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Clinical significance and antifungal susceptibility profile of 103 clinical isolates of Scedosporium species complex and Lomentospora prolificans obtained from NIH patients.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-03-07 DOI: 10.1128/jcm.01550-24
Mary M Czech, Jennifer Cuellar-Rodriguez, Kyung J Kwon-Chung, Frida Stock, Chioma I Aneke, Kenneth N Olivier, Kevin P Fennelly, Juan Gea-Banacloche, Christa S Zerbe, Alexandra F Freeman, Steven M Holland, Michail S Lionakis, Amir Seyedmousavi

Reduced susceptibility to antifungals is common among members of genera Scedosporium and Lomentospora, with optimal treatments still not fully defined. In vitro antifungal susceptibility results and clinical data do not comprehensively account for the advent of new Scedosporium species identified by molecular phylogenetics. Using Clinical and Laboratory Standards Institute (CLSI) methodology, we tested a total of 103 clinical isolates obtained from patients at the NIH Clinical Center. The most frequent species were Scedosporium apiospermum (63%) and Scedosporium boydii (11%), followed by Lomentospora prolificans (7%). The novel antifungal olorofim showed the lowest MICs against all Scedosporium spp. and L. prolificans, followed by micafungin. Among the triazoles, voriconazole showed lower MICs against Scedosporium spp. Amphotericin B and posaconazole demonstrated species-specific and inter-species variable activity. Itraconazole, isavuconazole, and terbinafine had higher MIC values against Scedosporium spp. and L. prolificans. Clinical data were retrospectively reviewed for 90 isolates, of which nine patients (28 isolates) had active disease/infection and received antifungal treatment that included voriconazole or posaconazole. Five of these patients (56%) died, while three patients (33%) with chronic granulomatous disease were cured following hematopoietic cell transplantation. In 24 patients (62 isolates), the presence of the fungus was considered airway colonization. In conclusion, our data support the existence of species-specific and inter-species differences in the antifungal susceptibility patterns among members of genera Scedosporium and L. prolificans. The novel investigational antifungal olorofim may be a promising therapy. Our clinical data suggest that host status and administration of antifungal therapy most effective for each Scedosporium species complex are important determinants of outcomes.IMPORTANCEUnderstanding the epidemiology and clinical spectrum of infections caused by Scedosporium species complex and Lomentospora prolificans is integral to improving outcomes, particularly in severely ill and immunocompromised patients. In vitro antifungal susceptibility testing can provide an estimate of antifungal activity against fungal pathogens. Our study showed that species-specific and inter-species differences exist in the distribution of antifungal susceptibility patterns between Scedosporium and L. prolificans. Our clinical data also highlight that host status, along with effective antifungal therapy, plays a crucial role in determining treatment outcomes.

{"title":"Clinical significance and antifungal susceptibility profile of 103 clinical isolates of <i>Scedosporium</i> species complex and <i>Lomentospora prolificans</i> obtained from NIH patients.","authors":"Mary M Czech, Jennifer Cuellar-Rodriguez, Kyung J Kwon-Chung, Frida Stock, Chioma I Aneke, Kenneth N Olivier, Kevin P Fennelly, Juan Gea-Banacloche, Christa S Zerbe, Alexandra F Freeman, Steven M Holland, Michail S Lionakis, Amir Seyedmousavi","doi":"10.1128/jcm.01550-24","DOIUrl":"https://doi.org/10.1128/jcm.01550-24","url":null,"abstract":"<p><p>Reduced susceptibility to antifungals is common among members of genera <i>Scedosporium</i> and <i>Lomentospora</i>, with optimal treatments still not fully defined. <i>In vitro</i> antifungal susceptibility results and clinical data do not comprehensively account for the advent of new <i>Scedosporium</i> species identified by molecular phylogenetics. Using Clinical and Laboratory Standards Institute (CLSI) methodology, we tested a total of 103 clinical isolates obtained from patients at the NIH Clinical Center. The most frequent species were <i>Scedosporium apiospermum</i> (63%) and <i>Scedosporium boydii</i> (11%), followed by <i>Lomentospora prolificans</i> (7%). The novel antifungal olorofim showed the lowest MICs against all <i>Scedosporium</i> spp. and <i>L. prolificans</i>, followed by micafungin. Among the triazoles, voriconazole showed lower MICs against <i>Scedosporium</i> spp. Amphotericin B and posaconazole demonstrated species-specific and inter-species variable activity. Itraconazole, isavuconazole, and terbinafine had higher MIC values against <i>Scedosporium</i> spp. and <i>L. prolificans</i>. Clinical data were retrospectively reviewed for 90 isolates, of which nine patients (28 isolates) had active disease/infection and received antifungal treatment that included voriconazole or posaconazole. Five of these patients (56%) died, while three patients (33%) with chronic granulomatous disease were cured following hematopoietic cell transplantation. In 24 patients (62 isolates), the presence of the fungus was considered airway colonization. In conclusion, our data support the existence of species-specific and inter-species differences in the antifungal susceptibility patterns among members of genera <i>Scedosporium</i> and <i>L. prolificans</i>. The novel investigational antifungal olorofim may be a promising therapy. Our clinical data suggest that host status and administration of antifungal therapy most effective for each <i>Scedosporium</i> species complex are important determinants of outcomes.IMPORTANCEUnderstanding the epidemiology and clinical spectrum of infections caused by <i>Scedosporium</i> species complex and <i>Lomentospora prolificans</i> is integral to improving outcomes, particularly in severely ill and immunocompromised patients. <i>In vitro</i> antifungal susceptibility testing can provide an estimate of antifungal activity against fungal pathogens. Our study showed that species-specific and inter-species differences exist in the distribution of antifungal susceptibility patterns between <i>Scedosporium</i> and <i>L. prolificans</i>. Our clinical data also highlight that host status, along with effective antifungal therapy, plays a crucial role in determining treatment outcomes.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0155024"},"PeriodicalIF":6.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Standard E TB-Feron ELISA and Standard F TB-Feron FIA positivity rates and agreement with QuantiFERON-TB Gold Plus among TB high-risk population in Bandung, Indonesia.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-03-07 DOI: 10.1128/jcm.01486-24
Dewi Kartika Turbawaty, Syifa Nur Maulida, Darin Rizka Anadhea, Mulyanusa Amarullah Ritonga, Basti Andriyoko, Rudi Wisaksana, Agnes Rengga Indrati, Nanny Natalia Mulyani Soetedjo, Laniyati Hamijoyo, Raspati Cundarani Koesoemadinata, Bachti Alisjahbana, Ida Parwati

Tuberculosis (TB) remains a global public health problem. The determination of tuberculosis infection (TBI) using interferon-gamma release assay has now been used widely. We aim to evaluate the positivity rates of Standard E TB-Feron enzyme-linked immunosorbent assay (TB-Feron ELISA) and Standard F TB-Feron fluorescent immunoassay (TB-Feron FIA) and their agreement with QuantiFERON-TB Gold Plus (QFT-Plus) among TB high-risk populations in Bandung City, Indonesia. We conducted a cross-sectional study, including people with a high risk of acquiring TB. We screened subjects for TB symptoms and offered chest X-ray (CXR). Anyone with cough or CXR suggestive of TB was asked to give sputum samples for GeneXpert MTB/RIF Ultra test. The positivity rates and corresponding 95% confidence intervals (CI) were calculated among patients with bacteriologically confirmed TB and among patients with no evidence of TB, no history of TB, and no known contact with TB patient (low risk of TBI). The agreement with QFT-Plus was calculated using Cohen's κ score. We enrolled 527 subjects, and the proportion of positive results among bacteriologically confirmed TB patients were 8 (53.3%; 95% CI 26.6-78.7), 9 (60.0%, 95% CI 32.3-83.7), and 10 (66.7%, 95% CI 38.4-88.8) by TB-Feron FIA, TB-Feron ELISA and QFT-Plus. The agreement between TB-Feron FIA and QFT-Plus among all subjects was similar to that of TB-Feron ELISA and QFT-Plus (84.1%, κ = 0.66, 95% CI 0.59-0.72). TB-Feron FIA and TB-Feron ELISA showed an acceptable clinical performance compared with QFT-Plus. These tests are useful alternatives for detecting TB infection.IMPORTANCEThis study evaluates the performance of two alternative interferon-gamma release assays, Standard E TB-Feron enzyme-linked immunosorbent assay and Standard F TB-Feron fluorescent immunoassay, for diagnosing tuberculosis infection (TBI) among high-risk populations in Bandung, Indonesia. Both assays demonstrated comparable clinical performance to the widely used QuantiFERON-TB Gold Plus (QFT-Plus). Given the global burden of tuberculosis, particularly in resource-limited settings, these findings suggest that the TB-Feron assays could serve as reliable alternatives to QFT-Plus for TBI detection. This research highlights the potential for these assays to improve tuberculosis diagnosis, offering a more accessible and efficient screening tool, especially for high-risk populations, and supporting broader tuberculosis surveillance.

{"title":"Standard E TB-Feron ELISA and Standard F TB-Feron FIA positivity rates and agreement with QuantiFERON-TB Gold Plus among TB high-risk population in Bandung, Indonesia.","authors":"Dewi Kartika Turbawaty, Syifa Nur Maulida, Darin Rizka Anadhea, Mulyanusa Amarullah Ritonga, Basti Andriyoko, Rudi Wisaksana, Agnes Rengga Indrati, Nanny Natalia Mulyani Soetedjo, Laniyati Hamijoyo, Raspati Cundarani Koesoemadinata, Bachti Alisjahbana, Ida Parwati","doi":"10.1128/jcm.01486-24","DOIUrl":"https://doi.org/10.1128/jcm.01486-24","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a global public health problem. The determination of tuberculosis infection (TBI) using interferon-gamma release assay has now been used widely. We aim to evaluate the positivity rates of Standard E TB-Feron enzyme-linked immunosorbent assay (TB-Feron ELISA) and Standard F TB-Feron fluorescent immunoassay (TB-Feron FIA) and their agreement with QuantiFERON-TB Gold Plus (QFT-Plus) among TB high-risk populations in Bandung City, Indonesia. We conducted a cross-sectional study, including people with a high risk of acquiring TB. We screened subjects for TB symptoms and offered chest X-ray (CXR). Anyone with cough or CXR suggestive of TB was asked to give sputum samples for GeneXpert MTB/RIF Ultra test. The positivity rates and corresponding 95% confidence intervals (CI) were calculated among patients with bacteriologically confirmed TB and among patients with no evidence of TB, no history of TB, and no known contact with TB patient (low risk of TBI). The agreement with QFT-Plus was calculated using Cohen's κ score. We enrolled 527 subjects, and the proportion of positive results among bacteriologically confirmed TB patients were 8 (53.3%; 95% CI 26.6-78.7), 9 (60.0%, 95% CI 32.3-83.7), and 10 (66.7%, 95% CI 38.4-88.8) by TB-Feron FIA, TB-Feron ELISA and QFT-Plus. The agreement between TB-Feron FIA and QFT-Plus among all subjects was similar to that of TB-Feron ELISA and QFT-Plus (84.1%, κ = 0.66, 95% CI 0.59-0.72). TB-Feron FIA and TB-Feron ELISA showed an acceptable clinical performance compared with QFT-Plus. These tests are useful alternatives for detecting TB infection.IMPORTANCEThis study evaluates the performance of two alternative interferon-gamma release assays, Standard E TB-Feron enzyme-linked immunosorbent assay and Standard F TB-Feron fluorescent immunoassay, for diagnosing tuberculosis infection (TBI) among high-risk populations in Bandung, Indonesia. Both assays demonstrated comparable clinical performance to the widely used QuantiFERON-TB Gold Plus (QFT-Plus). Given the global burden of tuberculosis, particularly in resource-limited settings, these findings suggest that the TB-Feron assays could serve as reliable alternatives to QFT-Plus for TBI detection. This research highlights the potential for these assays to improve tuberculosis diagnosis, offering a more accessible and efficient screening tool, especially for high-risk populations, and supporting broader tuberculosis surveillance.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0148624"},"PeriodicalIF":6.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct thin-layer agar for bedaquiline-susceptibility testing of Mycobacterium tuberculosis at BSL2 level yields high accuracy in 15 days from sputum processing.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-03-03 DOI: 10.1128/jcm.01806-24
I Cuella-Martin, D Runyambo, S De Bock, M Diels, H Niyompano, F Hakizayezu, J Keysers, W B De Rijk, Y M Habimana, N Gahamanyi, E Ardizzoni, C M Muvunyi, B C de Jong, J C S Ngabonziza, L Rigouts

This study evaluated thin-layer agar (TLA) as a faster alternative for both indirect minimum inhibitory concentration (MIC) determination of bedaquiline (BDQ) from culture isolates and direct drug-susceptibility testing (DST) from sputum samples. Indirect BDQ-MIC results from TLA were compared to the established 7H11 solid DST. Direct-TLA-DST performance was assessed using 143 baseline sputum samples from rifampicin-resistant TB cases. Direct-TLA tested susceptibility to rifampicin, isoniazid, levofloxacin, and BDQ, with results compared to Löwenstein-Jensen (LJ) and MGIT. For indirect BDQ-MIC determination, TLA accurately identified H37Rv MICs within the WHO control range (0.015-0.12μg/mL). Optimal results were obtained with standard incubation and day 7 reading of the plates. TLA correctly classified all wild-type clinical strains as BDQ-susceptible and detected 9 out of 10 BDQ-resistant strains with elevated MICs. Direct-TLA-DST detected MTB in 53.8% of samples, compared to 55.9% on LJ and 69.4% in MGIT. Uninterpretable results due to contamination or medium drying were low (4.9%). The median time to result was 15 days for smear-positive and 22 days for smear-negative samples, faster than WHO-endorsed methods. Sensitivity was 100% for rifampicin and 87.8% for isoniazid, with a specificity of 100% for all drugs except isoniazid (96.2%). No BDQ nor levofloxacin resistance was detected, thus direct TLA sensitivity could not be assessed. In conclusion, direct-TLA-DST offers a reliable and faster alternative to conventional DST methods for BDQ and other anti-TB drugs. Essentially, this technique can be operated at BioSafety Level 2, allowing decentralization of pDST for managing drug-resistant TB in settings with limited laboratory infrastructure.

Importance: This paper addresses the critical need for faster direct drug-susceptibility testing (DST) on sputum, especially for bedaquiline (BDQ), which is a key drug in treating drug-resistant TB. Currently, there is a lack of rapid, reliable methods for direct BDQ testing from sputum samples, limiting timely and accurate treatment decisions and monitoring. By demonstrating the potential of thin-layer agar (TLA) for direct BDQ-MIC determination, this study offers a promising solution that could significantly improve patient care.

{"title":"Direct thin-layer agar for bedaquiline-susceptibility testing of <i>Mycobacterium tuberculosis</i> at BSL2 level yields high accuracy in 15 days from sputum processing.","authors":"I Cuella-Martin, D Runyambo, S De Bock, M Diels, H Niyompano, F Hakizayezu, J Keysers, W B De Rijk, Y M Habimana, N Gahamanyi, E Ardizzoni, C M Muvunyi, B C de Jong, J C S Ngabonziza, L Rigouts","doi":"10.1128/jcm.01806-24","DOIUrl":"https://doi.org/10.1128/jcm.01806-24","url":null,"abstract":"<p><p>This study evaluated thin-layer agar (TLA) as a faster alternative for both indirect minimum inhibitory concentration (MIC) determination of bedaquiline (BDQ) from culture isolates and direct drug-susceptibility testing (DST) from sputum samples. Indirect BDQ-MIC results from TLA were compared to the established 7H11 solid DST. Direct-TLA-DST performance was assessed using 143 baseline sputum samples from rifampicin-resistant TB cases. Direct-TLA tested susceptibility to rifampicin, isoniazid, levofloxacin, and BDQ, with results compared to Löwenstein-Jensen (LJ) and MGIT. For indirect BDQ-MIC determination, TLA accurately identified H37Rv MICs within the WHO control range (0.015-0.12μg/mL). Optimal results were obtained with standard incubation and day 7 reading of the plates. TLA correctly classified all wild-type clinical strains as BDQ-susceptible and detected 9 out of 10 BDQ-resistant strains with elevated MICs. Direct-TLA-DST detected MTB in 53.8% of samples, compared to 55.9% on LJ and 69.4% in MGIT. Uninterpretable results due to contamination or medium drying were low (4.9%). The median time to result was 15 days for smear-positive and 22 days for smear-negative samples, faster than WHO-endorsed methods. Sensitivity was 100% for rifampicin and 87.8% for isoniazid, with a specificity of 100% for all drugs except isoniazid (96.2%). No BDQ nor levofloxacin resistance was detected, thus direct TLA sensitivity could not be assessed. In conclusion, direct-TLA-DST offers a reliable and faster alternative to conventional DST methods for BDQ and other anti-TB drugs. Essentially, this technique can be operated at BioSafety Level 2, allowing decentralization of pDST for managing drug-resistant TB in settings with limited laboratory infrastructure.</p><p><strong>Importance: </strong>This paper addresses the critical need for faster direct drug-susceptibility testing (DST) on sputum, especially for bedaquiline (BDQ), which is a key drug in treating drug-resistant TB. Currently, there is a lack of rapid, reliable methods for direct BDQ testing from sputum samples, limiting timely and accurate treatment decisions and monitoring. By demonstrating the potential of thin-layer agar (TLA) for direct BDQ-MIC determination, this study offers a promising solution that could significantly improve patient care.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0180624"},"PeriodicalIF":6.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biographical Feature: Ruth Ella Moore, Ph.D.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-27 DOI: 10.1128/jcm.01863-24
Marian C Johnson-Thompson
{"title":"Biographical Feature: Ruth Ella Moore, Ph.D.","authors":"Marian C Johnson-Thompson","doi":"10.1128/jcm.01863-24","DOIUrl":"https://doi.org/10.1128/jcm.01863-24","url":null,"abstract":"","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0186324"},"PeriodicalIF":6.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A call for the United States to continue investing in science.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-27 DOI: 10.1128/jcm.00348-25
Ira Blader, Felicia Goodrum, Michael J Imperiale, Arturo Casadevall, Cesar A Arias, Andreas Baumler, Carey-Ann D Burnham, Christina A Cuomo, Corrella S Detweiler, Graeme N Forrest, Jack A Gilbert, Susan Lovett, Stanley Maloy, Alexander McAdam, Irene Newton, Gemma Reguera, George A O'Toole, Patrick D Schloss, Ashley Shade, Marvin Whiteley
{"title":"A call for the United States to continue investing in science.","authors":"Ira Blader, Felicia Goodrum, Michael J Imperiale, Arturo Casadevall, Cesar A Arias, Andreas Baumler, Carey-Ann D Burnham, Christina A Cuomo, Corrella S Detweiler, Graeme N Forrest, Jack A Gilbert, Susan Lovett, Stanley Maloy, Alexander McAdam, Irene Newton, Gemma Reguera, George A O'Toole, Patrick D Schloss, Ashley Shade, Marvin Whiteley","doi":"10.1128/jcm.00348-25","DOIUrl":"10.1128/jcm.00348-25","url":null,"abstract":"","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0034825"},"PeriodicalIF":6.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A call for healing and unity.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-27 DOI: 10.1128/jcm.00338-25
Patrick D Schloss
{"title":"A call for healing and unity.","authors":"Patrick D Schloss","doi":"10.1128/jcm.00338-25","DOIUrl":"https://doi.org/10.1128/jcm.00338-25","url":null,"abstract":"","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0033825"},"PeriodicalIF":6.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Use of gastrointestinal syndromic multiplex molecular assays and detection of Escherichia coli pathotypes in pediatric wards.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-26 DOI: 10.1128/jcm.01073-24
Etienne Bizot, Stéphane Bonacorsi, Pauline Labé, Yael Pinhas, Aurélie Cointe, Agnès Ferroni, Jérémie F Cohen, Hervé Lécuyer, Julie Toubiana

Escherichia coli pathotypes are enteric pathogens detected in gastrointestinal multiplex polymerase chain reaction (mPCR), with controversial clinical relevance. Our study aimed to describe clinical features and therapeutic decisions associated with E. coli detections in gastrointestinal mPCR. Children with positive mPCR for enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), Shiga toxin-producing E. coli (STEC), and enteroinvasive E. coli (EIEC)/Shigella identified in two pediatric hospitals over 18 months (2020-2021) were included. We described the frequency of E. coli detection and subsequent modifications in antibiotic strategies. Among the 2,471 mPCRs performed, 338 (14%) tested positive for at least one E. coli pathotype. The patient's mean age was 4.2 years, with 95% experiencing gastrointestinal symptoms. Clinical presentation was generally comparable between E. coli pathotypes. A recent travel abroad was reported in 68/338 (20%) cases and was mainly observed in EIEC/Shigella infections. An E. coli was detected alone in 177/338 (52%) cases and with another virus, bacteria, or parasite in 161 (48%) cases. Multiple enteric pathogens were mainly detected with ETEC (n = 24/26, 92%) and EAEC (n = 82/121, 68%) detections. Antibiotic therapy was prescribed in 136/338 (40%) cases, with initiation based on mPCR results in 69/338 (20%). No antibiotic therapy was discontinued following positive mPCR results. Among the 69 initiations, 31 were deemed inappropriate after retrospective chart review. E. coli detection with mPCR tests may lead to inappropriate antibiotic initiation. Caution is advised when interpreting results from gastrointestinal mPCRs in children, as clinicians may be unaware of their often unclear or irrelevant clinical significance.IMPORTANCEEscherichia coli pathotypes are increasingly detected through the widely used syndromic gastrointestinal multiplex PCR panels. However, their clinical significance and impact on antibiotic therapy in children remain uncertain. This study describes the clinical and microbiological characteristics associated with E. coli detections, as well as the subsequent modifications in antibiotic strategies. It highlights the frequent detection of E. coli pathotypes, often in association with other enteric pathogens, and reveals that nearly half of the antibiotics prescribed following these results were deemed inappropriate. These results underscore the need to enhance clinicians' interpretation of E. coli-positive results and reassess treatment strategies to optimize patient care.

{"title":"Use of gastrointestinal syndromic multiplex molecular assays and detection of <i>Escherichia coli</i> pathotypes in pediatric wards.","authors":"Etienne Bizot, Stéphane Bonacorsi, Pauline Labé, Yael Pinhas, Aurélie Cointe, Agnès Ferroni, Jérémie F Cohen, Hervé Lécuyer, Julie Toubiana","doi":"10.1128/jcm.01073-24","DOIUrl":"https://doi.org/10.1128/jcm.01073-24","url":null,"abstract":"<p><p><i>Escherichia coli</i> pathotypes are enteric pathogens detected in gastrointestinal multiplex polymerase chain reaction (mPCR), with controversial clinical relevance. Our study aimed to describe clinical features and therapeutic decisions associated with <i>E. coli</i> detections in gastrointestinal mPCR. Children with positive mPCR for enteroaggregative (EAEC)<i>,</i> enteropathogenic (EPEC)<i>,</i> enterotoxigenic (ETEC), Shiga toxin-producing <i>E. coli</i> (STEC), and enteroinvasive <i>E. coli</i> (EIEC)/<i>Shigella</i> identified in two pediatric hospitals over 18 months (2020-2021) were included. We described the frequency of <i>E. coli</i> detection and subsequent modifications in antibiotic strategies. Among the 2,471 mPCRs performed, 338 (14%) tested positive for at least one <i>E. coli</i> pathotype. The patient's mean age was 4.2 years, with 95% experiencing gastrointestinal symptoms. Clinical presentation was generally comparable between <i>E. coli</i> pathotypes. A recent travel abroad was reported in 68/338 (20%) cases and was mainly observed in EIEC/<i>Shigella</i> infections. An <i>E. coli</i> was detected alone in 177/338 (52%) cases and with another virus, bacteria, or parasite in 161 (48%) cases. Multiple enteric pathogens were mainly detected with ETEC (<i>n</i> = 24/26, 92%) and EAEC (<i>n</i> = 82/121, 68%) detections. Antibiotic therapy was prescribed in 136/338 (40%) cases, with initiation based on mPCR results in 69/338 (20%). No antibiotic therapy was discontinued following positive mPCR results. Among the 69 initiations, 31 were deemed inappropriate after retrospective chart review. <i>E. coli</i> detection with mPCR tests may lead to inappropriate antibiotic initiation. Caution is advised when interpreting results from gastrointestinal mPCRs in children, as clinicians may be unaware of their often unclear or irrelevant clinical significance.IMPORTANCE<i>Escherichia coli</i> pathotypes are increasingly detected through the widely used syndromic gastrointestinal multiplex PCR panels. However, their clinical significance and impact on antibiotic therapy in children remain uncertain. This study describes the clinical and microbiological characteristics associated with <i>E. coli</i> detections, as well as the subsequent modifications in antibiotic strategies. It highlights the frequent detection of <i>E. coli</i> pathotypes, often in association with other enteric pathogens, and reveals that nearly half of the antibiotics prescribed following these results were deemed inappropriate. These results underscore the need to enhance clinicians' interpretation of <i>E. coli</i>-positive results and reassess treatment strategies to optimize patient care.</p>","PeriodicalId":15511,"journal":{"name":"Journal of Clinical Microbiology","volume":" ","pages":"e0107324"},"PeriodicalIF":6.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epidemiology of positive bacterial cultures and the coverage gaps in multiplex PCR diagnostics: a single-center retrospective study.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-26 DOI: 10.1128/jcm.01600-24
Vishwaratn Asthana, Rishi Chanderraj, J Scott VanEpps, Robert P Dickson
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引用次数: 0
2025 American Society for Microbiology Awards and Prize Program: honorees from clinical microbiology.
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-24 DOI: 10.1128/jcm.00001-25
Erik Munson
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引用次数: 0
Identification of a circulating carbohydrate antigen as a highly specific and sensitive target for schistosomiasis serology. 一种循环碳水化合物抗原作为血吸虫病血清学高度特异性和敏感性靶标的鉴定。
IF 6.1 2区 医学 Q1 MICROBIOLOGY Pub Date : 2025-02-19 Epub Date: 2025-01-13 DOI: 10.1128/jcm.01008-24
Anna O Kildemoes, Tom Veldhuizen, Stan T Hilt, Lisette van Lieshout, Taniawati Supali, Maria Yazdanbakhsh, Daniel Camprubí-Ferrer, Jose Muñoz, Joannes Clerinx, Mickey Harvey, Jeroen Codée, Paul L A M Corstjens, Govert J van Dam, Leo G Visser, Meta Roestenberg, Angela van Diepen, Cornelis H Hokke

The World Health Organization (WHO) 2030 roadmap for schistosomiasis calls for development of highly sensitive and specific diagnostic tools to continue and sustain progress towards elimination. Serological assays are excellent for sensitive detection of primary schistosome infections and for schistosomiasis surveillance in near- and post-elimination settings. To develop accurate assay formats, it is necessary to identify defined antibody targets with low cross-reactivity and potential for standardized production. Here we aim to identify such target(s) with focus on defined schistosome glycan antigens. Target identification was performed by assessing antibody responses in well-characterized cross-sectional and cohort sample sets (n = 366 individuals) on tailor-made antigen microarrays. IgM and IgG binding to candidate diagnostic targets was measured for serum/plasma samples from controlled human schistosome infection models, schistosome-infected travelers, soil-transmitted helminth-infected individuals, and non-infected individuals. We found that antibodies to a schistosome gut-associated glycan, the circulating anodic antigen (CAA), identify schistosome infection with high sensitivity (IgM ≥100%, IgG ≥97%) and specificity (IgM ≥93%, IgG ≥97%) in the test samples. Infection dose affected timing of anti-CAA antibody isotype switch. Furthermore, we demonstrate that other non-specific glycan epitopes in crude schistosome cercarial and egg antigen preparations can contribute to generation of false schistosomiasis positives, which is relevant for current serological assays based on these antigen mixtures. In conclusion, CAA is an excellent single glycan antigen target for development of highly sensitive and specific tools for schistosomiasis serology with use cases for travelers and surveillance in near- and post-elimination settings, as well as emerging transmission zones.

Importance: The WHO 2030 roadmap deems diagnostics developments for schistosomiasis critically needed. Here we present identification of an antibody target with superior performance compared to traditionally used crude antigens in schistosomiasis serology. Access to unique controlled human infection model samples, traveler samples, and negative controls enabled this discovery, which forms the basis for development of new diagnostic tools urgently needed in travel medicine, surveillance in emerging transmission zones driven by climate change, and in pre- and post-elimination scenarios.

世界卫生组织(世卫组织)《2030年血吸虫病路线图》呼吁开发高度敏感和专门的诊断工具,以继续并维持在消除血吸虫病方面取得的进展。血清学检测对于原发性血吸虫感染的敏感检测以及在接近和消除后的环境中进行血吸虫病监测是极好的。为了开发准确的检测格式,有必要确定具有低交叉反应性和标准化生产潜力的明确抗体靶标。在这里,我们的目标是识别这样的目标(s),重点是确定血吸虫聚糖抗原。在定制抗原微阵列上,通过评估具有良好特征的横断面和队列样本组(n = 366个个体)的抗体反应来进行靶标鉴定。测定对照人类血吸虫感染模型、血吸虫感染旅行者、土壤传播蠕虫感染个体和非感染个体的血清/血浆样本中IgM和IgG与候选诊断靶点的结合情况。我们发现血吸虫肠道相关聚糖循环阳极抗原(CAA)抗体在检测样品中具有高敏感性(IgM≥100%,IgG≥97%)和特异性(IgM≥93%,IgG≥97%)。感染剂量影响抗caa抗体同型开关时间。此外,我们证明,在粗血吸虫子宫颈和卵抗原制剂中的其他非特异性聚糖表位可能导致假血吸虫病阳性,这与目前基于这些抗原混合物的血清学检测有关。总之,CAA是一种优秀的单糖抗原靶点,可用于开发高度敏感和特异性的血吸虫病血清学工具,可用于旅行者和消除前后环境中的监测,以及新出现的传播区。重要性:世卫组织2030年路线图认为迫切需要发展血吸虫病的诊断方法。在这里,我们提出了一种抗体靶点的鉴定,与传统上使用的血吸虫病血清学粗抗原相比,它具有优越的性能。获得独特的受控人类感染模型样本、旅行者样本和阴性对照使这一发现成为可能,这为开发旅行医学、气候变化驱动的新传播区监测以及消除前和后情景中急需的新诊断工具奠定了基础。
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引用次数: 0
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Journal of Clinical Microbiology
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