Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Hu, Yi; Zhao, Qi; Werngren, Jim; Hoffner, Sven; Diwan, Vinod; Xu, Biao

doi:10.1186/s12879-015-1331-z

Cited by 18 publications

(15 citation statements)

References 21 publications

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“…On the other hand, molecular assays may not be sensitive enough to detect drug-resistant subpopulations (heteroresistance) at the critical 1% proportion level (10% for PZA) defining clinical resistance (17,18,23). The magnitude of mixed and polyclonal infections among TB patients is relatively unknown, although recent studies clearly showed that heteroresistance occurs frequently (ϳ20% to 45%) in specific TB populations and that it may also have a negative impact on the treatment outcome (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Non- pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

2017

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Pyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDR) tuberculosis (TB). gene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDR TB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-type gene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy: or mutations identified by whole-genome sequencing (WGS) ( = 7), heteroresistance ( = 8), and mixed populations with ( = 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDR clinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymous mutation (Thr87Met), whereas a nonsynonymous mutation was found in 17 isolates. None of these isolates carried a nonsynonymous mutation, while all 15 of the MDR isolates harbored a nonsynonymous mutation. Our findings indicate that it is necessary to consider the occurrence of mutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymous mutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role of in PZA resistance.

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Section: Discussionmentioning

confidence: 99%

Non- pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

2017

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“…Therefore, early identification of patients with mixed infections would enable prompt therapy with an optimized drug regimen increasing the cure rate18. High resolution whole genome sequencing analysis will elucidate more details in this regard19.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Kamakoli

Sadegh

Farmanfarmaei

et al. 2017

Sci Rep

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Mixed strain infections of Mycobacterium tuberculosis make diagnosis, treatment, and control of tuberculosis (TB) more difficult. This study was aimed to evaluate the relationship between mixed infections, antibiotic resistance patterns and treatment of TB patients. In this study, among 2850 suspected TB clinical samples, a total of ninety-six clinical samples from 66 TB confirmed patients were subjected to the 24-locus variable-number tandem repeat method to evaluate the prevalence of mixed infections. For all studied strains, 288 colonies (three individual clones for each sample) were isolated from different colonies and separately analyzed by the Drug Susceptibility Test (DST). For all patients, follow up was done after 6 months of treatment. Based on direct 24 loci MIRU-VNTR, in the 66 TB patients, 53% (35/66) showed mixed infection. In the mixed samples, 45.71% (16/35) showed different antibiotic resistant patterns. Among the mixed infection patients, eight (22.9%; 8/35) showed treatment failure after six- month therapy. Six of these non-treated patients (75%; 6/8) had different antibiotic resistant patterns. We conclude that mixed infections, have a negative impact on treatment of TB patients especially when co-infecting M. tuberculosis strains display heteroresistance.

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“…Less than 10 studies referred to daily or cumulative average number of medications in order to quantify the large number of medications consumed by children during hospitalization [43,96]. However, average number of medications seems to build from the World Health Organization (WHO) guidelines, stating that an average number of medications per prescription or patient encounter greater than two is considered polypharmacy and is commonly used in international settings [84]. Inpatient polypharmacy should be characterized to capture its magnitude and associated risks over a short period of time.…”

Section: Discussionmentioning

confidence: 99%

Defining pediatric polypharmacy: A scoping review

et al. 2018

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ObjectivesLack of consensus regarding the semantics and definitions of pediatric polypharmacy challenges researchers and clinicians alike. We conducted a scoping review to describe definitions and terminology of pediatric polypharmacy.MethodsMedline, PubMed, EMBASE, CINAHL, PsycINFO, Cochrane CENTRAL, and the Web of Science Core Collection databases were searched for English language articles with the concepts of “polypharmacy” and “children”. Data were extracted about study characteristics, polypharmacy terms and definitions from qualifying studies, and were synthesized by disease conditions.ResultsOut of 4,398 titles, we included 363 studies: 324 (89%) provided numeric definitions, 131 (36%) specified duration of polypharmacy, and 162 (45%) explicitly defined it. Over 81% (n = 295) of the studies defined polypharmacy as two or more medications or therapeutic classes. The most common comprehensive definitions of pediatric polypharmacy included: two or more concurrent medications for ≥1 day (n = 41), two or more concurrent medications for ≥31 days (n = 15), and two or more sequential medications over one year (n = 12). Commonly used terms included polypharmacy, polytherapy, combination pharmacotherapy, average number, and concomitant medications. The term polypharmacy was more common in psychiatry literature while epilepsy literature favored the term polytherapy.ConclusionsTwo or more concurrent medications, without duration, for ≥1 day, ≥31 days, or sequentially for one year were the most common definitions of pediatric polypharmacy. We recommend that pediatric polypharmacy studies specify the number of medications or therapeutic classes, if they are concurrent or sequential, and the duration of medications. We propose defining pediatric polypharmacy as “the prescription or consumption of two or more distinct medications for at least one day”. The term “polypharmacy” should be included among key words and definitions in manuscripts.

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Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Cited by 18 publications

References 21 publications

Non- pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

Non- pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

Evaluation of the impact of polyclonal infection and heteroresistance on treatment of tuberculosis patients

Defining pediatric polypharmacy: A scoping review

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