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Enfermedades Infecciosas Y... 2016
Topics: Antitubercular Agents; Consensus; Humans; Prothionamide; Tuberculosis
PubMed: 26298096
DOI: 10.1016/j.eimc.2015.07.008 -
The International Journal of... Jan 2018Nine countries in West and Central Africa. (Observational Study)
Observational Study
SETTING
Nine countries in West and Central Africa.
OBJECTIVE
To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs.
DESIGN
Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months.
RESULTS
Among the 1006 MDR-TB patients included in the study, 200 (19.9%) were infected with the human immunodeficiency virus (HIV). Outcomes were as follows: 728 (72.4%) cured, 93 (9.2%) treatment completed (81.6% success), 59 (5.9%) failures, 78 (7.8%) deaths, 48 (4.8%) lost to follow-up. The proportion of deaths was much higher among HIV-infected patients (19.0% vs. 5.0%). Treatment success did not differ by HIV status among survivors. Fluoroquinolone resistance was the main cause of failure, while resistance to PZA, ethionamide or EMB did not influence bacteriological outcome. The most important adverse drug event was hearing impairment (11.4% severe deterioration after 4 months).
CONCLUSIONS
The study results support the use of the short regimen recently recommended by the World Health Organization. Its high level of success even among HIV-positive patients promises substantial improvements in TB control.
Topics: Adolescent; Adult; Africa; Aged; Antitubercular Agents; Drug Resistance, Bacterial; Female; HIV Infections; Hearing Loss; Humans; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Failure; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 29149917
DOI: 10.5588/ijtld.17.0498 -
The International Journal of... May 2015Two specialised multidrug-resistant tuberculosis (MDR-TB) treatment units in Cameroon. (Observational Study)
Observational Study
SETTING
Two specialised multidrug-resistant tuberculosis (MDR-TB) treatment units in Cameroon.
OBJECTIVE
To assess outcome and adverse drug events with a standardised 12-month regimen for MDR-TB among second-line drug naïve patients.
DESIGN
Prospective observational study of MDR-TB patients treated with a standardised 12-month regimen including gatifloxacin, clofazimine, prothionamide, ethambutol and pyrazinamide throughout, supplemented by kanamycin and isoniazid during an intensive phase of a minimum of 4 months. Progress was monitored monthly until treatment completion and twice over one year after treatment cessation.
RESULTS
Eighty-seven potentially eligible patients were lost and never treated due to delayed availability of test results. Among the 150/236 eligible and treated patients, 134 (89%) successfully completed treatment, 10 died, 5 were lost, 1 failed and none relapsed. The patients' mean age was 33.7 years (range 17-68), 73 (49%) were females, 120 (80%) had failed on previous treatment, 30 (20%) were human immunodeficiency virus seropositive, 62 (43%) had a body mass index <18.5 kg/m(2) and 41 (27%) had radiographic involvement of five or six of the six lung zones. The most important adverse drug event was hearing impairment, which occurred in 46 of 106 (43%) patients.
CONCLUSIONS
These results add further evidence for the usefulness of shorter, standardised regimens among patients without second-line drug resistance.
Topics: Adolescent; Adult; Aged; Antitubercular Agents; Cameroon; Clofazimine; Cohort Studies; Confidence Intervals; Developing Countries; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ethambutol; Female; Fluoroquinolones; Gatifloxacin; Humans; Isoniazid; Kanamycin; Male; Medication Adherence; Middle Aged; Odds Ratio; Prospective Studies; Prothionamide; Pyrazinamide; Risk Assessment; Time Factors; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 25868018
DOI: 10.5588/ijtld.14.0535 -
Journal of Medical Case Reports May 2022Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and...
BACKGROUND
Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual.
CASE PRESENTATION
A 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air-fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice.
CONCLUSIONS
Complicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.
Topics: Adult; Coinfection; Fistula; HIV; HIV Infections; HIV Seropositivity; Humans; Male; Pleural Diseases; Pneumothorax; Tuberculosis, Multidrug-Resistant
PubMed: 35637524
DOI: 10.1186/s13256-022-03436-1 -
Zhonghua Jie He He Hu Xi Za Zhi =... Mar 2017To analyze the distribution and drug resistance of nontuberculous mycobacteria(NTM) in Beijing. Using PCR-fluorescence probe method we identified 1 552 mycobacterial...
To analyze the distribution and drug resistance of nontuberculous mycobacteria(NTM) in Beijing. Using PCR-fluorescence probe method we identified 1 552 mycobacterial isolates in 2009 and 1 553 mycobacterial isolates in 2013, which were stored by Beijing Research Institute for Tuberculosis Control.All identified NTM strains were confirmed by 16S rRNA gene sequencing, and drug sensitivity testing was performed by using 1% ratio method.SPSS 13.0 was used for statistical analysis. The isolation rate for NTM in 2009 and 2013 was 3.8%(59/1 552), and 4.6%(71/1 553) respectively. A total of 130 NTM strains were identified to 13 species by 16S rRNA gene sequencing, including . strains 39.2%(51/130), . strains 37.7%(49/130), . strains 6.9%(9/130), . strains 5.4%(7/130), . strains 3.0%(4/130), . strains 1.5%(2/130), . strains 1.5%(2/130), . . . . . . 1 strain each. For the patients infected with NTM, 87 were male and 43 were female, with an average age of 55 years. The results of drug sensitivity test from 97 strains of NTM showed that isoniazid and p-aminosalicylic acid showed the highest drug resistant rate of 98%(95/97), followed by streptomycin 94.8%(92/97), capreomycin 81.4%(79/97), amikacin 69.1%(67/97), levofloxacin 56.7%(55/97), rifampicin 54.6%(53/97), prothionamide 51.5%(50/97), and ethambutol 50.5%(49/97). and were the main strains isolated from patients infected with NTM in Beijing. Patients infected with NTM were mostly males. NTM showed high resistance to anti-tuberculosis drugs.
Topics: Antibiotics, Antitubercular; Beijing; Ethambutol; Female; Humans; Isoniazid; Male; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Rifampin
PubMed: 28297817
DOI: 10.3760/cma.j.issn.1001-0939.2017.03.013 -
BMC Bioinformatics Feb 2019It is possible to predict whether a tuberculosis (TB) patient will fail to respond to specific antibiotics by sequencing the genome of the infecting Mycobacterium...
BACKGROUND
It is possible to predict whether a tuberculosis (TB) patient will fail to respond to specific antibiotics by sequencing the genome of the infecting Mycobacterium tuberculosis (Mtb) and observing whether the pathogen carries specific mutations at drug-resistance sites. This advancement has led to the collation of TB databases such as PATRIC and ReSeqTB that possess both whole genome sequences and drug resistance phenotypes of infecting Mtb isolates. Bioinformatics tools have also been developed to predict drug resistance from whole genome sequencing (WGS) data. Here, we evaluate the performance of four popular tools (TBProfiler, MyKrobe, KvarQ, PhyResSE) with 6746 isolates compiled from publicly available databases, and subsequently identify highly probable phenotyping errors in the databases by genetically predicting the drug phenotypes using all four software.
RESULTS
Our results show that these bioinformatics tools generally perform well in predicting the resistance status for two key first-line agents (isoniazid, rifampicin), but the accuracy is lower for second-line injectables and fluoroquinolones. The error rates in the databases are also non-trivial, reaching as high as 31.1% for prothionamide, and that phenotypes from ReSeqTB are more susceptible to errors.
CONCLUSIONS
The good performance of the automated software for drug resistance prediction from TB WGS data shown in this study further substantiates the usefulness and promise of utilising genetic data to accurately profile TB drug resistance, thereby reducing misdiagnoses arising from error-prone culture-based drug susceptibility testing.
Topics: Algorithms; Antitubercular Agents; Benchmarking; Calibration; Databases, Genetic; Drug Resistance, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Sensitivity and Specificity; Software; Tuberculosis
PubMed: 30736750
DOI: 10.1186/s12859-019-2658-z -
Tuberculosis and Respiratory Diseases Jul 2023Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs...
Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching.
BACKGROUND
Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting.
METHODS
The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included.
RESULTS
The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success).
CONCLUSION
A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.
PubMed: 37254489
DOI: 10.4046/trd.2023.0040 -
Infection and Drug Resistance 2021This study aims to analyze the correlation between gene mutations by melting curve technology and phenotypic drug susceptibility (DST) results of ethionamide (ETH), and...
OBJECTIVE
This study aims to analyze the correlation between gene mutations by melting curve technology and phenotypic drug susceptibility (DST) results of ethionamide (ETH), and evaluate whether gene mutations detection can serve as a molecular marker in predicting ETH resistance.
METHODS
A retrospective analysis was conducted on 382 strains of (MTB) with the anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ETH, and others. Phenotypic drug susceptibility and the results of and katG genotypes (mutation and no mutation) were obtained using the melting curve technology MeltPro TB assay.
RESULTS
Of the 382 clinical strains of MTB tested, 118 (30.9%) were resistant to INH, and 28 (7.3%) were resistant to ETH. Among the 28 phenotypically ETH-resistant strains, mutations accounted for 42.9% (12/28). These ETH-resistant strains comprise 35.3% (12/34) of the 34 mutant strains. Of 8 single mutation strains (without or mutation), 4(50%) were resistant to INH; however, all of these 8 strains were sensitive to ETH.
CONCLUSION
The mutation test may not be a reliable predictor of ETH resistance. Mutant strains are not necessarily resistant to ETH. The strains with single inhA mutation (without or mutation) may be effective for ETH treatment. The use of ETH in clinical medicine should be guided by gene (other than alone) detection and phenotypic drug susceptibility testing.
PubMed: 33551644
DOI: 10.2147/IDR.S268799 -
Microbial Drug Resistance (Larchmont,... Jun 2015A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected...
A total of 92 Mycobacterium tuberculosis isolates were collected from patients with pulmonary tuberculosis (TB) in the Zunyi region between 2011 and 2012. Collected isolates were used to determine antibiotic susceptibility patterns against 13 anti-TB drugs: 4 first-line and 9 second-line (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, amikacin, capreomycin, kanamycin, and prothionamide) drugs. Results showed that among 57 new cases of TB only 66.7% were susceptible to all four first-line anti-TB drugs and 64.9% were susceptible to fluoroquinolones and second-line injectables; 10.5% of new and 22.9% of previously treated cases were multidrug-resistant TB (MDR-TB); and 1.8% of new and 2.9% of previously treated cases were extensively drug-resistant TB (XDR-TB). In addition, 14.3% of MDR-TB cases (2 out of 14) were XDR-TB, which is higher than the average numbers in China (about 8%) and in the world (9.6%). This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes.
Topics: Aminoglycosides; Aminosalicylic Acid; Antitubercular Agents; Capreomycin; China; Drug Resistance, Multiple, Bacterial; Extensively Drug-Resistant Tuberculosis; Fluoroquinolones; Humans; Incidence; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prothionamide; Tuberculosis, Pulmonary
PubMed: 25599413
DOI: 10.1089/mdr.2014.0094 -
Antimicrobial Agents and Chemotherapy Jun 2021Preexisting and newly emerging resistant pathogen subpopulations (heteroresistance) are potential risk factors for treatment failure of multi/extensively drug resistant...
Preexisting and newly emerging resistant pathogen subpopulations (heteroresistance) are potential risk factors for treatment failure of multi/extensively drug resistant (MDR/XDR) tuberculosis (TB). Intrapatient evolutionary dynamics of Mycobacterium tuberculosis complex (Mtbc) strains and their implications on treatment outcomes are still not completely understood. To elucidate how Mtbc strains escape therapy, we analyzed 13 serial isolates from a German patient by whole-genome sequencing. Sequencing data were compared with phenotypic drug susceptibility profiles and the patient's collective 27-year treatment history to further elucidate factors fostering intrapatient resistance evolution. The patient endured five distinct TB episodes, ending in resistance to 16 drugs and a nearly untreatable XDR-TB infection. The first isolate obtained, during the patient's 5th TB episode, presented fixed resistance mutations to 7 anti-TB drugs, including isoniazid, rifampin, streptomycin, pyrazinamide, prothionamide, para-aminosalicylic acid, and cycloserine-terizidone. Over the next 13 years, a dynamic evolution with coexisting, heterogeneous subpopulations was observed in 6 out of 13 sequential bacterial isolates. The emergence of drug-resistant subpopulations coincided with frequent changes in treatment regimens, which often included two or fewer active compounds. This evolutionary arms race between competing subpopulations ultimately resulted in the fixation of a single XDR variant. Our data demonstrate the complex intrapatient microevolution of Mtbc subpopulations during failing MDR/XDR-TB treatment. Designing effective treatment regimens based on rapid detection of (hetero) resistance is key to avoid resistance development and treatment failure.
Topics: Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Germany; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 33903103
DOI: 10.1128/AAC.02520-20