Epidemiology of first- and second-line drugs-resistant pulmonary tuberculosis in Iran: Systematic review and meta-analysis
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ABSTRACT:
SUBMITTER: Abbasian S
PROVIDER: S-EPMC10981085 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundDrug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study.MethodsA total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants' social-demographic characteristics were obtained using a pre-test checklist.ResultsOverall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5-31.6%). A total of 9.8% (13/132, 95% CI: 5.3-16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3-16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1-146.5%) to have drug-resistant TB than those who had no history of being treated for TB.ConclusionThis study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring.
| S-EPMC9855139 | biostudies-literature
Project description:BACKGROUND:Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. METHODS:We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. RESULTS:DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. CONCLUSIONS:DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.
| S-EPMC4296130 | biostudies-other
Project description:ObjectiveTo determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB).MethodsIn this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods.ResultsAltered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment.ConclusionSecond-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.
| S-EPMC10178494 | biostudies-literature
Project description:The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes.
| S-EPMC10376136 | biostudies-literature
Project description:For Mycobacterium tuberculosis, phenotypic methods for drug susceptibility testing of second-line drugs are poorly standardized and technically challenging. The Sensititre MYCOTB MIC plate (MYCOTB) is a microtiter plate containing lyophilized antibiotics and configured for determination of MICs to first- and second-line antituberculosis drugs. To evaluate the performance of MYCOTB for M. tuberculosis drug susceptibility testing using the Middlebrook 7H10 agar proportion method (APM) as the comparator, we conducted a two-site study using archived M. tuberculosis isolates from Uganda and the Republic of Korea. Thawed isolates were subcultured, and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, and 21; APM results were read at 21 days. A total of 222 isolates provided results on both platforms. By APM, 106/222 (47.7%) of isolates were resistant to at least isoniazid and rifampin. Agreement between MYCOTB and APM with respect to susceptibility or resistance was ≥92% for 7 of 12 drugs when a strict definition was used and ≥96% for 10 of 12 drugs when agreement was defined by allowing a ± one-well range of dilutions around the APM critical concentration. For ethambutol, agreement was 80% to 81%. For moxifloxacin, agreement was 83% to 85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91% to 96%. For MYCOTB, the median time to plate interpretation was 10 days and interreader agreement was ≥95% for all drugs. MYCOTB provided reliable results for M. tuberculosis susceptibility testing of first- and second-line drugs except ethambutol, and results were available sooner than those determined by APM.
| S-EPMC3910714 | biostudies-literature
Project description:N-acetylcysteine (NAC) is most commonly used for the treatment of acetaminophen overdose and acetaminophen-induced liver injury. In patients infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), NAC is given to treat hepatotoxicity induced by TB drugs. We had previously shown that cysteine, a derivative of NAC, potentiated the activity of isoniazid, a first-line TB drug, by preventing the emergence of INH resistance and persistence in M. tuberculosis in vitro. Herein, we demonstrate that in vitro, NAC has the same boosting activity with various combinations of first- and second-line TB drugs against drug-susceptible and multidrug-resistant M. tuberculosis strains. Similar to cysteine, NAC increased M. tuberculosis respiration. However, in M. tuberculosis-infected mice, the addition of NAC did not augment the activity of first- or second-line TB drugs. A comparison of the activity of NAC combined with TB drugs in murine and human macrophage cell lines revealed that studies in mice might not be recapitulated during host infection in vivo.
| S-EPMC8092890 | biostudies-literature
Project description:BackgroundAmong pediatric patients with multidrug-resistant tuberculosis (MDR-TB), limited data exist regarding treatment outcomes in the context of the new and repurposed second-line TB drugs (SLDs). We aimed to describe the treatment outcomes among pediatric MDR-TB patients receiving new and repurposed SLDs including the proportion who achieved favorable outcomes.MethodsWe conducted a retrospective cohort study among pediatric patients (age ≤18 years) treated for MDR-TB in the country of Georgia from 2009 to 2016. A "new and repurposed" SLD regimen was defined as a regimen that included linezolid, bedaquiline, and/or delamanid. Favorable treatment outcome was defined by treatment completion or documented microbial "cure" status at the end of treatment. We assessed the association between the use of the new and repurposed SLDs with MDR-TB treatment outcomes using bivariate analyses and log-binomial regression.ResultsThere were 124 pediatric MDR-TB patients (median age: 13.7; interquartile range: 4.6-16.0) initiating treatment; 119 (96.0%) had a treatment outcome recorded and were included in our analyses. Eighteen (15.1%) patients received new and repurposed SLDs from 2015 or later. After adjusting for potential confounders, the proportion achieving favorable MDR-TB treatment outcomes was higher among patients treated with SLD regimens that included new and/or repurposed drugs when compared with those treated without (adjusted risk ratio: 1.17; 95% confidence interval: 0.51-2.72).ConclusionsWe observed a high proportion of favorable treatment outcomes among pediatric patients with MDR-TB receiving the new and repurposed SLDs. Further studies to evaluate the efficacy and children's tolerability of the new and repurposed SLDs are still warranted.
| S-EPMC8087132 | biostudies-literature
Project description:Isoniazid-resistant tuberculosis (Hr-TB) is an important drug-resistant tuberculosis (TB). In addition to rifampicin, resistance to other medications for Hr-TB can impact the course of treatment; however, there are currently limited data in the literature. In this study, the drug susceptibility profiles of Hr-TB treatment and resistance-conferring mutations were investigated for Hr-TB clinical isolates from Thailand. Phenotypic drug susceptibility testing (pDST) and genotypic drug susceptibility testing (gDST) were retrospectively and prospectively investigated using the Mycobacterium Growth Indicator Tube (MGIT), the broth microdilution (BMD) method, and whole-genome sequencing (WGS)-based gDST. The prevalence of Hr-TB cases was 11.2% among patients with TB. Most Hr-TB cases (89.5%) were newly diagnosed patients with TB. In the pDST analysis, approximately 55.6% (60/108) of the tested Hr-TB clinical isolates exhibited high-level isoniazid resistance. In addition, the Hr-TB clinical isolates presented co-resistance to ethambutol (3/161, 1.9%), levofloxacin (2/96, 2.1%), and pyrazinamide (24/118, 20.3%). In 56 Hr-TB clinical isolates, WGS-based gDST predicted resistance to isoniazid [katG S315T (48.2%) and fabG1 c-15t (26.8%)], rifampicin [rpoB L430P and rpoB L452P (5.4%)], and fluoroquinolones [gyrA D94G (1.8%)], but no mutation for ethambutol was detected. The categorical agreement for the detection of resistance to isoniazid, rifampicin, ethambutol, and levofloxacin between WGS-based gDST and the MGIT or the BMD method ranged from 80.4% to 98.2% or 82.1% to 100%, respectively. pDST and gDST demonstrated a low co-resistance rate between isoniazid and second-line TB drugs in Hr-TB clinical isolates.ImportanceThe prevalence of isoniazid-resistant tuberculosis (Hr-TB) is the highest among other types of drug-resistant tuberculosis. Currently, the World Health Organization (WHO) guidelines recommend the treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months. The susceptibility profiles of Hr-TB clinical isolates, especially when they are co-resistant to second-line drugs, are critical in the selection of the appropriate treatment regimen to prevent treatment failure. This study highlights the susceptibility profiles of the WHO-recommended treatment regimen in Hr-TB clinical isolates from a tertiary care hospital in Thailand and the concordance and importance of using the phenotypic drug susceptibility testing or genotypic drug susceptibility testing for accurate and comprehensive interpretation of results.
| S-EPMC10913473 | biostudies-literature
Project description:Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir-ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir-ritonavir and drugs routinely used for MDR-TB treatment in HIV-infected children. A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 with MDR-TB receiving treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin and 16 without TB) who were established on a lopinavir-ritonavir-containing antiretroviral regimen. One-compartment models with first-order absorption and elimination for both lopinavir and ritonavir were combined into an integrated model. The dynamic inhibitory effect of the ritonavir concentration on lopinavir clearance was described using a maximum inhibition model. Even after adjustment for the effect of body weight with allometric scaling, a large variability in lopinavir and ritonavir exposure, together with strong correlations between the pharmacokinetic parameters of lopinavir and ritonavir, was detected. MDR-TB treatment did not have a significant effect on the bioavailability, clearance, or absorption rate constants of lopinavir or ritonavir. Most children (81% of children with MDR-TB, 88% of controls) achieved therapeutic lopinavir trough concentrations (>1 mg/liter). The coadministration of lopinavir-ritonavir with drugs routinely used for the treatment of MDR-TB was found to have no significant effect on the key pharmacokinetic parameters of lopinavir or ritonavir. These findings should be considered in the context of the large interpatient variability found in the present study and the study's modest sample size.
| S-EPMC5786799 | biostudies-literature
Project description:The second-line injectable drugs (SLID, i.e., amikacin, kanamycin, capreomycin) are key drugs for the treatment of multidrug-resistant tuberculosis. Mutations in rrs region 1400, tlyA, and eis promoter are associated with resistance to SLID, to capreomycin, and to kanamycin, respectively. In this study, the sequencing data of SLID resistance-associated genes were compared to the results of phenotypic drug susceptibility testing by the proportion method for the SLID in 206 multidrug-resistant clinical isolates of Mycobacterium tuberculosis collected in France. Among the 153 isolates susceptible to the 3 SLID, 145 showed no mutation, 1 harbored T1404C and G1473A mutations in rrs, and 7 had an eis promoter mutation. Among the 53 strains resistant to at least 1 of the SLID, mutations in rrs accounted for resistance to amikacin, capreomycin, and kanamycin for 81%, 75%, and 44% of the isolates, respectively, while mutations in eis promoter were detected in 44% of the isolates resistant to kanamycin. In contrast, no mutations in tlyA were observed in the isolates resistant to capreomycin. The discrepancies observed between the genotypic (on the primary culture) and phenotypic drug susceptibility testing were explained by (i) resistance to SLID with MICs close to the critical concentration used for routine DST and not detected by phenotypic testing (n = 8, 15% of SLID-resistant strains), (ii) low-frequency heteroresistance not detected by sequencing of drug resistance-associated genes on the primary culture (n = 8, 15% of SLID-resistant strains), and (iii) other resistance mechanisms not yet characterized (n = 7, 13% of SLID-resistant strains).
| S-EPMC5278698 | biostudies-literature