Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tuberculosis, Multidrug-Resistant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1990

Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues.

The transmission of tuberculosis is a recognized risk in health-care settings. Several recent outbreaks of tuberculosis in health-care settings, including outbreaks involving multidrug-resistant strains of Mycobacterium tuberculosis, have heightened concern about nosocomial transmission. In addition, increases in tuberculosis cases in many areas are related to the high risk of tuberculosis among persons infected with the human immunodeficiency virus (HIV). Transmission of tuberculosis to persons with HIV infection is of particular concern because they are at high risk of developing active tuberculosis if infected. Health-care workers should be particularly alert to the need for preventing tuberculosis transmission in settings in which persons with HIV infection receive care, especially settings in which cough-inducing procedures (e.g., sputum induction and aerosolized pentamidine [AP] treatments) are being performed. Transmission is most likely to occur from patients with unrecognized pulmonary or laryngeal tuberculosis who are not on effective antituberculosis therapy and have not been placed in tuberculosis (acid-fast bacilli [AFB]) isolation. Health-care facilities in which persons at high risk for tuberculosis work or receive care should periodically review their tuberculosis policies and procedures, and determine the actions necessary to minimize the risk of tuberculosis transmission in their particular settings. The prevention of tuberculosis transmission in health-care settings requires that all of the following basic approaches be used: a) prevention of the generation of infectious airborne particles (droplet nuclei) by early identification and treatment of persons with tuberculous infection and active tuberculosis, b) prevention of the spread of infectious droplet nuclei into the general air circulation by applying source-control methods, c) reduction of the number of infectious droplet nuclei in air contaminated with them, and d) surveillance of health-care-facility personnel for tuberculosis and tuberculous infection. Experience has shown that when inadequate attention is given to any of these approaches, the probability of tuberculosis transmission is increased. Specific actions to reduce the risk of tuberculosis transmission should include a) screening patients for active tuberculosis and tuberculous infection, b) providing rapid diagnostic services, c) prescribing appropriate curative and preventive therapy, d) maintaining physical measures to reduce microbial contamination of the air, e) providing isolation rooms for persons with, or suspected of having, infectious tuberculosis, f) screening health-care-facility personnel for tuberculous infection and tuberculosis, and g) promptly investigating and controlling outbreaks. Although completely eliminating the risk of tuberculosis transmission in all health-care settings may be impossible, adhering to these guidelines should minimize the risk to persons in these settings.

Air Microbiology↗
PubMed1992

The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis.

Tuberculosis is responsible for one in four of all avoidable adult deaths in developing countries. Increased frequency and accelerated fatality of the disease among individuals infected with human immunodeficiency virus has raised worldwide concern that control programmes may be inadequate, and the emergence of multidrug-resistant strains of Mycobacterium tuberculosis has resulted in several recent fatal outbreaks in the United States. Isonicotinic acid hydrazide (isoniazid, INH) forms the core of antituberculosis regimens; however, clinical isolates that are resistant to INH show reduced catalase activity and a relative lack of virulence in guinea-pigs. Here we use mycobacterial genetics to study the molecular basis of INH resistance. A single M. tuberculosis gene, katG, encoding both catalase and peroxidase, restored sensitivity to INH in a resistant mutant of Mycobacterium smegmatis, and conferred INH susceptibility in some strains of Escherichia coli. Deletion of katG from the chromosome was associated with INH resistance in two patient isolates of M. tuberculosis.

Amino Acid Sequence↗
PubMed1995

Genotypic detection of Mycobacterium tuberculosis rifampin resistance: comparison of single-strand conformation polymorphism and dideoxy fingerprinting.

Detection of mutations in the rpoB gene of Mycobacterium tuberculosis can be used as an accurate predictor of rifampin resistance in the majority of strains tested. Simple but highly accurate screening methods must be developed for the detection of these mutations. Either DNA sequence analysis or single-strand conformation polymorphism (SSCP) screening can be used to detect rpoB mutations, but these techniques either are expensive or yield results that may prove difficult to interpret when used in a clinical setting. This report describes the use of dideoxy fingerprinting (ddF) as a postamplification screening method to identify rifampin-resistant genotypes. The ddF protocol was performed on the amplified rpoB fragment with no preparatory steps, thus making ddF practical for laboratories equipped for polyacrylamide gel electrophoresis. When compared with the results of SSCP analysis, ddF results were more easily interpreted and contained more sequence-dependent information that facilitated differentiation of functionally significant and silent mutations. The ddF method was used for genotypic determination of rifampin susceptibility of 20 multidrug-resistant strains of M. tuberculosis. The results of this analysis were concordant with DNA sequence analysis and conventional clinical laboratory methods.

DNA Fingerprinting↗
PubMed2026

MIC-based tuberculosis drug susceptibility testing using Sensititre MYCOTB: a diagnostic accuracy meta-analysis.

Accurate drug susceptibility testing (DST) is crucial for designing effective regimens for multidrug-resistant (MDR) and pre-extensively drug-resistant tuberculosis (pre-XDR TB). Sensititre MYCOTB enables simultaneous determination of minimum inhibitory concentrations (MICs) for multiple drugs, but its diagnostic performance varies across studies. This meta-analysis evaluated the diagnostic performance of Sensititre MYCOTB for key MDR and pre-XDR TB drugs. The protocol was registered in PROSPERO (CRD420251230599). PubMed, Cochrane, Google Scholar, Scopus, ONOS, Web of Science, ScienceDirect, and registries were systematically searched for studies published between 2010 and 2025. Studies comparing the Sensititre MYCOTB with reference DST for Mycobacterium tuberculosis complex (MTBC) were included. Bias assessment and pooled diagnostic accuracy estimates were generated. Fourteen studies, including 1,728 isolates, were analyzed. Rifampicin and isoniazid demonstrated high sensitivity (0.976 [95% CI: 0.94-0.99] and 0.977 [95% CI: 0.95-0.99]) and specificity (0.958 [95% CI: 0.84-0.98] and 0.957 [95% CI: 0.83-0.99], respectively) with low heterogeneity. Amikacin, kanamycin, and ofloxacin demonstrate good diagnostic accuracy, with high specificity (>0.98 [95% CI]). Moderate diagnostic accuracy was observed for ethambutol, streptomycin, ethionamide, and rifabutin. Cycloserine, moxifloxacin, and para-aminosalicylic acid showed inconsistent performance despite excellent specificity (>0.97 [95% CI]). Sensitivity analysis partially improved pooled sensitivity for moxifloxacin 0.801 (95% CI: 0.585-0.924) and para-aminosalicylic acid 0.76 (95% CI: 0.518-0.894), whereas cycloserine remained at 0.436 (95% CI: 0.190-0.725), although heterogeneity persisted. Sensititre MYCOTB DST demonstrates high diagnostic accuracy for MDR-TB and pre-XDR-TB drugs, while caution is required with cycloserine, moxifloxacin, and para-aminosalicylic acid. These findings support the integration of MIC-based testing into clinical decision-making.

Microbial Sensitivity Tests↗
PubMedDate not supplied

Health-care expenditures for tuberculosis in the United States.

BACKGROUND: The resurgence of tuberculosis (TB) and the increase in multidrug-resistant TB prompted this study, which estimates direct expenditures for TB treatment and public health activities in the United States. METHODS: This retrospective cost of illness study estimated 1991 direct expenditures for TB-related outpatient and inpatient diagnosis and treatment, screening, preventive therapy, contact investigations, surveillance, and outbreak investigations. Existing databases at the Centers for Disease Control and Prevention (Atlanta, Ga) and the Codman Research Group, Lebanon, NH, were supplemented by surveys of state and local TB programs and interviews of organizations that conduct large-scale screening. No estimates of indirect costs were made. RESULTS: The direct medical expenditures for TB in 1991 were estimated at $703.1 million. This cost includes $423.8 million for inpatient care, $182.3 million for outpatient care, $72.1 million for screening, $3.4 million for contact investigations, $17.9 for preventive therapy, and $3.6 million for surveillance and outbreak investigations. Sensitivity analyses yielded a range of expenditures between $515.7 million and $934.5 million. CONCLUSIONS: Treatment accounted for more than 86% of all TB-related expenditures; inpatient treatment accounted for 60% of the total. Prevention activities made up only 14% of all costs. Direct medical expenditures may be underestimated because of limitations in the database on hospital expenditures and health department cost-accounting systems and because of the lack of a national database on screening activities. Greater emphasis should be placed on outpatient treatment and prevention in high-risk populations, and improved cost-accounting systems should be developed in state and local health department TB control programs to facilitate economic evaluation and improve the allocation of health dollars.

Cost of Illness↗
PubMed1995

SHEA-CDC TB survey, Part I: Status of TB infection control programs at member hospitals, 1989-1992. Society for Healthcare Epidemiology of America.

OBJECTIVE: To determine trends in Mycobacterium tuberculosis infection in healthcare workers, tuberculosis (TB) control measures, and compliance with the 1990 Centers for Disease Control and Prevention (CDC) guideline for preventing transmission of TB in healthcare facilities. DESIGN: Voluntary questionnaire sent to all members of the Society for Healthcare Epidemiology of America, representing 359 hospitals. RESULTS: Respondents' hospitals (210 [58%]) had a median of 2,400 healthcare workers (range, 396 to 13,745), 437 beds (range, 48 to 1,250), 5.6 patients with TB per year (range, 0 to 492), and 0 multidrug-resistant (MDR) TB patients per year (range, 0 to 33). Of 166 respondents' hospitals for which data were provided for 1989 through 1992, the number caring for MDR-TB patients increased from 10 (6%) in 1989 to 49 (30%) in 1992. Reported policies for routine healthcare worker tuberculin skin testing varied. The median skin-test positivity rate for healthcare workers at the time of hire increased from 0.54% in 1989 to 0.81% in 1992, but the median conversion rate during routine testing remained similar: 0.35% in 1989 and 0.33% in 1992. Among 196 hospitals with reported data on respiratory protection use for 1989 through 1992, the use of either surgical submicron, dust-mist, or dust-fume-mist respirators for healthcare workers increased from 9 (5%) in 1989 to 85 (43%) in 1992. Of 181 hospitals with reported data, 113 (62%) had acid-fast bacilli isolation facilities consistent with the 1990 CDC guideline (ie, a single patient room, negative air pressure relative to the hallway, air exhausted directly outside, and > or = 6 air exchanges per hour). CONCLUSIONS: While the number of surveyed hospitals caring for TB and MDR-TB patients increased during 1989 through 1992, TB infection control measures at many hospitals still did not meet the 1990 CDC guideline recommendations.

Centers for Disease Control and Prevention, U.S.↗
PubMed2026

Draft genome sequences of non-endemic Mycobacterium tuberculosis Indo-Oceanic and West African lineages recovered in Panama.

We report the draft genome sequences of three Mycobacterium tuberculosis isolates recovered from Panamanian residents belonging to the Indo-Oceanic (Lineage 1) and West African (Lineage 5) lineages. These isolates exhibit various drug-resistance profiles, including rifampicin-resistant and multidrug-resistant phenotypes. This highlights the changing molecular epidemiology of tuberculosis in Central America.

DNA sequencing↗
PubMed1992

Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection.

A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1-infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available.

AIDS-Related Opportunistic Infections↗
PubMed1992

Attacking today's tuberculosis problem: a multifaceted, coordinated effort.

Tuberculosis is making a comeback in communities across the nation. Increased rates of the disease, particularly with those having HIV/AIDS, have sounded the alarm that quick and decisive action is needed to halt the spread of TB. Multidrug-resistant TB is becoming a primary concern with public health officials. Specific plans and efforts, instigated by the Centers for Disease Control, have outlined the appropriate steps local public health workers, the medical community, and civic and community organizations should take in order to eliminate TB by the year 2010. With the creation of the Task Force on Drug Resistant Tuberculosis, Louisiana has a vehicle with which to combat its growing TB problem.

Acquired Immunodeficiency Syndrome↗
PubMed2025

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development. It critically evaluates cutting-edge technologies including CRISPR-based diagnostics, whole-genome sequencing, and digital adherence tools, alongside therapeutic innovations such as shorter multidrug-resistant TB regimens and host-directed therapies. Special emphasis is placed on the translational gap-highlighting barriers to real-world implementation such as cost, infrastructure, and policy fragmentation. While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven. Implementation science, cost-effectiveness analyses, and health equity considerations are vital to scaling up these tools. Moreover, the expansion of the TB vaccine pipeline and integration of AI in diagnostics signal a transformative period in TB control. Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB.

diagnostic innovation↗
PubMed2026

Genetic diversity of clinical Mycobacterium bovis BCG isolates from an immunocompromised patient with BCG infection.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is widely administered to prevent severe tuberculosis but can cause serious adverse events, including disseminated BCGosis, in immunocompromised individuals. However, studies investigating the in vivo genetic adaptation and microevolution of this live-attenuated vaccine during prolonged infection remain limited. METHODS: Two clinical Mycobacterium bovis BCG isolates (BCG01 and BCG02) and a lot-matched vaccine strain (VAC) underwent whole-genome sequencing. Phenotypic drug susceptibility testing was performed on the clinical isolates. Genomic relatedness was assessed using SNP-distance clustering and maximum-likelihood phylogeny against global reference strains. Comparative variant analysis was performed to identify mutations specific to BCG01 and BCG02 relative to VAC, and genotypic drug resistance was assessed using TB-Profiler. RESULTS: Phylogenomic analyses and SNP distance confirmed that both clinical isolates were derived from the BCG Tokyo 172 vaccine strain. BCG02 exhibited twice the mutational burden of BCG01, acquiring mutations in genes associated with cell wall biosynthesis (mas, ppsA), regulatory adaptation (pknK, dnaA), and surface antigens (pecA, PE/PPE). Crucially, whereas BCG01 remained susceptible to first-line drugs, BCG02 acquired a canonical rpoB Ser450Leu mutation (100% frequency) and a heteroresistant inhA Ile194Thr mutation (13% frequency), resulting in multidrug-resistant (MDR) BCGosis. CONCLUSION: Although structurally stable, the BCG Tokyo 172 vaccine strain can undergo rapid, clinically significant microevolution and clonal selection within immunocompromised hosts. The in vivo acquisition of multidrug resistance underscores the critical need for pre-vaccination immune screening and comprehensive laboratory monitoring of BCG-associated adverse events.

BCGosis↗
PubMed2026

Patterns of Drug Resistance, Drug Resistance Conferring Mutations and Genomic DNA Methylation Revealed in Mycobacterium tuberculosis From South Africa.

Tuberculosis remains a major public health threat globally, with drug-resistant strains undermining treatment efficacy. We analyzed 126 Mycobacterium tuberculosis (M. tuberculosis) isolates with diverse drug resistance spectra and selected 35 for whole genome sequencing (WGS) using Illumina NextSeq, SMRT PacBio Onso and SMRT PacBio Revio sequencing platforms. The study aimed to characterize drug resistance profiles, compare short- and long-read sequencing performance, identify lineages among South African isolates, detect known drug resistance mutations and their lineage-specific patterns, and utilize long-read SMRT platforms for epigenetic profiling. Multiple drug resistance mutations were identified, some lineage-specific, and notably, East-African-Indian (EAI) Lineage 1 isolates often considered less pathogenic, showed significant potential for multidrug-resistance development, including higher fluoroquinolone resistance as compared to other lineages. Three DNA motifs with methylated adenines, namely CACGCaG, CtCCaG and GaTNNNNRtAC, were detected, with methylation patterns varying by lineage and strain due to mutations in the corresponding methyltransferases (MTases). A particularly notable finding was the stable maintenance of a genetic heterogeneity in the mamB MTase, performing methylation at CACGCaG motifs. These results highlight the combined role of genetic and epigenetic variation in M. tuberculosis adaptive evolution and underscore the value of integrating long-read sequencing into TB surveillance and research.

Mycobacterium tuberculosis↗
PubMed2026

Genomic insights into low-level rifampicin resistance mediated by borderline rpoB mutations in Mycobacterium tuberculosis: prevalence and phylogeny in Northeast China.

The emergence of low-level rifampicin (RIF) resistance in Mycobacterium tuberculosis poses a challenge to tuberculosis (TB) control, as it often leads to discordance between genotypic resistance detected by molecular assays (e.g., Xpert MTB/RIF) and phenotypic susceptibility in conventional drug susceptibility testing (DST). In this study, we performed whole-genome sequencing (WGS) on 17 clinical isolates from Changchun, Northeast China, which exhibited such discordance. All isolates harbored functional borderline mutations in the rpoB RRDR region, predominantly Leu452Pro and Leu430Pro (29% each), followed by His445Asn (18%). RIF minimum inhibitory concentration (MIC) values ranged from ≤0.25 to 1.0 mg/L, confirming low-level resistance. Notably, 53% (9/17) of the isolates were co-resistant to fluoroquinolones and 24% (4/17) to isoniazid (INH). According to WHO classification, 59% (10/17) were pre-extensively drug-resistant TB (Pre-XDR-TB) or multidrug-resistant TB (MDR-TB). Phylogenetic analysis revealed that 94% (16/17) belonged to the East Asian Beijing lineage (Lineage 2.2.1), with no evidence of recent local transmission. These findings underscore the complexity of low-level RIF resistance and its frequent association with broader drug resistance in a dominant lineage, highlighting the need for integrating MIC and WGS into diagnostic algorithms to guide appropriate treatment and surveillance.IMPORTANCEThe accurate detection of RIF resistance is critical for the management of TB, yet standard phenotypic methods often fail to identify strains with low-level resistance conferred by borderline rpoB mutations. This study provides the first genomic characterization of such discordant isolates in Northeast China, revealing a high prevalence of co-resistance to other key drugs and a strong association with the locally dominant Beijing lineage. The findings emphasize that reliance on phenotypic DST alone may lead to underestimation of drug resistance and inappropriate treatment, potentially contributing to the emergence and spread of Pre-XDR-TB and MDR-TB. Incorporating MIC determination and WGS into routine diagnostics could enhance detection, inform tailored therapy, and improve surveillance of these clinically significant strains.

Mycobacterium tuberculosis↗
PubMed1984

Emergence of multidrug-resistant Mycobacterium fortuitum during treatment.

We present a case of pulmonary infection with Mycobacterium fortuitum demonstrating the development of multidrug resistance during therapy with multiple drugs. Emergence of drug resistance in a previously sensitive M fortuitum has been described with single drug therapy, but never before with multiple drug treatment. Development of resistance in the setting of multiple drug therapy illustrates the importance of repeated susceptibility testing during therapy.

Carcinoma, Squamous Cell↗