Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104669
Daniela Anderson da Silva, Gabriel Berg de Almeida, Bruno Cardoso de Macedo, Ana Luiza Borges de Sá Sforcin, Adriana Vieira de Souza, Gabriela Nagem de Aragão, Douglas Otomo Duarte, Jonas Atique Sawazaki
Introduction/Objectives
Infections caused by multidrug-resistant Gram-negative bacilli represent a growing challenge in hospitals, often associated with high mortality rates and the use of antimicrobials with significant toxicity. Ceftazidime-avibactam is a potent and less toxic alternative, particularly in infections caused by carbapenemase-producing Enterobacterales. This study aimed to identify factors associated with 30-day mortality among patients treated with ceftazidime-avibactam in a public university hospital.
Methods
A retrospective cohort study included adult inpatients between 2022 and 2024 with documented infection by carbapenem-resistant Gram-negative bacilli, treated with intravenous ceftazidime-avibactam for at least 48 hours. Patients with incomplete data were excluded. Variables included demographics, Charlson comorbidity score, NEWS-2 severity score, etiologic agent, infection type, clinical justification, treatment duration, and 30-day mortality. Multivariate logistic regression with backward stepwise selection was used.
Results
The cohort included 277 patients, median age 60 years (IQR 48–69), predominantly male (63%). Thirty-day mortality was 30.5%. Independent predictors of death were male sex (OR 2.15; 95%CI: 1.13–4.20), higher Charlson comorbidity score (OR 1.20; 95%CI: 1.06–1.38), and higher NEWS-2 score (OR 1.32; 95%CI: 1.21–1.45). The final model showed good discrimination (AUC = 0.81).
Conclusion
Thirty-day mortality among patients treated with ceftazidime-avibactam was high, reflecting case severity. Male sex, higher comorbidity burden, and greater admission severity were independent predictors of poorer outcomes. These findings underscore the importance of integrated clinical assessment and the therapeutic potential of ceftazidime-avibactam in managing severe infections caused by multidrug-resistant Gram-negative bacilli.
{"title":"PREDICTORS OF 30-DAY MORTALITY AFTER CEFTAZIDIME-AVIBACTAM TREATMENT IN A HIGH-COMPLEXITY UNIVERSITY HOSPITAL","authors":"Daniela Anderson da Silva, Gabriel Berg de Almeida, Bruno Cardoso de Macedo, Ana Luiza Borges de Sá Sforcin, Adriana Vieira de Souza, Gabriela Nagem de Aragão, Douglas Otomo Duarte, Jonas Atique Sawazaki","doi":"10.1016/j.bjid.2026.104669","DOIUrl":"10.1016/j.bjid.2026.104669","url":null,"abstract":"<div><h3>Introduction/Objectives</h3><div>Infections caused by multidrug-resistant Gram-negative bacilli represent a growing challenge in hospitals, often associated with high mortality rates and the use of antimicrobials with significant toxicity. Ceftazidime-avibactam is a potent and less toxic alternative, particularly in infections caused by carbapenemase-producing Enterobacterales. This study aimed to identify factors associated with 30-day mortality among patients treated with ceftazidime-avibactam in a public university hospital.</div></div><div><h3>Methods</h3><div>A retrospective cohort study included adult inpatients between 2022 and 2024 with documented infection by carbapenem-resistant Gram-negative bacilli, treated with intravenous ceftazidime-avibactam for at least 48 hours. Patients with incomplete data were excluded. Variables included demographics, Charlson comorbidity score, NEWS-2 severity score, etiologic agent, infection type, clinical justification, treatment duration, and 30-day mortality. Multivariate logistic regression with backward stepwise selection was used.</div></div><div><h3>Results</h3><div>The cohort included 277 patients, median age 60 years (IQR 48–69), predominantly male (63%). Thirty-day mortality was 30.5%. Independent predictors of death were male sex (OR 2.15; 95%CI: 1.13–4.20), higher Charlson comorbidity score (OR 1.20; 95%CI: 1.06–1.38), and higher NEWS-2 score (OR 1.32; 95%CI: 1.21–1.45). The final model showed good discrimination (AUC = 0.81).</div></div><div><h3>Conclusion</h3><div>Thirty-day mortality among patients treated with ceftazidime-avibactam was high, reflecting case severity. Male sex, higher comorbidity burden, and greater admission severity were independent predictors of poorer outcomes. These findings underscore the importance of integrated clinical assessment and the therapeutic potential of ceftazidime-avibactam in managing severe infections caused by multidrug-resistant Gram-negative bacilli.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104669"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104677
Tatianne dos Santos , Luciano Henrique Pinto , Priscila Gabriella Cararo Merlos , Fernando Merlos
Introduction/Objective
Inappropriate antimicrobial (ATM) use in hospitals represents a growing public health threat due to the rise of multidrug-resistant microorganisms. Antimicrobial Stewardship Programs (ASP) are essential to optimize prescriptions and mitigate negative impacts. This study evaluated the impact of the ASP implemented in the emergency department of a public hospital in Northern Santa Catarina between June 1 and November 30, 2023, emphasizing changes in prescribing patterns, particularly of broad-spectrum antimicrobials, according to WHO (2014) and ANVISA (2020) guidelines.
Methods
Retrospective observational study with a non-probabilistic sample including all cases within the study period. Hospitalized emergency patients who received ATM prescriptions during the 90 days before and after ASP implementation (September 1, 2023) were analyzed. Patients of both sexes, regardless of age or diagnosis, were included. Topical antimicrobials, antiparasitics, and antifungals were excluded. ASP-selected ATM (cefepime, ertapenem, imipenem/cilastatin, meropenem, piperacillin/tazobactam, teicoplanin, and vancomycin) were analyzed separately. Data were obtained from electronic medical records and administrative databases. Variables such as number of hospitalizations, ATM prescriptions, eligible antimicrobials, diagnoses, and clinical outcomes were evaluated. Statistical analysis was performed using Excel with descriptive and comparative tests, adopting a significance level of α = 0.05.
Results
Pearson’s chi-square test was applied to compare pre- and post-ASP periods. Total antimicrobial prescriptions: 739/674 (p = 0.7605); ASP-included antimicrobials: 179/134 (p = 0.0627). Piperacillin/tazobactam prescriptions decreased from 138 to 102 (p = 0.0886) and further to 85 after program adjustments (p = 0.003), showing a statistically significant reduction. Total hospitalizations were 3,139 in the pre-implementation period and 2,908 afterward.
Conclusion
Although not all reductions reached statistical significance, a positive impact of the ASP was observed, particularly among broad-spectrum antimicrobials. Implementation of the ASP contributed to the rational use of antimicrobials and to combating microbial resistance, proving to be an effective and replicable intervention consistent with national and international guidelines.
{"title":"IMPACT OF AN ANTIMICROBIAL STEWARDSHIP PROGRAM (ASP) IN A HOSPITAL EMERGENCY DEPARTMENT IN NORTHERN SANTA CATARINA: A RETROSPECTIVE OBSERVATIONAL STUDY","authors":"Tatianne dos Santos , Luciano Henrique Pinto , Priscila Gabriella Cararo Merlos , Fernando Merlos","doi":"10.1016/j.bjid.2026.104677","DOIUrl":"10.1016/j.bjid.2026.104677","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>Inappropriate antimicrobial (ATM) use in hospitals represents a growing public health threat due to the rise of multidrug-resistant microorganisms. Antimicrobial Stewardship Programs (ASP) are essential to optimize prescriptions and mitigate negative impacts. This study evaluated the impact of the ASP implemented in the emergency department of a public hospital in Northern Santa Catarina between June 1 and November 30, 2023, emphasizing changes in prescribing patterns, particularly of broad-spectrum antimicrobials, according to WHO (2014) and ANVISA (2020) guidelines.</div></div><div><h3>Methods</h3><div>Retrospective observational study with a non-probabilistic sample including all cases within the study period. Hospitalized emergency patients who received ATM prescriptions during the 90 days before and after ASP implementation (September 1, 2023) were analyzed. Patients of both sexes, regardless of age or diagnosis, were included. Topical antimicrobials, antiparasitics, and antifungals were excluded. ASP-selected ATM (cefepime, ertapenem, imipenem/cilastatin, meropenem, piperacillin/tazobactam, teicoplanin, and vancomycin) were analyzed separately. Data were obtained from electronic medical records and administrative databases. Variables such as number of hospitalizations, ATM prescriptions, eligible antimicrobials, diagnoses, and clinical outcomes were evaluated. Statistical analysis was performed using Excel with descriptive and comparative tests, adopting a significance level of α = 0.05.</div></div><div><h3>Results</h3><div>Pearson’s chi-square test was applied to compare pre- and post-ASP periods. Total antimicrobial prescriptions: 739/674 (p = 0.7605); ASP-included antimicrobials: 179/134 (p = 0.0627). Piperacillin/tazobactam prescriptions decreased from 138 to 102 (p = 0.0886) and further to 85 after program adjustments (p = 0.003), showing a statistically significant reduction. Total hospitalizations were 3,139 in the pre-implementation period and 2,908 afterward.</div></div><div><h3>Conclusion</h3><div>Although not all reductions reached statistical significance, a positive impact of the ASP was observed, particularly among broad-spectrum antimicrobials. Implementation of the ASP contributed to the rational use of antimicrobials and to combating microbial resistance, proving to be an effective and replicable intervention consistent with national and international guidelines.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104677"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104661
Bianca Azeredo Mello, Ana Carolina Carvalho de Oliveira, Nicolle Félix Lima Ramos, Ivano Raffaele Victorio de Filippis Capasso
Introduction/Objective
AmpC β-lactamase confers resistance to several antibiotics, including penicillins, second- and third-generation cephalosporins, and monobactams, but does not hydrolyze cefepime or carbapenems. Its origin may be chromosomal, inducible in some species after cephalosporin exposure, or plasmid-mediated (pAmpC), characterized by constitutive and abundant expression in different bacteria. This study aimed to develop specific primers for pAmpC gene identification using qPCR-HRM, a technique that combines the sensitivity of qPCR with High-Resolution Melting analysis, enabling differentiation of resistance genes based on melting temperature (Tm), including the detection of mutant variants.
Methods
A total of 148 clinical Enterobacteriaceae isolates from hospitals and clinics in Rio de Janeiro (2021–2024) were analyzed. Bacterial identification was performed using VITEK-2 and MALDI-TOF. Antimicrobial susceptibility was determined by VITEK-2 and disk diffusion according to BRCAST (2024). Forty-six β-lactam-resistant isolates were screened for pAmpC genes using conventional PCR, followed by sequencing and analysis in PubMLST and Institut Pasteur MLST databases.
Results
Three pAmpC-producing strains were confirmed: two Escherichia coli and one Klebsiella pneumoniae, carrying CMY-44, CMY-69, and ACT-5 genes, respectively. These variants had not been previously reported in Brazil. qPCR-HRM showed Tm values of 82.0°C (± 0.5) for CMY in Salmonella enterica, 84.0°C (± 0.5) in E. coli, and 86.0°C (± 0.5) for ACT in K. pneumoniae, allowing clear distinction between CIT and EBC targets.
Conclusion
qPCR-HRM proved to be a rapid (2 h), sensitive, specific, cost-effective, and efficient tool for detecting and differentiating pAmpC genes, even in the presence of mutations. The observed prevalence was 6.52% among β-lactam-resistant strains. These findings underscore the importance of broader surveillance studies to monitor pAmpC epidemiology in Brazil.
{"title":"DETECTION OF AMPC BLACMY AND BLAACT VARIANTS USING QPCR-HRM IN ENTEROBACTERIACEAE","authors":"Bianca Azeredo Mello, Ana Carolina Carvalho de Oliveira, Nicolle Félix Lima Ramos, Ivano Raffaele Victorio de Filippis Capasso","doi":"10.1016/j.bjid.2026.104661","DOIUrl":"10.1016/j.bjid.2026.104661","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>AmpC β-lactamase confers resistance to several antibiotics, including penicillins, second- and third-generation cephalosporins, and monobactams, but does not hydrolyze cefepime or carbapenems. Its origin may be chromosomal, inducible in some species after cephalosporin exposure, or plasmid-mediated (pAmpC), characterized by constitutive and abundant expression in different bacteria. This study aimed to develop specific primers for pAmpC gene identification using qPCR-HRM, a technique that combines the sensitivity of qPCR with High-Resolution Melting analysis, enabling differentiation of resistance genes based on melting temperature (Tm), including the detection of mutant variants.</div></div><div><h3>Methods</h3><div>A total of 148 clinical <em>Enterobacteriaceae</em> isolates from hospitals and clinics in Rio de Janeiro (2021–2024) were analyzed. Bacterial identification was performed using VITEK-2 and MALDI-TOF. Antimicrobial susceptibility was determined by VITEK-2 and disk diffusion according to BRCAST (2024). Forty-six β-lactam-resistant isolates were screened for pAmpC genes using conventional PCR, followed by sequencing and analysis in PubMLST and Institut Pasteur MLST databases.</div></div><div><h3>Results</h3><div>Three pAmpC-producing strains were confirmed: two <em>Escherichia coli</em> and one <em>Klebsiella pneumoniae</em>, carrying CMY-44, CMY-69, and ACT-5 genes, respectively. These variants had not been previously reported in Brazil. qPCR-HRM showed Tm values of 82.0°C (± 0.5) for CMY in <em>Salmonella enterica</em>, 84.0°C (± 0.5) in <em>E. coli</em>, and 86.0°C (± 0.5) for ACT in <em>K. pneumoniae</em>, allowing clear distinction between CIT and EBC targets.</div></div><div><h3>Conclusion</h3><div>qPCR-HRM proved to be a rapid (2 h), sensitive, specific, cost-effective, and efficient tool for detecting and differentiating pAmpC genes, even in the presence of mutations. The observed prevalence was 6.52% among β-lactam-resistant strains. These findings underscore the importance of broader surveillance studies to monitor pAmpC epidemiology in Brazil.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104661"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ceftazidime-avibactam (CAZAVI) has been the therapy of choice for class A carbapenemase-producing Klebsiella pneumoniae (KPCP), and, combined with aztreonam (ATM), for class B KPCP or co-producers (A+B). Our objective was to compare 30-day mortality in patients treated with regimens containing CAZAVI ± ATM versus other regimens, in a Brazilian hospital that recommends CAZAVI±ATM as first-line therapy for KPCP.
Methods
Retrospective cohort study. Eligible were adult patients who had ≥1 blood culture with KPCP, collected > 2 days after hospital admission between Jan/14 and Dec/24 and who received ≥ 2 days of adequate therapy (≥ 1 in vitro active antimicrobial). Two univariate analyses were performed comparing 1) CAZAVI±ATM group vs other treatments, and 2) deaths vs survival at 30 days. A Cox regression model for the primary outcome was performed including, one by one, all independent variables with P ≤ 0.20 in the univariate analyses.
Results
Excluding 79 duplicates, 172 patients were eligible, of whom 43 were excluded for absence of treatment/death ≤ 2 days, resulting in 129 analyzed: mean age = 68 ± 19 years, 73 (57%) male, and 61 (47%) were in ICU. The most common primary sites were CVC (31%), respiratory (23%), and urinary (22%). Class A, B, and A+B KPCP corresponded to 82%, 9%, and 9%, respectively. A total of 73 (57%) patients received CAZAVI±ATM (58 CAZAVI only) and 56 (43%) other treatments (79% with regimens containing polymyxins). Covariates were quite similar between the two groups. Selected for the model were: time to therapy initiation (P < 0.001), BMI (P = 0.17), baseline eGFR (P = 0.05), and high-risk primary site (P = 0.03). Mortality was 31% (n = 40): 23.3% (17/73) in the CAZAVI±ATM group and 41.1% (23/56) in the other treatments group (P = 0.05). Variables associated with death included in the model were age (P = 0.09), Pitt score (P = 0.01), mechanical ventilation (P = 0.09), high-risk site (P = 0.03), and baseline eGFR (P = 0.05). In the final model adjusted for high-risk site (P = 0.02) and age (P = 0.09), treatment with CAZAVI±ATM was independently associated with a lower risk of 30-day death (hazard ratio 0.47; 95% CI 0.25–0.89, P = 0.02).
Conclusion
CAZAVI±ATM was associated with lower 30-day mortality in patients with bloodstream infection due to KPCP who had quite similar baseline characteristics.
{"title":"CEFTAZIDIME-AVIBACTAM WITH OR WITHOUT AZTREONAM VERSUS OTHER ANTIMICROBIALS IN THE TREATMENT OF BLOODSTREAM INFECTIONS CAUSED BY CARBAPENEMASE-PRODUCING KLEBSIELLA PNEUMONIAE","authors":"Rodrigo Chiavaro da Fonseca , Adriana Schmidt , Emerson dos Santos Hoffmann , Nadiana Inocente , Amanda de Farias Balbinot , Jaysa Pizzi , Erik Menezes Martins , Renata Dortzbacher Feil Klafke , Luiza Martinez Perez , Letícia Camargo Marinho , Guilherme Geraldo Lovato Sório , Beatriz Arns , Alexandre Prehn Zavascki","doi":"10.1016/j.bjid.2026.104652","DOIUrl":"10.1016/j.bjid.2026.104652","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>Ceftazidime-avibactam (CAZAVI) has been the therapy of choice for class A carbapenemase-producing <em>Klebsiella pneumoniae</em> (KPCP), and, combined with aztreonam (ATM), for class B KPCP or co-producers (A+B). Our objective was to compare 30-day mortality in patients treated with regimens containing CAZAVI ± ATM versus other regimens, in a Brazilian hospital that recommends CAZAVI±ATM as first-line therapy for KPCP.</div></div><div><h3>Methods</h3><div>Retrospective cohort study. Eligible were adult patients who had ≥1 blood culture with KPCP, collected > 2 days after hospital admission between Jan/14 and Dec/24 and who received ≥ 2 days of adequate therapy (≥ 1 <em>in vitro</em> active antimicrobial). Two univariate analyses were performed comparing 1) CAZAVI±ATM group vs other treatments, and 2) deaths vs survival at 30 days. A Cox regression model for the primary outcome was performed including, one by one, all independent variables with P ≤ 0.20 in the univariate analyses.</div></div><div><h3>Results</h3><div>Excluding 79 duplicates, 172 patients were eligible, of whom 43 were excluded for absence of treatment/death ≤ 2 days, resulting in 129 analyzed: mean age = 68 ± 19 years, 73 (57%) male, and 61 (47%) were in ICU. The most common primary sites were CVC (31%), respiratory (23%), and urinary (22%). Class A, B, and A+B KPCP corresponded to 82%, 9%, and 9%, respectively. A total of 73 (57%) patients received CAZAVI±ATM (58 CAZAVI only) and 56 (43%) other treatments (79% with regimens containing polymyxins). Covariates were quite similar between the two groups. Selected for the model were: time to therapy initiation (P < 0.001), BMI (P = 0.17), baseline eGFR (P = 0.05), and high-risk primary site (P = 0.03). Mortality was 31% (n = 40): 23.3% (17/73) in the CAZAVI±ATM group and 41.1% (23/56) in the other treatments group (P = 0.05). Variables associated with death included in the model were age (P = 0.09), Pitt score (P = 0.01), mechanical ventilation (P = 0.09), high-risk site (P = 0.03), and baseline eGFR (P = 0.05). In the final model adjusted for high-risk site (P = 0.02) and age (P = 0.09), treatment with CAZAVI±ATM was independently associated with a lower risk of 30-day death (hazard ratio 0.47; 95% CI 0.25–0.89, P = 0.02).</div></div><div><h3>Conclusion</h3><div>CAZAVI±ATM was associated with lower 30-day mortality in patients with bloodstream infection due to KPCP who had quite similar baseline characteristics.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104652"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Since the aztreonam/avibactam combination has not yet been approved for use in Brazil, the treatment of infections caused by Enterobacterales producing New Delhi metallo-beta-lactamase (NDM), either alone or in co-production with the serine-carbapenemase Klebsiella pneumoniae carbapenemase (KPC), is empirically performed using ceftazidime/avibactam (CZA) combined with aztreonam (ATM). The objective of this study was to compare the performance of an innovative method (IM) with the gold standard method for the in vitro detection of synergism between ATM and CZA in Enterobacterales producing NDM or NDM and KPC.
Methods
Sixty Enterobacterales isolates producing NDM or NDM and KPC were selected from a bacterial isolate bank with reduced susceptibility to meropenem. Half were NDM producers only, and the other half were coproducers of NDM and KPC. The type of carbapenemase was determined by high-resolution melting PCR (HRM-qPCR) and/or NG-Test® Carba 5 (NG Biotech®, France). For isolates producing NDM as the only carbapenemase, a phenotypic test for Extended-Spectrum Beta-Lactamase (ESBL) was performed, which was positive in 17 isolates. Synergism between CZA and ATM was detected by broth microdilution (gold standard), defined as a reduction of at least two concentrations compared to each agent tested alone. The IM consists of inoculating a solid culture medium with the bacterial suspension, followed by placing a CZA disk and adding 10 µL of ATM solution onto it. A synergistic effect is observed when the inhibition zone increases by more than 5 mm compared with each disk tested alone.
Results
Synergism between CZA and ATM was detected by both methods in all coproducing NDM and KPC isolates and in NDM producers that also produced ESBL (78%). Among the isolates producing only NDM, seven showed synergism, four did not, and two could not be evaluated due to limitations of the gold standard method. The IM detected synergism in only one isolate producing NDM alone; the others could not be evaluated due to technical limitations.
Conclusion
The IM showed 100% concordance with the gold standard method, demonstrating its feasibility for incorporation into routine laboratory practice, offering lower cost and easier execution.
{"title":"COMPARISON BETWEEN BROTH MICRODILUTION AND AN INNOVATIVE DISK DIFFUSION METHOD SUPPLEMENTED WITH AZTREONAM SOLUTION FOR DETECTING SYNERGISM WITH CEFTAZIDIME/AVIBACTAM IN ENTEROBACTERALES PRODUCING NDM OR NDM AND KPC","authors":"Lívia Medeiros , Larissa Lutz , Luana Silva Dornelles , Everton Inamine , Gabriela da Silva Collar , Natália Kehl Moreira , Rodrigo Minuto Paiva , Dariane Castro Pereira , Mariana Preussler Mott","doi":"10.1016/j.bjid.2026.104656","DOIUrl":"10.1016/j.bjid.2026.104656","url":null,"abstract":"<div><h3>Introduction/Objectives</h3><div>Since the aztreonam/avibactam combination has not yet been approved for use in Brazil, the treatment of infections caused by <em>Enterobacterales</em> producing New Delhi metallo-beta-lactamase (NDM), either alone or in co-production with the serine-carbapenemase <em>Klebsiella pneumoniae</em> carbapenemase (KPC), is empirically performed using ceftazidime/avibactam (CZA) combined with aztreonam (ATM). The objective of this study was to compare the performance of an innovative method (IM) with the gold standard method for the <em>in vitro</em> detection of synergism between ATM and CZA in <em>Enterobacterales</em> producing NDM or NDM and KPC.</div></div><div><h3>Methods</h3><div>Sixty <em>Enterobacterales</em> isolates producing NDM or NDM and KPC were selected from a bacterial isolate bank with reduced susceptibility to meropenem. Half were NDM producers only, and the other half were coproducers of NDM and KPC. The type of carbapenemase was determined by high-resolution melting PCR (HRM-qPCR) and/or NG-Test® Carba 5 (NG Biotech®, France). For isolates producing NDM as the only carbapenemase, a phenotypic test for Extended-Spectrum Beta-Lactamase (ESBL) was performed, which was positive in 17 isolates. Synergism between CZA and ATM was detected by broth microdilution (gold standard), defined as a reduction of at least two concentrations compared to each agent tested alone. The IM consists of inoculating a solid culture medium with the bacterial suspension, followed by placing a CZA disk and adding 10 µL of ATM solution onto it. A synergistic effect is observed when the inhibition zone increases by more than 5 mm compared with each disk tested alone.</div></div><div><h3>Results</h3><div>Synergism between CZA and ATM was detected by both methods in all coproducing NDM and KPC isolates and in NDM producers that also produced ESBL (78%). Among the isolates producing only NDM, seven showed synergism, four did not, and two could not be evaluated due to limitations of the gold standard method. The IM detected synergism in only one isolate producing NDM alone; the others could not be evaluated due to technical limitations.</div></div><div><h3>Conclusion</h3><div>The IM showed 100% concordance with the gold standard method, demonstrating its feasibility for incorporation into routine laboratory practice, offering lower cost and easier execution.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104656"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104658
Bianca Sestren, Stella Bispo, Beatriz Nayra Dias de Andrade, Stephanie Becker Carneiro, Laura de Almeida Lanzoni, Fabio de Araujo Motta, Marinei Campo Ricieri
Introduction
The increasing use of carbapenems has been associated with the emergence of multidrug-resistant microorganisms, particularly Enterobacterales producing carbapenemases. This highlights the urgency of implementing carbapenem-sparing strategies to preserve antimicrobial effectiveness.
Objective
To evaluate carbapenem consumption and usage profile in inpatient units following the progressive adoption of the carbapenem-sparing strategy implemented by the antimicrobial stewardship team in 2022.
Methods
A retrospective analysis was conducted in a pediatric hospital in southern Brazil (CAAE: 68382723.9.0000.5580), assessing meropenem consumption in non-critical clinical wards (15 total), which represent 71% of hospital beds. Consumption was measured using the indicator days of therapy (DOT/1,000 patient-days) between 2022 and 2025, with 2025 data extrapolated from January–June to the full year. Additionally, medical records of all patients receiving meropenem from January to June 2025 were reviewed to assess prescribing patterns.
Results
Regarding the 5-year historical series of DOT/1000 patient-days, the results were 562 (2021), 384 (2022), 428 (2023), 334 (2024), and 148 (2025). This demonstrates that the carbapenem-sparing actions, such as case monitoring and daily discussions by the antimicrobial stewardship team were effective, as there were significant reductions in therapy days of 30% (between 2021 and 2022), 22% (from 2023 to 2024), and 55% (estimated from 2024 to 2025). The exception was between 2022 and 2023, when an 11% increase in DOT was observed, which is considered an acceptable variation. Regarding the carbapenem use profile, data from 65 patients corresponded to 95 treatment courses, with a median age of 4.5 years. Empirical use accounted for 61% of cases, while 39% were guided. The ward with the highest indication for meropenem was Infectious Diseases (23% of patients). The mean treatment duration was 6 days, and the main infection sites were bloodstream (32%), urinary tract (21%), and pulmonary (19%).
Conclusion
This use profile indicates the presence of patients with some degree of clinical severity in the wards, but with an acceptable treatment duration. Furthermore, the progressive decrease in DOT over the years demonstrates the effectiveness of the carbapenem-sparing strategy.
{"title":"CARBAPENEM CONSUMPTION AND USE PROFILE IMPACTED BY A CARBAPENEM-SPARING STRATEGY","authors":"Bianca Sestren, Stella Bispo, Beatriz Nayra Dias de Andrade, Stephanie Becker Carneiro, Laura de Almeida Lanzoni, Fabio de Araujo Motta, Marinei Campo Ricieri","doi":"10.1016/j.bjid.2026.104658","DOIUrl":"10.1016/j.bjid.2026.104658","url":null,"abstract":"<div><h3>Introduction</h3><div>The increasing use of carbapenems has been associated with the emergence of multidrug-resistant microorganisms, particularly <em>Enterobacterales</em> producing carbapenemases. This highlights the urgency of implementing carbapenem-sparing strategies to preserve antimicrobial effectiveness.</div></div><div><h3>Objective</h3><div>To evaluate carbapenem consumption and usage profile in inpatient units following the progressive adoption of the carbapenem-sparing strategy implemented by the antimicrobial stewardship team in 2022.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted in a pediatric hospital in southern Brazil (CAAE: 68382723.9.0000.5580), assessing meropenem consumption in non-critical clinical wards (15 total), which represent 71% of hospital beds. Consumption was measured using the indicator days of therapy (DOT/1,000 patient-days) between 2022 and 2025, with 2025 data extrapolated from January–June to the full year. Additionally, medical records of all patients receiving meropenem from January to June 2025 were reviewed to assess prescribing patterns.</div></div><div><h3>Results</h3><div>Regarding the 5-year historical series of DOT/1000 patient-days, the results were 562 (2021), 384 (2022), 428 (2023), 334 (2024), and 148 (2025). This demonstrates that the carbapenem-sparing actions, such as case monitoring and daily discussions by the antimicrobial stewardship team were effective, as there were significant reductions in therapy days of 30% (between 2021 and 2022), 22% (from 2023 to 2024), and 55% (estimated from 2024 to 2025). The exception was between 2022 and 2023, when an 11% increase in DOT was observed, which is considered an acceptable variation. Regarding the carbapenem use profile, data from 65 patients corresponded to 95 treatment courses, with a median age of 4.5 years. Empirical use accounted for 61% of cases, while 39% were guided. The ward with the highest indication for meropenem was Infectious Diseases (23% of patients). The mean treatment duration was 6 days, and the main infection sites were bloodstream (32%), urinary tract (21%), and pulmonary (19%).</div></div><div><h3>Conclusion</h3><div>This use profile indicates the presence of patients with some degree of clinical severity in the wards, but with an acceptable treatment duration. Furthermore, the progressive decrease in DOT over the years demonstrates the effectiveness of the carbapenem-sparing strategy.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104658"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-19DOI: 10.1016/j.bjid.2026.105791
Ivonne Denisse Bautista-Rojas , Jesus Figueroa-Navarrete , Diana Laura Reyes-Hernandez, Evelyn Rivera-Toledo
Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory CD4⁺ T-cells and alveolar macrophages) sustain local immune dysregulation. Extracellular vesicles carrying viral proteins or nucleic acids activate oncogenic pathways, while HIV integration disrupts tumor suppressor genes such as PTEN and induces epigenetic silencing of regulators like P16INK4a. These alterations, together with oxidative stress, promote a pro-tumorigenic microenvironment. A deeper understanding of these mechanisms may enable early biomarker identification and the design of targeted preventive and therapeutic strategies for lung cancer in PLWH.
{"title":"Molecular factors associated with lung cancer in people living with HIV","authors":"Ivonne Denisse Bautista-Rojas , Jesus Figueroa-Navarrete , Diana Laura Reyes-Hernandez, Evelyn Rivera-Toledo","doi":"10.1016/j.bjid.2026.105791","DOIUrl":"10.1016/j.bjid.2026.105791","url":null,"abstract":"<div><div>Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory CD4⁺ T-cells and alveolar macrophages) sustain local immune dysregulation. Extracellular vesicles carrying viral proteins or nucleic acids activate oncogenic pathways, while HIV integration disrupts tumor suppressor genes such as PTEN and induces epigenetic silencing of regulators like P16<sup>INK4a</sup>. These alterations, together with oxidative stress, promote a pro-tumorigenic microenvironment. A deeper understanding of these mechanisms may enable early biomarker identification and the design of targeted preventive and therapeutic strategies for lung cancer in PLWH.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 2","pages":"Article 105791"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuberculosis (TB) remains a major public health concern globally and in Brazil. Although ambulatory treatment is recommended for most patients, hospitalizations still occur due to severe clinical presentations, social vulnerability, or treatment complications.
Methods
We conducted a retrospective, observational study of TB-related hospitalizations at a regional referral tertiary public hospital in São Paulo, Brazil, from 2013 to 2022. Medical records were reviewed to collect epidemiological, clinical, laboratory, and microbiological data.
Results
Among 197 hospitalizations for TB, 73.1% were male, with a mean age of 41.8 years. TB-HIV coinfection was identified in 55.3% of cases, with 83.5% of these patients having CD4+ T-cell counts ≤ 200 cells/mm3. Malnutrition (40.1%), smoking (64.0%), alcohol use (51.6%), and illicit drug use (58.1%) were common. Pulmonary TB occurred in 48.7%, while 29.4% had extrapulmonary TB and 21.8% disseminated forms. Diagnostic confirmation was achieved in 74.1%, including bacilloscopy, culture, molecular test, ADA and biopsy. The main reason for hospitalization was diagnostic work-up (74.1%), with a median symptom duration of 3.6 months. ICU care was required in 23.8% of cases. In-hospital mortality was 17.3%, and significant risk factors included malnutrition and thrombocytopenia.
Conclusions
In this high-burden setting, TB hospitalizations were associated with social vulnerability, HIV coinfection, and delayed diagnosis. The high frequency of severe presentations highlights the importance of early detection and access to molecular testing. Improved integration between outpatient care and hospital services may reduce the need for hospitalization and improve outcomes.
{"title":"Tuberculosis-related hospitalizations in Brazil: a nine-year experience in a high-burden setting","authors":"Gabriela Pizarro Ossa Ferro Henriques , Guilherme Barbosa Pinto , Erika Yukie Ishigaki , Nicoly Caroline de Andrade Delmondes , Daniel Ayabe Ninomiya , Olavo Henrique Munhoz Leite , Marcello Mihailenko Chaves Magri","doi":"10.1016/j.bjid.2026.105789","DOIUrl":"10.1016/j.bjid.2026.105789","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB) remains a major public health concern globally and in Brazil. Although ambulatory treatment is recommended for most patients, hospitalizations still occur due to severe clinical presentations, social vulnerability, or treatment complications.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, observational study of TB-related hospitalizations at a regional referral tertiary public hospital in São Paulo, Brazil, from 2013 to 2022. Medical records were reviewed to collect epidemiological, clinical, laboratory, and microbiological data.</div></div><div><h3>Results</h3><div>Among 197 hospitalizations for TB, 73.1% were male, with a mean age of 41.8 years. TB-HIV coinfection was identified in 55.3% of cases, with 83.5% of these patients having CD4+ T-cell counts ≤ 200 cells/mm<sup>3</sup>. Malnutrition (40.1%), smoking (64.0%), alcohol use (51.6%), and illicit drug use (58.1%) were common. Pulmonary TB occurred in 48.7%, while 29.4% had extrapulmonary TB and 21.8% disseminated forms. Diagnostic confirmation was achieved in 74.1%, including bacilloscopy, culture, molecular test, ADA and biopsy. The main reason for hospitalization was diagnostic work-up (74.1%), with a median symptom duration of 3.6 months. ICU care was required in 23.8% of cases. In-hospital mortality was 17.3%, and significant risk factors included malnutrition and thrombocytopenia.</div></div><div><h3>Conclusions</h3><div>In this high-burden setting, TB hospitalizations were associated with social vulnerability, HIV coinfection, and delayed diagnosis. The high frequency of severe presentations highlights the importance of early detection and access to molecular testing. Improved integration between outpatient care and hospital services may reduce the need for hospitalization and improve outcomes.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 2","pages":"Article 105789"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104709
André Piccolo Pereira , Marcelo Carneiro , Rochele Mosmann Menezes , Paula Trevisan , Manuela Jacques , Ingrid Pilz , Anna Júlia Castoldi Ravazio , Bruna Bombel da Luz , Felipe Provensi Rangel , Maísa Miguel Benette , Hoberdan Oliveira Pereira , Iagro Cesar de Almeida , Jessica Vieira
Introduction/Objective
The use of antibiotics in end-of-life patients remains a controversial practice. Despite their limited clinical effectiveness in this context, these medications are frequently prescribed, often in the absence of an identifiable infectious focus, contributing to adverse events, bacterial resistance, and increased healthcare costs. The scarcity of national data on the subject hampers the development of guidelines to support more appropriate clinical conduct. This study aimed to analyze patterns of antibiotic prescription and factors associated with their use during hospitalization of adult patients who died in a teaching hospital in Southern Brazil.
Methods
A cross-sectional, analytical, and retrospective study was conducted with patients (aged ≥ 18 years) who died between January 1 and June 15, 2025, in both critical and non-critical care units. Incomplete medical records were excluded. Data were extracted from electronic records and included clinical, epidemiological, and therapeutic variables, with emphasis on antibiotic use.
Results
A total of 192 deaths were analyzed, of which 106 had end-of-life care records. After applying inclusion criteria, 88 patients were included in the evaluation. The median age was 81.5 years, with a predominance of males (56%). Antibiotics were used in 83% of cases, and 27% had no identified infectious focus. The most prescribed antimicrobials were ceftriaxone, piperacillin-tazobactam, and meropenem. The median duration of use was 8.5 days, and 54% of patients continued antibiotic therapy until death.
Conclusion
The high frequency of antibiotic use in end-of-life patients without an evident infectious focus highlights the need for institutional guidelines and physician training in palliative care. Early implementation of comfort-centered strategies can prevent disproportionate interventions, improve the quality of end-of-life care, and promote the rational use of antimicrobials.
{"title":"WHEN TREATMENT NO LONGER MAKES SENSE: ANTIBIOTICS IN END-OF-LIFE PATIENTS — A PRACTICE THAT NEEDS TO CHANGE?","authors":"André Piccolo Pereira , Marcelo Carneiro , Rochele Mosmann Menezes , Paula Trevisan , Manuela Jacques , Ingrid Pilz , Anna Júlia Castoldi Ravazio , Bruna Bombel da Luz , Felipe Provensi Rangel , Maísa Miguel Benette , Hoberdan Oliveira Pereira , Iagro Cesar de Almeida , Jessica Vieira","doi":"10.1016/j.bjid.2026.104709","DOIUrl":"10.1016/j.bjid.2026.104709","url":null,"abstract":"<div><h3>Introduction/Objective</h3><div>The use of antibiotics in end-of-life patients remains a controversial practice. Despite their limited clinical effectiveness in this context, these medications are frequently prescribed, often in the absence of an identifiable infectious focus, contributing to adverse events, bacterial resistance, and increased healthcare costs. The scarcity of national data on the subject hampers the development of guidelines to support more appropriate clinical conduct. This study aimed to analyze patterns of antibiotic prescription and factors associated with their use during hospitalization of adult patients who died in a teaching hospital in Southern Brazil.</div></div><div><h3>Methods</h3><div>A cross-sectional, analytical, and retrospective study was conducted with patients (aged ≥ 18 years) who died between January 1 and June 15, 2025, in both critical and non-critical care units. Incomplete medical records were excluded. Data were extracted from electronic records and included clinical, epidemiological, and therapeutic variables, with emphasis on antibiotic use.</div></div><div><h3>Results</h3><div>A total of 192 deaths were analyzed, of which 106 had end-of-life care records. After applying inclusion criteria, 88 patients were included in the evaluation. The median age was 81.5 years, with a predominance of males (56%). Antibiotics were used in 83% of cases, and 27% had no identified infectious focus. The most prescribed antimicrobials were ceftriaxone, piperacillin-tazobactam, and meropenem. The median duration of use was 8.5 days, and 54% of patients continued antibiotic therapy until death.</div></div><div><h3>Conclusion</h3><div>The high frequency of antibiotic use in end-of-life patients without an evident infectious focus highlights the need for institutional guidelines and physician training in palliative care. Early implementation of comfort-centered strategies can prevent disproportionate interventions, improve the quality of end-of-life care, and promote the rational use of antimicrobials.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104709"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-14DOI: 10.1016/j.bjid.2026.104713
Ana Lídia Pires de Assis Pinto, Fabio Faria da Mota
Introduction
The genus Pseudomonas includes opportunistic pathogens frequently exhibiting multidrug resistance and involved in hospital infections, in which urease remains an unexplored therapeutic target for virulence attenuation. Urease is a nickel-dependent metalloenzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide, contributing to bacterial adaptation through environmental pH increase. Acetohydroxamic acid (AHA) is a well-characterized reversible urease inhibitor, approved in some countries for treating chronic urinary tract infections.
Objective
This study evaluated the binding of AHA to immature (apoenzyme) and mature (holoenzyme) forms of urease from clinical Pseudomonas spp. isolates.
Methods
Structural models were generated using AlphaFold3 (apoenzyme) and modified with AlphaFill (holoenzyme) for nickel ion insertion. Docking was performed using AutoDock Vina, and interactions were analyzed structurally in ChimeraX (v1.10). Interactions with AHA and with urease’s natural substrate, urea, were analyzed.
Results
Docking simulations revealed similar binding affinities for AHA in both forms, –4.3 kcal/mol (apoenzyme) and –4.4 kcal/mol (holoenzyme); and for urea, –3.9 and –4.1 kcal/mol, respectively. In both cases, AHA interacted with a conserved set of catalytic residues, including His218, His245, His359, and Ala362. In the apoenzyme, AHA also interacted via hydrogen bonds with His133 and His135, while in the holoenzyme it established additional interactions with His271, KCX (carboxylated lysine), and coordinated with both nickel ions. Although AHA interacted with catalytic residues in both forms, stronger interactions were observed through metal coordination with Ni in the holoenzyme.
Conclusion
These findings reinforce the potential of AHA as a broad-spectrum urease inhibitor and highlight the need for further studies on its use in infections caused by Pseudomonas, beyond current therapeutic indications for urinary and gastric infections caused by Proteus mirabilis and Helicobacter pylori.
{"title":"EVOLUTIONARILY CONSERVED CATALYTIC RESIDUES IN UREASES FROM CLINICAL PSEUDOMONAS SPP. ISOLATES ARE IMPORTANT FOR INHIBITION BY ACETOHYDROXAMIC ACID","authors":"Ana Lídia Pires de Assis Pinto, Fabio Faria da Mota","doi":"10.1016/j.bjid.2026.104713","DOIUrl":"10.1016/j.bjid.2026.104713","url":null,"abstract":"<div><h3>Introduction</h3><div>The genus <em>Pseudomonas</em> includes opportunistic pathogens frequently exhibiting multidrug resistance and involved in hospital infections, in which urease remains an unexplored therapeutic target for virulence attenuation. Urease is a nickel-dependent metalloenzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide, contributing to bacterial adaptation through environmental pH increase. Acetohydroxamic acid (AHA) is a well-characterized reversible urease inhibitor, approved in some countries for treating chronic urinary tract infections.</div></div><div><h3>Objective</h3><div>This study evaluated the binding of AHA to immature (apoenzyme) and mature (holoenzyme) forms of urease from clinical <em>Pseudomonas</em> spp. isolates.</div></div><div><h3>Methods</h3><div>Structural models were generated using AlphaFold3 (apoenzyme) and modified with AlphaFill (holoenzyme) for nickel ion insertion. Docking was performed using AutoDock Vina, and interactions were analyzed structurally in ChimeraX (v1.10). Interactions with AHA and with urease’s natural substrate, urea, were analyzed.</div></div><div><h3>Results</h3><div>Docking simulations revealed similar binding affinities for AHA in both forms, –4.3 kcal/mol (apoenzyme) and –4.4 kcal/mol (holoenzyme); and for urea, –3.9 and –4.1 kcal/mol, respectively. In both cases, AHA interacted with a conserved set of catalytic residues, including His218, His245, His359, and Ala362. In the apoenzyme, AHA also interacted via hydrogen bonds with His133 and His135, while in the holoenzyme it established additional interactions with His271, KCX (carboxylated lysine), and coordinated with both nickel ions. Although AHA interacted with catalytic residues in both forms, stronger interactions were observed through metal coordination with Ni in the holoenzyme.</div></div><div><h3>Conclusion</h3><div>These findings reinforce the potential of AHA as a broad-spectrum urease inhibitor and highlight the need for further studies on its use in infections caused by <em>Pseudomonas</em>, beyond current therapeutic indications for urinary and gastric infections caused by <em>Proteus mirabilis</em> and <em>Helicobacter pylori</em>.</div></div>","PeriodicalId":56327,"journal":{"name":"Brazilian Journal of Infectious Diseases","volume":"30 ","pages":"Article 104713"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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