{"title":"Correction to: Prediction of antimicrobial resistance in Klebsiella pneumoniae using genomic and metagenomic next-generation sequencing data.","authors":"","doi":"10.1093/jac/dkae289","DOIUrl":"10.1093/jac/dkae289","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897503","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}
Ainoa Ugarte, Lorena De La Mora, Elisa De Lazzari, Iván Chivite, Emma Fernández, Alexy Inciarte, Montserrat Laguno, Juan Ambrosioni, Estela Solbes, Leire Berrocal, Ana González-Cordón, María Martínez-Rebollar, Alberto Foncillas, Júlia Calvo, José Luis Blanco, Esteban Martínez, Josep Mallolas, Berta Torres
Introduction: Rapid initiation of ART after HIV diagnosis is recommended for individual and public health benefits. However, certain clinical and ART-related considerations hinder immediate initiation of therapy.
Methods: An open-label, single-arm, single-centre 48-week prospective clinical trial involving ART-naïve HIV-diagnosed adults who started bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) within a week from the first hospital visit, before the availability of baseline laboratory and genotype results. The primary aim was to determine the proportion of people with at least one condition that would hinder immediate initiation of any recommended ART regimen other than BIC/FTC/TAF. Clinicaltrials.gov: NCT04416906.
Results: We included 100 participants: 79% men, 64% from Latin America, median age 32 years. According to European AIDS Clinical Society (EACS) and US Department of Health and Human Services 2023 guidelines, 11% (95%CI 6; 19) of participants had at least one condition that made any ART different from BIC/FTC/TAF less appropriate for a rapid ART strategy. Seventy-nine percent of the people started BIC/FTC/TAF within the first 48 hours of their first hospital visit. There were 16 early discontinuations (11 lost to follow-up). By week 48, 92% (95%CI 86; 98) of the participants of the ITT population with observed data achieved viral suppression. Eight grade 3-4 adverse events (AEs), five serious AEs and six ART-related AEs were identified. Adherence remained high.
Conclusions: BIC/FTC/TAF is an optimal treatment for rapid initiation of ART. However, additional strategies to improve retention in care must be implemented.
{"title":"Rapid initiation of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy in HIV infection. A prospective study.","authors":"Ainoa Ugarte, Lorena De La Mora, Elisa De Lazzari, Iván Chivite, Emma Fernández, Alexy Inciarte, Montserrat Laguno, Juan Ambrosioni, Estela Solbes, Leire Berrocal, Ana González-Cordón, María Martínez-Rebollar, Alberto Foncillas, Júlia Calvo, José Luis Blanco, Esteban Martínez, Josep Mallolas, Berta Torres","doi":"10.1093/jac/dkae235","DOIUrl":"10.1093/jac/dkae235","url":null,"abstract":"<p><strong>Introduction: </strong>Rapid initiation of ART after HIV diagnosis is recommended for individual and public health benefits. However, certain clinical and ART-related considerations hinder immediate initiation of therapy.</p><p><strong>Methods: </strong>An open-label, single-arm, single-centre 48-week prospective clinical trial involving ART-naïve HIV-diagnosed adults who started bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) within a week from the first hospital visit, before the availability of baseline laboratory and genotype results. The primary aim was to determine the proportion of people with at least one condition that would hinder immediate initiation of any recommended ART regimen other than BIC/FTC/TAF. Clinicaltrials.gov: NCT04416906.</p><p><strong>Results: </strong>We included 100 participants: 79% men, 64% from Latin America, median age 32 years. According to European AIDS Clinical Society (EACS) and US Department of Health and Human Services 2023 guidelines, 11% (95%CI 6; 19) of participants had at least one condition that made any ART different from BIC/FTC/TAF less appropriate for a rapid ART strategy. Seventy-nine percent of the people started BIC/FTC/TAF within the first 48 hours of their first hospital visit. There were 16 early discontinuations (11 lost to follow-up). By week 48, 92% (95%CI 86; 98) of the participants of the ITT population with observed data achieved viral suppression. Eight grade 3-4 adverse events (AEs), five serious AEs and six ART-related AEs were identified. Adherence remained high.</p><p><strong>Conclusions: </strong>BIC/FTC/TAF is an optimal treatment for rapid initiation of ART. However, additional strategies to improve retention in care must be implemented.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751791","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}
Ying Huang, Zhongpeng Cai, Luchao Lv, Chao Yue, Jian-Hua Liu
{"title":"Emergence of mcr-8.1 gene coexisting with blaNDM in Citrobacter werkmanii isolated from a chicken farm in China.","authors":"Ying Huang, Zhongpeng Cai, Luchao Lv, Chao Yue, Jian-Hua Liu","doi":"10.1093/jac/dkae223","DOIUrl":"10.1093/jac/dkae223","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727281","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}
Fátima Aguilar-Del-Castillo, Miriam Álvarez-Aguilera, José Tinoco-González, Iván Vaca, Laura Herrera-Hidalgo, María Paniagua, José Miguel Cisneros, Francisco Javier Padillo-Ruiz, Rosa M Jiménez-Rodríguez
Background: The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital.
Methods: A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed.
Results: A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption.
Conclusions: The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years.
{"title":"Influence of the COVID-19 pandemic on the defined daily dose of antimicrobials in patients requiring elective and emergency surgical procedures.","authors":"Fátima Aguilar-Del-Castillo, Miriam Álvarez-Aguilera, José Tinoco-González, Iván Vaca, Laura Herrera-Hidalgo, María Paniagua, José Miguel Cisneros, Francisco Javier Padillo-Ruiz, Rosa M Jiménez-Rodríguez","doi":"10.1093/jac/dkae222","DOIUrl":"10.1093/jac/dkae222","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital.</p><p><strong>Methods: </strong>A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed.</p><p><strong>Results: </strong>A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption.</p><p><strong>Conclusions: </strong>The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579737","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}
Yasmeen Abouelhassan, David P Nicolau, Kamilia Abdelraouf
Objectives: We evaluated the efficacies of human-simulated regimens (HSRs) of two clinically utilized sulbactam regimens: 1 g q6h 0.5 h infusion (maximum FDA-approved dosage) and 3 g q8h 4 h infusion (high-dose, prolonged-infusion regimen), against Acinetobacter baumannii in a translational murine model.
Methods: Thirty-two clinical A. baumannii isolates were investigated, of which 16 were sulbactam resistant (MIC ≥ 16 mg/L), 6 were sulbactam intermediate (MIC = 8 mg/L) and 10 were sulbactam susceptible (MIC ≤ 4 mg/L). Efficacies of the two sulbactam HSRs were assessed in the neutropenic murine pneumonia model. Changes in log10 cfu/lungs at 24 h compared with 0 h controls were measured, and efficacy was defined as achieving 1 log kill relative to baseline. WGS of the isolates and bioinformatics analysis were performed to explore potential associations between the genomic backgrounds and the in vivo responses.
Results: Eleven isolates harboured blaOXA-23, of which 10 were sulbactam resistant, 1 was sulbactam intermediate while none was sulbactam susceptible. Both sulbactam HSRs achieved >1 log kill against sulbactam-susceptible isolates. Against sulbactam-intermediate and sulbactam-resistant isolates, lack of efficacy correlated with the presence of the blaOXA-23 gene; sulbactam 1 g HSR and 3 g HSR did not show efficacy against 11/11 and 9/11 blaOXA-23-positive isolates, respectively, while efficacy was observed against all 11 blaOXA-23-negative sulbactam-intermediate and sulbactam-resistant isolates (i.e. harbouring other resistance genes).
Conclusions: A sulbactam high-dose prolonged-infusion regimen provides comparable activity to the standard dose against isolates currently considered sulbactam susceptible. However, the activity against isolates with intermediate and resistant susceptibility could be predicted by the detection of blaOXA-23. Enhancing detection capabilities of common diagnostic modalities to include OXA-23 can improve patient outcome.
{"title":"Defining optimal sulbactam regimens for treatment of Acinetobacter baumannii pneumonia and impact of blaOXA-23 on efficacy.","authors":"Yasmeen Abouelhassan, David P Nicolau, Kamilia Abdelraouf","doi":"10.1093/jac/dkae229","DOIUrl":"10.1093/jac/dkae229","url":null,"abstract":"<p><strong>Objectives: </strong>We evaluated the efficacies of human-simulated regimens (HSRs) of two clinically utilized sulbactam regimens: 1 g q6h 0.5 h infusion (maximum FDA-approved dosage) and 3 g q8h 4 h infusion (high-dose, prolonged-infusion regimen), against Acinetobacter baumannii in a translational murine model.</p><p><strong>Methods: </strong>Thirty-two clinical A. baumannii isolates were investigated, of which 16 were sulbactam resistant (MIC ≥ 16 mg/L), 6 were sulbactam intermediate (MIC = 8 mg/L) and 10 were sulbactam susceptible (MIC ≤ 4 mg/L). Efficacies of the two sulbactam HSRs were assessed in the neutropenic murine pneumonia model. Changes in log10 cfu/lungs at 24 h compared with 0 h controls were measured, and efficacy was defined as achieving 1 log kill relative to baseline. WGS of the isolates and bioinformatics analysis were performed to explore potential associations between the genomic backgrounds and the in vivo responses.</p><p><strong>Results: </strong>Eleven isolates harboured blaOXA-23, of which 10 were sulbactam resistant, 1 was sulbactam intermediate while none was sulbactam susceptible. Both sulbactam HSRs achieved >1 log kill against sulbactam-susceptible isolates. Against sulbactam-intermediate and sulbactam-resistant isolates, lack of efficacy correlated with the presence of the blaOXA-23 gene; sulbactam 1 g HSR and 3 g HSR did not show efficacy against 11/11 and 9/11 blaOXA-23-positive isolates, respectively, while efficacy was observed against all 11 blaOXA-23-negative sulbactam-intermediate and sulbactam-resistant isolates (i.e. harbouring other resistance genes).</p><p><strong>Conclusions: </strong>A sulbactam high-dose prolonged-infusion regimen provides comparable activity to the standard dose against isolates currently considered sulbactam susceptible. However, the activity against isolates with intermediate and resistant susceptibility could be predicted by the detection of blaOXA-23. Enhancing detection capabilities of common diagnostic modalities to include OXA-23 can improve patient outcome.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141599915","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}
Federico Barone, Andrea Giacomelli, Giacomo Casalini, Mario Corbellino, Alessia Lai, Andrea Gori, Spinello Antinori
{"title":"Comment on: Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients.","authors":"Federico Barone, Andrea Giacomelli, Giacomo Casalini, Mario Corbellino, Alessia Lai, Andrea Gori, Spinello Antinori","doi":"10.1093/jac/dkae234","DOIUrl":"10.1093/jac/dkae234","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788091","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}
Hongyu Zhou, Niccolò Buetti, Salvador Pérez-Galera, Jose Bravo-Ferrer, Belén Gutiérrez-Gutiérrez, María Paniagua-García, Jan Feifel, Julien Sauser, Tomi Kostyanev, Rafael Canton, Lionel K Tan, Dimitris Basoulis, Vicente Pintado, Emmanuel Roilides, Gorana Dragovac, Julian Torre-Cisneros, Deana Mediç, Murat Akova, Herman Goossens, Marc Bonten, Stephan Harbarth, Jesus Rodriguez-Baño, Marlieke E A De Kraker
Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients).
Methods: A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied.
Results: From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment.
Conclusions: Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.
{"title":"Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.","authors":"Hongyu Zhou, Niccolò Buetti, Salvador Pérez-Galera, Jose Bravo-Ferrer, Belén Gutiérrez-Gutiérrez, María Paniagua-García, Jan Feifel, Julien Sauser, Tomi Kostyanev, Rafael Canton, Lionel K Tan, Dimitris Basoulis, Vicente Pintado, Emmanuel Roilides, Gorana Dragovac, Julian Torre-Cisneros, Deana Mediç, Murat Akova, Herman Goossens, Marc Bonten, Stephan Harbarth, Jesus Rodriguez-Baño, Marlieke E A De Kraker","doi":"10.1093/jac/dkae157","DOIUrl":"10.1093/jac/dkae157","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients).</p><p><strong>Methods: </strong>A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied.</p><p><strong>Results: </strong>From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65-32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01-1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51-34.24; acute care hospital: IRR 5.26; 95% CI 1.61-17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33-40.56), haemodialysis (IRR 8.59; 95% CI 1.82-40.53), invasive procedures (IRR 5.66; 95% CI 2.11-15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68-9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06-7.11) exposure within 3 months before enrolment.</p><p><strong>Conclusions: </strong>Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yonatan M Mesfin, Joseph E Blais, Kelemu Tilahun Kibret, Teketo Kassaw Tegegne, Benjamin J Cowling, Peng Wu
Objective: To determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated and unvaccinated non-hospitalized adults with COVID-19.
Methods: Observational studies of nirmatrelvir/ritonavir or molnupiravir compared to no antiviral drug treatment for COVID-19 in non-hospitalized adults with data on vaccination status were included. We searched MEDLINE, EMBASE, Scopus, Web of Science, WHO COVID-19 Research Database and medRxiv for reports published between 1 January 2022 and 8 November 2023. The primary outcome was a composite of hospitalization or mortality up to 35 days after COVID-19 diagnosis. Risk of bias was assessed with ROBINS-I. Risk ratios (RR), hazard ratios (HR) and risk differences (RD) were separately estimated using random-effects models.
Results: We included 30 cohort studies on adults treated with nirmatrelvir/ritonavir (n = 462 279) and molnupiravir (n = 48 008). Nirmatrelvir/ritonavir probably reduced the composite outcome (RR 0.62, 95%CI 0.55-0.70; I2 = 0%; moderate certainty) with no evidence of effect modification by vaccination status (RR Psubgroup = 0.47). In five studies, RD estimates against the composite outcome for nirmatrelvir/ritonavir were 1.21% (95%CI 0.57% to 1.84%) in vaccinated and 1.72% (95%CI 0.59% to 2.85%) in unvaccinated subgroups.Molnupiravir may slightly reduce the composite outcome (RR 0.75, 95%CI 0.67-0.85; I2 = 32%; low certainty). Evidence of effect modification by vaccination status was inconsistent among studies reporting different effect measures (RR Psubgroup = 0.78; HR Psubgroup = 0.08). In two studies, RD against the composite outcome for molnupiravir were -0.01% (95%CI -1.13% to 1.10%) in vaccinated and 1.73% (95%CI -2.08% to 5.53%) in unvaccinated subgroups.
Conclusions: Among cohort studies of non-hospitalized adults with COVID-19, nirmatrelvir/ritonavir is effective against the composite outcome of severe COVID-19 independent of vaccination status. Further research and a reassessment of molnupiravir use among vaccinated adults are warranted.
{"title":"Effectiveness of nirmatrelvir/ritonavir and molnupiravir in non-hospitalized adults with COVID-19: systematic review and meta-analysis of observational studies.","authors":"Yonatan M Mesfin, Joseph E Blais, Kelemu Tilahun Kibret, Teketo Kassaw Tegegne, Benjamin J Cowling, Peng Wu","doi":"10.1093/jac/dkae163","DOIUrl":"10.1093/jac/dkae163","url":null,"abstract":"<p><strong>Objective: </strong>To determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated and unvaccinated non-hospitalized adults with COVID-19.</p><p><strong>Methods: </strong>Observational studies of nirmatrelvir/ritonavir or molnupiravir compared to no antiviral drug treatment for COVID-19 in non-hospitalized adults with data on vaccination status were included. We searched MEDLINE, EMBASE, Scopus, Web of Science, WHO COVID-19 Research Database and medRxiv for reports published between 1 January 2022 and 8 November 2023. The primary outcome was a composite of hospitalization or mortality up to 35 days after COVID-19 diagnosis. Risk of bias was assessed with ROBINS-I. Risk ratios (RR), hazard ratios (HR) and risk differences (RD) were separately estimated using random-effects models.</p><p><strong>Results: </strong>We included 30 cohort studies on adults treated with nirmatrelvir/ritonavir (n = 462 279) and molnupiravir (n = 48 008). Nirmatrelvir/ritonavir probably reduced the composite outcome (RR 0.62, 95%CI 0.55-0.70; I2 = 0%; moderate certainty) with no evidence of effect modification by vaccination status (RR Psubgroup = 0.47). In five studies, RD estimates against the composite outcome for nirmatrelvir/ritonavir were 1.21% (95%CI 0.57% to 1.84%) in vaccinated and 1.72% (95%CI 0.59% to 2.85%) in unvaccinated subgroups.Molnupiravir may slightly reduce the composite outcome (RR 0.75, 95%CI 0.67-0.85; I2 = 32%; low certainty). Evidence of effect modification by vaccination status was inconsistent among studies reporting different effect measures (RR Psubgroup = 0.78; HR Psubgroup = 0.08). In two studies, RD against the composite outcome for molnupiravir were -0.01% (95%CI -1.13% to 1.10%) in vaccinated and 1.73% (95%CI -2.08% to 5.53%) in unvaccinated subgroups.</p><p><strong>Conclusions: </strong>Among cohort studies of non-hospitalized adults with COVID-19, nirmatrelvir/ritonavir is effective against the composite outcome of severe COVID-19 independent of vaccination status. Further research and a reassessment of molnupiravir use among vaccinated adults are warranted.</p><p><strong>Registration: </strong>PROSPERO CRD42023429232.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zenaw T Wolie, Jason A Roberts, Mark Gilchrist, Kate McCarthy, Fekade B Sime
Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.
为控制感染而延长住院时间会增加住院治疗成本和发生与医疗相关的不良事件(包括感染)的风险。全球对医疗保健的需求不断增长,医院床位越来越少,病人越来越倾向于在自己家中接受治疗,这些都是扩大住院治疗计划的主要推动力。这些计划包括在门诊环境中使用静脉注射抗菌药物,即门诊肠外抗菌疗法(OPAT)。然而,全球各地的 OPAT 实践各不相同。这篇综述文章旨在介绍目前世界各地的 OPAT 实践和挑战。OPAT 实践首先是根据资格标准对患者进行评估和选择,这需要跨学科 OPAT 团队、患者和护理人员之间的合作。根据护理要求,符合条件的患者可加入各种护理模式,由专业医护人员在门诊输液中心、医院诊所、家访或通过自我给药的方式接受药物治疗。OPAT 可用于治疗许多缺乏有效口服治疗选择的感染。在全球 OPAT 实践中使用的肠外抗菌药种类繁多,包括 β-内酰胺类、氨基糖苷类、糖肽类、氟喹诺酮类和棘白菌素类等抗真菌药。尽管 OPAT 有很多优点,但它也面临着许多挑战,包括给药装置引起的并发症、抗菌药物副作用、监测要求、抗菌药物不稳定、患者不依从、患者对 OPAT 排斥以及与 OPAT 团队结构和管理相关的挑战,所有这些都会影响其结果。负面结果可能包括计划外的再次入院。未来的研究应侧重于减轻这些挑战,以优化 OPAT 服务,从而最大限度地提高医疗系统、患者和医疗服务提供者的文件效益。
{"title":"Current practices and challenges of outpatient parenteral antimicrobial therapy: a narrative review.","authors":"Zenaw T Wolie, Jason A Roberts, Mark Gilchrist, Kate McCarthy, Fekade B Sime","doi":"10.1093/jac/dkae177","DOIUrl":"10.1093/jac/dkae177","url":null,"abstract":"<p><p>Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jongwook Park, Dongju Lee, Hyojeong Yi, Cheol-Won Yun, Heenam Stanley Kim
Objectives: Bacterial persistence is a significant cause of the intractability of chronic and relapsing infections. Despite its importance, many of the underlying mechanisms are still not well understood.
Methods: Antibiotic-tolerant mutants of Burkholderia thailandensis were isolated through exposure to lethal doses of AMP or MEM, followed by whole-genome sequencing to identify mutations. Subsequently, these mutants underwent comprehensive characterization via killing curves, growth curves, and persistence-fraction plots. Northern blot analysis was employed to detect uncharged tRNA, while the generation of relA and spoT null mutations served to confirm the involvement of the stringent response in this persistence mechanism. Phenotypic reversion of the persistence mutation was demonstrated by incubating the mutants without antibiotics for 2 weeks.
Results: We have discovered a novel mechanism of persistence triggered by specific mutations at positions 32 or 38 within the anticodon loop of tRNAAsp. This leads to heightened persistence through a RelA-dependent stringent response. Notably, this persistence can be easily reverted to wild-type physiology by losing the mutant tRNA allele within the tRNA gene cluster when persistence is no longer essential for survival.
Conclusions: This distinct form of persistence underscores the novel function of tRNA mutations at positions 32 or 38 within the anticodon loop, as well as the significance of the tRNA gene cluster in conferring adaptability to regulate persistence for enhanced survival.
{"title":"Bacterial persistence to antibiotics activated by tRNA mutations.","authors":"Jongwook Park, Dongju Lee, Hyojeong Yi, Cheol-Won Yun, Heenam Stanley Kim","doi":"10.1093/jac/dkae307","DOIUrl":"https://doi.org/10.1093/jac/dkae307","url":null,"abstract":"<p><strong>Objectives: </strong>Bacterial persistence is a significant cause of the intractability of chronic and relapsing infections. Despite its importance, many of the underlying mechanisms are still not well understood.</p><p><strong>Methods: </strong>Antibiotic-tolerant mutants of Burkholderia thailandensis were isolated through exposure to lethal doses of AMP or MEM, followed by whole-genome sequencing to identify mutations. Subsequently, these mutants underwent comprehensive characterization via killing curves, growth curves, and persistence-fraction plots. Northern blot analysis was employed to detect uncharged tRNA, while the generation of relA and spoT null mutations served to confirm the involvement of the stringent response in this persistence mechanism. Phenotypic reversion of the persistence mutation was demonstrated by incubating the mutants without antibiotics for 2 weeks.</p><p><strong>Results: </strong>We have discovered a novel mechanism of persistence triggered by specific mutations at positions 32 or 38 within the anticodon loop of tRNAAsp. This leads to heightened persistence through a RelA-dependent stringent response. Notably, this persistence can be easily reverted to wild-type physiology by losing the mutant tRNA allele within the tRNA gene cluster when persistence is no longer essential for survival.</p><p><strong>Conclusions: </strong>This distinct form of persistence underscores the novel function of tRNA mutations at positions 32 or 38 within the anticodon loop, as well as the significance of the tRNA gene cluster in conferring adaptability to regulate persistence for enhanced survival.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119862","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}