.11.

Conclusion: The two genetic variations of the IFN-γ gene polymorphisms (rs1861494 and rs2069718) and their association with TB were confirmed by the meta-analysis conducted. More in-depth research into the molecular basis of the association is necessary, and larger-scale epidemiological studies are needed to confirm these findings.

Background: The guidelines for the requirement of Legionella urinary antigen tests on admission for patients hospitalized with community-acquired pneumonia differ in Japan, the United States, and Europe. We aimed to evaluate the association between the timing of Legionella urinary antigen testing and inhospital mortality in patients with atypical pneumonia.

Methods: We identified 654,708 patients with atypical pneumonia from July 2010 to March 2021 using the Japanese national inpatient database. The patients were divided into groups that underwent Legionella urinary antigen tests on the day of admission (test group, n = 229,649) and those that underwent testing after the day of admission or were untested (control group, n = 425,059). A propensity score-stabilized inverse probability of treatment weighting analysis was performed to compare inhospital mortality, length of hospital stay, and total hospitalization costs between the two groups. Odds ratios (ORs) or differences and their 95% confidence intervals (CIs) were calculated using generalized linear models.

Results: The tested group had a significantly lower 30-day inhospital mortality than that of the control group (7.7% vs. 9.0%; OR: 0.83 [95% CIs, 0.81-0.86]). The tested group also had a significantly shorter length of stay (difference, -2.3 [-2.6 to - 2.0] days and total hospitalization costs (-396 [-508 to - 285] US dollars) than that of the control group.

Conclusions: Legionella urinary antigen testing upon admission is associated with better outcomes in patients with atypical pneumonia. Legionella urinary antigen testing performed on the day of admission is recommended for hospitalized patients with atypical pneumonia.

Background: Fluoroquinolone (FQ) antibiotics are among the most potent second-line antitubercular drugs these days. The aim of the study was to analyze the frequency and pattern of genetic mutation in preextensive (pre-XDR) and extensively drug-resistant Mycobacterium tuberculosis using second-line line probe assay (LPA) and to compare drug-resistant mutations with different treatment outcomes.

Methods: Sputum, lymph node aspirate, and cold accesses from patients with rifampicin-resistant Tuberculosis (TB) were subjected to first-line and second-line LPA (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluoroquinolones (levofloxacin and moxifloxacin). Final treatment outcomes as per the National TB Elimination Program were assessed and compared with the mutation profile.

Results: One hundred and fifty subjects were observed to have mutations associated with resistance to FQs and constituted the final study population. The most frequent mutation observed among GyrA drug resistance mutation was D94G (Gyr A MUT3C, 44/150, 66%) corresponding to high-level resistance to levofloxacin and moxifloxacin. The same mutation was associated with poor treatment outcome as died or treatment failure (odds ratio 2.50, relative risk 1.67, P = 0.043). The most common hetero-resistance mutation pattern observed in GyrA gene was wild type plus Asp94Gly mutation in 24.6% of isolates.

Conclusions: GyrA MUT3C hybridization corresponding to single-point mutation of aspartic acid to glycine at codon 94 constitutes the most common mutation in GyrA gene locus in M. tuberculosis with significant association with treatment outcome as died compared to those with treatment outcome as cured.