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1.
Sensors (Basel) ; 23(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36679772

RESUMO

This review summarizes the literature data reported from 2000 up to the present on the development of various electrochemical (voltammetric, amperometric, potentiometric and photoelectrochemical), optical (UV-Vis and IR) and luminescence (chemiluminescence and fluorescence) methods and the corresponding sensors for rifamycin antibiotics analysis. The discussion is focused mainly on the foremost compound of this class of macrocyclic drugs, namely rifampicin (RIF), which is a first-line antituberculosis agent derived from rifampicin SV (RSV). RIF and RSV also have excellent therapeutic action in the treatment of other bacterial infectious diseases. Due to the side-effects (e.g., prevalence of drug-resistant bacteria, hepatotoxicity) of long-term RIF intake, drug monitoring in patients is of real importance in establishing the optimum RIF dose, and therefore, reliable, rapid and simple methods of analysis are required. Based on the studies published on this topic in the last two decades, the sensing principles, some examples of sensors preparation procedures, as well as the performance characteristics (linear range, limits of detection and quantification) of analytical methods for RIF determination, are compared and correlated, critically emphasizing their benefits and limitations. Examples of spectrometric and electrochemical investigations of RIF interaction with biologically important molecules are also presented.


Assuntos
Mycobacterium tuberculosis , Rifamicinas , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Rifamicinas/farmacologia , Antituberculosos
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(1): 62-66, 2023 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-36617931

RESUMO

At present, the number of cases with multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in China ranks fourth in the world, and the prevention and control situation is still serious. Chemotherapy, as the most important treatment for MDR/RR-TB, was studied and explored by domestic and foreign researchers in 2022. New chemotherapeutic drugs such as delpazolid, sutezolid, telacebec and independently developed anti-tuberculosis drugs such as pyrifazimine, sudapyridine and JBD0131 are still in clinical trials. The efficacy, safety, tolerability, adverse reactions and drug resistance of bedaquiline, linezolid, delamanid and pretomanid have been studied extensively. Meanwhile, different new chemotherapy regimens centered on new drugs have been explored in-depth by international scholars. In this article, we reviewed the progress of chemotherapy of multidrug/rifampicin-resistant tuberculosis from October 2021 to September.


Assuntos
Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Linezolida/uso terapêutico
3.
BMC Genomics ; 24(1): 26, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646991

RESUMO

BACKGROUND: Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) is a frequently used typing method for identifying the Beijing genotype of Mycobacterium tuberculosis (Mtb), which is easily transformed into rifampicin (RIF) resistance. The RIF resistance of Mtb is considered to be highly related with the mutation of rpoB gene. Therefore, this study aimed to analyze the relationship between the repetitive number of MIRU loci and the mutation of rpoB gene. METHODS: An open-source whole-genome sequencing data of Mtb was used to detect the mutation of rpoB gene and the repetitive number of MIRU loci by bioinformatics methods. Cochran-Armitage analysis was performed to analyze the trend of the rpoB gene mutation rate and the repetitive number of MIRU loci. RESULTS: Among 357 rifampicin-resistant tuberculosis (RR-TB), 304 strains with mutated rpoB genes were detected, and 6 of 67 rifampicin susceptible strains were detected mutations. The rpoB gene mutational rate showed an upward trend with the increase of MIRU10, MIRU39, QUB4156 and MIRU16 repetitive number, but only the repetitive number of MIRU10, MRIU39 and QUB4156 were risk factors for rpoB gene mutation. The Hunter-Gaston discriminatory index (HGDI) of MIRU10 (0.65) and QUB4156 (0.62) was high in the overall sample, while MIRU39 (0.39) and MIRU16 (0.43) showed a moderate discriminatory Power. CONCLUSION: The mutation rate of rpoB gene increases with the addition of repetitive numbers of MIRU10, QUB4156 and MIRU39 loci.


Assuntos
Proteínas de Bactérias , DNA Polimerase Dirigida por DNA , Taxa de Mutação , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Técnicas de Tipagem Bacteriana/métodos , Genótipo , Repetições Minissatélites , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , DNA Polimerase Dirigida por DNA/genética , Proteínas de Bactérias/genética
4.
PLoS One ; 18(1): e0280020, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36603010

RESUMO

Hydrocephalus is a neurological disease caused by an unusually high level of cerebrospinal fluid (CSF), which can be relieved by external ventricular drainage (EVD) insertion. However, the infection can lead to complications during the use of EVD. In this study, EVD was impregnated with three synergistic antibiotics, including rifampicin, clindamycin, and trimethoprim, to improve the antibacterial property. The impregnated drainage was studied for its characteristics in vitro and in vivo. Drug loading determination revealed that rifampicin had the highest concentration in the tube, followed by clindamycin and trimethoprim, respectively. In vitro cytotoxicity and hemolytic studies showed no toxic effects from antibiotics-impregnated EVD on fibroblast and red blood cells. For antibacterial testing, the impregnated EVD exhibited antibacterial activity against Staphylococcus aureus MRSA and Staphylococcus epidermidis up to 14 and 90 days, respectively. Moreover, biocompatibility and drug release into the bloodstream and surrounding tissues were investigated by implantation in rabbits for 30 days. Histology and morphology results showed that fibroblast cells began to adhere to the drainage surface and inflammatory cell numbers were noticeably small after the long-term implantation. In addition, there was no drug leakage to the bloodstream and surrounding tissues. Hence, this impregnated EVD can potentially be used for antibacterial application.


Assuntos
Infecções Relacionadas a Cateter , Doença pelo Vírus Ebola , Hidrocefalia , Animais , Coelhos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clindamicina/farmacologia , Rifampina/farmacologia , Infecções Relacionadas a Cateter/etiologia , Doença pelo Vírus Ebola/complicações , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Trimetoprima , Drenagem/efeitos adversos , Hidrocefalia/cirurgia , Estudos Retrospectivos
5.
Proc Natl Acad Sci U S A ; 120(2): e2216216120, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36595701

RESUMO

The rise of antibiotic-resistant bacterial infections poses a global threat. Antibiotic resistance development is generally studied in batch cultures which conceals the heterogeneity in cellular responses. Using single-cell imaging, we studied the growth response of Escherichia coli to sub-inhibitory and inhibitory concentrations of nine antibiotics. We found that the heterogeneity in growth increases more than what is expected from growth rate reduction for three out of the nine antibiotics tested. For two antibiotics (rifampicin and nitrofurantoin), we found that sub-populations were able to maintain growth at lethal antibiotic concentrations for up to 10 generations. This perseverance of growth increased the population size and led to an up to 40-fold increase in the frequency of antibiotic resistance mutations in gram-negative and gram-positive species. We conclude that antibiotic perseverance is a common phenomenon that has the potential to impact antibiotic resistance development across pathogenic bacteria.


Assuntos
Antibacterianos , Escherichia coli , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Rifampina/farmacologia , Mutação , Bactérias , Farmacorresistência Bacteriana/genética
6.
Sci Rep ; 13(1): 623, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635309

RESUMO

Resistance to isoniazid (INH) and rifampicin (RIF) first-line drugs in Mycobacterium tuberculosis (Mtb), together called multi-drug resistance, threatens tuberculosis control. Resistance mutations in katG (for INH) and rpoB (RIF) genes often come with fitness costs. To overcome these costs, Mtb compensatory mutations have arisen in rpoC/rpoA (RIF) and ahpC (INH) loci. By leveraging the presence of known compensatory mutations, we aimed to detect novel resistance mutations occurring in INH and RIF target genes. Across ~ 32 k Mtb isolates with whole genome sequencing (WGS) data, there were 6262 (35.7%) with INH and 5435 (30.7%) with RIF phenotypic resistance. Known mutations in katG and rpoB explained ~ 99% of resistance. However, 188 (0.6%) isolates had ahpC compensatory mutations with no known resistance mutations in katG, leading to the identification of 31 putative resistance mutations in katG, each observed in at least 3 isolates. These putative katG mutations can co-occur with other INH variants (e.g., katG-Ser315Thr, fabG1 mutations). For RIF, there were no isolates with rpoC/rpoA compensatory mutations and unknown resistance mutations. Overall, using WGS data we identified putative resistance markers for INH that could be used for genotypic drug-resistance profiling. Establishing the complete repertoire of Mtb resistance mutations will assist the clinical management of tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Tuberculose/microbiologia , Rifampina/farmacologia , Genômica , Proteínas de Bactérias/genética , Testes de Sensibilidade Microbiana
7.
J Clin Microbiol ; 61(1): e0108622, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36602360

RESUMO

The World Health Organization recently lowered the rifampin (RIF) critical concentration (CC) for drug-susceptibility testing (DST) of Mycobacterium tuberculosis complex (MTBC) using the mycobacterial growth indicator tube (MGIT) 960 system. Here, we evaluated the diagnostic performance of the MGIT system with the revised CC for determining MTBC RIF resistance with 303 clinical MTBC isolates, including 122 isolates with rpoB mutations, of which 32 had single borderline-resistance mutations, and 181 wild-type rpoB isolates. The phenotypic RIF resistance was determined via the absolute concentration method (AC) and via MGIT using both previous (1 mg/L) and revised (0.5 mg/L) CCs for the latter method. The diagnostic accuracy of each phenotypic DST (pDST) was assessed based on rpoB genotyping as the reference standard. The overall sensitivity of the AC was 95.1% (95% confidence interval [CI], 89.6 to 98.2%), while the MGIT results with previous and revised CCs were 82.0% (95% CI 74.0 to 88.3%) and 83.6% (95% CI 75.8 to 89.7%), respectively. The 32 MTBC isolates with single borderline-resistance mutations showed a wide range of MICs, and sensitivity was not significantly increased by reducing the MGIT CC. All 181 wild-type rpoB isolates were RIF-susceptible in the AC and with MGIT using the previous CC, whereas 1 isolate was misclassified as RIF-resistant with the revised CC. Our results demonstrate that the overall diagnostic performances of the MGIT DST with the revised RIF CC and previous CC were comparable. A further large-scale study is required to demonstrate the optimal RIF CC for MGIT.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/farmacologia , Mutação , Testes de Sensibilidade Microbiana , RNA Polimerases Dirigidas por DNA/genética , Antituberculosos/farmacologia
8.
Trop Med Int Health ; 28(1): 43-52, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36477995

RESUMO

OBJECTIVE: To investigate the time to treatment initiation (TTI) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients after diagnosis in Indonesia and biological, psychological and social factors associated with the time interval. METHODS: This study was conducted in Persahabatan Hospital, Jakarta using a mixed-methods approach. Registry data and medical records of MDR/RR-TB patients were collected and matched (hospital dataset), and linked with psychosocial assessment results (linked dataset). Descriptive analysis was conducted to understand patient characteristics and the distribution of TTI after RR-TB diagnosis by GeneXpert. Generalised linear regression was used to analyse factors associated with delay duration, and logistic regression to explore factors associated with the delay longer than the median duration for both datasets (basic vs. extended model). In-depth interviews were conducted with patients and healthcare workers to understand the procedure of treatment initiation and how different factors led to delay. RESULTS: The hospital dataset included 275 patient-matched cases, and 188 were further linked with psychosocial assessment results. The median time interval was 24 days [interquartile range (IQR) 23.5] and 26 days (IQR 21.25), respectively. Regression analysis showed that in the extended model, comorbidities (exp [coefficient]= 1.93), unemployment (exp [coefficient] = 1.80) and poor knowledge of MDR/RR-TB (exp (coefficient) = 1.67) seemed to have the strongest effects on prolonging the time interval (p < 0.05). Unsuccessful TB treatment history was the only factor that significantly increased the risk of delay longer than the median duration (p < 0.05) in the basic model, while none of the factors were significant in the extended model. The qualitative study identified provider-side factors (centralised service provision and insufficient human resources) and patient-side factors (physical weakness, psychological stress and financial concern) associated with treatment delay. CONCLUSION: MDR/RR-TB patients in Persahabatan Hospital, Jakarta, Indonesia waited around 25 days for treatment initiation after RR-TB diagnosis. Health system solutions are needed to address challenges facing both MDR/RR-TB patients and healthcare providers to reduce delay in treatment initiation.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/uso terapêutico , Rifampina/farmacologia , Tempo para o Tratamento , Indonésia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia
9.
Braz. j. biol ; 83: e244311, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285616

RESUMO

Abstract Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.


Resumo A tuberculose é uma doença transmissível com altas taxas de morbimortalidade nos países em desenvolvimento. O objetivo principal do estudo é comparar métodos convencionais, como cultura de bacilo álcool-ácido resistente (BAAR) e microscopia, com métodos de diagnóstico rápido. O objetivo secundário é comparar os achados histopatológicos e microbiológicos em pacientes com suspeita de linfadenite tubercular. Um total de 111 amostras (agosto de 2018 a setembro de 2019) de gânglios linfáticos foi processado ​​para microscopia de AFB, culturas de AFB, teste de susceptibilidade a drogas (DST), histopatologia e Xpert Mycobacterium tuberculosis (MTB)/ensaios de resistência à rifampicina (RIF). Das 111 amostras de linfonodos, 6 (5,4%) foram positivas para baciloscopia de AFB, 84 (75,6%) foram positivas para cultura de AFB, 80 (70,7%) foram positivas para o GeneXpert e 102 (91,8%) foram indicativas de tuberculose para estudos histopatológicos. A positividade da cultura do tubo indicador de crescimento de micobactérias (MGIT) foi 84 (75,6%), maior que a cultura sólida de Lowenstein-Jensen (LJ), 74 (66,6%). As culturas positivas foram submetidas a DST fenotípico. Dois casos eram multirresistentes (MDR) ao DST, enquanto três casos eram resistentes à rifampicina no GeneXpert. A sensibilidade do GeneXpert foi 62% contra o método convencional de cultura AFB. O fraco desempenho dos métodos convencionais de diagnóstico de linfadenite requer metodologia de diagnóstico precoce e precisa. O teste Xpert MTB/RIF pode ajudar no tratamento de casos de tuberculose multirresistente. No entanto, métodos rápidos e convencionais devem ser usados ​​para o isolamento completo do Mycobacterium tuberculosis.


Assuntos
Humanos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos , Mycobacterium tuberculosis , Rifampina/uso terapêutico , Rifampina/farmacologia
10.
Indian J Tuberc ; 69(4): 635-640, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36460401

RESUMO

AIMS: The aim of the study was to determine the performance of Xpert MTB/RIF assay in diagnosing tuberculosis on thoracoscopic pleural biopsies in exudative pleural effusion. METHODS: Patients who underwent thoracoscopic pleural biopsy in the defined period were included in the study. Histopathology was done for all and Xpert MTB RIF assay and AFB culture of pleural biopsy specimen and pleural fluid were done as per the clinician's discretion. RESULTS: Total of 110 patients underwent pleural biopsy and tissue Xpert MTB/RIF and MTB culture were done in 29 patients. XpertMTB/RIF assay and MTB culture had a sensitivity of 59% and 35% respectively and specificity of specificity of 100. CONCLUSION: The study described the ability of XPERT MTB/RIF in getting additional diagnostic information from thoracoscopic Pleural biopsy. Pleural biopsy Xpert MTB/RIF had sensitivity of 59% and specificity of 100% in diagnosing TPE. In addition to the diagnosis, Xpert MTB/RIF can also give valuable information about rifampicin resistance too. XPERT MTB/RIF assay also helped in getting diagnosis when histopathology alone was not able to confirm or rule out the diagnosis of TPE. Pleural fluid ADA of 38 IU/L had a sensitivity of 71% and a specificity of 86% for diagnosis of TPE in present study.


Assuntos
Derrame Pleural , Rifampina , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Pleura , Derrame Pleural/diagnóstico , Biópsia , Exsudatos e Transudatos
11.
Sci Rep ; 12(1): 20766, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456664

RESUMO

Whiteflies are among the most important global insect pests in agriculture; their sustainable control has proven challenging and new methods are needed. Bacterial symbionts of whiteflies are poorly understood potential target of novel whitefly control methods. Whiteflies harbour an obligatory bacterium, Candidatus Portiera aleyrodidarum, and a diverse set of facultative bacterial endosymbionts. Function of facultative microbial community is poorly understood largely due to the difficulty in their selective elimination without removal of the primary endosymbiont. Since the discovery of secondary endosymbionts, antibiotic rifampicin has emerged as the most used tool for their manipulation. Its effectiveness is however much less clear, with contrasting reports on its effects on the endosymbiont community. The present study builds upon most recent method of rifampicin application in whiteflies and evaluates its ability to eliminate obligatory Portiera and two facultative endosymbionts (Rickettsia and Arsenophnus). Our results show that rifampicin reduces but does not eliminate any of the three endosymbionts. Additionally, rifampicin causes direct negative effect on whiteflies, likely by disrupting mitochondria. Taken together, results signify the end of a rifampicin era in whitefly endosymbiont studies. Finally, we propose refinement of current quantification and data analysis methods which yields additional insights in cellular metabolic scaling.


Assuntos
Halomonadaceae , Hemípteros , Rickettsia , Animais , Rifampina/farmacologia , Antibacterianos/farmacologia
12.
N Engl J Med ; 387(25): 2331-2343, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36546625

RESUMO

BACKGROUND: In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed. METHODS: We conducted an open-label, phase 2-3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points. RESULTS: Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%). CONCLUSIONS: In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782.).


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Moxifloxacina/administração & dosagem , Moxifloxacina/efeitos adversos , Moxifloxacina/uso terapêutico , Rifampina/efeitos adversos , Rifampina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto Jovem , Adulto , Linezolida/administração & dosagem , Linezolida/efeitos adversos , Linezolida/uso terapêutico , Administração Oral
13.
Front Public Health ; 10: 1047659, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523585

RESUMO

Background: As one of the high multi-drug resistance tuberculosis countries, it is critical for China to understand patterns of drug resistance to better formulate effective treatment regimens. Methods: The anti-TB Drug resistance surveillance has been conducted in Zheijang Province in years 1999, 2004, 2008, 2013, and 2018 respectively. We compared the prevalence of DR-TB from the latest survey with that of the previous four surveys in terms of all four first-line anti-TB drugs. We also examined the prevalence of rifampin-resistant TB (RR-TB) between the last two surveys and routine surveillance data. Results: Among 996 patients surveyed in 2018, the prevalence of RR-TB in new and previously treated TB cases was 2.5 and 4.3%, respectively. The prevalence of RR-TB among previously treated cases was much higher than for new cases in the four surveys from 1999 to 2013, while there was no significant difference between these groups in the 2018 survey. The percentage of TB cases resistant to fluoroquinolones in new patients was 3.8%. The prevalence of non-tuberculous mycobacteria increased over time; the prevalence of RR-TB among new cases slowly decreased. The prevalence of RR-TB in both new and previously treated TB cases from the latest two surveys was consistent with routine surveillance data. Conclusions: This consistency between routine surveillance and periodic surveys for TB cases implies that with universal testing in Zhejiang Province, data from routine surveillance could be used instead of periodic surveys to improve access to timely and appropriate treatment for DR-TB. Levels of resistance were lower than whole-country and global estimates, further indicating the value of universal drug susceptibility testing.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Testes de Sensibilidade Microbiana , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Rifampina/farmacologia , Rifampina/uso terapêutico , Estudos Longitudinais , China/epidemiologia , Resistência a Medicamentos
14.
Eur J Med Res ; 27(1): 300, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539899

RESUMO

BACKGROUND: According to reports, between 30 and 40 percent of extrapulmonary tuberculosis (EPTB) cases are caused by urinary tract tuberculosis (UTB). It is critical to identify UTB quickly since it frequently precedes delayed medical attention, which can have detrimental effects. This study examined the use of Xpert MTB/RIF, a PCR test that can detect MTB as well as resistance to an important drug, rifampicin (RIF), in UTB particularly, for the early identification of UTB. METHODS: 180 participants with clinically presumptive UTB whose urine samples were chosen for urine sediment smear, culture, Xpert MTB/RIF, and TB-DNA testing at Henan Chest Hospital between January 2019 and July 2022. Evaluation of test performance using Composite Reference Standards (CRSs). We studied and compared the positivity rate for various tests using the t-test. The effectiveness of smear, culture, Xpert MTB/RIF, and TB-DNA was assessed using McNemar test. RESULTS: In this subject, a total of 108 participants were diagnosed with UTB, and the positivity rate was 67.1%. Compared with CRS, the positivity rate of Xpert MTB/RIF, smear, culture, and TB-DNA was 29.69% (19/64, P < 0.001), 7.56% (9/119, P < 0.1), 12.12% (4/33, P > 0.05), and 18.75% (6/32, P < 0.1), respectively. The sensitivity of Xpert MTB/RIF assay was significantly better than that of smear and culture tests (78.9% vs. 77.8%, P < 0.05; 78.9% vs. 75%, P < 0.05). Under CRS, the positivity rate for Xpert, culture, and TB-DNA was 31.6% (6/19, P < 0.1), 6.2% (1/16, P > 0.05), and 26.7% (4/15, P > 0.05) for TB-DNA, respectively, compared to smear negative. Xpert MTB/RIF assay specificity was significant for culture and TB-DNA (53.6% vs. 25%, P < 0.01; 53.6% vs. 38.9%, P < 0.05), and Xpert MTB/RIF assay FPV was significant for culture and TB-DNA (53.6% vs. 0%, P < 0.001; 53.6% vs. 0%, P < 0.001). CONCLUSION: Xpert MTB/RIF outperforms smear, cultures, and TB-DNA in detecting UTB, plus Xpert MTB/RIF is better suited for early diagnosis in smear-negative UTB.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Rifampina/farmacologia , Tuberculose Pulmonar/diagnóstico , Mycobacterium tuberculosis/genética , Farmacorresistência Bacteriana/genética , Sensibilidade e Especificidade , Diagnóstico Precoce , Escarro
15.
Artigo em Inglês | MEDLINE | ID: mdl-36554951

RESUMO

Early diagnosis of drug susceptibility for tuberculosis (TB) patients could guide the timely initiation of effective treatment. We evaluated a novel multiplex xMAP TIER (Tuberculosis-Isoniazid-Ethambutol-Rifampicin) assay based on the Luminex xMAP system to detect first-line anti-tuberculous drug resistance. Deoxyribonucleic acid samples from 353 Mycobacterium tuberculosis clinical isolates were amplified by multiplex polymerase chain reaction, followed by hybridization and analysis through the xMAP system. Compared with the broth microdilution method, the sensitivity and specificity of the xMAP TIER assay for detecting resistance was 94.9% (95%CI, 90.0-99.8%) and 98.9% (95%CI, 97.7-100.0%) for rifampicin; 89.1% (95%CI, 83.9-94.3%) and 100.0% (95%CI, 100.0-100.0%) for isoniazid; 82.1% (95% CI, 68.0-96.3%) and 99.7% (95% CI, 99.0-100.0%) for ethambutol. With DNA sequencing as the reference standard, the sensitivity and specificity of xMAP TIER for detecting resistance were 95.0% (95% CI, 90.2-99.8%) and 99.6% (95% CI, 98.9-100.0%) for rifampicin; 96.9% (95% CI, 93.8-99.9%) and 100.0% (95% CI, 100.0-100.0%) for isoniazid; 86.1% (95% CI, 74.8-97.4%) and 100.0% (95% CI, 100.0-100.0%) for ethambutol. The results achieved showed that the xMAP TIER assay had good performance for detecting first-line anti-tuberculosis drug resistance, and it has the potential to diagnose drug-resistant tuberculosis more accurately due to the addition of more optimal design primers and probes on open architecture xMAP system.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Etambutol/farmacologia , Rifampina/farmacologia , Rifampina/uso terapêutico , Microesferas , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico
16.
Sci Rep ; 12(1): 22239, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564395

RESUMO

Milvexian (BMS-986177/JNJ-70033093) is a potent, oral small molecule that inhibits the active form of factor XI with high affinity and selectivity. This study assessed the single-dose pharmacokinetic and pharmacodynamic properties of milvexian co-administered with rifampin, an organic anion transport protein (OATP) inhibitor and potent cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp) inducer. In this open-label, nonrandomized, single-sequence study, healthy participants (N = 16) received single doses of milvexian on Day 1 (100 mg), milvexian and rifampin (600 mg) on Day 4, rifampin on Days 5-11, milvexian and rifampin on Day 12, and rifampin on Days 13-14. Pharmacokinetic data were summarized using descriptive statistics. Administration of milvexian, alone or in combination with rifampin, was generally safe and well tolerated. Single-dose co-administration of rifampin and milvexian demonstrated no meaningful changes in milvexian exposure versus milvexian alone (Cmax, 110%; AUC[0-T], 102%; AUC[INF], 101%). After multiple doses of rifampin and milvexian, peak and total milvexian exposure substantially decreased versus milvexian alone (Cmax, 22%; AUC[0-T], 15%; AUC[INF], 15%). Results were consistent with preclinical data, indicating that milvexian is a substrate for CYP3A4/5 and P-gp but not OATP. The implications of these results on the need for dose adjustment of milvexian will be further elucidated following the completion of phase 2 and 3 trials.Trial registration The study was registered with ClinicalTrials.gov (NCT02959060; submitted 7/11/2016, first posted 8/11/2016).


Assuntos
Fator XIa , Rifampina , Humanos , Área Sob a Curva , Citocromo P-450 CYP3A/metabolismo , Interações Medicamentosas , Fator XIa/metabolismo , Voluntários Saudáveis , Rifampina/farmacologia
17.
PLoS One ; 17(12): e0277145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584037

RESUMO

BACKGROUND: Globally, TB is the leading cause of infectious disease morbidity and mortality with many diagnostic uncertainties. Access to affordable and rapid diagnostics remained a major challenge for many developing countries which bear the greatest burden of TB delaying the initiation time to treatment. OBJECTIVE: This study aimed to assess the GeneXpert MTBRIF assay probe utility for the detection of pulmonary TB and Rifampicin-resistant TB cases in Addis Ababa, Ethiopia. MATERIALS AND METHODS: A cross-sectional study was performed from October 2019 to July 2020 in Saint Peter TB Specialized Hospital in Addis Ababa metropolitan area, Ethiopia. This study enrolled 216 clinically suspected new presumptive pulmonary TB cases confirmed by GeneXpert MTB/RIF Assay. Sociodemographic and clinical characteristics were captured using a structured tool. Data were entered in Microsoft Excel 2019, checked for inconsistency, cleaned promptly, and exported to IBM SPSS Statistics for Windows, Version 26.0. Armonk, N.Y: IBM Corp, the USA for analysis. Descriptive analysis and binary and multivariate logistics regression were performed and all statistical significance was determined at a 95% confidence level. RESULTS: The majority of the study participants, 55.1% [119/216] were males aged 6-80 years. The prevalence of RR MTB was 11.11% [24/216]. A higher proportion of RR TB was found in female patients [54.2%, 13/24], in patients in the age group of 30-50 years [45.8%, 11/24], in married individuals [62.5%, 15/24], in persons whose residence is urban [79.2%, 19/24], in persons who had a previous history of TB symptoms [100%, 24/24], in persons who had a history of contact with active and LTBI [33.3%, 8/24], and in persons who had a history of HIV and IDUs [41.7%, 10/24]. Occupation (AOR 22.868, 95% CI 1.655-316.022, p = 0.019), history of previous PTB+ (AOR 4.222, 95% CI 1.020-17.47, p = 0.047), and history of HIV and IDUs (AOR 4.733, 95% CI 1.416-15.819, p = 0.012) were independent predictors associated with RR-TB emergence. The commonest mutation 62.5% [15/24] was found in probe E (codons 529-533) region. There was no mutation associated with probe A (codons 507-511), probe B (codons 511-518), and probe C (codons 518-523) regions, as well as no combination of missed probes, was revealed. However, 12.5% [3/24] of RR TB patients were found without unidentified missed probe types detected outside of the RRDR. The delta Ct max was >4.0 and the highest proportion of 35.6% [77/216] RR TB was detected in samples of medium DNA load. CONCLUSION: The proportion of RR-TB we observed in this study was high. Similarly, a higher proportion of RR TB was detected outside of the RRDR. Moreover, a significant number of the GeneXpert MTB/RIF Assay probes were identified as unhybridized and this critical observation would mean that most of the probes had no or minimal utility in this geographical region. This calls for further studies to uncover mutation in the rpoB gene conferring RR and reshape TB triage and definite diagnostic algorithm in Ethiopia.


Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Rifampina/farmacologia , Rifampina/uso terapêutico , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Etiópia/epidemiologia , Estudos Transversais , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Códon , Infecções por HIV/tratamento farmacológico
18.
Drug Discov Ther ; 16(6): 305-308, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36529510

RESUMO

Clinical diagnosis of tuberculosis (TB) in people living with the human immunodeficiency virus (HIV) poses a challenge. The Xpert MTB/RIF Ultra (Ultra) has displayed greater sensitivity at diagnosing tuberculosis and rifampicin resistance compared to the Xpert MTB/RIF (Xpert). However, whether Ultra is able to facilitate an auxiliary diagnosis of TB in patients with an HIV-TB co-infection remains unclear. Accordingly, the current study evaluated the use of Ultra in patients with an HIV-TB co-infection by summarizing relevant studies. The sensitivity and specificity of Ultra and Xpert at diagnosing patients with an HIV-TB co-infection have been summarized and compared. The performance of Ultra in diagnosing extrapulmonary tuberculosis was also summarized. Although a large-cohort, multi-center study needs to be conducted to assess Ultra's ability to detect TB in AIDS patients in the future, the current evidence supports the use of Ultra for the assessment of patients with an HIV-TB co-infection.


Assuntos
Antibióticos Antituberculose , Coinfecção , Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Humanos , Rifampina/farmacologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Mycobacterium tuberculosis/genética , HIV/genética , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Sensibilidade e Especificidade
19.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555855

RESUMO

Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen-hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies.


Assuntos
Hidrogéis , Rifampina , Rifampina/farmacologia , Hidrogéis/química , Ácido Hialurônico/química , Cicatrização , Colágeno/metabolismo , Desenvolvimento de Medicamentos
20.
Sci Rep ; 12(1): 21429, 2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-36504241

RESUMO

Concentration dependency of phenotypic and genotypic isoniazid-rifampicin resistance emergence was investigated to obtain a mechanistic understanding on how anti-mycobacterial drugs facilitate the emergence of bacterial populations that survive throughout treatment. Using static kill curve experiments, observing two evolution cycles, it was demonstrated that rifampicin resistance was the result of non-specific mechanisms and not associated with accumulation of drug resistance encoding SNPs. Whereas, part of isoniazid resistance could be accounted for by accumulation of specific SNPs, which was concentration dependent. Using a Hollow Fibre Infection Model it was demonstrated that emergence of resistance did not occur at concentration-time profiles mimicking the granuloma. This study showed that disentangling and quantifying concentration dependent emergence of resistance provides an improved rational for drug and dose selection although further work to understand the underlying mechanisms is needed to improve the drug development pipeline.


Assuntos
Mycobacterium tuberculosis , Mycobacterium tuberculosis/genética , Antibacterianos , Farmacorresistência Bacteriana/genética , Genótipo , Isoniazida/farmacologia , Rifampina/farmacologia
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