Pub Date : 2024-10-18DOI: 10.1016/j.jinf.2024.106314
Nathella Pavan Kumar , Sarath Balaji , Poorna Ganga Devi , Balaji Ramraj , Arul Nancy , Nandhini Selvaraj , Shaik Fayaz Ahamed , Karthik M , Suba S , A. Gunasundari , A. Seetha , Poovazhagi Varadarajan , Elilarasi S , Aishwarya Venkataraman , Subash Babu
Objectives
To characterize the inflammatory cytokine profiles in children with TB in the presence and absence of SARS-CoV2 seropositivity.
Methods
This study evaluated cytokine responses in two groups of children with TB: CoV2+ (TB and SARS-CoV2 seropositive) and CoV2- (TB and SARS-CoV2 seronegative). Each group had 30 children, and cytokine levels were measured at baseline, months 3 and 6.
Results
At baseline, CoV2+ children exhibited significantly elevated levels of cytokines, including IFN-γ, IL-2, TNFα, IL-1α, and IL-6, and reduced levels of IL-1β and IL-18, compared to CoV2- children. No significant differences in cytokine levels between the groups were observed at months 3 and 6. Additionally, a general decline in cytokine levels was noted over the course of treatment in both groups. A positive correlation was found between most cytokines and SARS-CoV2 IgG spike protein levels at baseline and at month 3 in the CoV2+ group.
Conclusions
This study is one of the first studies to characterize the systemic inflammatory responses in SARS-CoV2 seropositive and seronegative children with TB from a TB endemic country. The findings enhance our understanding of the immunopathogenesis of TB and SARS-CoV2 seropositivity in children and may inform future therapeutic strategies
{"title":"Inflammatory cytokine responses in pediatric tuberculosis with or without SARS-CoV-2 seropositivity","authors":"Nathella Pavan Kumar , Sarath Balaji , Poorna Ganga Devi , Balaji Ramraj , Arul Nancy , Nandhini Selvaraj , Shaik Fayaz Ahamed , Karthik M , Suba S , A. Gunasundari , A. Seetha , Poovazhagi Varadarajan , Elilarasi S , Aishwarya Venkataraman , Subash Babu","doi":"10.1016/j.jinf.2024.106314","DOIUrl":"10.1016/j.jinf.2024.106314","url":null,"abstract":"<div><h3>Objectives</h3><div>To characterize the inflammatory cytokine profiles in children with TB in the presence and absence of SARS-CoV2 seropositivity.</div></div><div><h3>Methods</h3><div>This study evaluated cytokine responses in two groups of children with TB: CoV2+ (TB and SARS-CoV2 seropositive) and CoV2- (TB and SARS-CoV2 seronegative). Each group had 30 children, and cytokine levels were measured at baseline, months 3 and 6.</div></div><div><h3>Results</h3><div>At baseline, CoV2+ children exhibited significantly elevated levels of cytokines, including IFN-γ, IL-2, TNFα, IL-1α, and IL-6, and reduced levels of IL-1β and IL-18, compared to CoV2- children. No significant differences in cytokine levels between the groups were observed at months 3 and 6. Additionally, a general decline in cytokine levels was noted over the course of treatment in both groups. A positive correlation was found between most cytokines and SARS-CoV2 IgG spike protein levels at baseline and at month 3 in the CoV2+ group.</div></div><div><h3>Conclusions</h3><div>This study is one of the first studies to characterize the systemic inflammatory responses in SARS-CoV2 seropositive and seronegative children with TB from a TB endemic country. The findings enhance our understanding of the immunopathogenesis of TB and SARS-CoV2 seropositivity in children and may inform future therapeutic strategies</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106314"},"PeriodicalIF":14.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1016/j.jinf.2024.106318
Tomer David Meirman , Bracha Shapira , Ran D. Balicer , Lior Rokach , Noa Dagan
Background
Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers.
Methods
We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences.
Results
The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1–4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7–8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3–5 months. Vaccinated individuals’ data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis.
Conclusions
This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.
{"title":"Trends of common laboratory biomarkers after SARS-CoV-2 infection","authors":"Tomer David Meirman , Bracha Shapira , Ran D. Balicer , Lior Rokach , Noa Dagan","doi":"10.1016/j.jinf.2024.106318","DOIUrl":"10.1016/j.jinf.2024.106318","url":null,"abstract":"<div><h3>Background</h3><div>Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers.</div></div><div><h3>Methods</h3><div>We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences.</div></div><div><h3>Results</h3><div>The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1–4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7–8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3–5 months. Vaccinated individuals’ data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis.</div></div><div><h3>Conclusions</h3><div>This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106318"},"PeriodicalIF":14.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1016/j.jinf.2024.106319
Anne Marie Rosendahl Madsen , Lise Gehrt , Frederik Schaltz-Buchholzer , Sören Möller , Rikke Christiansen , Lars Schellerup , Lene Annette Norberg , Tyra Grove Krause , Sebastian Nielsen , Mette Bliddal , Peter Aaby , Christine Stabell Benn
Objectives
The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.
Methods
Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).
Results
The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).
Conclusion
BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.
Trial registration
ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.
Summary
In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.
{"title":"Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial","authors":"Anne Marie Rosendahl Madsen , Lise Gehrt , Frederik Schaltz-Buchholzer , Sören Möller , Rikke Christiansen , Lars Schellerup , Lene Annette Norberg , Tyra Grove Krause , Sebastian Nielsen , Mette Bliddal , Peter Aaby , Christine Stabell Benn","doi":"10.1016/j.jinf.2024.106319","DOIUrl":"10.1016/j.jinf.2024.106319","url":null,"abstract":"<div><h3>Objectives</h3><div>The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.</div></div><div><h3>Methods</h3><div>Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).</div></div><div><h3>Results</h3><div>The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).</div></div><div><h3>Conclusion</h3><div>BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.</div></div><div><h3>Summary</h3><div>In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106319"},"PeriodicalIF":14.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.
Methods
Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.
Results
The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.
Conclusions
The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.
{"title":"Assessment of neutralizing antibody response as a correlate of protection against symptomatic SARS-CoV-2 infections after administration of two doses of the CoronaVac inactivated COVID-19 vaccine: A phase III randomized controlled trial","authors":"Xinhua Chen , Xing Meng , Qianhui Wu , Wey Wen Lim , Qianqian Xin , Benjamin J. Cowling , Weining Meng , Hongjie Yu , Dimas Tadeu Covasa","doi":"10.1016/j.jinf.2024.106315","DOIUrl":"10.1016/j.jinf.2024.106315","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.</div></div><div><h3>Methods</h3><div>Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.</div></div><div><h3>Results</h3><div>The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.</div></div><div><h3>Conclusions</h3><div>The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106315"},"PeriodicalIF":14.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.jinf.2024.106317
Anthony M. Marchese , Louis Fries , Hadi Beyhaghi , Muruga Vadivale , Mingzhu Zhu , Shane Cloney-Clark , Joyce S. Plested , Amy W. Chung , Lisa M. Dunkle , Raj Kalkeri
Vaccine-induced immunoglobulin G (IgG) profiles can vary with respect to the predominant subclasses that characterize the response. Among IgG subclasses, IgG4 is reported to have anti-inflammatory properties, but can also exhibit reduced capacity for virus neutralization and activation of Fc-dependent effector functions. Here, we review evidence that IgG4 subclass responses can be disproportionately increased in response to some types of vaccines targeting an array of diseases, including pertussis, HIV, malaria, and COVID-19. The basis for enhanced IgG4 induction by vaccines is poorly understood but may be associated with platform- or dose regimen–specific differences in antigen exposure and/or cytokine stimulation. The clinical implications of vaccine-induced IgG4 responses remain uncertain, though collective evidence suggests that proportional increases in IgG4 might reduce vaccine antigen-specific immunity. Additional work is needed to determine underlying mechanisms and to elucidate what role IgG4 may play in modifications of vaccine-induced immunity to disease.
疫苗诱导的免疫球蛋白 G (IgG) 可因反应的主要亚类而有所不同。据报道，在 IgG 亚类中，IgG4 具有抗炎特性，但也会表现出中和病毒和激活 Fc 依赖性效应器功能的能力下降。在此，我们回顾了一些证据，这些证据表明，在接种某些类型的疫苗时，IgG4 亚类的反应会不成比例地增加，这些疫苗针对的疾病包括百日咳、艾滋病、疟疾和 COVID-19。疫苗诱导 IgG4 增高的原因尚不清楚，但可能与抗原暴露和/或细胞因子刺激的平台或剂量方案特异性差异有关。疫苗诱导的 IgG4 反应对临床的影响仍不确定，但有综合证据表明，IgG4 的比例增加可能会降低疫苗抗原特异性免疫力。还需要做更多的工作来确定潜在的机制，并阐明 IgG4 在改变疫苗诱导的疾病免疫中可能扮演的角色。
{"title":"Mechanisms and implications of IgG4 responses to SARS-CoV-2 and other repeatedly administered vaccines","authors":"Anthony M. Marchese , Louis Fries , Hadi Beyhaghi , Muruga Vadivale , Mingzhu Zhu , Shane Cloney-Clark , Joyce S. Plested , Amy W. Chung , Lisa M. Dunkle , Raj Kalkeri","doi":"10.1016/j.jinf.2024.106317","DOIUrl":"10.1016/j.jinf.2024.106317","url":null,"abstract":"<div><div>Vaccine-induced immunoglobulin G (IgG) profiles can vary with respect to the predominant subclasses that characterize the response. Among IgG subclasses, IgG4 is reported to have anti-inflammatory properties, but can also exhibit reduced capacity for virus neutralization and activation of Fc-dependent effector functions. Here, we review evidence that IgG4 subclass responses can be disproportionately increased in response to some types of vaccines targeting an array of diseases, including pertussis, HIV, malaria, and COVID-19. The basis for enhanced IgG4 induction by vaccines is poorly understood but may be associated with platform- or dose regimen–specific differences in antigen exposure and/or cytokine stimulation. The clinical implications of vaccine-induced IgG4 responses remain uncertain, though collective evidence suggests that proportional increases in IgG4 might reduce vaccine antigen-specific immunity. Additional work is needed to determine underlying mechanisms and to elucidate what role IgG4 may play in modifications of vaccine-induced immunity to disease.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106317"},"PeriodicalIF":14.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.jinf.2024.106316
Jaap L.J. Hanssen , Maaike G.J. Gademan , Marjan Wouthuyzen-Bakker , Joshua S. Davis , David Dewar , Laurens Manning , David Campbell , Joffrey van Prehn , Andy O. Miller , Robert J.P. van der Wal , Henrica M.J. van der Linden , Nicolás W. Cortés-Penfield , Alex Soriano , Mark G.J. de Boer , Henk Scheper
Objectives
To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).
Methods
An online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups.
Results
Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months–3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%).
Conclusions
Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.
{"title":"Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study","authors":"Jaap L.J. Hanssen , Maaike G.J. Gademan , Marjan Wouthuyzen-Bakker , Joshua S. Davis , David Dewar , Laurens Manning , David Campbell , Joffrey van Prehn , Andy O. Miller , Robert J.P. van der Wal , Henrica M.J. van der Linden , Nicolás W. Cortés-Penfield , Alex Soriano , Mark G.J. de Boer , Henk Scheper","doi":"10.1016/j.jinf.2024.106316","DOIUrl":"10.1016/j.jinf.2024.106316","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).</div></div><div><h3>Methods</h3><div>An online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups.</div></div><div><h3>Results</h3><div>Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months–3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%).</div></div><div><h3>Conclusions</h3><div>Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106316"},"PeriodicalIF":14.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-13DOI: 10.1016/j.jinf.2024.106313
Nicolas Fourré , Virgile Zimmermann , Laurence Senn , Marion Aruanno , Benoit Guery , Matthaios Papadimitriou-Olivgeris
Objectives
Duration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5–10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11–18 days).
Methods
This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days.
Results
During the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7–14); 184 (55%) and 152 (45%) episodes received a short (5–10 days) and long (11–18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; P 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08–7.71), and septic shock (1.67, 1.04–2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57–1.12).
Conclusions
This study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.
{"title":"Duration of antimicrobial treatment for uncomplicated streptococcal bacteraemia: Another example of shorter is better","authors":"Nicolas Fourré , Virgile Zimmermann , Laurence Senn , Marion Aruanno , Benoit Guery , Matthaios Papadimitriou-Olivgeris","doi":"10.1016/j.jinf.2024.106313","DOIUrl":"10.1016/j.jinf.2024.106313","url":null,"abstract":"<div><h3>Objectives</h3><div>Duration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5–10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11–18 days).</div></div><div><h3>Methods</h3><div>This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days.</div></div><div><h3>Results</h3><div>During the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7–14); 184 (55%) and 152 (45%) episodes received a short (5–10 days) and long (11–18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; <em>P</em> 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08–7.71), and septic shock (1.67, 1.04–2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57–1.12).</div></div><div><h3>Conclusions</h3><div>This study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106313"},"PeriodicalIF":14.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.jinf.2024.106312
Oskar Ljungquist , Michal Magda , Christian G. Giske , Chaitanya Tellapragada , Oleksandr Nazarchuk , Dmytro Dmytriiev , Oskar Thofte , Valdemar Öhnström , Erika Matuschek , Anna M. Blom , Kristian Riesbeck
Objectives
Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.
Methods
Klebsiella pneumoniae clinical isolates (n = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.
Results
Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in pmrB and phoP genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant K. pneumoniae were more serum-resistant, more virulent against G. mellonella larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The iucA, peg-344, rmpA, rmpC, and rmpD genes were associated with increased virulence in animals.
Conclusions
Pandrug-resistant K. pneumoniae in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.
{"title":"Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent","authors":"Oskar Ljungquist , Michal Magda , Christian G. Giske , Chaitanya Tellapragada , Oleksandr Nazarchuk , Dmytro Dmytriiev , Oskar Thofte , Valdemar Öhnström , Erika Matuschek , Anna M. Blom , Kristian Riesbeck","doi":"10.1016/j.jinf.2024.106312","DOIUrl":"10.1016/j.jinf.2024.106312","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenem- and colistin-resistant <em>Klebsiella pneumoniae</em> were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant <em>K. pneumoniae</em> are pathogenic and capable of causing disease in a broader context.</div></div><div><h3>Methods</h3><div><em>Klebsiella pneumoniae</em> clinical isolates (<em>n</em> = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.</div></div><div><h3>Results</h3><div>Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in <em>pmrB</em> and <em>phoP</em> genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant <em>K. pneumoniae</em> were more serum-resistant, more virulent against <em>G. mellonella</em> larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The <em>iucA</em>, <em>peg-344</em>, <em>rmpA</em>, <em>rmpC</em>, and <em>rmpD</em> genes were associated with increased virulence in animals.</div></div><div><h3>Conclusions</h3><div>Pandrug-resistant <em>K. pneumoniae</em> in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106312"},"PeriodicalIF":14.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.jinf.2024.106310
Yunhui Li , Xiaohan Zhang , Jingkun Yi , Yuan Chen , Jing Liang , Li Wang , Jiayue Ma , Renlong Zhu , Xiaomei Zhang , Di Hu , Yan Jia , Xiaobo Yu , Yajie Wang
Objectives
SARS-CoV-2 is continually evolving with new variants to evade protective immunity and cause new infections. This study aimed to assess infection-acquired immunity and hybrid immunity against re-infection or severe COVID-19.
Methods
During 2020–2023, we collected 890 serum samples from individuals infected with SARS-CoV-2 variants including wild type, D614G, Alpha, Delta, BA.1, BA.2, BA.2.76, BA.5.2, BF.7, XBB, and EG.5. The levels of serum neutralizing antibodies (NAbs) against 18 diverse SARS-CoV-2 variants were determined using a bead-based high-throughput broad neutralizing-antibody assay.
Results
In the initial wave of the COVID-19 pandemic, >75% of the patients demonstrated robust NAb responses against the ancestral SARS-CoV-2, during a period when vaccines were not yet available. After the emergence of the Omicron variant, the seroprevalence of anti-Omicron NAbs among the patients increased rapidly. By April 2023, when XBB variant was predominant, approximately 80% of the patients demonstrated >50% neutralization against the highly immune-evasive XBB lineages. Three serotypes of SARS-CoV-2, namely non-Omicron, Omicron, and XBB serotypes, were identified, with the strong likelihood of further changes occurring as the virus mutating. Generally, NAbs elicited by a previous serotype could not typically effectively protect against another serotype that emerges later in the evolutionary stages.
Conclusion
Our results firstly demonstrated the synergistic evolution between host immunity and SARS-CoV-2 variants in the real world, which would be helpful to develop future vaccines and public health strategies.
{"title":"Synergistic evolution: The dynamic adaptation of SARS-CoV-2 and human protective immunity in the real world","authors":"Yunhui Li , Xiaohan Zhang , Jingkun Yi , Yuan Chen , Jing Liang , Li Wang , Jiayue Ma , Renlong Zhu , Xiaomei Zhang , Di Hu , Yan Jia , Xiaobo Yu , Yajie Wang","doi":"10.1016/j.jinf.2024.106310","DOIUrl":"10.1016/j.jinf.2024.106310","url":null,"abstract":"<div><h3>Objectives</h3><div>SARS-CoV-2 is continually evolving with new variants to evade protective immunity and cause new infections. This study aimed to assess infection-acquired immunity and hybrid immunity against re-infection or severe COVID-19.</div></div><div><h3>Methods</h3><div>During 2020–2023, we collected 890 serum samples from individuals infected with SARS-CoV-2 variants including wild type, D614G, Alpha, Delta, BA.1, BA.2, BA.2.76, BA.5.2, BF.7, XBB, and EG.5. The levels of serum neutralizing antibodies (NAbs) against 18 diverse SARS-CoV-2 variants were determined using a bead-based high-throughput broad neutralizing-antibody assay.</div></div><div><h3>Results</h3><div>In the initial wave of the COVID-19 pandemic, >75% of the patients demonstrated robust NAb responses against the ancestral SARS-CoV-2, during a period when vaccines were not yet available. After the emergence of the Omicron variant, the seroprevalence of anti-Omicron NAbs among the patients increased rapidly. By April 2023, when XBB variant was predominant, approximately 80% of the patients demonstrated >50% neutralization against the highly immune-evasive XBB lineages. Three serotypes of SARS-CoV-2, namely non-Omicron, Omicron, and XBB serotypes, were identified, with the strong likelihood of further changes occurring as the virus mutating. Generally, NAbs elicited by a previous serotype could not typically effectively protect against another serotype that emerges later in the evolutionary stages.</div></div><div><h3>Conclusion</h3><div>Our results firstly demonstrated the synergistic evolution between host immunity and SARS-CoV-2 variants in the real world, which would be helpful to develop future vaccines and public health strategies.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106310"},"PeriodicalIF":14.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.jinf.2024.106307
David J. Muscatello , Nectarios Rose , Kishor Kumar Paul , Sandra Ware , Michael M. Dinh , Mohammed Mohsin , Adam T. Craig , Amalie Dyda , Roberto Forero
Background
COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection.
Methods
De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death).
Results
Influenza infection was notified in 2335 and COVID-19 in 5053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period.
Conclusions
The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.
{"title":"Epidemiological comparison of emergency department presentations with seasonal influenza or COVID-19 and an outcome of intensive care admission or death: A population-based records linkage study in New South Wales, Australia","authors":"David J. Muscatello , Nectarios Rose , Kishor Kumar Paul , Sandra Ware , Michael M. Dinh , Mohammed Mohsin , Adam T. Craig , Amalie Dyda , Roberto Forero","doi":"10.1016/j.jinf.2024.106307","DOIUrl":"10.1016/j.jinf.2024.106307","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 and seasonal influenza are endemic causes of morbidity and mortality. This study aimed to compare the epidemiology of severe illness and risk of death among patients following emergency department (ED) presentation with either infection.</div></div><div><h3>Methods</h3><div>De-identified, population-based, emergency department records in New South Wales, Australia, were probabilistically linked to population-level health outcome databases for the period 1 January 2015 to 28 February 2023. Included were patients allocated an ED diagnosis consistent with an acute respiratory infection. Logistic regression was used to examine the association of infecting virus with risk of a severe outcome (intensive care unit admission or death).</div></div><div><h3>Results</h3><div>Influenza infection was notified in 2335 and COVID-19 in 5053 patients with a severe outcome. The age distribution was similar for both viruses, except in <15-year-olds, where severe influenza was nearly three times more frequent. Overall, the odds of death among patients with COVID-19 was 1.65 (95% CI 1.43, 1.89) times higher than among those with influenza. This declined to 1.49 (95% CI 1.08, 2.06) times during the COVID-19 Omicron variant period.</div></div><div><h3>Conclusions</h3><div>The Omicron variant arrived when background population COVID-19 vaccination coverage was >90%. Despite that, death was more frequent for COVID-19 than influenza.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106307"},"PeriodicalIF":14.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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