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Decline of community-acquired alveolar pneumonia positive for respiratory syncytial virus in hospitalized children following implementation of PCV in Israel.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-07 DOI: 10.1093/cid/ciaf102
Ron Dagan, Bart Adriaan van der Beek, Tal Grupel, David Greenberg, Ayelet Keren-Naus, Shalom Ben-Shimol, Daniel M Weinberger

Background: We assessed the impact of pneumococcal conjugate vaccine (PCV) implementation on respiratory syncytial virus-positive community-acquired alveolar pneumonia (RSV-CAAP) in young children in southern Israel.

Methods: This study was nested within a prospective population-based active surveillance system during 2004-2019. All children <60 months residing in the region and served by the region's only hospital were included. A negative binomial regression model was used to evaluate the impact of PCV on the incidence of all-cause CAAP and RSV-CAAP and was the basis for estimating averted episodes.

Results: 7,640 all-cause CAAP episodes were observed; 50% were tested for RSV, of which 42% were positive. Shortly after PCV13 implementation, all-cause CAAP and RSV-CAAP rates markedly declined, stabilizing within 3-4 years. The mean annual hospitalization rates for all-cause CAAP and RSV-CAAP declined by 47% (95% CI: 40%; 53%) and 29% (95% CI: -2%; 51%), respectively, during the late-PCV period, compared with the expected rates. This translated to a reduction in the mean annual incidence of 3.73 cases of all-cause CAAP/1,000 children (95% CI: 2.98;4.58) and 0.50 cases of RSV-CAAP per 1,000 children (95% CI: -0.05;1.13). The highest incidences of averted cases occurred in children aged 12-23 months.

Conclusions: The observed dynamics of hospitalizations due to all-cause CAAP and RSV-CAAP following PCV implementation are consistent with the notion of a synergistic role of RSV and pneumococcus in CAAP in young children.

{"title":"Decline of community-acquired alveolar pneumonia positive for respiratory syncytial virus in hospitalized children following implementation of PCV in Israel.","authors":"Ron Dagan, Bart Adriaan van der Beek, Tal Grupel, David Greenberg, Ayelet Keren-Naus, Shalom Ben-Shimol, Daniel M Weinberger","doi":"10.1093/cid/ciaf102","DOIUrl":"https://doi.org/10.1093/cid/ciaf102","url":null,"abstract":"<p><strong>Background: </strong>We assessed the impact of pneumococcal conjugate vaccine (PCV) implementation on respiratory syncytial virus-positive community-acquired alveolar pneumonia (RSV-CAAP) in young children in southern Israel.</p><p><strong>Methods: </strong>This study was nested within a prospective population-based active surveillance system during 2004-2019. All children <60 months residing in the region and served by the region's only hospital were included. A negative binomial regression model was used to evaluate the impact of PCV on the incidence of all-cause CAAP and RSV-CAAP and was the basis for estimating averted episodes.</p><p><strong>Results: </strong>7,640 all-cause CAAP episodes were observed; 50% were tested for RSV, of which 42% were positive. Shortly after PCV13 implementation, all-cause CAAP and RSV-CAAP rates markedly declined, stabilizing within 3-4 years. The mean annual hospitalization rates for all-cause CAAP and RSV-CAAP declined by 47% (95% CI: 40%; 53%) and 29% (95% CI: -2%; 51%), respectively, during the late-PCV period, compared with the expected rates. This translated to a reduction in the mean annual incidence of 3.73 cases of all-cause CAAP/1,000 children (95% CI: 2.98;4.58) and 0.50 cases of RSV-CAAP per 1,000 children (95% CI: -0.05;1.13). The highest incidences of averted cases occurred in children aged 12-23 months.</p><p><strong>Conclusions: </strong>The observed dynamics of hospitalizations due to all-cause CAAP and RSV-CAAP following PCV implementation are consistent with the notion of a synergistic role of RSV and pneumococcus in CAAP in young children.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Dolutegravir/Lamivudine for Maintenance of Virological Suppression in Persons with Historical Suspected or Confirmed Resistance to Lamivudine: Week 48 Results of a Single-Arm, Open-Label, Multicentre, Phase IIA Clinical Trial.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-07 DOI: 10.1093/cid/ciaf100
Rosa De Miguel, María de Lagarde Sebastian, José Luis Blanco Arévalo, Adriana Pinto-Martinez, Rocío Montejano, Angela Gutiérrez Liarte, Roser Navarro-Soler, Esperanza Cañas-Ruano, Alexis Inciarte, Luz Martin-Carbonero, Arkaitz Imaz, Cristina Hernández Gutiérrez, Antonio Ocampo, Pedro Gil Divasson, Rafael Delgado, Federico Pulido, Jose R Arribas

Background: We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with HIV and previous lamivudine resistance.

Methods: Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose ART was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples. Primary endpoint was proportion of participants with HIV-1 RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm.

Results: 121 participants enrolled, 114 with a prior genotype with M184V/I, mean virological suppression of 9 years. 24 (19·8%) had the M184V/I in baseline proviral DNA NGS (>5% threshold). At 48 weeks, 4 participants had a VL ≥50 copies/mL (3·3%, 95% CI: 0·9%-8·2%, FDA-Snapshot ITT-e): 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal and 2 discontinued from study treatment for other reasons with last VL ≥ 50 copies/mL; none had M184V/I in baseline proviral DNA NGS and there was no emergent integrase resistance. 90·1% participants (109/121) had a VL<50 copies/mL (95% CI: 83·3%-94·8%) and there were no data for 6·6 % (8/121 participants) at 48 weeks.

Conclusions: After excluding lamivudine mutations in proviral DNA by population sequencing, dolutegravir/lamivudine effectively maintained virological suppression in PWH with CD4+ >200 cells/mm3 and history of lamivudine resistance. Notably, no treatment-emergent resistance was observed.

{"title":"Dolutegravir/Lamivudine for Maintenance of Virological Suppression in Persons with Historical Suspected or Confirmed Resistance to Lamivudine: Week 48 Results of a Single-Arm, Open-Label, Multicentre, Phase IIA Clinical Trial.","authors":"Rosa De Miguel, María de Lagarde Sebastian, José Luis Blanco Arévalo, Adriana Pinto-Martinez, Rocío Montejano, Angela Gutiérrez Liarte, Roser Navarro-Soler, Esperanza Cañas-Ruano, Alexis Inciarte, Luz Martin-Carbonero, Arkaitz Imaz, Cristina Hernández Gutiérrez, Antonio Ocampo, Pedro Gil Divasson, Rafael Delgado, Federico Pulido, Jose R Arribas","doi":"10.1093/cid/ciaf100","DOIUrl":"https://doi.org/10.1093/cid/ciaf100","url":null,"abstract":"<p><strong>Background: </strong>We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with HIV and previous lamivudine resistance.</p><p><strong>Methods: </strong>Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose ART was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples. Primary endpoint was proportion of participants with HIV-1 RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm.</p><p><strong>Results: </strong>121 participants enrolled, 114 with a prior genotype with M184V/I, mean virological suppression of 9 years. 24 (19·8%) had the M184V/I in baseline proviral DNA NGS (>5% threshold). At 48 weeks, 4 participants had a VL ≥50 copies/mL (3·3%, 95% CI: 0·9%-8·2%, FDA-Snapshot ITT-e): 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal and 2 discontinued from study treatment for other reasons with last VL ≥ 50 copies/mL; none had M184V/I in baseline proviral DNA NGS and there was no emergent integrase resistance. 90·1% participants (109/121) had a VL<50 copies/mL (95% CI: 83·3%-94·8%) and there were no data for 6·6 % (8/121 participants) at 48 weeks.</p><p><strong>Conclusions: </strong>After excluding lamivudine mutations in proviral DNA by population sequencing, dolutegravir/lamivudine effectively maintained virological suppression in PWH with CD4+ >200 cells/mm3 and history of lamivudine resistance. Notably, no treatment-emergent resistance was observed.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Are We Being Gaslit? A Primer for Recognizing Corporate Jargon to Overcome Gaslighting for the Infectious Disease Workforce.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-06 DOI: 10.1093/cid/ciaf097
Gonzalo Bearman, Priya Nori
{"title":"Are We Being Gaslit? A Primer for Recognizing Corporate Jargon to Overcome Gaslighting for the Infectious Disease Workforce.","authors":"Gonzalo Bearman, Priya Nori","doi":"10.1093/cid/ciaf097","DOIUrl":"https://doi.org/10.1093/cid/ciaf097","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Case Definitions in Encephalitis.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-06 DOI: 10.1093/cid/ciaf099
Ralph Habis, Anna Kolchinski, Ashley N Heck, Paris Bean, John C Probasco, Rodrigo Hasbun, Arun Venkatesan
{"title":"Case Definitions in Encephalitis.","authors":"Ralph Habis, Anna Kolchinski, Ashley N Heck, Paris Bean, John C Probasco, Rodrigo Hasbun, Arun Venkatesan","doi":"10.1093/cid/ciaf099","DOIUrl":"https://doi.org/10.1093/cid/ciaf099","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Low diagnostic accuracy of encephalitis criteria hinders interpretation of the absence of CSF pleiocytosis.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-05 DOI: 10.1093/cid/ciaf096
Steven L Staal, Sabine E Olie, Diederik van de Beek, Matthijs C Brouwer
{"title":"Low diagnostic accuracy of encephalitis criteria hinders interpretation of the absence of CSF pleiocytosis.","authors":"Steven L Staal, Sabine E Olie, Diederik van de Beek, Matthijs C Brouwer","doi":"10.1093/cid/ciaf096","DOIUrl":"https://doi.org/10.1093/cid/ciaf096","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Effectiveness of electrocautery, topical cidofovir and topical sinecatechins for the Treatment of Anal High-grade Squamous Intraepithelial Lesions in Persons with HIV: an open-label, randomized controlled trial 电灼法、西多福韦局部外用药和正卡因局部外用药治疗艾滋病病毒感染者肛门高级别鳞状上皮内病变的疗效:开放标签随机对照试验
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-04 DOI: 10.1093/cid/ciaf086
Joaquin Burgos, Adrià Curran, Jorge Garcia, David Campany, Vicente Descalzo, Paula Suanzes, Jordi Navarro, Bibiana Planas, Marta Sanchiz, Stefania Landolfi, Carme Dinares, Javier Hernádez-Losa, Vicenç Falcó
Background Doubts remain about the best treatment for managing premalignant lesions (HSIL) associated with anal cancer. Methods The TREATAIN trial was an open-label, randomized study conducted at Hospital Vall d’Hebron (Spain). Persons with HIV and anal HSIL were randomly assigned 1:1:1 to receive treatment with electrocautery, topical cidofovir 1% ointment, or topical sinecatechins 10%. The primary outcome was histological resolution of HSIL. Secondary outcomes included adverse events, participant satisfaction, HPV clearance, and HSIL recurrence. EudraCT: 2018-001730-18. ClinicalTrials.gov: NCT04055142. Results Between October 2020 and November 2022, 100 participants were enrolled (36 in the electrocautery arm, 28 in cidofovir arm, and 36 in the sinecatechins arm). Modified intention-to-treat analysis showed a response rate of 69·4% [95% CI; 54·4-84·5] of patients in the electrocautery group, 82·1% [95% CI; 67·9-96·3] in the cidofovir group, and 61·1% [95% CI; 45·2-77] in the sinecatechins group (p=0.189). During the 48-weeks follow-up period, recurrence was observed in 7 participants (28%) in the electrocautery group, 7 (30·4%) in the cidofovir group, and 8 (36·4%) in the sinecatechins group (Log-rank test p=0·811). Side effects were reported by 97·2% of patients in the electrocautery group, 85·7% in the cidofovir group, and 33% in the sinecatechins group (p&lt;0·001). Patients were more satisfied with the sinecatechins treatment (5·6 ± 0·4), followed by electrocautery (5·1 ± 0·8), while lower satisfaction was reported with cidofovir treatment (4·77 ± 0·96), p&lt;0.001. Conclusion No statistically significant difference was observed in efficacy between treatments; in contrast, sinecatechins was the most accepted and well-tolerated treatment.
{"title":"Effectiveness of electrocautery, topical cidofovir and topical sinecatechins for the Treatment of Anal High-grade Squamous Intraepithelial Lesions in Persons with HIV: an open-label, randomized controlled trial","authors":"Joaquin Burgos, Adrià Curran, Jorge Garcia, David Campany, Vicente Descalzo, Paula Suanzes, Jordi Navarro, Bibiana Planas, Marta Sanchiz, Stefania Landolfi, Carme Dinares, Javier Hernádez-Losa, Vicenç Falcó","doi":"10.1093/cid/ciaf086","DOIUrl":"https://doi.org/10.1093/cid/ciaf086","url":null,"abstract":"Background Doubts remain about the best treatment for managing premalignant lesions (HSIL) associated with anal cancer. Methods The TREATAIN trial was an open-label, randomized study conducted at Hospital Vall d’Hebron (Spain). Persons with HIV and anal HSIL were randomly assigned 1:1:1 to receive treatment with electrocautery, topical cidofovir 1% ointment, or topical sinecatechins 10%. The primary outcome was histological resolution of HSIL. Secondary outcomes included adverse events, participant satisfaction, HPV clearance, and HSIL recurrence. EudraCT: 2018-001730-18. ClinicalTrials.gov: NCT04055142. Results Between October 2020 and November 2022, 100 participants were enrolled (36 in the electrocautery arm, 28 in cidofovir arm, and 36 in the sinecatechins arm). Modified intention-to-treat analysis showed a response rate of 69·4% [95% CI; 54·4-84·5] of patients in the electrocautery group, 82·1% [95% CI; 67·9-96·3] in the cidofovir group, and 61·1% [95% CI; 45·2-77] in the sinecatechins group (p=0.189). During the 48-weeks follow-up period, recurrence was observed in 7 participants (28%) in the electrocautery group, 7 (30·4%) in the cidofovir group, and 8 (36·4%) in the sinecatechins group (Log-rank test p=0·811). Side effects were reported by 97·2% of patients in the electrocautery group, 85·7% in the cidofovir group, and 33% in the sinecatechins group (p&amp;lt;0·001). Patients were more satisfied with the sinecatechins treatment (5·6 ± 0·4), followed by electrocautery (5·1 ± 0·8), while lower satisfaction was reported with cidofovir treatment (4·77 ± 0·96), p&amp;lt;0.001. Conclusion No statistically significant difference was observed in efficacy between treatments; in contrast, sinecatechins was the most accepted and well-tolerated treatment.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"59 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Tuberculosis preventive treatment for household contacts at health facility and community settings in Pakistan
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-04 DOI: 10.1093/cid/ciaf088
Maria R Jaswal, Leonardo Martinez, Meredith Brooks, Saira Farooq, Nauman Safdar, Jinsar Ali Shah, Zafar Islam, Kumail Nasir, Usama Fareed, Shadab Manzar, Rabia Maniar, Sara Siddiqui, Saira Khowaja, Aamir J Khan, Hamidah Hussain, Amyn A Malik
We assessed incremental completion of tuberculosis preventive treatment cascade in household contacts by offering services in community settings. This improved clinical evaluation by 12.4 (95% CI:11.7–13.0) percentage points (pp), treatment completion by 11.6 (95% CI: 10.6–12.7) pp, and cascade completion by 5.9 (95% CI: 5.1–6.7) pp.
{"title":"Tuberculosis preventive treatment for household contacts at health facility and community settings in Pakistan","authors":"Maria R Jaswal, Leonardo Martinez, Meredith Brooks, Saira Farooq, Nauman Safdar, Jinsar Ali Shah, Zafar Islam, Kumail Nasir, Usama Fareed, Shadab Manzar, Rabia Maniar, Sara Siddiqui, Saira Khowaja, Aamir J Khan, Hamidah Hussain, Amyn A Malik","doi":"10.1093/cid/ciaf088","DOIUrl":"https://doi.org/10.1093/cid/ciaf088","url":null,"abstract":"We assessed incremental completion of tuberculosis preventive treatment cascade in household contacts by offering services in community settings. This improved clinical evaluation by 12.4 (95% CI:11.7–13.0) percentage points (pp), treatment completion by 11.6 (95% CI: 10.6–12.7) pp, and cascade completion by 5.9 (95% CI: 5.1–6.7) pp.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"32 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Emergence and Spread of Clostridioides difficile Isolates With Reduced Fidaxomicin Susceptibility in an Acute Care Hospital
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-04 DOI: 10.1093/cid/ciaf028
Sarah N Redmond, Jennifer L Cadnum, Annette L Jencson, Claire E Kaple, Brigid M Wilson, Andrew M Skinner, Amy S Gargis, Munok Hwang, Hosoon Choi, Piyali Chatterjee, Chetan Jinadatha, Curtis J Donskey
Background There have been several recent reports of Clostridioides difficile infection (CDI) due to isolates with reduced fidaxomicin susceptibility (minimum inhibitory concentration [MIC] ≥ 2 µg/mL). However, the clinical implications are uncertain because fidaxomicin achieves high concentrations in the intestinal tract. Methods In an acute care hospital, we conducted a 3-year cohort study of patients with CDI to determine the frequency of infection with isolates with reduced fidaxomicin susceptibility and the impact on response to fidaxomicin treatment. Stool specimens were cultured for C. difficile, and susceptibility testing was performed using agar dilution. Whole-genome sequencing was used to identify mutations associated with reduced fidaxomicin susceptibility and to determine relatedness of isolates. For genomically related susceptible and reduced susceptibility isolates from the same patient, we compared rates of growth, sporulation, and toxin production. Results Of 108 fidaxomicin-treated patients, 6 (5.6%) were infected with isolates that possessed reduced fidaxomicin susceptibility (MICs 8–32 µg/mL), including 3 with initially susceptible isolates followed by clinical failure with subsequent recovery of genomically related isolates with reduced susceptibility. Isolates with reduced fidaxomicin susceptibility harbored mutations in RNA polymerase associated with reduced susceptibility and exhibited reduced toxin production, and 20% to 40% of isolates tested had reduced growth and/or sporulation in comparison with susceptible isolates. Three patients were infected with genomically indistinguishable ribotype 097 isolates with reduced fidaxomicin susceptibility. Conclusions Our findings highlight the potential for the emergence on therapy of clinically relevant reduced fidaxomicin susceptibility in C. difficile and its spread via transmission to other patients.
{"title":"Emergence and Spread of Clostridioides difficile Isolates With Reduced Fidaxomicin Susceptibility in an Acute Care Hospital","authors":"Sarah N Redmond, Jennifer L Cadnum, Annette L Jencson, Claire E Kaple, Brigid M Wilson, Andrew M Skinner, Amy S Gargis, Munok Hwang, Hosoon Choi, Piyali Chatterjee, Chetan Jinadatha, Curtis J Donskey","doi":"10.1093/cid/ciaf028","DOIUrl":"https://doi.org/10.1093/cid/ciaf028","url":null,"abstract":"Background There have been several recent reports of Clostridioides difficile infection (CDI) due to isolates with reduced fidaxomicin susceptibility (minimum inhibitory concentration [MIC] ≥ 2 µg/mL). However, the clinical implications are uncertain because fidaxomicin achieves high concentrations in the intestinal tract. Methods In an acute care hospital, we conducted a 3-year cohort study of patients with CDI to determine the frequency of infection with isolates with reduced fidaxomicin susceptibility and the impact on response to fidaxomicin treatment. Stool specimens were cultured for C. difficile, and susceptibility testing was performed using agar dilution. Whole-genome sequencing was used to identify mutations associated with reduced fidaxomicin susceptibility and to determine relatedness of isolates. For genomically related susceptible and reduced susceptibility isolates from the same patient, we compared rates of growth, sporulation, and toxin production. Results Of 108 fidaxomicin-treated patients, 6 (5.6%) were infected with isolates that possessed reduced fidaxomicin susceptibility (MICs 8–32 µg/mL), including 3 with initially susceptible isolates followed by clinical failure with subsequent recovery of genomically related isolates with reduced susceptibility. Isolates with reduced fidaxomicin susceptibility harbored mutations in RNA polymerase associated with reduced susceptibility and exhibited reduced toxin production, and 20% to 40% of isolates tested had reduced growth and/or sporulation in comparison with susceptible isolates. Three patients were infected with genomically indistinguishable ribotype 097 isolates with reduced fidaxomicin susceptibility. Conclusions Our findings highlight the potential for the emergence on therapy of clinically relevant reduced fidaxomicin susceptibility in C. difficile and its spread via transmission to other patients.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"29 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Effects of the COVID-19 pandemic on TB outcomes in the United States: a Bayesian analysis
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-04 DOI: 10.1093/cid/ciaf092
Nicole A Swartwood, Ted Cohen, Suzanne M Marks, Andrew N Hill, Garrett R Beeler Asay, Julie Self, Pei-Jean I Feng, C Robert Horsburgh, Joshua A Salomon, Nicolas A Menzies
Background Tuberculosis (TB) notifications and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends. Methods We identified four mechanisms potentially contributing to observed TB trends during 2020–2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons experiencing TB disease. We employed a Bayesian approach to synthesize evidence on how these mechanisms changed during the pandemic and how they might have combined to produce observed 2020–2023 TB data, using a transmission-dynamic model to link mechanisms to TB outcomes. We also simulated a no-pandemic-counterfactual scenario that assumed mechanisms followed pre-pandemic trends. We estimated TB outcomes associated with the pandemic until 2035 to capture lagged effects. We evaluated additional scenarios to estimate the individual effect of each mechanism. Results Over 2020–2035, we estimate an additional 2,784 (95% uncertainty interval: 2,164–3,461) TB notifications and 1,138 (1,076–1,201) TB deaths in the United States associated with changes occurring during the COVID-19 pandemic. Mechanisms had offsetting effects – decreases in TB diagnosis rates led to more TB deaths and notifications, while reductions in contact rates reduced TB deaths and notifications. Immigration changes initially reduced TB deaths, but increased deaths and notifications over time. Higher TB mortality rates increased TB deaths, but decreased TB notifications. Conclusions While direct impacts of the COVID-19 pandemic occurred between 2020–2023, these changes may continue to influence TB incidence and mortality in future years.
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引用次数: 0
Potential Impact of Doxycycline Post-Exposure Prophylaxis on Tetracycline Resistance in Neisseria gonorrhoeae and Colonization with Tetracycline-Resistant Staphylococcus aureus and Group A Streptococcus
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2025-03-04 DOI: 10.1093/cid/ciaf089
Olusegun O Soge, Christina S Thibault, Chase A Cannon, Stephanie E McLaughlin, Tim W Menza, Julia C Dombrowski, Ferric C Fang, Matthew R Golden
Background Doxycycline post-exposure prophylaxis (doxy PEP) is increasingly used among men who have sex with men (MSM). Its impact on antimicrobial resistance and the microbiome is uncertain. Methods We used Neisseria gonorrhoeae (NG) surveillance data from King County, WA and joinpoint regression to investigate trends in NG-tetracycline resistance (tetR), 2017-2024 and, among sexual health clinic (SHC) patients, evaluated the association of NG-tetR with doxy PEP use. We evaluated nasopharyngeal colonization with Staphylococcus aureus and Group A Streptococcus (GAS) 703 MSM SHC patients, August 2023-July 2024. Results Among 2,312 MSM with NG, tetR was stable 2017 to quarter 1 (Q1) 2023 (mean=27%) and thereafter rose to 70% in Q2 2024 (p&lt;0.0001). (King County released doxy PEP guidelines in Q2 2023.) NG with high-level (HL) tetR increased Q1 2021 to Q2 2024 (2% to 65%) (p&lt;0.0001). Taking &gt;3 doses of doxy PEP/month was associated with both tetR and HL tetR (p≤0.01 for both), though any use of doxy PEP was not associated with tetR or HL tetR. S. aureus colonization was less common among doxy PEP users than non-users (27% vs. 36%, p=0.02), but colonization with both tetracycline-resistant S. aureus and GAS were more common among doxy PEP users than non-users (18% vs. 8%, p&lt;0.0001 and 9% vs. 4%, p=0.008, respectively). Conclusions TetR in NG rapidly increased from 2021 to 2024, and most NG among King County MSM now have HL tetR. Doxy PEP use is associated with colonization with GAS and tetracycline-resistant S. aureus, suggesting that doxy PEP impacts off-target bacteria.
背景 多西环素暴露后预防疗法(doxy PEP)越来越多地用于男男性行为者(MSM)。它对抗菌药耐药性和微生物组的影响尚不确定。方法 我们利用华盛顿州金县的淋病奈瑟菌(NG)监测数据和连接点回归法调查了 2017-2024 年 NG-四环素耐药性(tetR)的趋势,并在性健康诊所(SHC)患者中评估了 NG-tetR 与强力 PEP 使用的相关性。我们对 2023 年 8 月至 2024 年 7 月期间 703 名 MSM SHC 患者的金黄色葡萄球菌和 A 组链球菌(GAS)鼻咽部定植情况进行了评估。结果 在 2312 名患有 NG 的 MSM 患者中,tetR 在 2017 年至 2023 年第 1 季度(Q1)期间保持稳定(平均值=27%),此后在 2024 年第 2 季度上升至 70%(p&lt;0.0001)。(金县于 2023 年第 2 季度发布了强力 PEP 指南。)2021 年第 1 季度至 2024 年第 2 季度,患有高水平 (HL) tetR 的 NG 增加(2% 至 65%)(p&lt;0.0001)。每月服用&gt;3次强力PEP与tetR和HL tetR有关(两者的p均≤0.01),但任何强力PEP的使用均与tetR或HL tetR无关。金黄色葡萄球菌定植在多西 PEP 使用者中的发生率低于非使用者(27% 对 36%,p=0.02),但耐四环素金黄色葡萄球菌和 GAS 定植在多西 PEP 使用者中的发生率高于非使用者(分别为 18% 对 8%,p&lt;0.0001 和 9% 对 4%,p=0.008)。结论 从 2021 年到 2024 年,NG 中的 TetR 迅速增加,目前金县 MSM 中的大多数 NG 都有 HL tetR。强力杀菌剂 PEP 的使用与 GAS 和耐四环素金黄色葡萄球菌的定植有关,这表明强力杀菌剂 PEP 会对非目标细菌产生影响。
{"title":"Potential Impact of Doxycycline Post-Exposure Prophylaxis on Tetracycline Resistance in Neisseria gonorrhoeae and Colonization with Tetracycline-Resistant Staphylococcus aureus and Group A Streptococcus","authors":"Olusegun O Soge, Christina S Thibault, Chase A Cannon, Stephanie E McLaughlin, Tim W Menza, Julia C Dombrowski, Ferric C Fang, Matthew R Golden","doi":"10.1093/cid/ciaf089","DOIUrl":"https://doi.org/10.1093/cid/ciaf089","url":null,"abstract":"Background Doxycycline post-exposure prophylaxis (doxy PEP) is increasingly used among men who have sex with men (MSM). Its impact on antimicrobial resistance and the microbiome is uncertain. Methods We used Neisseria gonorrhoeae (NG) surveillance data from King County, WA and joinpoint regression to investigate trends in NG-tetracycline resistance (tetR), 2017-2024 and, among sexual health clinic (SHC) patients, evaluated the association of NG-tetR with doxy PEP use. We evaluated nasopharyngeal colonization with Staphylococcus aureus and Group A Streptococcus (GAS) 703 MSM SHC patients, August 2023-July 2024. Results Among 2,312 MSM with NG, tetR was stable 2017 to quarter 1 (Q1) 2023 (mean=27%) and thereafter rose to 70% in Q2 2024 (p&amp;lt;0.0001). (King County released doxy PEP guidelines in Q2 2023.) NG with high-level (HL) tetR increased Q1 2021 to Q2 2024 (2% to 65%) (p&amp;lt;0.0001). Taking &amp;gt;3 doses of doxy PEP/month was associated with both tetR and HL tetR (p≤0.01 for both), though any use of doxy PEP was not associated with tetR or HL tetR. S. aureus colonization was less common among doxy PEP users than non-users (27% vs. 36%, p=0.02), but colonization with both tetracycline-resistant S. aureus and GAS were more common among doxy PEP users than non-users (18% vs. 8%, p&amp;lt;0.0001 and 9% vs. 4%, p=0.008, respectively). Conclusions TetR in NG rapidly increased from 2021 to 2024, and most NG among King County MSM now have HL tetR. Doxy PEP use is associated with colonization with GAS and tetracycline-resistant S. aureus, suggesting that doxy PEP impacts off-target bacteria.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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Clinical Infectious Diseases
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