Towards national systems for continuous surveillance of antimicrobial resistance: Lessons from tuberculosis

Suthar, Amitabh B.; Moonan, Patrick K.; Alexander, Heather

doi:10.1371/journal.pmed.1002658

Cited by 6 publications

(4 citation statements)

References 9 publications

(14 reference statements)

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“…Similar to other findings, predominance of East-African-Indian lineage 3 and Euro-American lineage 4 in this report (Freschi et al, 2021;Senghore et al, 2020) which have low transmissibility, virulence, and drug resistance compared to East-Asian lineage 2 (Beijing family) may partly support the low RR/MDR-TB burden in Tanzania (Freschi et al, 2021;Rutaihwa et al, 2019;Wu et al, 2021). Collectively, these demonstrate the need for continuous anti-drug resistance surveillance by WGS and phenotypic methods including the MycoTB assay (Suthar et al, 2018;World Health Organization, 2015a).…”

Section: Discussionsupporting

confidence: 85%

Application of molecular methods in optimizing clinical management of patients with pulmonary multidrug resistant tuberculosis in Tanzania

Mbelele

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Rifampicin or multidrug-resistant tuberculosis (RR/MDR-TB) accounts for considerable morbidity and mortality. Differences among Mycobacterium tuberculosis complex (MTBC) species may predict drug-resistance or treatment success. This thesis aimed at identifying MTBC at species level, their drug-resistance patterns, and mycobactericidal effect of different regimens in patients treated for RR/MDR-TB and drug-susceptible (DS-TB). This was a cross sectional study nested in a longitudinal design that followed patients on RR/MDR-TB and DS TB treatment for 4 months. While RR/MDR-TB patients received bedaquiline with or without an injectable-aminoglycoside based regimen, DS-TB patients received a fixed-dose combination comprised of rifampicin-isoniazid-pyrazinamid-ethambutol (RHZE). The genotype MTBC assay was used to identify MTBC species. WGS-based drug resistant mutations predicted the minimum-inhibitory-concentration (MIC) of antibiotics measured in the MycoTB-Sensitire™ assay. An isolate was categorised as resistant and susceptible if it had a MIC above and at or below the epidemiological-cut-off (ECOFF) value, respectively. Non linear-mixed effects modelled the MTBC killing rates measured by Tuberculosis molecular bacterial load assay and culture. The median MIC at their 25th and 75th interquartile range (IQR) were compared using Mann-Whitney U test. Among 126 patients, 89 (71%) had positive culture whereas 87 (98%) were identified as M. tuberculosis. Overall, mutant (gNWT-R) MTBC isolates correlated with MIC values above the ECOFF. For instance, the median MIC (µg/mL) for rifampicin-gNWT-R strains was > 4.0 (IQR; 4.0 – 4.0) compared to 0.5 (IQR; 0.38 – 0.50) in non-mutant (gWT-S, p < 0.001); isoniazid-gNWT-R > 4.0 (IQR; 2.0 – 4.0) compared to 0.25 (IQR; 0.12 – 1.00) among gWT-S (p = 0.001); ethionamide-gNWT-R 15.0 (IQR; 10.0 – 20.0) compared to 2.50 (IQR; 2.50 – 5.00) among gWT-S (p < 0.001). There were no detectable mutations in genes previously known to confer fluoroquinolones, aminoglycosides, capreomycin, bedaquiline, delamanid, linezolid, clofazimine, cycloserine, and p aminosalicylic acid resistance. Compared to the adjusted M. tuberculosis killing rate of -0.17 (95% CI; -0.23 to -0.12) for the injectable without bedaquiline reference regimen, the killing rates were -0.62 (95% CI; -1.05 to -0.20) log10 eCFU/mL for the injectable with bedaquiline containing regimen (p = 0.019), -0.35 (95% CI; -0.65 to -0.13) log10 eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and -0.29 (95% CI; -0.78 to +0.22) log10 eCFU/mL for RHZE (p = 0.332). The detected M. tuberculosis was susceptible to core drugs including bedaquiline, fluoroquinolones, linezolid, and clofazimine, supporting their central use in the RR/MDRTB treatment regimens. M. tuberculosis killing rates were higher among patients who received bedaquiline but were further improved with addition of an injectable aminoglycoside.

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Section: Discussionsupporting

confidence: 85%

Application of molecular methods in optimizing clinical management of patients with pulmonary multidrug resistant tuberculosis in Tanzania

Mbelele

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“…Continuous antimicrobial resistance surveillance is an essential part of national containment strategies ( 37 ). The last result of our study was the remarkable consistency between routine surveillance data and periodic drug-resistance surveys for both new and previously treated TB cases, which suggests that Zhejiang Province, a setting with universal access to drug susceptibility testing, could use data from routine surveillance instead of periodic surveys to improve access to timely and appropriate treatment and care for DR-TB.…”

Section: Discussionmentioning

confidence: 99%

Drug resistance patterns and dynamics of tuberculosis in Zhejiang Province, China: Results from five periodic longitudinal surveys

Zhou

Huang

et al. 2022

Front. Public Health

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BackgroundAs one of the high multi-drug resistance tuberculosis countries, it is critical for China to understand patterns of drug resistance to better formulate effective treatment regimens.MethodsThe anti-TB Drug resistance surveillance has been conducted in Zheijang Province in years 1999, 2004, 2008, 2013, and 2018 respectively. We compared the prevalence of DR-TB from the latest survey with that of the previous four surveys in terms of all four first-line anti-TB drugs. We also examined the prevalence of rifampin-resistant TB (RR-TB) between the last two surveys and routine surveillance data.ResultsAmong 996 patients surveyed in 2018, the prevalence of RR-TB in new and previously treated TB cases was 2.5 and 4.3%, respectively. The prevalence of RR-TB among previously treated cases was much higher than for new cases in the four surveys from 1999 to 2013, while there was no significant difference between these groups in the 2018 survey. The percentage of TB cases resistant to fluoroquinolones in new patients was 3.8%. The prevalence of non-tuberculous mycobacteria increased over time; the prevalence of RR-TB among new cases slowly decreased. The prevalence of RR-TB in both new and previously treated TB cases from the latest two surveys was consistent with routine surveillance data.ConclusionsThis consistency between routine surveillance and periodic surveys for TB cases implies that with universal testing in Zhejiang Province, data from routine surveillance could be used instead of periodic surveys to improve access to timely and appropriate treatment for DR-TB. Levels of resistance were lower than whole-country and global estimates, further indicating the value of universal drug susceptibility testing.

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“…Antimicrobial resistance (AMR), a major threat to global health and a growing concern worldwide [ 1 , 2 ], is mainly attributed to the excessive use and misuse of antibiotics [ 3 ]. AMR related to tuberculosis (TB) has been extensively reported in clinical studies [ 4 , 5 , 6 ]. South Africa has one of the highest recorded prevalence of drug-resistant tuberculosis (DR-TB) patients globally [ 7 , 8 ] and particularly with the increasing burden of human immunodefiency virus (HIV) coinfection [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Wastewater-Based Surveillance of Antibiotic Resistance Genes Associated with Tuberculosis Treatment Regimen in KwaZulu Natal, South Africa

et al. 2021

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Essential components of public health include strengthening the surveillance of infectious diseases and developing early detection and prevention policies. This is particularly important for drug-resistant tuberculosis (DR-TB), which can be explored by using wastewater-based surveillance. This study aimed to use molecular techniques to determine the occurrence and concentration of antibiotic-resistance genes (ARGs) associated with tuberculosis (TB) resistance in untreated and treated wastewater. Raw/untreated and treated (post-chlorination) wastewater samples were taken from three wastewater treatment plants (WWTPs) in South Africa. The ARGs were selected to target drugs used for first- and second-line TB treatment. Both conventional polymerase chain reaction (PCR) and the more advanced droplet digital PCR (ddPCR) were evaluated as surveillance strategies to determine the distribution and concentration of the selected ARGs. The most abundant ARG in the untreated wastewater was the rrs gene, associated with resistance to the aminoglycosides, specifically streptomycin, with median concentration ranges of 4.69–5.19 log copies/mL. In contrast, pncA gene, associated with resistance to the TB drug pyrazinamide, was the least detected (1.59 to 2.27 log copies/mL). Resistance genes associated with bedaquiline was detected, which is a significant finding because this is a new drug introduced in South Africa for the treatment of multi-drug resistant TB. This study, therefore, establishes the potential of molecular surveillance of wastewater for monitoring antibiotic resistance to TB treatment in communities.

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Towards national systems for continuous surveillance of antimicrobial resistance: Lessons from tuberculosis

Cited by 6 publications

References 9 publications

Application of molecular methods in optimizing clinical management of patients with pulmonary multidrug resistant tuberculosis in Tanzania

Application of molecular methods in optimizing clinical management of patients with pulmonary multidrug resistant tuberculosis in Tanzania

Drug resistance patterns and dynamics of tuberculosis in Zhejiang Province, China: Results from five periodic longitudinal surveys

Wastewater-Based Surveillance of Antibiotic Resistance Genes Associated with Tuberculosis Treatment Regimen in KwaZulu Natal, South Africa

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