Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates

Zheng, Chang‐Ji; Li, Shangyuan; Luo, Zhangjie; Pi, Rui; Sun, Hongli; He, Qingxia; Tang, Ke; Luo, Moulun; Li, Yuqing; Couvin, David; Rastogi, Nalin; Sun, Qun

doi:10.1128/jcm.03507-14

Cited by 37 publications

(32 citation statements)

References 44 publications

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“…Polyclonal M. tuberculosis infections may have a negative impact on drug resistance testing performed by both phenotypic ( e.g., proportional test) and genotypic methods ( e.g., GeneXpert MTB/RIF)1112. Another problem for diagnosis and treatment of TB patients, which is more difficult to detect by the usual phenotypic DST is hetero-resistance13.…”

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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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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“…Manu2, one of the genotypes sorted by spoligotype number, was found to be significantly associated with mixed infections among the 499 tested clinical isolates (odds ratio 47.72; confidence interval 9.68–235.23; p < 0.01). Four isolates (1.37%) were confirmed to be hetero-resistant, out of which three (75%) were caused by mixed infections and belonged to Manu2 [ 64 ]. That study first revealed that Manu2 was the most predominant genotype in cases of mixed infections and potentially the main reason behind development of hetero-resistance.…”

Section: Bacterial Changesmentioning

confidence: 99%

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes

Xu¹,

Wu²,

Liao³

et al. 2017

Ann Clin Microbiol Antimicrob

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Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts’ body weight, metabolic processing of the drug, malabsorption and/or drug–drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen’s physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

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“…[3,4] Polyclonal infections may be associated with Hetero-resistance. [5][6][7][8]. , showed that false-negative results using Gene-Xpert MTB/RIF were significantly associated with mixed infections and that it fails to detect rifampicin (RIF)resistance in vitro when resistant sub-populations accounted for <90%.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

Pandey

Bhatnagar²,

Sachdeva

et al. 2020

PLoS ONE

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Background Mixed/polyclonal infections due to different genotypes are reported in Tuberculosis. The current study was designed to understand the fate of mixed infections during the course of treatment and follow-up and its role in disease pathogenesis. Methods Sputum samples were collected on 0,1,2,3,6,12 and 24 months from 157 treatment-naïve patients, cultures subjected to Drug-Susceptibility-testing (MGIT 960), spoligotyping, MIRU-VNTR and SNP genotyping. All isolated colonies on thin layer agar (7H11) were subjected to spoligotyping. Findings One thirty three baseline cultures were positive (133/157, 84.7%), 43(32.3%) had mixture of genotypes. Twenty-four of these patients (55.8%) showed change in genotype while six showed different drug-susceptibility patterns while on treatment. Twenty-three (53.5%) patients with polyclonal infections showed resistance to at least one drug compared to 10/ 90 (11.1%) monoclonal infections (P<0.0001). Eight patients had recurrent TB, two with a new genotype and two with altered phenotypic DST. Conclusions The coexistence of different genotypes and change of genotypes during the same disease episode, while on treatment, confirms constancy of polyclonal infections. The composition of the mixture of genotypes and the relative predominance may be missed by culture due to its limit of detection. Polyclonal infections in TB could be a rule rather than exception and challenges the age-old dogma of reactivation/reinfection.

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Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates

Cited by 37 publications

References 44 publications

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

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

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence

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