Multidrug-resistant tuberculosis in Europe, 2010-2011.
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ABSTRACT:
SUBMITTER: Gunther G
PROVIDER: S-EPMC4344280 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia.
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Project description:In Ulaanbaatar, Mongolia, multidrug-resistant tuberculosis (MDR TB) was diagnosed for more than a third of new sputum smear-positive tuberculosis patients for whom treatment had failed. This finding suggests a significant risk for community-acquired MDR TB and a need to make rapid molecular drug susceptibility testing available to more people.
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Project description:In Japan and Australia, multidrug-resistant Mycoplasma genitalium infections are reported with increasing frequency. Although macrolide-resistant M. genitalium strains are common in Europe and North America, fluoroquinolone-resistant strains are still exceptional. However, an increase of multidrug-resistant M. genitalium in Europe and America is to be expected. The aim of this paper is to increase awareness on the rising number of multidrug-resistant M. genitalium strains. Here, one of the first cases of infection with a genetically proven multidrug-resistant M. genitalium strain in Europe is described. The patient was a native Dutch 47-year-old male patient with urethritis. Mycoplasma genitalium was detected, but treatment failed with azithromycin, doxycycline and moxifloxacin. A urogenital sample was used to determine the sequence of the 23S rRNA, gyrA, gyrB and parC genes. The sample contained an A2059G single nucleotide polymorphism (SNP) in the 23S rRNA gene and an SNP in the parC gene, resulting in an amino acid change of Ser83 → Ile, explaining both azithromycin and moxifloxacin treatment failure. The SNPs associated with resistance were probably generated de novo, as a link with high-prevalence areas was not established. It is, thus, predictable that there is going to be an increase of multidrug-resistant M. genitalium strains in Europe. As treatment options for multidrug-resistant M. genitalium are limited, the treatment of M. genitalium infections needs to be carefully considered in order to limit the rapid increase of resistance to macrolides and fluoroquinolones.
| S-EPMC5554300 | biostudies-other
Project description:BACKGROUND:In 2016, the World Health Organization (WHO) recommended a shorter (9-12 month) multidrug-resistant tuberculosis (MDR-TB) treatment regimen (as compared to the conventional 18-24 month regimen) for patients without extrapulmonary TB, pregnancy, a previous second-line TB medication exposure, or drug resistance to pyrazinamide, ethambutol, kanamycin, moxifloxacin, ethionamide, or clofazimine. The recommendation was based on successful clinical trials conducted in Asia and Africa, but studies, using mainly European data, have shown few patients in higher-resource settings would meet WHO eligibility criteria. METHODS:We assessed eligibility for the shorter regimen among US MDR-TB cases that had full drug susceptibility testing (DST) results and were reported during 2011-2016 to the US National TB Surveillance System. We estimated costs by applying the eligibility criteria for the shorter regimen, and proportional inpatient/outpatient costs from a previous, population-based study, to all MDR-TB patients reported to the National TB Surveillance System. RESULTS:Of 586 reported MDR-TB cases, 10% (59) were eligible for the shorter regimen. Of 527 ineligible patients, 386 had full DST, of which 246 were resistant to ethambutol and 217 were resistant to pyrazinamide. Compared with conventional MDR-TB treatment, implementing the shorter regimen would have reduced the US annual societal MDR-TB cost burden by 4%, but the cost burden for eligible individuals would have been reduced by 37-46%. CONCLUSIONS:Relying on full DST use, our analysis found a minority of US MDR-TB patients would have been eligible for the shorter regimen. Cost reductions would have been minimal for society, but large for eligible individuals.
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Project description:Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population.
| S-EPMC7138297 | biostudies-literature
Project description:Of 150 Escherichia coli strains we cultured from specimens taken from cattle in Europe, 3 had elevated MICs against colistin. We assessed all 3 strains for the presence of the plasmid-mediated mcr-1 gene and identified 1 isolate as mcr-1-positive and co-resistant to β-lactam, florfenicol, and fluoroquinolone antimicrobial compounds.
| S-EPMC4994333 | biostudies-literature
Project description:Antimicrobial drug resistance rates for Mycoplasma pneumoniae was determined in clinical specimens and isolates obtained during 2011-2012 in Ontario, Canada. Of 91 M. pneumoniae drug-resistant specimens, 11 (12.1%) carried nucleotide mutations associated with macrolide resistance in the 23S rRNA gene. None of the M. pneumoniae specimens were resistant to fluoroquinolones or tetracyclines.
| S-EPMC3810904 | biostudies-literature
Project description:BACKGROUND:Multidrug-resistant tuberculosis (MDR-TB) is burgeoning globally, and has been a serious challenge in TB management. Clinically, the ability to identify MDR-TB is still limited, especially in smear-negative TB. The aim of this study was to develop a nomogram for predicting MDR-TB. METHODS:Demographics and clinical characteristics of both MDR-TB and drug-susceptible TB patients were utilized to develop a nomogram for predicting MDR-TB. The LASSO regression method was applied to filter variables and select predictors, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). Moreover, calibration analysis and decision curve analysis (DCA) of the model were performed. This study involved a second analysis of a completed prospective cohort study conducted in a country with a high TB burden. RESULTS:Five variables of TB patients were selected through the LASSO regression method, and a nomogram was built based on these variables. The predictive model yielded an AUC of 0.759 (95% CI, 0.719-0.799), and in the internal validation, the AUC was 0.757 (95% CI, 0.715-0.793). The predictive model was well-calibrated, and DCA showed that if the threshold probability of MDR-TB was between 70 and 90%, using the proposed nomogram to predict MDR-TB would obtain a net benefit. CONCLUSIONS:In this study, a nomogram was constructed that incorporated five demographic and clinical characteristics of TB patients. The nomogram may be of great value for the prediction of MDR-TB in patients with sputum-free or smear-negative TB.
| S-EPMC7276074 | biostudies-literature
Project description:BackgroundThis study investigated the time to appropriate treatment and factors affecting late treatment initiation in patients with multidrug-resistant tuberculosis (MDR-TB) in South Korea.MethodsData from patients with culture-confirmed pulmonary MDR-TB who received treatment at Pusan National University Hospital (PNUH) between January 2010 and July 2018 were reviewed retrospectively. Patients were divided into two groups according to the first institution they visited [patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) and patients who were initially diagnosed with TB at PNUH (Group B)].ResultsA total of 100 patients were included (53 in Group A and 47 in Group B). The percentage of patients in whom line probe assays (LPAs) for isoniazid and rifampin or Xpert MTB/RIF assays were performed was higher in Group B than in Group A [20.8 vs. 57.4% (P < 0.001) and 17.0 vs. 46.8% (P = 0.001), respectively]. The median time from the first visit to appropriate treatment initiation was longer in Group A (102.0 vs. 77.0 days, P = 0.002). However, a subgroup analysis of patients with pre-extensively or extensively drug-resistant TB (pre-XDR- or XDR-TB) revealed that the time to appropriate treatment did not differ between Groups A and B. Although the time to appropriate treatment decreased during the study period in both Groups A and B, this trend was not evident in patients with pre-XDR- or XDR-TB in Group B. Based on multivariate analyses, performance of LPAs for isoniazid and rifampin, performance of Xpert MTB/RIF assays, and the presence of uncomplicated MDR-TB were protective against delays in appropriate treatment initiation.ConclusionsThe time to appropriate treatment in patients with MDR-TB in South Korea was not acceptable, particularly for patients diagnosed outside of PNUH and for patients with pre-XDR- or XDR-TB. The use of rapid molecular drug susceptibility tests in various healthcare settings and introduction of second-line LPAs are required.
| S-EPMC6483266 | biostudies-literature
Project description:BackgroundDespite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.Methods and findingsWe developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.ConclusionsTreatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
| S-EPMC1483913 | biostudies-literature