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PURPOSE OF REVIEW: This review describes the latest information in the management of bloodstream infections caused by multidrug-resistant Gram-negative bacilli (MDRGNB) in critically ill patients. RECENT FINDINGS: The prevalence of bloodstream infections due to MDRGNB is high, and they pose a significant risk in critically ill patients. Recently, novel antimicrobial agents, including new ß-lactam/ß-lactamase inhibitor combinations and cefiderocol, have been introduced for treating these infections. Concurrently, updated guidelines have been issued to aid in treatment decisions. Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy. Current studies, especially with observational design, and with limited sample sizes and patients with bacteremia, suggest that the use of these new antibiotics is associated with improved outcomes in critically ill patients with MDRGNB bloodstream infections. SUMMARY: For critically ill patients with bloodstream infections caused by MDRGNB, the use of newly developed antibiotics is recommended based on limited observational evidence. Further randomized clinical trials are necessary to determine the most effective antimicrobial therapies among the available options.
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Antibacterianos , Bacteriemia , Estado Terminal , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas , Humanos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Guias de Prática Clínica como Assunto , Bactérias Gram-Negativas/efeitos dos fármacos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Gastrointestinal endoscopic procedures (GIEP's) are an essential part of patient care both diagnostically and therapeutically. Post-GIEP infections may be higher than previously reported and may not have been accurately captured in the past. The aim of this study was to determine the incidence and associated factors of bacteremia associated with GIEP's. METHODS: This is retrospective study of GIEPs performed over a five-year period (2018-2022) at an academic medical center. Electronic health records (EHR) identified GIEPs and positive blood cultures within 30 days of procedure. Statistical analysis was performed using non-parametric testing to compare variables due to the small number of positive blood cultures. RESULTS: EHR identified 18,986 GIEP's and 52 true and unique bacteremia out of 17,093 blood cultures during the five-year study period. The highest rate of positive blood culture of 2.84% (18/ 634) was associated with ERCP and the lowest 0.08% (7/ 9029) was associated with colonoscopy. DISCUSSION: Our study showed a reflection of the endemic rate of bacteremia post GIEP's. Our study cannot differentiate endogenous infection versus contaminated (exogenous) endoscopes. ERCP procedures are disproportionately associated with higher incidence of bacteremia. CONCLUSIONS: Clinical surveillance in non-outbreak settings is essential for estimating GIEP related infections. It should be combined with endoscopic reprocessing audits for appropriate prevention of GIEP associated infections.
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Bacteriemia , Endoscopia Gastrointestinal , Centros de Atenção Terciária , Humanos , Bacteriemia/epidemiologia , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Incidência , Idoso , Adulto , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologiaRESUMO
PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.
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Antibacterianos , Bacteriemia , Infecções por Enterobacteriaceae , Neutropenia , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neutropenia/complicações , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/mortalidade , Infecções por Enterobacteriaceae/microbiologia , Adulto , Idoso , Enterobacteriaceae/efeitos dos fármacos , Resultado do Tratamento , Tempo de Internação , Neoplasias Hematológicas/complicações , Adulto JovemRESUMO
The rapid identification of microorganisms that cause bacteremia and their possible resistance markers are extremely important for the timely initiation of effective antibiotic therapy. The FilmArray® panel BCID2 (an automated rapid multiplex PCR assay) detects microorganisms and resistance genes from positive blood cultures within one hour. The aim of this study was to compare the results obtained from the FilmArray® Panel BCID2 and conventional culture in pediatric patients, as well as the reporting times of both methods. Sixty (60) FilmArray® results were included in the analysis. BCID2 showed high agreement with culture in the identification of microorganisms in monomicrobial bacteremias. However, in polymicrobial blood cultures, BCID2 detected a greater number of microorganisms compared to conventional culture, specifically,1 Staphylococcus aureus, 3 Staphylococcus epidermidis, 1 Enterococcus faecium, 2 Klebsiella oxytoca, 1 Acinetobacter calcoaceticus-baumannii complex, 1 Bacteroides fragilis and 1 Haemophilus influenzae. Furthermore, 88.3% (95%CI: 78.7-94.8) of the FilmArray® results coincided with conventional culture, while in polymicrobial bacteremias, BCID2 detected a greater number of microorganisms with respect to conventional culture [70% (95%CI: 39.3-91.5)]. The agreement of resistance genes was good with a few exceptions (one ESBL was not detected by FilmArray® and one S. aureus strain was characterized as methicillin-resistant by BCID2 and methicillin-sensitive by culture). When comparing the time elapsing since the blood culture was reported as positive up to the results were obtained, BCID2 had a median of 2h 50min (IQR of 1 h 58min to 9h 27min) while the conventional culture had a median of 45h 20min (IQR of 24h 57min to 63h 50min).
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Bacteriemia , Hemocultura , Hospitais Pediátricos , Reação em Cadeia da Polimerase Multiplex , Humanos , Hemocultura/métodos , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Criança , Farmacorresistência Bacteriana/genética , Pré-Escolar , Genes Bacterianos , Lactente , Bactérias/isolamento & purificação , Bactérias/genéticaRESUMO
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
Staphylococcus aureus are extremely important microorganisms, either from an epidemiological point of view or as a pathogen, responsible for causing a series of infectious processes, whether simple, restricted to the skin, or invasive infections such as bacteremia. The emergence of Oxacillin Sensitive-Methicillin Resistant S.aureus (OS-MRSA) isolates has imposed difficulties in the treatment of patients with staphylococcal infection, as such isolates can be mistakenly classified as sensitive and lead to failure of the therapy used. Thus, the objective of this study is to evaluate the prevalence, and genotypic and phenotypic characteristics, of OS-MRSA isolates, from bloodstream infections, collected from patients admitted to a hospital in southern Brazil, as well as to evaluate the treatment used. For this, 801 unique isolates of S. aureus, collected from blood cultures, between January 2011 and December 2020 were evaluated. Of these, 96 isolates were classified as sensitive to oxacillin. The isolates were identified and had their sensitivity profile performed by manual and automated methods. The minimum inhibitory concentration for vancomycin, daptomycin, oxacillin, linezolid and teicoplanine was performed by e-test. The mecA, vanA genes, typing of the SCCmec elements, as well as the search for the icaA, tst-1 and pvl virulence genes were performed by PCR. Biofilm formation was performed using the crystal violet technique. The Sequence Type (ST), as well as the Clonal Complex (CC) of the isolates was evaluated by the RTq -PCR. The clinical characteristics of the patients were evaluated through an active search in medical records. After investigating the mecA gene, 27.1% (26/96) of the isolates were considered OS-MRSA, with SCCmec type I being the most prevalent, 46.1% (12/26). Among the evaluated isolates, 41% (9/22) were included in CC5 and ST9. As for virulence, all isolates were positive for the icaA gene and characterized as strong biofilm formers. The pvl gene was found in 92.3% (24/26) of the isolates and the toxic shock syndrome toxin was present in 61.5% of the isolates (16/26). All isolates were negative for the presence of the van A gene. As for the clinical outcome, 73% (19/26) of the patients were discharged from the hospital and 27% (7/26) died. It was possible to observe a high frequency of OS-MRSA isolates causing bloodstream infections. Furthermore, such isolates contain several virulence genes, which may contribute to a worse clinical outcome.
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Antibacterianos , Bacteriemia , Proteínas de Bactérias , Genótipo , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Oxacilina , Proteínas de Ligação às Penicilinas , Infecções Estafilocócicas , Centros de Atenção Terciária , Humanos , Oxacilina/farmacologia , Brasil , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Centros de Atenção Terciária/estatística & dados numéricos , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Proteínas de Ligação às Penicilinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/classificação , FenótipoRESUMO
BACKGROUND: CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels. METHODS: This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes. RESULTS: The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2). CONCLUSIONS: We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.
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Antibacterianos , Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Diálise Renal , Insuficiência Renal Crônica , Infecções Estafilocócicas , Vancomicina , Humanos , Vancomicina/uso terapêutico , Estudos Retrospectivos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Masculino , Diálise Renal/efeitos adversos , Feminino , Insuficiência Renal Crônica/complicações , Idoso , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Idoso de 80 Anos ou mais , Testes de Sensibilidade MicrobianaRESUMO
INTRODUCTION: Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus. METHODS: Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors. RESULTS: 152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62). CONCLUSION: In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.
Introducción: A pesar de las mejoras en los cuidados de la salud, la mortalidad asociada a neumonía continúa siendo alta. El objetivo de este estudio fue analizar los factores asociados a mortalidad en neumonía bacteriémica por neumococo. Métodos: Estudio de cohorte retrospectiva en pacientes adultos con diagnóstico de neumonía y neumococo aislado en hemocultivos, entre enero 2012 y mayo 2021. Se analizaron: variables clínicas y de laboratorio, compromiso radiológico, evolución y mortalidad durante la internación. Se comparó el grupo de pacientes fallecidos con el de sobrevivientes. Resultados: Se incluyeron 152 pacientes. La mediana de edad fue de 58 años y el 58.9% fueron hombres. El 33% presentó un CURB-65 mayor a 2 al momento de internación. La mortalidad global fue 34% (n=52). Los pacientes fallecidos se encontraban más frecuentemente taquipneicos al ingreso (frecuencia respiratoria 26 vs. 22; p=0.003), presentaban más frecuentemente alteración del sensorio (58% vs. 14%; p< 0.001), PaO2/fracción inspirada de oxígeno (PAFI) < 250 (58% vs. 22%; p<0.001), compromiso radiológico bilateral (50% vs. 32%; p=0.03), necesidad de asistencia respiratoria mecánica (ARM) (50% vs. 12%; p< 0.001), mayor valor de creatinina en sangre (1.6 vs. 1.15; p=0.01), menor recuento de glóbulos blancos (10 900 vs. 17 400; p=0.002), menor valor de glucemia (111 vs. 120; p=0.01) y menos días de estancia hospitalaria (6 vs. 9; p=0.015). En el análisis de regresión logística multivariable se mantuvieron diferencias significativas en los siguientes factores asociados a mortalidad: ventilación mecánica (OR=3.54), confusión (OR=5.95), radiografía con compromiso bilateral (OR= 3.20) y PAFI < 250 (OR=3.62). Conclusión: Los factores relacionados con mortalidad, a pesar de la presencia de bacteriemia, no difieren de los publicados en la literatura y forman parte de los scores pronósticos de práctica habitual.
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Pneumonia Pneumocócica , Humanos , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Idoso , Pneumonia Pneumocócica/mortalidade , Fatores de Risco , Adulto , Streptococcus pneumoniae , Mortalidade Hospitalar , Bacteriemia/mortalidade , Bacteriemia/microbiologiaRESUMO
PURPOSE: To evaluate the performance of the rapid colorimetric polymyxin B microelution (RCPEm) in determining polymyxin B resistance directly from Enterobacterales-positive blood cultures. METHODS: A set volume of positive blood culture bottles (diluted 1:10) was inoculated into a glucose-broth-phenol red solution (NP solution), where a polymyxin B disk was previously eluted (final concentration of 3 µg/mL). Test was read each 1 h for up to 4 h. Color change from red/orange to yellow indicated resistant isolates. Results were compared to the reference method, broth microdilution (BMD), performed from colonies grown on solid media from the same blood culture bottle. RESULTS: One hundred fifty-two Enterobacterales-positive blood cultures were evaluated, 22.4% (34/152) of them resistant to polymyxin B (including 6.6% with borderline MICs). When performing directly from positive blood cultures (RCPEm-BC), specificity and sensitivity were 99.1% and 94.1%, respectively. Of note, 79.4% (27/34) of truly resistant isolates required 3 h of incubation, compared to the 18 ± 2 h incubation that microtiter plates of BMD demand before reading can be performed. CONCLUSIONS: RCPEm directly from blood cultures has great potential to be part of the routine of clinical microbiology laboratories to establish polymyxin B susceptibility, impacting outcome of patients with bloodstream infections caused by carbapenem-resistant Enterobacterales.
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Antibacterianos , Hemocultura , Colorimetria , Testes de Sensibilidade Microbiana , Polimixina B , Polimixina B/farmacologia , Humanos , Colorimetria/métodos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Hemocultura/métodos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Sensibilidade e Especificidade , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/diagnóstico , Farmacorresistência Bacteriana , Bacteriemia/microbiologia , Bacteriemia/diagnósticoRESUMO
Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.