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Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.
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Antituberculeux , Méthode Delphi , Tuberculose pulmonaire , Tuberculose , Humains , Singapour , Antituberculeux/usage thérapeutique , Tuberculose pulmonaire/traitement médicamenteux , Tuberculose pulmonaire/diagnostic , Tuberculose/traitement médicamenteux , Tuberculose/diagnostic , ConsensusRÉSUMÉ
Tuberculosis (TB) is a public health challenge globally, and molecular testing is recommended to expedite diagnosis. Concerns that Xpert MTB/RIF assay (Xpert) may be less sensitive when testing paucibacillary samples led to the development of the Xpert MTB/RIF Ultra assay (Ultra). We evaluated the performance of Ultra against Xpert on clinical samples sent to the national reference laboratory in Singapore. In total, 149 samples collected between January 2019 and November 2020 were analysed. Mycobacterium tuberculosis complex (MTBC) was isolated from 55 cultures. Using culture as the reference standard, Ultra demonstrated higher sensitivity (96.4% vs 85.5%) and marginally lower specificity (88.3% vs 89.4%) compared to Xpert in the full cohort. When considering only paucibacillary specimens such as extrapulmonary and smear-negative samples, similar results were obtained. Reclassifying Ultra trace results (low levels of MTB are detected but no rifampicin resistant result is detected) as negative in the full cohort led to a decrease in sensitivity by 10.9% and a marginal increase in specificity by 1.1%. In instances of low bacillary load, Ultra also identified rifampicin resistance more accurately than Xpert, when corroborated against other methods such as broth microdilution, line probe assay and whole genome sequencing (WGS). One isolate tested rifampicin-resistant using Xpert and Ultra, but was phenotypically susceptible and WGS demonstrated the presence of the silent mutation Thr444Thr. Ultra is more sensitive than Xpert in the detection of MTBC and rifampicin resistance in our local setting. Nevertheless, the results of molecular testing should still be correlated with phenotypic studies.
Sujet(s)
Antibiotiques antituberculeux , Mycobacterium tuberculosis , Humains , Rifampicine/pharmacologie , Antibiotiques antituberculeux/pharmacologie , Sensibilité et spécificité , Résistance bactérienne aux médicaments/génétiqueRÉSUMÉ
INTRODUCTION: Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population. METHODS: This retrospective study was conducted using a large, prospectively maintained bladder cancer database. 336 patients received intravesical BCG therapy for bladder cancer in our institution between 2004 and 2016, with an average follow-up duration of 63 months. RESULTS: The study included 258 (76.8%) male and 78 (23.2%) female patients. The median age of the patients at diagnosis of bladder cancer was 69 (range 17-94) years, and the median number of BCG instillations was 6 (range 1-27). 52 (15.5%) patients received maintenance therapy. The most common complications included urinary tract infection with/without sepsis (n = 18, 5.4%), haematuria (n = 9, 2.7%) and acute urinary retention (n = 4, 1.2%). 93.3% of the patients with complications presented early, within one month of completion of therapy. 22 out of 30 complications were Clavien-Dindo grade ≤ 2. 10 (33.3%) patients were admitted to hospital because of BCG-related adverse effects. The most common reasons for termination were urosepsis (2/30, 6.7%) and acute urinary retention (2/30, 6.7%). Patients aged ≥ 80 years at diagnosis were at higher risk of developing BCG-related complications (19.0% vs. 7.5%, p = 0.01). CONCLUSION: This retrospective cohort and subgroup study showed that intravesical BCG therapy is well tolerated and has a low incidence of complications even in the elderly and patients with multiple comorbidities.
Sujet(s)
Adjuvants immunologiques , Vaccin BCG , Tumeurs de la vessie urinaire , Rétention d'urine , Adjuvants immunologiques/usage thérapeutique , Administration par voie vésicale , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Vaccin BCG/administration et posologie , Vaccin BCG/effets indésirables , Femelle , Hématurie/complications , Humains , Mâle , Adulte d'âge moyen , Invasion tumorale/anatomopathologie , Récidive tumorale locale , Études rétrospectives , Tumeurs de la vessie urinaire/traitement médicamenteux , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/chirurgie , Rétention d'urine/complications , Infections urinaires/complications , Jeune adulteRÉSUMÉ
OBJECTIVE: To describe the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) and factors associated with its transmission in Singapore. METHODS: Spoligotyping, 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats (MIRU-VNTR) typing and demographic data from the national TB notification registry of MTBC culture-positive cases notified from January 2011 to December 2017 were analysed. RESULTS: Of the 12,046 culture-positive cases notified, complete spoligotyping and MIRU-VNTR typing results were available for 8690 (72.1%) belonging to 4950 (57.0%) local-born and 3740 (43.0%) foreign-born persons. From these, 4810 (55.3%) were identified in 883 clusters. The proportion of recent transmission was 45.2%. The East-Asian Lineage 2 accounted for 4045 (47.1%) of isolates, and disproportionately accounted for large clusters. Clustered cases were more likely to be older than 50 years, male, Malay, local-born, Singapore citizens or Permanent Residents, of lower socioeconomic status, imprisoned; to harbour East-Asian Lineage 2 strain; to have cavitary pulmonary TB, positive sputum smear or be recalcitrant treatment defaulters. They were less likely to have multidrug-resistant, or isoniazid or rifampicin mono-resistant TB. CONCLUSION: We demonstrated the diversity of MTBC strains and, notwithstanding the likely over-estimation of clustering using these genotyping methods, elucidated factors associated with TB transmission in Singapore.
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Mycobacterium tuberculosis , Tuberculose pulmonaire , Génotype , Humains , Mâle , Répétitions minisatellites , Épidémiologie moléculaire , Mycobacterium tuberculosis/génétique , Singapour/épidémiologie , Tuberculose pulmonaire/diagnostic , Tuberculose pulmonaire/épidémiologie , Tuberculose pulmonaire/microbiologieRÉSUMÉ
BACKGROUND: Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%-8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases. METHODS: Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses. RESULTS: Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09-3.61), male sex (aOR, 2.29 [95% CI, 1.22-4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59-6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12-13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI, .27-.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50-42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36-13.10]). CONCLUSIONS: Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse.
RÉSUMÉ
There were 290 multidrug-resistant (MDR)-TB cases diagnosed in Singapore from 2006 to 2018. Eighty-one percent were foreign-born. Spoligotyping and MIRU-VNTR methods identified 108 patients in 24 clusters. The Beijing spoligotype accounted for 22 clusters. Whole genome sequencing (WGS) analysis reduced the number of clustered patients and clusters to 43 and nine respectively. One MIRU cluster was redefined into three WGS clusters. All the clusters had foreign-born source cases. Forty percent of local-born, versus 9% of foreign-born, MDR-TB cases belonged to WGS clusters. WGS more accurately elucidated potential MDR-TB transmission which was overestimated by conventional genotyping methods in Singapore.
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Antituberculeux/pharmacologie , Tuberculose multirésistante/microbiologie , Multirésistance bactérienne aux médicaments , Génotype , Humains , Épidémiologie moléculaire , Mycobacterium tuberculosis/effets des médicaments et des substances chimiques , Mycobacterium tuberculosis/génétique , Singapour/épidémiologie , Séquençage du génome entierRÉSUMÉ
BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.
Sujet(s)
Vaccin BCG/effets indésirables , Mycobacterium bovis , Maladies d'immunodéficience primaire/complications , Tuberculose/étiologie , Vaccin BCG/usage thérapeutique , Femelle , Humains , Nourrisson , Nouveau-né , Mâle , Maladies d'immunodéficience primaire/thérapie , Études rétrospectives , Singapour , Tuberculose/traitement médicamenteux , Tuberculose/ethnologieRÉSUMÉ
BACKGROUND: Information on non-tuberculosis mycobacterial (NTM) diseases remains limited in Singapore and other Southeast Asian countries. This study aimed to delineate epidemiological and clinical features of pulmonary NTM disease. METHODS: A retrospective review was performed on all NTM isolates identified in Singapore General Hospital from 2012 to 2016 using the 2007 ATS/IDSA diagnostic criteria. RESULTS: A total of 2026 NTM isolates from 852 patients were identified. M. abscessus-chelonae group (1010, 49.9%) was the most commonly isolated and implicated in pulmonary NTM disease. Pulmonary cases (352, 76%) had the highest prevalence among patients diagnosed with NTM diseases (465/852, 54.6%) with no gender difference. Male patients were older (68.5 years, P = 0.014) with a higher incidence of chronic obstructive pulmonary disease (COPD) (23.6%, P < 0.001) and recurrent cough with phlegm production (51.6%, P = 0.035). In contrast, more female patients had bronchiectasis (50%, P < 0.001) and haemoptysis (37.6%, P = 0.042). Age and COPD were associated with multiple NTM species isolation per patient. CONCLUSIONS: M. abscessus-chelonae group was the commonest NTM species isolated in Singapore. Pulmonary NTM infection has the highest frequency with male and female patients associated with a higher incidence of COPD and bronchiectasis respectively. Age and COPD were associated with multiple NTM species isolation per patient.
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Maladies pulmonaires/microbiologie , Infections à mycobactéries non tuberculeuses/épidémiologie , Infections à mycobactéries non tuberculeuses/étiologie , Mycobactéries non tuberculeuses/isolement et purification , Sujet âgé , Dilatation des bronches/épidémiologie , Dilatation des bronches/microbiologie , Comorbidité , Femelle , Hémoptysie/épidémiologie , Hémoptysie/microbiologie , Hôpitaux généraux , Humains , Incidence , Maladies pulmonaires/épidémiologie , Mâle , Adulte d'âge moyen , Infections à mycobactéries non tuberculeuses/microbiologie , Mycobactéries non tuberculeuses/pathogénicité , Prévalence , Broncho-pneumopathie chronique obstructive/épidémiologie , Broncho-pneumopathie chronique obstructive/microbiologie , Études rétrospectives , Facteurs sexuels , Singapour/épidémiologieRÉSUMÉ
BACKGROUND: Unfamiliarity with the presentation, diagnostic process, and treatment of cutaneous non-tuberculous mycobacterium (NTM) infection leads to poorer outcomes. We describe our experience with managing cutaneous NTM infection in a regional hospital in Singapore from 2005 to 2014. METHODS: Adult patients with cutaneous NTM infections were identified through positive skin tissue cultures in this retrospective case series. We excluded patients younger than 21 years of age, patients whose care was transferred to another hospital, and patients with catheter-related infections. Data including demographic variables, as well as disease and treatment outcomes, were collected. We compared the data between patients with and without risk factors for immunosuppression to look for any significant difference. RESULTS: Fifty-eight cases were reviewed. Mycobacterium abscessus was the commonest organism isolated (51.7%), and abscesses or inflamed cysts were the most common presentation. Nineteen specimens (57.6%) showed suppurative or necrotizing granulomatous dermatitis on biopsy and acid-fast bacilli were identified in 2 of 21 histologic specimens (9.5%) stained for mycobacterium. Treatment included systemic antibiotics, surgery, or both. In total, 33 cases had clinical resolution while 25 cases were lost to follow-up. Our study was limited by the under-reporting of cases, bias due to data from a single center, and high dropout rates, thereby precluding a detailed assessment of treatment outcomes. CONCLUSIONS: A high index of suspicion is required to diagnose cutaneous NTM infection. Education of both patients and physicians will help to raise the level of awareness and reduce treatment delays.
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Antibactériens/usage thérapeutique , Procédures chirurgicales dermatologiques , Infections à mycobactéries non tuberculeuses/épidémiologie , Mycobacterium abscessus/isolement et purification , Dermatoses bactériennes/épidémiologie , Adulte , Sujet âgé , Femelle , Études de suivi , Humains , Sujet immunodéprimé , Mâle , Adulte d'âge moyen , Infections à mycobactéries non tuberculeuses/microbiologie , Infections à mycobactéries non tuberculeuses/thérapie , Mycobacterium abscessus/immunologie , Études rétrospectives , Facteurs de risque , Singapour/épidémiologie , Peau/microbiologie , Peau/anatomopathologie , Dermatoses bactériennes/microbiologie , Dermatoses bactériennes/thérapie , Résultat thérapeutiqueRÉSUMÉ
INTRODUCTION: Leprosy is rarely reported in developed countries with low-prevalence settings. Its diagnosis may be missed due to its low frequency in non-endemic regions, as well as its long incubation period. The report describes an imported leprosy case of a healthcare worker in Singapore. CASE PRESENTATION: A Filipino nursing personnel presented with a persistent non-tender erythematous plaque over his right upper back for many years despite topical treatment. He had the lesion before coming to Singapore but decided to seek medical consultation only after the lesion progressed with new erythematous papules developing over his face, trunk and upper limbs. Punch biopsies of skin lesions revealed fite-positive bacilli, which were identified to be Mycobacterium leprae by GenoType LepraeDR v1 assay (Hain LifeScience, Germany). No mutation was detected at rpoB (rifampicin), gyrA (ofloxacin) and folP1 (dapsone) gene targets. He was started on multi-drug therapy and responded to the treatment. The only prolonged close contact he had was his housemate who was screened and given a single dose of rifampicin as chemoprophylaxis. CONCLUSION: In non-endemic settings, awareness is crucial in diagnosing leprosy. The availability of molecular testing and multi-disciplinary management are essential in the confirmation and control of this disease of public health importance.
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Accurate and reliable drug susceptibility testing (DST) is essential for the effective treatment and control of tuberculosis. With the increase in drug-resistant organisms, newer and less conventional antimicrobial agents are used for treatment. Recently, we found an unprecedented rise in the number of clofazimine-resistant Mycobacterium tuberculosis isolates in our laboratory. An investigation found that this phenomenon was due to a change in the method of drug preparation. We performed studies to assess the impact of water and dimethyl sulfoxide (DMSO) as a final diluent for clofazimine drug testing. Based on our findings, the use of DMSO as a solvent for M. tuberculosis DST was optimised using the BACTEC MGIT 960 platform.
Sujet(s)
Clofazimine/pharmacologie , Mycobacterium tuberculosis/effets des médicaments et des substances chimiques , Tuberculose/traitement médicamenteux , Exactitude des données , Humains , Laboratoires , Tests de sensibilité microbienneRÉSUMÉ
OBJECTIVE: Between February 2012 and May 2016, six residents of an 11-storey apartment block were diagnosed with MDR-TB. Based on initial tests, all isolates had similar genotypic profiles, although there were no identifiable epidemiological transmission patterns between three cases. We present findings from the cluster investigation and results of a mass screening exercise. DESIGN: Free voluntary TB screening was offered to past and current residents of the apartment block, comprising an interview, Chest X-Ray, and Interferon Gamma Release Assay or Tuberculin skin test. Expected latent TB proportions were calculated using a reference population, and whole genome sequencing (WGS) was performed. RESULTS: The index case was involved in a separate gaming centre outbreak involving five patrons. 241 current (67.9% of 355 residents) and 18 past residents were screened. The latent TB proportion was 19.9%, which was at the higher end of the expected range. WGS confirmed relatedness of cases' MDR-TB isolates- eight of 10 isolates were genetically identical, while the remaining two were one Single Nucleotide Polymorphism apart. CONCLUSION: With WGS, TB clusters not apparent through regular activity-based contact tracing may be detected. Mass screening may help inform the extent of transmission, but is limited by participation and difficulties in interpretation.
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Épidémies de maladies , Tuberculose multirésistante/épidémiologie , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Enfant , Enfant d'âge préscolaire , Analyse de regroupements , Femelle , Génotype , Logement , Humains , Nourrisson , Mâle , Dépistage de masse , Adulte d'âge moyen , Mycobacterium tuberculosis/génétique , Polymorphisme de nucléotide simple , Singapour/épidémiologie , Tuberculose multirésistante/diagnostic , Séquençage du génome entier , Jeune adulteRÉSUMÉ
The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.
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Prise en charge de la maladie , Médecine factuelle/méthodes , Gouvernement , Guides de bonnes pratiques cliniques comme sujet , Tuberculose , Humains , Morbidité/tendances , Singapour/épidémiologie , Tuberculose/diagnostic , Tuberculose/épidémiologie , Tuberculose/prévention et contrôleRÉSUMÉ
BACKGROUND: Nontuberculous mycobacterium (NTM) infections are rare in children, with limited published studies. The course of the disease can be variable and there are no accepted treatment guidelines for the management of NTM infections in children. OBJECTIVE: To review a cohort of pediatric patients admitted to a tertiary pediatric hospital in Singapore for cutaneous NTM infections. METHODS: A retrospective review was performed of all children admitted to KK Women's and Children's Hospital with cutaneous NTM infections from 2002 to 2012. RESULTS: Sixty-seven patients with positive NTM cultures from various body sites were identified. Eight of the 67 patients (11.9%) presented with cutaneous NTM without evidence of systemic involvement. The mean age at diagnosis for these eight patients was 10 years (range 5-21 yrs). Mycobacterium abscessus was the most common NTM isolated (five patients), followed by Mycobacterium hemophilium (two patients) and Mycobacterium kansasii (one patient). Most patients presented with isolated skin abscesses. Two patients were immunocompromised. Six patients required multidrug antibiotic treatment for a median duration of 5.5 months (range 3-17 mos). The median follow-up duration was 8.5 months (range 2 wks-29 mos). CONCLUSION: Although the incidence of cutaneous NTM is rare, the diagnosis should be considered in patients presenting with chronic wounds. Most patients require treatment with multidrug antibiotic therapy, although uncomplicated abscesses can be treated with surgical incision and drainage alone.
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Infections à mycobactéries non tuberculeuses/épidémiologie , Infections de la peau/épidémiologie , Infections de la peau/microbiologie , Adolescent , Antituberculeux/usage thérapeutique , Enfant , Enfant d'âge préscolaire , Association de médicaments , Femelle , Humains , Mâle , Infections à mycobactéries non tuberculeuses/traitement médicamenteux , Études rétrospectives , Singapour/épidémiologie , Infections de la peau/traitement médicamenteux , Jeune adulteRÉSUMÉ
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.
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Mycobacterium tuberculosis/classification , Tuberculose multirésistante/microbiologie , Évolution biologique , Évolution moléculaire , Génome bactérien , Génotype , Santé mondiale , Humains , Mutation , Mycobacterium tuberculosis/génétique , Mycobacterium tuberculosis/isolement et purification , Phylogenèse , Tuberculose multirésistante/épidémiologieRÉSUMÉ
Mycobacterium tuberculosis Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing.