Journal Article > ResearchFull Text
EBioMedicine. 2017 March 19; Volume 18; 225-235.; DOI:10.1016/j.ebiom.2017.03.024
Rhee SY, Varghese B, Holmes SP, Van Zyl GU, Steegen K, et al.
EBioMedicine. 2017 March 19; Volume 18; 225-235.; DOI:10.1016/j.ebiom.2017.03.024
Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.
Journal Article > ResearchFull Text
EBioMedicine. 2024 March 1; Volume 101; 105004.; DOI:10.1016/j.ebiom.2024.105004
Hardy L, Vermoesen T, Genbrugge E, Natale A, Franquesa C, et al.
EBioMedicine. 2024 March 1; Volume 101; 105004.; DOI:10.1016/j.ebiom.2024.105004
BACKGROUND
Bloodstream infections (BSI) pose a significant threat due to high mortality rates and the challenges posed by antimicrobial resistance (AMR). In 2019, an estimated 4.95 million deaths were linked to bacterial AMR. The highest impact was seen in resource-limited settings (RLS). For diagnosis of BSI, performant continuously-monitoring blood culture systems (CMBCS) have been optimized. However, in RLS, the implementation of CMBCS is hindered by budget constraints and unsuitable environmental conditions. Manufacturers from growing economies are currently producing affordable in vitro diagnostics, which could fill the gap in capacity, but so far these are not established outside their domestic markets.
METHODS
This study evaluated the performance, usability, and interchangeability of Chinese CMBCS in a laboratory setting using simulated blood cultures with a panel of 20 BSI-associated strains. Four systems were selected for the assessment: Autobio BC60, Mindray TDR60, Scenker Labstar50, and DL-biotech DL-60.
FINDINGS
Overall, all evaluated CMBCS demonstrated good performance with high yield (96.7-100%) and specificity (97.5-100%), comparable to the reference system (bioMérieux 3D). In addition, when used as "manual" blood cultures in a conventional incubator with visual growth detection, performance was also satisfactory: yield was between 90 and 100% and specificity was 100% for all BCBs. Both the CMBCS and the BCBs were easy to use and lot-to-lot variability in BCBs was minimal. The interchangeability testing indicated that the BCBs from different brands (all except Scenker) were compatible with the various automates, further highlighting the potential for a harmonized "universal BCB."
INTERPRETATION
Based on this in vitro study, we recommend the use of these systems in settings with challenging environments and limited resources. The Autobio system performed best for automatic detection and DL-Biotech BCBs for manual cultures respectively (combination of performance, price, usability). The appropriateness for use in RLS should still be confirmed in a field study.
Bloodstream infections (BSI) pose a significant threat due to high mortality rates and the challenges posed by antimicrobial resistance (AMR). In 2019, an estimated 4.95 million deaths were linked to bacterial AMR. The highest impact was seen in resource-limited settings (RLS). For diagnosis of BSI, performant continuously-monitoring blood culture systems (CMBCS) have been optimized. However, in RLS, the implementation of CMBCS is hindered by budget constraints and unsuitable environmental conditions. Manufacturers from growing economies are currently producing affordable in vitro diagnostics, which could fill the gap in capacity, but so far these are not established outside their domestic markets.
METHODS
This study evaluated the performance, usability, and interchangeability of Chinese CMBCS in a laboratory setting using simulated blood cultures with a panel of 20 BSI-associated strains. Four systems were selected for the assessment: Autobio BC60, Mindray TDR60, Scenker Labstar50, and DL-biotech DL-60.
FINDINGS
Overall, all evaluated CMBCS demonstrated good performance with high yield (96.7-100%) and specificity (97.5-100%), comparable to the reference system (bioMérieux 3D). In addition, when used as "manual" blood cultures in a conventional incubator with visual growth detection, performance was also satisfactory: yield was between 90 and 100% and specificity was 100% for all BCBs. Both the CMBCS and the BCBs were easy to use and lot-to-lot variability in BCBs was minimal. The interchangeability testing indicated that the BCBs from different brands (all except Scenker) were compatible with the various automates, further highlighting the potential for a harmonized "universal BCB."
INTERPRETATION
Based on this in vitro study, we recommend the use of these systems in settings with challenging environments and limited resources. The Autobio system performed best for automatic detection and DL-Biotech BCBs for manual cultures respectively (combination of performance, price, usability). The appropriateness for use in RLS should still be confirmed in a field study.