Ayumi Akinaga, Andreas H Diacon, Remous Ocloo, Atsushi Yanagida, Naofumi Yoda, Masanori Kawasaki, Yongge Liu
{"title":"在肺结核治疗的头14天,使用PATHFAST TB LAM Ag测定法定量杀菌活性。","authors":"Ayumi Akinaga, Andreas H Diacon, Remous Ocloo, Atsushi Yanagida, Naofumi Yoda, Masanori Kawasaki, Yongge Liu","doi":"10.3389/frabi.2025.1574688","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) remains a global health challenge. Culture-free, rapid, and quantitative biomarkers to monitor treatment response are critical to accelerate development of better TB treatments. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), a desktop chemiluminescent enzyme immunoassay that measures mycobacterial lipoarabinomannan (LAM) in sputum within 1 hour, is a promising candidate for this purpose. This study aimed to assess whether the PATHFAST-LAM can serve as a rapid, reliable biomarker for monitoring early treatment response in pulmonary TB.</p><p><strong>Methods: </strong>We conducted a retrospective longitudinal repository study using stored sputum samples from 14-day early bactericidal activity trials involving 75 pulmonary TB patients who received one of five different regimens. The results were compared with those from the TB LAM ELISA \"Otsuka\" (LAM-ELISA), which was previously shown to measure early bactericidal activity but takes more than 5 hours to obtain results, and conventional culture-based methods.</p><p><strong>Results: </strong>The LAM concentrations in both raw and decontaminated sputum showed strong correlations between the PATHFAST-LAM and the LAM-ELISA, with Spearman's correlation coefficients of 0.975 (95% CI: 0.971 - 0.979) and 0.987 (95% CI: 0.984 - 0.989), respectively. LAM concentrations in raw and decontaminated sputum by the PATHFAST-LAM were also highly correlated with a Spearman coefficient of 0.957 (95% CI: 0.950 - 0.964). Importantly, the LAM concentrations by the PATHFAST-LAM correlated with bacterial loads determined by culture-based methods in all five treatment arms (Spearman's coefficients: 0.723 - 0.947). Furthermore, the change in LAM levels over the treatment period mirrored the changes in bacterial load. Additionally, culture-based methods often result in missing data due to contamination: in our study, we observed a missing data rate of 9.6% (62/649) on quantifying CFU counts and 4.2% (27/649) on obtaining a valid MGIT TTD, while we obtained a valid LAM value with the PATHFAST-LAM (0/634 in raw samples and 0/637 in decontaminated samples).</p><p><strong>Conclusion: </strong>Our findings suggest that the PATHFAST-LAM can quantify bactericidal activity in the first 14 days of treatment with a quick turnaround time. The test's utility to monitor conversion from positive to negative and to predict relapse-free cure compared to culture-based methods should be determined in longer trials.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"4 ","pages":"1574688"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120838/pdf/","citationCount":"0","resultStr":"{\"title\":\"Quantification of bactericidal activity using the PATHFAST TB LAM Ag assay during the first 14 days of pulmonary tuberculosis treatment.\",\"authors\":\"Ayumi Akinaga, Andreas H Diacon, Remous Ocloo, Atsushi Yanagida, Naofumi Yoda, Masanori Kawasaki, Yongge Liu\",\"doi\":\"10.3389/frabi.2025.1574688\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tuberculosis (TB) remains a global health challenge. Culture-free, rapid, and quantitative biomarkers to monitor treatment response are critical to accelerate development of better TB treatments. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), a desktop chemiluminescent enzyme immunoassay that measures mycobacterial lipoarabinomannan (LAM) in sputum within 1 hour, is a promising candidate for this purpose. This study aimed to assess whether the PATHFAST-LAM can serve as a rapid, reliable biomarker for monitoring early treatment response in pulmonary TB.</p><p><strong>Methods: </strong>We conducted a retrospective longitudinal repository study using stored sputum samples from 14-day early bactericidal activity trials involving 75 pulmonary TB patients who received one of five different regimens. The results were compared with those from the TB LAM ELISA \\\"Otsuka\\\" (LAM-ELISA), which was previously shown to measure early bactericidal activity but takes more than 5 hours to obtain results, and conventional culture-based methods.</p><p><strong>Results: </strong>The LAM concentrations in both raw and decontaminated sputum showed strong correlations between the PATHFAST-LAM and the LAM-ELISA, with Spearman's correlation coefficients of 0.975 (95% CI: 0.971 - 0.979) and 0.987 (95% CI: 0.984 - 0.989), respectively. LAM concentrations in raw and decontaminated sputum by the PATHFAST-LAM were also highly correlated with a Spearman coefficient of 0.957 (95% CI: 0.950 - 0.964). Importantly, the LAM concentrations by the PATHFAST-LAM correlated with bacterial loads determined by culture-based methods in all five treatment arms (Spearman's coefficients: 0.723 - 0.947). Furthermore, the change in LAM levels over the treatment period mirrored the changes in bacterial load. Additionally, culture-based methods often result in missing data due to contamination: in our study, we observed a missing data rate of 9.6% (62/649) on quantifying CFU counts and 4.2% (27/649) on obtaining a valid MGIT TTD, while we obtained a valid LAM value with the PATHFAST-LAM (0/634 in raw samples and 0/637 in decontaminated samples).</p><p><strong>Conclusion: </strong>Our findings suggest that the PATHFAST-LAM can quantify bactericidal activity in the first 14 days of treatment with a quick turnaround time. The test's utility to monitor conversion from positive to negative and to predict relapse-free cure compared to culture-based methods should be determined in longer trials.</p>\",\"PeriodicalId\":73065,\"journal\":{\"name\":\"Frontiers in antibiotics\",\"volume\":\"4 \",\"pages\":\"1574688\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120838/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in antibiotics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/frabi.2025.1574688\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in antibiotics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/frabi.2025.1574688","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Quantification of bactericidal activity using the PATHFAST TB LAM Ag assay during the first 14 days of pulmonary tuberculosis treatment.
Background: Tuberculosis (TB) remains a global health challenge. Culture-free, rapid, and quantitative biomarkers to monitor treatment response are critical to accelerate development of better TB treatments. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), a desktop chemiluminescent enzyme immunoassay that measures mycobacterial lipoarabinomannan (LAM) in sputum within 1 hour, is a promising candidate for this purpose. This study aimed to assess whether the PATHFAST-LAM can serve as a rapid, reliable biomarker for monitoring early treatment response in pulmonary TB.
Methods: We conducted a retrospective longitudinal repository study using stored sputum samples from 14-day early bactericidal activity trials involving 75 pulmonary TB patients who received one of five different regimens. The results were compared with those from the TB LAM ELISA "Otsuka" (LAM-ELISA), which was previously shown to measure early bactericidal activity but takes more than 5 hours to obtain results, and conventional culture-based methods.
Results: The LAM concentrations in both raw and decontaminated sputum showed strong correlations between the PATHFAST-LAM and the LAM-ELISA, with Spearman's correlation coefficients of 0.975 (95% CI: 0.971 - 0.979) and 0.987 (95% CI: 0.984 - 0.989), respectively. LAM concentrations in raw and decontaminated sputum by the PATHFAST-LAM were also highly correlated with a Spearman coefficient of 0.957 (95% CI: 0.950 - 0.964). Importantly, the LAM concentrations by the PATHFAST-LAM correlated with bacterial loads determined by culture-based methods in all five treatment arms (Spearman's coefficients: 0.723 - 0.947). Furthermore, the change in LAM levels over the treatment period mirrored the changes in bacterial load. Additionally, culture-based methods often result in missing data due to contamination: in our study, we observed a missing data rate of 9.6% (62/649) on quantifying CFU counts and 4.2% (27/649) on obtaining a valid MGIT TTD, while we obtained a valid LAM value with the PATHFAST-LAM (0/634 in raw samples and 0/637 in decontaminated samples).
Conclusion: Our findings suggest that the PATHFAST-LAM can quantify bactericidal activity in the first 14 days of treatment with a quick turnaround time. The test's utility to monitor conversion from positive to negative and to predict relapse-free cure compared to culture-based methods should be determined in longer trials.