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INTRODUCTION: Novel beta-lactam/beta-lactamase inhibitor (BIBLI) combinations are commercially available and have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profiles and resistance mechanism identification are necessary to monitor the evolution of resistance within these agents. OBJECTIVE: The purpose of this study was to evaluate the susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolated from patients with bloodstream infections who underwent screening for a randomized clinical trial in Brazil. METHODS: Minimum inhibitory concentrations (MICs) were determined for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam using the gradient diffusion strip method. Carbapenemase genes were detected by multiplex real-time polymerase chain reaction. Klebsiella pneumoniae carbapenemase (KPC)-producing isolates showing resistance to any BLBLI and New Delhi Metallo-beta-lactamase (NDM)-producing isolates with susceptibility to any BLBLI isolates were further submitted for whole-genome sequencing. RESULTS: From a total of 69 CRKP isolates, 39 were positive for blaKPC, 19 for blaNDM and 11 for blaKPC and blaNDM. KPC-producing isolates demonstrated susceptibility rates above 94â¯% for all BLBLIs. Two isolates with resistance to meropenem/vaborbactam demonstrated a Gly and Asp duplication at the porin OmpK36 as well as a truncated OmpK35. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0â¯%, 9.1-21.1â¯% and 9.1-26.3â¯%, respectively. Five NDM-producing isolates that presented susceptibility to BLBLIs also had porin alterations CONCLUSIONS: This study showed that, although high susceptibility rates to BLBLIs were found, KPC-2 isolates were able to demonstrate resistance probably as a result of porin mutations. Additionally, NDM-1 isolates showed susceptibility to BLBLIs in vitro.
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Antibacterianos , Compostos Azabicíclicos , Enterobacteriáceas Resistentes a Carbapenêmicos , Ceftazidima , Combinação de Medicamentos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases , beta-Lactamases , Humanos , Brasil , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Inibidores de beta-Lactamases/farmacologia , Infecções por Klebsiella/microbiologia , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Proteínas de Bactérias/genética , Meropeném/farmacologia , Imipenem/farmacologia , Bacteriemia/microbiologia , Ácidos Borônicos/farmacologia , Compostos Heterocíclicos com 1 AnelRESUMO
OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.
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Antibacterianos , Compostos Azabicíclicos , Infecções por Bactérias Gram-Negativas , Adulto , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Inibidores de beta-Lactamases/efeitos adversos , Ceftazidima/efeitos adversos , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Estudos ProspectivosRESUMO
Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52-1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55-1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17-1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47-1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI.
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BACKGROUND: Ideal therapy duration for Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex (ABC) bloodstream infections (BSI) is not defined, especially in the context of carbapenem resistance. In this study, we compared short- (≤7 days) and long-term (>7 days) antimicrobial therapy duration for these infections. METHODS: We performed a retrospective cohort study in two tertiary-care hospitals in Porto Alegre, Brazil, from 2013 to 2019. Eligible patients aged ≥18 years were included and excluded for the following criteria: polymicrobial infections, treatment with non-susceptible antibiotics, complicated infections, or early mortality (<8 days of active antimicrobial therapy). The 30-day mortality risk was evaluated using a Cox regression model. RESULTS: We included 237 BSI episodes, 51.5% caused by ABC and 48.5% by Pseudomonas aeruginosa. Short-term therapy was not associated with 30-day mortality, adjusted hazard ratio 1.01, 95% confidence interval 0.47-2.20, p = 0.98, when adjusted for Pitt score (p = 0.02), Charlson Comorbidity Index score (p < 0.01), and carbapenem resistance (p < 0.01). Among patients who survived, short-term therapy was associated with shorter hospital stay (p < 0.01). Results were maintained in the subgroups of BSI caused by carbapenem-resistant bacteria (p = 0.76), ABC (p = 0.61), and Pseudomonas aeruginosa (p = 0.39). CONCLUSIONS: Long-term therapies for non-complicated Pseudomonas aeruginosa and ABC BSI were not superior to short-term therapy for 30-day mortality.
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BACKGROUND: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. METHODS: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. RESULTS: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. CONCLUSIONS: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.
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Bacteriemia , Neutropenia Febril , Infecções por Bactérias Gram-Negativas , Neoplasias Hematológicas , Sepse , Humanos , Adolescente , Adulto , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Prevalência , Bacteriemia/microbiologia , Estudos Retrospectivos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Neoplasias Hematológicas/complicações , Neutropenia Febril/tratamento farmacológicoRESUMO
ABSTRACT Background: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. Methods: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. Results: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. Conclusions: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.
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OBJECTIVES: To investigate the effect of double-, single- and none-carbapenem-containing antimicrobial regimens in the treatment of patients with carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs). METHODS: We conducted a retrospective cohort study from 2013 to 2020 in two Brazilian hospitals. Patients ≥18â years old with CRE BSI were included and excluded if death or treatment duration for ≤48â h after BSI or non-Class A-producing carbapenemase isolates. We evaluated the impact of different carbapenem-containing regimens on 30â day mortality through a propensity score adjusted model and a Cox proportional hazards model. RESULTS: Two-hundred and seventy-nine patients were included for analyses: 47 (16.9%), 149 (53.4%) and 83 (29.8%) were treated with double-, single- and none-carbapenem-containing regimens, respectively. One-hundred and seventeen (41.9%) patients died in 30â days. Treatment with a single-carbapenem regimen was associated with a lower risk of death in 30â days compared with therapies containing no carbapenem [adjusted HR (aHR) 0.66, 95% CI 0.44-0.99, Pâ=â0.048], when adjusted for Charlson score and ICU admission at baseline, while double-carbapenem regimens were not associated with a lower risk of death (aHR 0.78, 95% CI 0.46-1.32, Pâ=â0.35). Propensity score adjusted model results went in the same direction. CONCLUSIONS: Double-carbapenem- was not superior to single-carbapenem-containing regimens in patients with CRE BSIs. Single-carbapenem-containing schemes were associated with a lower mortality risk.
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Bacteriemia , Enterobacteriáceas Resistentes a Carbapenêmicos , Sepse , Humanos , Adolescente , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Estudos Retrospectivos , Bacteriemia/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Estudos de Coortes , Sepse/tratamento farmacológicoRESUMO
OBJECTIVES: This study analysed the impact of antimicrobial stewardship team (AST) evaluation on time to susceptible in vitro therapy and mortality of patients with carbapenem-resistant Enterobacterales (CRE) bacteraemia. METHODS: We performed a retrospective cohort study (February 2018 to July 2020) to evaluate the impact of AST evaluation, along with other clinical and microbiological variables, on time to appropriate antibiotics, 14-day mortality and in-hospital mortality in patients aged >18 years with CRE bacteraemia. A Cox regression model was used for multivariate analysis. RESULTS: A total of 142 patients were included. The proportion of patients who received appropriate antibiotics in the first 5 days after bacteraemia was 82/92 (89.1%) versus 29/50 (58.0%) evaluated and not evaluated by the AST, respectively (P < 0.01). AST evaluation reduced the median time to appropriate therapy (49.8 h vs. 71.1 h; P = 0.01). AST intervention was independently associated with earlier prescription of appropriate therapy (P = 0.02) when controlled for septic shock (P < 0.01) and CRE isolation in the previous 90 days (P = 0.04). Regarding mortality, 51 patients (35.9%) died within 14 days (25.8% vs. 44.7% with and without AST intervention, respectively; P = 0.02) and 82 patients (57.7%) in hospital (52.2% vs. 68.0% evaluated and not evaluated by the AST, respectively; P = 0.08). AST intervention was independently protective for 14-day mortality (P = 0.03) when controlled for septic shock status (P < 0.01). CONCLUSION: AST guidance improves the quality of antibiotic prescriptions and clinical outcomes in patients with CRE bacteraemia.
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Gestão de Antimicrobianos , Bacteriemia , Farmacorresistência Bacteriana , Gammaproteobacteria , Choque Séptico , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Estudos de Coortes , Humanos , Prescrições , Estudos Retrospectivos , Choque Séptico/tratamento farmacológicoRESUMO
Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 µg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.