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Frontiers in Pharmacology 2022Linezolid (LNZ) is an effective antibiotic to treat patients with multidrug-resistant tuberculosis (MDR-TB) treatment failure. strains resistant to isoniazid and...
Linezolid (LNZ) is an effective antibiotic to treat patients with multidrug-resistant tuberculosis (MDR-TB) treatment failure. strains resistant to isoniazid and rifampin are defined as MDR-TB. In recent years, resistance to LNZ among MDR-TB cases has been reported in several different countries. In this study, we performed a systematic review and meta-analysis to investigate the prevalence of LNZ resistance among MDR-TB isolates. The databases of Embase, PubMed/Medline, and Web of Science were searched systematically from January 2000 to April 2021. Statistical analyses were performed by using Comprehensive Meta-Analysis software. Heterogeneity was reported by using the t-squared statistic and Q-statistic. Begg's rank correlation in combination with the funnel plot were used to evaluate any possible publication bias. In total, 25 studies were selected for meta-analysis from 14 different countries; the majority was from China (n = 5) and Turkey (n = 4). Moreover, 7,366 patients were infected with MDR . Among the study population, 98 patients were co-infected with HIV, and 18 patients with hepatitis C virus (HCV). Furthermore, 28 cases had diabetes, and139 cases were alcohol abuser. Overall, 4,956 MDR strains were isolated from TB patients. The pooled frequency of LNZ resistance among the clinical isolates of MDR was 4.2% (95%). Begg's ( = 0.72) test showed no evidence of publication bias. LNZ resistance among MDR M. tuberculosis isolates is increasing. On the other hand, long-term treatment of MDR-TB cases with LNZ alone is associated with several adverse effects. Thus, it is recommended that newer anti-TB drugs, including bedaquiline and delamanid, in combination with linezolid could increase its effectiveness and decrease toxicities. However, more studies should be done in this field.
PubMed: 36110536
DOI: 10.3389/fphar.2022.955050 -
American Journal of Epidemiology Jun 2017The individual- and population-level impact of household tuberculosis exposure on transmission is unclear but may have implications for the effectiveness and... (Meta-Analysis)
Meta-Analysis Review
The individual- and population-level impact of household tuberculosis exposure on transmission is unclear but may have implications for the effectiveness and implementation of control interventions. We systematically searched for and included studies in which latent tuberculosis infection was assessed in 2 groups: children exposed and unexposed to a household member with tuberculosis. We also extracted data on the smear and culture status of index cases, the age and bacillus Calmette-Guérin vaccination status of contacts, and study design characteristics. Of 6,176 citations identified from our search strategy, 26 studies (13,999 children with household exposure to tuberculosis and 174,097 children without) from 1929-2015 met inclusion criteria. Exposed children were 3.79 (95% confidence interval (CI): 3.01, 4.78) times more likely to be infected than were their community counterparts. Metaregression demonstrated higher infection among children aged 0-4 years of age compared with children aged 10-14 years (ratio of odds ratios = 2.24, 95% CI: 1.43, 3.51) and among smear-positive versus smear-negative index cases (ratio of odds ratios = 5.45, 95% CI: 3.43, 8.64). At the population level, we estimated that a small proportion (<20%) of transmission was attributable to household exposure. Our results suggest that targeting tuberculosis prevention efforts to household contacts is highly effective. However, a large proportion of transmission at the population level may occur outside the household.
Topics: Adolescent; Child; Child, Preschool; Community-Acquired Infections; Environmental Exposure; Family Characteristics; Female; Humans; Infant; Infant, Newborn; Latent Tuberculosis; Male; Mycobacterium tuberculosis; Odds Ratio; Risk Factors; Tuberculosis; Vaccination
PubMed: 28982226
DOI: 10.1093/aje/kwx025 -
Oral Diseases Oct 2023This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow-up data on the occurrence of oral and maxillofacial... (Review)
Review
OBJECTIVES
This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow-up data on the occurrence of oral and maxillofacial tuberculosis (OMTB).
METHODS
Electronic searches without publication date restrictions were undertaken in four databases. Case reports and case series describing the occurrence of OMTB were included. Critical evaluation of studies was done using the Joanna Briggs Institute - University of Adelaide tool for case reports or case series.
RESULTS
A total of 217 studies were included in the qualitative synthesis, for a total of 301 cases of OMTB. Of these patients, 192 (63.7%) were male, with an average age of 39.6 ± 19.8 (15 months to 81 years). The tongue (n = 80/26.6%) represented the most common affected site, followed by the mandible (n = 43/14.3%). The clinical presentation consisted mainly of a painful ulcerated lesion (n = 156/56.5%). Histopathological analysis showed a granulomatous inflammation in most cases (n = 156/63.1%). The main diagnostic methods used were sputum test (n = 53/26.8%), culture (n = 49/24.7%) and purified protein derivative (PPD), or Mantoux test (n = 49/24.7%). Antituberculosis therapy was used in 244 cases (100.0%) and 5.2% of patients died.
CONCLUSIONS
This systematic review provided clinical, demographic data and information about diagnostic methods of OMTB lesions and served as an important guide to assist health professionals in the early diagnosis of these lesions.
Topics: Humans; Male; Young Adult; Adult; Middle Aged; Female; Tuberculosis; Oral Ulcer; Mandible; Tongue; Health Personnel
PubMed: 35785411
DOI: 10.1111/odi.14290 -
EBioMedicine Aug 2019Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host.
METHODS
To estimate the diagnostic accuracy of breath test with electronic-nose and other devices against culture or other tests for TB, we screened multiple databases until January 6, 2019.
FINDINGS
We included fourteen studies, with 1715 subjects in the analysis. The pooled sensitivity and specificity of electronic-nose were 0.93 (95% CI 0.82-0.97) and 0.93 (95% CI 0.82-0.97), respectively, and no heterogeneity was found. The sensitivity and specificity of other breath test devices ranged from 0.62 to 1.00, and 0.11 to 0.84, respectively.
INTERPRETATION
The low to moderate evidence of these studies shows that breath tests can diagnose TB accurately, however, to give a real-time test result, additional development is needed. Research should also focus on sputum smear negative TB, children, and the positioning of breath testing in the diagnostic work flow.
FUNDING
The authors received no specific funding for this work.
Topics: Biosensing Techniques; Breath Tests; Electronic Nose; Female; Humans; Male; Mycobacterium tuberculosis; ROC Curve; Reproducibility of Results; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Pulmonary; Volatile Organic Compounds
PubMed: 31401197
DOI: 10.1016/j.ebiom.2019.07.056 -
PloS One 2023Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately 1% of all active TB cases. The diagnosis of Tuberculosis meningitis is notably difficult due to its rapid onset, nonspecific symptoms, and the difficulty of detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF). In 2019, 78,200 adults died of TB meningitis. This study aimed to assess the microbiological diagnosis TB meningitis using CSF and estimated the risk of death from TBM.
METHODS
Relevant electronic databases and gray literature sources were searched for studies that reported presumed TBM patients. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools designed for prevalence studies. Data were summarized using Microsoft excel ver 16. The proportion of culture confirmed TBM, prevalence of drug resistance and risk of death were calculated using the random-effect model. Stata version 16.0 was used perform the statistical analysis. Moreover, subgroup analysis was conducted.
RESULTS
After systematic searching and quality assessment, 31 studies were included in the final analysis. Ninety percent of the included studies were retrospective studies in design. The overall pooled estimates of CSF culture positive TBM was 29.72% (95% CI; 21.42-38.02). The pooled prevalence of MDR-TB among culture positive TBM cases was 5.19% (95% CI; 3.12-7.25). While, the proportion of INH mono-resistance was 9.37% (95% CI; 7.03-11.71). The pooled estimate of case fatality rate among confirmed TBM cases was 20.42% (95%CI; 14.81-26.03). Based on sub group analysis, the pooled case fatality rate among HIV positive and HIV negative TBM individuals was 53.39% (95%CI; 40.55-66.24) and 21.65% (95%CI;4.27-39.03) respectively.
CONCLUSION
Definite diagnosis of TBM still remains global treat. Microbiological confirmation of TBM is not always achievable. Early microbiological confirmation of TBM has great importance to reduce mortality. There was high rate of MDR-TB among confirmed TBM patients. All TB meningitis isolates should be cultured and drug susceptibility tested using standard techniques.
Topics: Adult; Humans; Tuberculosis, Meningeal; Retrospective Studies; Sensitivity and Specificity; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36795648
DOI: 10.1371/journal.pone.0279203 -
The Cochrane Database of Systematic... Jan 2021Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum. To extend our previous review on extrapulmonary tuberculosis (Kohli 2018), we performed this update to inform updated WHO policy (WHO Consolidated Guidelines (Module 3) 2020).
OBJECTIVES
To estimate diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for extrapulmonary tuberculosis and rifampicin resistance in adults with presumptive extrapulmonary tuberculosis.
SEARCH METHODS
Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, 2 August 2019 and 28 January 2020 (Xpert Ultra studies), without language restriction.
SELECTION CRITERIA
Cross-sectional and cohort studies using non-respiratory specimens. Forms of extrapulmonary tuberculosis: tuberculous meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, disseminated tuberculosis. Reference standards were culture and a study-defined composite reference standard (tuberculosis detection); phenotypic drug susceptibility testing and line probe assays (rifampicin resistance detection).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias and applicability using QUADAS-2. For tuberculosis detection, we performed separate analyses by specimen type and reference standard using the bivariate model to estimate pooled sensitivity and specificity with 95% credible intervals (CrIs). We applied a latent class meta-analysis model to three forms of extrapulmonary tuberculosis. We assessed certainty of evidence using GRADE.
MAIN RESULTS
69 studies: 67 evaluated Xpert MTB/RIF and 11 evaluated Xpert Ultra, of which nine evaluated both tests. Most studies were conducted in China, India, South Africa, and Uganda. Overall, risk of bias was low for patient selection, index test, and flow and timing domains, and low (49%) or unclear (43%) for the reference standard domain. Applicability for the patient selection domain was unclear for most studies because we were unsure of the clinical settings. Cerebrospinal fluid Xpert Ultra (6 studies) Xpert Ultra pooled sensitivity and specificity (95% CrI) against culture were 89.4% (79.1 to 95.6) (89 participants; low-certainty evidence) and 91.2% (83.2 to 95.7) (386 participants; moderate-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 168 would be Xpert Ultra-positive: of these, 79 (47%) would not have tuberculosis (false-positives) and 832 would be Xpert Ultra-negative: of these, 11 (1%) would have tuberculosis (false-negatives). Xpert MTB/RIF (30 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 71.1% (62.8 to 79.1) (571 participants; moderate-certainty evidence) and 96.9% (95.4 to 98.0) (2824 participants; high-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 99 would be Xpert MTB/RIF-positive: of these, 28 (28%) would not have tuberculosis; and 901 would be Xpert MTB/RIF-negative: of these, 29 (3%) would have tuberculosis. Pleural fluid Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity against culture were 75.0% (58.0 to 86.4) (158 participants; very low-certainty evidence) and 87.0% (63.1 to 97.9) (240 participants; very low-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 192 would be Xpert Ultra-positive: of these, 117 (61%) would not have tuberculosis; and 808 would be Xpert Ultra-negative: of these, 25 (3%) would have tuberculosis. Xpert MTB/RIF (25 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 49.5% (39.8 to 59.9) (644 participants; low-certainty evidence) and 98.9% (97.6 to 99.7) (2421 participants; high-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 60 would be Xpert MTB/RIF-positive: of these, 10 (17%) would not have tuberculosis; and 940 would be Xpert MTB/RIF-negative: of these, 50 (5%) would have tuberculosis. Lymph node aspirate Xpert Ultra (1 study) Xpert Ultra sensitivity and specificity (95% confidence interval) against composite reference standard were 70% (51 to 85) (30 participants; very low-certainty evidence) and 100% (92 to 100) (43 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 70 would be Xpert Ultra-positive and 0 (0%) would not have tuberculosis; 930 would be Xpert Ultra-negative and 30 (3%) would have tuberculosis. Xpert MTB/RIF (4 studies) Xpert MTB/RIF pooled sensitivity and specificity against composite reference standard were 81.6% (61.9 to 93.3) (377 participants; low-certainty evidence) and 96.4% (91.3 to 98.6) (302 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 118 would be Xpert MTB/RIF-positive and 37 (31%) would not have tuberculosis; 882 would be Xpert MTB/RIF-negative and 19 (2%) would have tuberculosis. In lymph node aspirate, Xpert MTB/RIF pooled specificity against culture was 86.2% (78.0 to 92.3), lower than that against a composite reference standard. Using the latent class model, Xpert MTB/RIF pooled specificity was 99.5% (99.1 to 99.7), similar to that observed with a composite reference standard. Rifampicin resistance Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity were 100.0% (95.1 to 100.0), (24 participants; low-certainty evidence) and 100.0% (99.0 to 100.0) (105 participants; moderate-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 100 would be Xpert Ultra-positive (resistant): of these, zero (0%) would not have rifampicin resistance; and 900 would be Xpert Ultra-negative (susceptible): of these, zero (0%) would have rifampicin resistance. Xpert MTB/RIF (19 studies) Xpert MTB/RIF pooled sensitivity and specificity were 96.5% (91.9 to 98.8) (148 participants; high-certainty evidence) and 99.1% (98.0 to 99.7) (822 participants; high-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 105 would be Xpert MTB/RIF-positive (resistant): of these, 8 (8%) would not have rifampicin resistance; and 895 would be Xpert MTB/RIF-negative (susceptible): of these, 3 (0.3%) would have rifampicin resistance.
AUTHORS' CONCLUSIONS
Xpert Ultra and Xpert MTB/RIF may be helpful in diagnosing extrapulmonary tuberculosis. Sensitivity varies across different extrapulmonary specimens: while for most specimens specificity is high, the tests rarely yield a positive result for people without tuberculosis. For tuberculous meningitis, Xpert Ultra had higher sensitivity and lower specificity than Xpert MTB/RIF against culture. Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity for rifampicin resistance. Future research should acknowledge the concern associated with culture as a reference standard in paucibacillary specimens and consider ways to address this limitation.
Topics: Adult; Antibiotics, Antitubercular; Bias; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Reagent Kits, Diagnostic; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pleural
PubMed: 33448348
DOI: 10.1002/14651858.CD012768.pub3 -
Clinical Microbiology and Infection :... Feb 2020The Mycobacterium tuberculosis Beijing genotype was first described in 1995 and is now the predominant strain among patients with tuberculosis in many Asian countries.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The Mycobacterium tuberculosis Beijing genotype was first described in 1995 and is now the predominant strain among patients with tuberculosis in many Asian countries. The rapid global spread of the Beijing genotype is receiving increasing attention because it can cause a higher risk of treatment failures. Our objective was to assess the association between the Beijing genotype and unfavourable treatment outcomes of tuberculosis.
METHODS
We searched for eligible studies through PubMed, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data. We included cohort studies that evaluated treatment outcomes and Beijing genotype strains. Participants were individuals with active pulmonary tuberculosis. The association between Beijing genotype and the risk of unfavourable treatment outcomes was assessed using the pooled odds ratios (ORs) with corresponding confidence intervals (CIs).
RESULTS
In total, 7489 tuberculosis patients were involved in the analysis. Patients infected with the Beijing genotype were more likely to have unfavourable treatment outcomes, with the OR of 2.04 (95% CI 1.52-2.75). The pooled OR was 2.33 (95% CI 1.71-3.16) for recurrence, 2.36 (95% CI 1.69-3.30) for relapse and 2.62 (95% CI 1.90-3.61) for treatment failure, respectively. Subgroup analysis revealed that Beijing genotype was a significant risk factor for unfavourable treatment outcomes in Asians (OR 2.28, 95% CI 1.82-2.86) or in drug-susceptible TB patients (OR 2.11, 95% CI 1.31-3.39). No significant association was observed among non-Asian populations (OR 1.17, 95% CI 0.73-1.86) or patients with multidrug-resistant (MDR) tuberculosis (OR 0.97, 95% CI 0.48-1.94).
CONCLUSIONS
Our results suggest that Mycobacterium tuberculosis Beijing genotype is associated with an increased risk of unfavourable treatment outcomes, including treatment failure and relapse.
Topics: Antitubercular Agents; Asia; Beijing; Genotype; Humans; Mycobacterium tuberculosis; Odds Ratio; Prognosis; Risk Factors; Treatment Failure; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 31336202
DOI: 10.1016/j.cmi.2019.07.016 -
The Cochrane Database of Systematic... Sep 2022Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert... (Review)
Review
BACKGROUND
Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents.
OBJECTIVES
To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021.
SELECTION CRITERIA
Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE.
MAIN RESULTS
We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results.
AUTHORS' CONCLUSIONS
We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.
Topics: Adolescent; Antibiotics, Antitubercular; Child; Cross-Sectional Studies; HIV Infections; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary
PubMed: 36065889
DOI: 10.1002/14651858.CD013359.pub3 -
International Journal of... 2023Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium... (Review)
Review
Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
Topics: Humans; beta-Lactamase Inhibitors; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium tuberculosis; Carbapenems; Penicillins; Clavulanic Acid; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous
PubMed: 37721224
DOI: 10.4103/ijmy.ijmy_131_23 -
Laboratory Cross-Contamination of Mycobacterium tuberculosis: A Systematic Review and Meta-analysis.Lung Oct 2019Microbiological cultures are the mainstay of the diagnosis of tuberculosis (TB). False-positive TB results lead to significant unnecessary therapeutic and economic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Microbiological cultures are the mainstay of the diagnosis of tuberculosis (TB). False-positive TB results lead to significant unnecessary therapeutic and economic burden and are frequently caused by laboratory cross-contamination. The aim of this meta-analysis was to quantify the prevalence of laboratory cross-contamination.
METHODS
Through a systematic review of five electronic databases, we identified studies reporting rates of laboratory cross-contamination, confirmed by molecular techniques in TB cultures. We evaluated the quality of the identified studies using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and conducted a meta-analysis using standard methodology recommended by the Cochrane Collaboration.
RESULTS
Based on 31 eligible studies evaluating 29,839 TB cultures, we found that 2% (95% confidence intervals [CI] 1-2%) of all positive TB cultures represent false-positive results secondary to laboratory cross-contamination. More importantly, we evaluated the rate of laboratory cross-contamination in cases where a single-positive TB culture was available in addition to at least one negative TB culture, and we found a rate of 15% (95% CI 6-33%). Moreover, 9.2% (91/990) of all patients with a preliminary diagnosis of TB had false-positive results and received unnecessary and potentially harmful treatments.
CONCLUSIONS
Our results highlight a remarkably high prevalence of false-positive TB results as a result of laboratory cross-contamination, especially in single-positive TB cultures, leading to the administration of unnecessary, harmful treatments. The need for the adoption of strict technical standards for mycobacterial cultures cannot be overstated.
Topics: Bacteriological Techniques; False Positive Reactions; Humans; Mycobacterium tuberculosis; Predictive Value of Tests; Reproducibility of Results; Tuberculosis; Unnecessary Procedures
PubMed: 31203380
DOI: 10.1007/s00408-019-00241-4