RESUMO
Introduction. Sepsis rates are increasing, with Gram-negative organisms representing a large proportion of bloodstream infections. Rapid antibiotic administration, alongside diagnostic investigations, is required for the effective management of these patients.Gap statement. Current diagnostics take ~48 h for a final report; therefore, rapid diagnostics are required.Aim. This study investigated a novel antibiotic sensitivity method, the scattered light integrating collector (SLIC), combined with a rapid identification method using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) technology to determine if an accurate identification and susceptibility result can be provided within 4 h of a positive blood culture report.Methodology. A total of 47 blood cultures containing Gram-negative bacteria from 46 patients were processed using the MALDI-TOF Biotyper Sepsityper for identification directly from the blood and the SLIC instrument for susceptibility testing. All organisms were also tested using the current standard workflow used in the host laboratory. Categorical agreement (CA), major errors (MaEs) and very major errors (VMEs) were determined.Results. SLIC produced susceptibility results with a 71.9% CA, 30.6% MaE and 17.5% VME. The median difference in time to the final result was 44.14 (43â:â05-45â:â15) h earlier compared to the current method.Conclusion. We conclude that SLIC was unable to consistently provide sufficiently accurate antibiotic susceptibility results compared to the current standard method.
Assuntos
Antibacterianos , Hemocultura , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Hemocultura/métodos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/instrumentação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Antibacterianos/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Sepse/diagnóstico , Sepse/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , LuzRESUMO
Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes Gram-negative lung infections and fatal pneumonic sepsis for which limited therapeutic options are available. The lungs are densely innervated by nociceptor sensory neurons that mediate breathing, cough, and bronchoconstriction. The role of nociceptors in defense against Gram-negative lung pathogens is unknown. Here, we found that lung-innervating nociceptors promote CRKP pneumonia and pneumonic sepsis. Ablation of nociceptors in mice increased lung CRKP clearance, suppressed trans-alveolar dissemination of CRKP, and protected mice from hypothermia and death. Furthermore, ablation of nociceptors enhanced the recruitment of neutrophils and Ly6Chi monocytes and cytokine induction. Depletion of Ly6Chi monocytes, but not of neutrophils, abrogated lung and extrapulmonary CRKP clearance in ablated mice, suggesting that Ly6Chi monocytes are a critical cellular population to regulate pneumonic sepsis. Further, neuropeptide calcitonin gene-related peptide suppressed the induction of reactive oxygen species in Ly6Chi monocytes and their CRKP-killing abilities. Targeting nociceptor signaling could be a therapeutic approach for treating multidrug-resistant Gram-negative infection and pneumonic sepsis.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Pulmão , Nociceptores , Sepse , Animais , Klebsiella pneumoniae/fisiologia , Camundongos , Infecções por Klebsiella/microbiologia , Sepse/metabolismo , Sepse/microbiologia , Pulmão/microbiologia , Pulmão/metabolismo , Carbapenêmicos/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Nociceptores/metabolismo , Monócitos/metabolismo , Células Receptoras Sensoriais/metabolismo , Neutrófilos/metabolismo , Modelos Animais de Doenças , Antígenos Ly/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/patologia , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Invasive Listeria monocytogenes infection is rare, but can lead to life-threatening complications among high-risk patients. Our aim was to assess characteristics and follow-up of adults hospitalized with invasive L. monocytogenes infection. METHODS: A retrospective observational cohort study was conducted at a national referral center between 2004 and 2019. Patients with proven invasive listeriosis, defined by the European Centre for Disease Prevention and Control criteria, were included. Data collection and follow-up were performed using the hospital electronic system, up until the last documented visit. The primary outcome was in-hospital all-cause mortality, secondary outcomes included residual neurological symptoms, brain abscess occurrence, and requirement for intensive care unit (ICU) admission. RESULTS: Altogether, 63 cases were identified (57.1% male, median age 58.8 ± 21.7 years), and 28/63 developed a complicated disease course (44.4%). At diagnosis, 38/63 (60.3%) presented with sepsis, 54/63 (85.7%) had central nervous system involvement, while 9/63 (14.3%) presented with isolated bacteremia. Frequent clinical symptoms included fever (53/63, 84.1%), altered mental state (49/63, 77.8%), with immunocompromised conditions apparent in 56/63 (88.9%). L. monocytogenes was isolated from blood (37/54, 68.5%) and cerebrospinal fluid (48/55, 87.3%), showing in vitro full susceptibility to ampicillin and meropenem (100% each), gentamicin (86.0%) and trimethoprim/sulfamethoxazole (97.7%). In-hospital all-cause mortality was 17/63 (27.0%), and ICU admission was required in 28/63 (44.4%). At discharge, residual neurological deficits (11/46, 23.9%) and brain abscess formation (6/46, 13.0%) were common. CONCLUSION: Among hospitalized adult patients with comorbidities, invasive L. monocytogenes infections are associated with high mortality and neurological complications during follow-up.
Assuntos
Hospitalização , Listeria monocytogenes , Listeriose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Listeriose/mortalidade , Listeriose/microbiologia , Listeriose/epidemiologia , Listeriose/tratamento farmacológico , Listeria monocytogenes/patogenicidade , Listeria monocytogenes/isolamento & purificação , Listeria monocytogenes/efeitos dos fármacos , Estudos Retrospectivos , Idoso , Hungria/epidemiologia , Adulto , Hospitalização/estatística & dados numéricos , Seguimentos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Idoso de 80 Anos ou mais , Sepse/microbiologia , Sepse/mortalidade , Sepse/epidemiologia , Sepse/tratamento farmacológico , Mortalidade HospitalarRESUMO
BACKGROUND: Thrombocytopenia is commonly observed in patients with sepsis and is an independent risk factor for poor prognosis. However, the changes of platelet count caused by different pathogens can vary significantly. Our study aims to evaluate the quantitative changes in platelet count in response to various pathogens. MATERIAL AND METHODS: We retrospectively analysed data of 3044 patients with sepsis from Medical Information Mart for Intensive Care (MIMIC, 2008-2019) database and prospectively collected data of 364 patients with sepsis from our local cohort of the Shandong Bloodstream Infection and Sepsis Collaboration Study (SBISC, 2020-2022). Propensity score matching (PSM) was employed to control for baseline differences in variables, except for the causative pathogen. RESULTS: Multivariate logistic analyses of both original and PSM populations identified Candida, Escherichia, Klebsiella, and Serratia species posing a higher risk for thrombocytopenia compared to others. Restricted cubic spline (RCS) curves showed L- or U-shaped associations between platelet count and 28-mortality with various cut-off values among different pathogens: ranging from 96 × 109/L in Candida species - 190 × 109/L in Klebsiella species. CONCLUSION: Our present findings indicate a pathogen-specific effect on platelet count, highlighting the importance of monitoring thrombocytopenia in patients infected with above microorganisms. Clinicians need to consider pathogen-specific thresholds when intervene on platelet count.
This study validated the differential incidence of thrombocytopenia among various pathogens within two distinct populations.Candida, Escherichia, Klebsiella, and Serratia species were identified as having a notably higher risk of causing thrombocytopenia compared to other pathogens.We observed L- or U-shaped relationships between platelet counts and 28-day mortality in Candida species, Enterococcus species, Escherichia species, Enterobacter species, Staphylococcus species, and Klebsiella species with platelet count cutoff values of 96 × 109/L, 100 × 109/L, 100 × 109/L, 146 × 109/L, 152 × 109/L, and 190 × 109/L, respectively.
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Sepse , Trombocitopenia , Humanos , Masculino , Feminino , Sepse/sangue , Sepse/microbiologia , Estudos Retrospectivos , Contagem de Plaquetas , Pessoa de Meia-Idade , Trombocitopenia/sangue , Trombocitopenia/microbiologia , Idoso , Estudos Prospectivos , Klebsiella/isolamento & purificação , Fatores de Risco , Candida/isolamento & purificação , Serratia/isolamento & purificação , Pontuação de PropensãoRESUMO
BACKGROUND: Mitochondria play a crucial role in shaping the macrophage inflammatory response during bacterial infections. Spinster homolog 2 (Spns2), responsible for sphingosine-1-phosphate (S1P) secretion, acts as a key regulator of mitochondrial dynamics in macrophages. However, the link between Spns2/S1P signaling and mitochondrial functions remains unclear. METHODS: Peritoneal macrophages were isolated from both wild-type and Spns2 knockout rats, followed by non-targeted metabolomics and RNA sequencing analysis to identify the potential mediators through which Spns2/S1P signaling influences the mitochondrial functions in macrophages. Various agonists and antagonists were used to modulate the activation of Spns2/S1P signaling and its downstream pathways, with the underlying mechanisms elucidated through western blotting. Mitochondrial functions were assessed using flow cytometry and oxygen consumption assays, as well as morphological analysis. The impact on inflammatory response was validated through both in vitro and in vivo sepsis models, with the specific role of macrophage-expressed Spns2 in sepsis evaluated using Spns2flox/floxLyz2-Cre mice. Additionally, the regulation of mitochondrial functions by Spns2/S1P signaling was confirmed using THP-1 cells, a human monocyte-derived macrophage model. RESULTS: In this study, we unveil prostaglandin E2 (PGE2) as a pivotal mediator involved in Spns2/S1P-mitochondrial communication. Spns2/S1P signaling suppresses PGE2 production to support malate-aspartate shuttle activity. Conversely, excessive PGE2 resulting from Spns2 deficiency impairs mitochondrial respiration, leading to intracellular lactate accumulation and increased reactive oxygen species (ROS) generation through E-type prostanoid receptor 4 activation. The overactive lactate-ROS axis contributes to the early-phase hyperinflammation during infections. Prolonged exposure to elevated PGE2 due to Spns2 deficiency culminates in subsequent immunosuppression, underscoring the dual roles of PGE2 in inflammation throughout infections. The regulation of PGE2 production by Spns2/S1P signaling appears to depend on the coordinated activation of multiple S1P receptors rather than any single one. CONCLUSIONS: These findings emphasize PGE2 as a key effector of Spns2/S1P signaling on mitochondrial dynamics in macrophages, elucidating the mechanisms through which Spns2/S1P signaling balances both early hyperinflammation and subsequent immunosuppression during bacterial infections.
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Dinoprostona , Inflamação , Lisofosfolipídeos , Transdução de Sinais , Esfingosina , Animais , Dinoprostona/metabolismo , Humanos , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Lisofosfolipídeos/metabolismo , Camundongos , Mitocôndrias/metabolismo , Macrófagos/metabolismo , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Infecções Bacterianas/metabolismo , Ratos , Masculino , Proteínas de Transporte de Ânions/metabolismo , Proteínas de Transporte de Ânions/genética , Células THP-1 , Sepse/metabolismo , Sepse/microbiologia , Sepse/patologia , Sepse/imunologia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND Gas in the portal venous system, or hepatic portal venous gas, is a rare occurrence associated with ischemic colitis, inflammatory bowel disease, or any cause of bowel perforation, including from a necrotic tumor. This report presents the case of a 72-year-old man with diabetes who had carcinoma of the ileocecal region, sepsis due to Klebsiella pneumoniae, and hepatic portal venous gas. CASE REPORT A 72-year-old man with ileocecal cancer was admitted to our hospital for preoperative diabetes control. He developed a fever and septic shock, without abdominal symptoms or signs of peritoneal irritation. Klebsiella pneumoniae was detected in blood cultures. Abdominal ultrasonography showed hepatic portal venous gas, and a simple computed tomography scan revealed gas in the vasculature and hepatic portal vein in the lateral segment, which led us to believe that the ileocecal mass was the source of infection, and emergency surgery was performed. The patient was discharged from the hospital on postoperative day 34 with good progress despite dehydration due to high-output syndrome. CONCLUSIONS Sepsis due to necrosis of ileocecal cancer is often difficult to diagnose because it is not accompanied by abdominal symptoms, as in our case. However, abdominal ultrasound is useful because it allows for a broad evaluation. This report has demonstrated and highlighted that the findings of hepatic portal venous gas on imaging should be regarded seriously, requiring urgent investigation to identify the cause and commence treatment in cases of infection or sepsis.
Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Veia Porta , Sepse , Humanos , Masculino , Idoso , Veia Porta/diagnóstico por imagem , Sepse/microbiologia , Sepse/complicações , Infecções por Klebsiella/complicações , Infecções por Klebsiella/diagnóstico , Neoplasias do Íleo/complicações , Embolia Aérea/diagnóstico por imagem , Embolia Aérea/etiologia , Tomografia Computadorizada por Raios XRESUMO
We present the case of a 71-year-old man who developed sepsis caused by Capnocytophaga canimorsus as a result of being bitten by his own dog. Positive blood cultures were obtained, but due to difficulties in determining the bacterial species, the patient was treated empirically with ceftriaxone and levofloxacin. After using the recommended empirical therapy, the patient's condition improved. Capnocytophaga canimorsus is difficult to identify, among others, due to its long growth time and specific development conditions (capnophiles). These Gram-negative bacilli cause a number of diseases in humans, ranging from infections of the skin and subcutaneous tissue, through peritonitis, to sepsis. The portal of infection with these bacteria is most often a wound caused by an animal bite. Additional risk factors that increase the risk of developing a severe infection and even death include older age, concomitant chronic diseases, and immunosuppression.
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Antibacterianos , Mordeduras e Picadas , Capnocytophaga , Infecções por Bactérias Gram-Negativas , Humanos , Cães , Mordeduras e Picadas/microbiologia , Mordeduras e Picadas/complicações , Animais , Masculino , Idoso , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Capnocytophaga/isolamento & purificação , Antibacterianos/uso terapêutico , Sepse/microbiologia , Sepse/etiologia , Sepse/tratamento farmacológico , Levofloxacino/uso terapêutico , Ceftriaxona/uso terapêuticoRESUMO
Background: Accurate identification of infectious diseases using molecular techniques, such as PCR and NGS, is well-established. This study aims to assess the utility of Bactfast and Fungifast in diagnosing bloodstream infections in ICU settings, comparing them against traditional culture methods. The objectives include evaluating sensitivity and specificity and identifying a wide range of pathogens, including non-culturable species. Methods: We collected 500 non-duplicate blood samples from ICU patients between January 2023 and December 2023. Specimens underwent traditional culture, MALDI-TOF, VITEK®2 compact system, and NGS-based Bactfast and Fungifast analyses. Results: Out of the 500 samples, 26.8% (n=134) showed bacterial growth via traditional culture methods, while 4.8% (n=24) were positive for fungal growth. MALDI-TOF and VITEK®2 compact system yielded comparable results, identifying 26.4% (n=132) of specimens with bacterial growth. NGS-based Bactfast detected bacterial presence in 38.2% (n=191) of samples, including non-culturable bacteria missed by traditional methods. However, NGS-based Fungifast showed concordant fungal detection rates with culture methods. Among identified pathogens by culture method included Klebsiella pneumoniae 20.89% (n=28), Enterococcus faecalis 18.65% (n=25), Escherichia coli 15.67% (n=21), Pseudomonas aeruginosa 12.68% (n=17), Acinetobacter baumannii 10.44% (n=14), various Streptococcus species 7.46% (n=10), Mycobacterium tuberculosis 6.71% (n=9), Mycobacterium abscessus 4.47% (n=6), and Salmonella spp 2.98% (n=4). Non-culture-based NGS identified additional (n=33) pathogens, including Klebsiella pneumoniae 27.27% (n=9), Bacteroides fragilis 21.21% (n=7), Aerococcus viridans 15.15% (n=5), Elizabethkingia anopheles 12.12% (n=4), Aeromonas salmonicida 9% (n=3), Clostridium 9% (n=3), and Bacteroides vulgatus 6% (n=2). Candida albicans was reported in 5% (n=24) of samples by both methods. Conclusion: NGS-based Bactfast and Fungifast demonstrate high sensitivity in identifying a wide array of bacterial and fungal pathogens in ICU patients, outperforming traditional culture methods in detecting non-culturable organisms. These molecular assays offer rapid and comprehensive diagnostic capabilities, potentially improving clinical outcomes through timely and accurate pathogen identification.
Assuntos
Bactérias , Fungos , Sequenciamento de Nucleotídeos em Larga Escala , Unidades de Terapia Intensiva , Sensibilidade e Especificidade , Humanos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/genética , Fungos/isolamento & purificação , Fungos/classificação , Fungos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Técnicas de Diagnóstico Molecular/métodos , Sepse/diagnóstico , Sepse/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Hemocultura/métodos , Cuidados Críticos/métodosRESUMO
BACKGROUND: Early detection and proper management of maternal sepsis caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) can significantly reduce severe complications and maternal mortality. This study aimed to describe the epidemiology, antimicrobial resistance profile, and management of carbapenem-resistant K. pneumoniae among sepsis-suspected maternal cases in Ethiopia. METHODS: A prospective cross-sectional study was conducted in five tertiary hospitals from June 2021 to December 2023. Isolation, identification, and antimicrobial susceptibility testing of the isolates were carried out following standard microbiological procedures as stated in the CLSI guidelines. Data on socio-demographics, risk factors, and management strategies were collected with structured questionnaires. Associations between variables were determined using logistic regression analysis in STATA-21. A p-value of less than 0.05 was statistically significant. RESULTS: Of the 5613 total women suspected of having maternal sepsis, 609 (10.8%) of them were infected with K. pneumoniae. The prevalence rates of MDR, XDR, and PDR K. pneumoniae strains were 93.9%, 24.3%, and 10.9%, respectively. The resistance rates for the last-resort antibiotics; amikacin, tigecycline, carbapenem, and third-generation cephalosporin were 16.4%, 29.1%, 31.9%, and 93.0%, respectively. The combination of carbapenem with tigecycline or amikacin therapy was used to manage maternal sepsis caused by cephalosporin-and carbapenem-resistant strains. Sepsis associated risk factors, including septic abortion [AOR = 5.3; 95%CI:2.2-14.4]; extended hospitalization [AOR = 3.7; 95%CI: 1.6-19.4]; dilatation and curettage [AOR = 2.2; 95%CI:1.3-13.4]; cesarean wound infection [AOR = 4.1; 95%CI:2.0-9.2]; indwelling catheterization [AOR = 2.1;95%CI: 1.4-6.2]; ICU admission [AOR = 4.3; 95%CI:2.4-11.2]; post abortion [AOR = 9.8; 95%CI:5.7-16.3], and recurrent UTI [AOR = 3.3; 95%CI: 1.6-13.2] were significantly associated with maternal sepsis caused by K. pneumoniae. CONCLUSIONS: The prevalence of maternal sepsis caused by carbapenem- resistant K. pneumoniae is high and serious attention needs to be given to combat transmission. Therefore, improving awareness, early diagnosis, IPC, integrated maternal surveillance, improved sanitation and efficient antimicrobial stewardship are crucial to combating bacterial maternal sepsis.
Assuntos
Antibacterianos , Infecções por Klebsiella , Klebsiella pneumoniae , Sepse , Humanos , Feminino , Klebsiella pneumoniae/efeitos dos fármacos , Etiópia/epidemiologia , Estudos Transversais , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Estudos Prospectivos , Sepse/microbiologia , Sepse/tratamento farmacológico , Sepse/epidemiologia , Gravidez , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Testes de Sensibilidade Microbiana , Adulto Jovem , Farmacorresistência Bacteriana Múltipla , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Prevalência , Fatores de Risco , Mães , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Centros de Atenção TerciáriaRESUMO
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.
Assuntos
Modelos Animais de Doenças , Progressão da Doença , Sepse , Animais , Sepse/microbiologia , Humanos , Camundongos , Injeções IntravenosasRESUMO
Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Sepsis-induced cardiomyopathy (SICM), as a serious complication of sepsis, is an acute reversible cardiac dysfunction syndrome unrelated to myocardial ischemia, which affects the outcome and prognosis of sepsis. As a complex microbial system, gut microbiota has been confirmed to be involved in the development of coronary heart disease, hypertension, heart failure and other cardiovascular diseases, and is also related to the occurrence and development of sepsis. However, there are few studies on the relationship between gut microbiota and SICM. This paper reviews the current research progress on gut microbiota and SICM, aiming at provide a new idea for clinical treatment of SICM.
Assuntos
Cardiomiopatias , Disbiose , Microbioma Gastrointestinal , Sepse , Sepse/complicações , Sepse/microbiologia , Humanos , Cardiomiopatias/etiologia , Cardiomiopatias/microbiologiaRESUMO
BACKGROUND: Sepsis remains a leading cause of mortality in intensive care units, and rapid and accurate pathogen detection is crucial for effective treatment. This study evaluated the clinical application of multi-site metagenomic next-generation sequencing (mNGS) for the diagnosis of sepsis, comparing its performance against conventional methods. METHODS: A retrospective analysis was conducted on 69 patients with sepsis consecutively admitted to the Department of Intensive Care Medicine, Meizhou People's Hospital. Samples of peripheral blood and infection sites were collected for mNGS and conventional method tests to compare the positive rate of mNGS and traditional pathogen detection methods and the distribution of pathogens. The methods used in this study included a comprehensive analysis of pathogen consistency between peripheral blood and infection site samples. Additionally, the correlation between the pathogens detected and clinical outcomes was investigated. RESULTS: Of the patients with sepsis, 57.97% experienced dyspnea, and 65.2% had underlying diseases, with hypertension being the most common. mNGS demonstrated a significantly higher pathogen detection rate (88%) compared to the conventional method tests (26%). The pathogen consistency rate was 60% between plasma and bronchoalveolar lavage fluid samples, and that of plasma and local body fluid samples was 63%. The most frequently detected pathogens were gram-negative bacteria, and Klebsiella pneumonia. There were no significant differences in the clinical features between the pathogens. CONCLUSION: mNGS is significantly superior to conventional methods in pathogen detection. There was a notable high pathogen consistency detection between blood and local body fluid samples, supporting the clinical relevance of mNGS. This study highlights the superiority of mNGS in detecting a broad spectrum of pathogens quickly and accurately. TRIAL REGISTRATION: Not applicable.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Unidades de Terapia Intensiva , Metagenômica , Sepse , Humanos , Sepse/diagnóstico , Sepse/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Metagenômica/métodos , Adulto , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analysed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analysed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, P < 0.001 in Model 1; 23.5% vs. 58.6%, P = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.
Assuntos
Antibacterianos , Gestão de Antimicrobianos , Hemocultura , Estado Terminal , Unidades de Terapia Intensiva , Pontuação de Propensão , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Hemocultura/métodos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Sepse/tratamento farmacológico , Sepse/mortalidade , Sepse/microbiologiaRESUMO
Two distinct defense strategies, disease resistance (DR) and disease tolerance (DT), enable a host to survive infectious diseases. Newborns, constrained by limited energy reserves, predominantly rely on DT to cope with infection. However, this approach may fail when pathogen levels surpass a critical threshold, prompting a shift to DR that can lead to dysregulated immune responses and sepsis. The mechanisms governing the interplay between DR and DT in newborns remain poorly understood. Here, we compare metabolic traits and defense strategies between survivors and non-survivors in Staphylococcus epidermidis (S. epidermidis)-infected preterm piglets, mimicking infection in preterm infants. Compared to non-survivors, survivors displayed elevated DR during the initial phase of infection, followed by stronger DT in later stages. In contrast, non-survivors showed clear signs of respiratory and metabolic acidosis and hyperglycemia, together with exaggerated inflammation and organ dysfunctions. Hepatic transcriptomics revealed a strong association between the DT phenotype and heightened oxidative phosphorylation in survivors, coupled with suppressed glycolysis and immune signaling. Plasma metabolomics confirmed the findings of metabolic regulations associated with DT phenotype in survivors. Our study suggests a significant association between the initial DR and subsequent DT, which collectively contributes to improved infection survival. The regulation of metabolic processes that optimize the timing and balance between DR and DT holds significant potential for developing novel therapeutic strategies for neonatal infection.
Assuntos
Animais Recém-Nascidos , Infecções Estafilocócicas , Staphylococcus epidermidis , Animais , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Suínos , Resistência à Doença , Humanos , Fosforilação Oxidativa , Recém-Nascido , Glicólise , Sepse/metabolismo , Sepse/imunologia , Sepse/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Fígado/metabolismo , Fígado/patologiaRESUMO
Non-diphtheroid Corynebacterium sepsis is rare and has affected only immunocompromised or particularly predisposed patients so far. We present the first case of urosepsis caused by Corynebacterium aurimucosum in a 67-year-old woman, without any known immunodeficiencies and in absence of any immunosuppressive therapy, admitted to the hospital for fever and acute dyspnea. This work suggests a new approach in evaluating the isolation of Corynebacteria, especially if isolated from blood. In particular, it highlights the potential infectious role of C. aurimucosum (often considered a contaminant and only rarely identified as an etiological agent of infections) and its clinical consequences, detailing also interesting aspects about its microbiological diagnosis and relative therapy and clarifying contrasting data of literature.
[Box: see text].
Assuntos
Infecções por Corynebacterium , Corynebacterium , Sepse , Infecções Urinárias , Humanos , Corynebacterium/isolamento & purificação , Corynebacterium/genética , Corynebacterium/patogenicidade , Corynebacterium/classificação , Idoso , Feminino , Infecções por Corynebacterium/microbiologia , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/tratamento farmacológico , Sepse/microbiologia , Sepse/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnóstico , Antibacterianos/uso terapêuticoRESUMO
Vibrio vulnificus is a halophilic gram-negative bacillus that can cause fulminant septicaemia in immunocompromised patients. A 67-year-old man who was immunosuppressed as a result of cytotoxic chemotherapy presented with a brief history of fever, lethargy, myalgia, and reduced oral intake. He had recently travelled to the beach to consume seafood. His blood pressure was 81/47 mm Hg, necessitating fluid resuscitation followed by inotropic support and admission to the intensive care unit. His blood culture was positive for curved gram-negative bacilli. The isolate was oxidase-positive and produced an acid butt with an alkaline slant in triple sugar iron agar. Matrix-assisted laser desorption ionization-time of flight mass spectrometry conclusively identified the isolate as V. vulnificus. Intravenous ceftazidime plus ciprofloxacin were administered, and by the fifth day of admission, he was successfully transferred out to the general ward. In total, the patient completed a 14-day course of antibiotic therapy.
Assuntos
Antibacterianos , Sepse , Vibrioses , Vibrio vulnificus , Humanos , Masculino , Idoso , Vibrio vulnificus/isolamento & purificação , Antibacterianos/uso terapêutico , Sepse/microbiologia , Hospedeiro Imunocomprometido , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ciprofloxacina/uso terapêutico , Ceftazidima/uso terapêuticoRESUMO
In Chile, Piscirickettsia salmonis contains two genetically isolated genogroups, LF-89 and EM-90. However, the impact of a potential co-infection with these two variants on Salmonid Rickettsial Septicemia (SRS) in Atlantic salmon (Salmo salar) remains largely unexplored. In our study, we evaluated the effect of P. salmonis LF-89-like and EM-90-like co-infection on post-smolt Atlantic salmon after an intraperitoneal challenge to compare changes in disease dynamics and host immune response. Co-infected fish had a significantly lower survival rate (24.1%) at 21 days post-challenge (dpc), compared with EM-90-like single-infected fish (40.3%). In contrast, all the LF-89-like single-infected fish survived. In addition, co-infected fish presented a higher presence of clinical lesions than any of the single-infected fish. The gene expression of salmon immune-related biomarkers evaluated in the head kidney, spleen, and liver showed that the EM-90-like isolate and the co-infection induced the up-regulation of cytokines (e.g., il-1ß, ifnγ, il8, il10), antimicrobial peptides (hepdicin) and pattern recognition receptors (PRRs), such as TLR5s. Furthermore, in serum samples from EM-90-like and co-infected fish, an increase in the total IgM level was observed. Interestingly, specific IgM against P. salmonis showed greater detection of EM-90-like antigens in LF-89-like infected fish serum (cross-reaction). These data provide evidence that P. salmonis LF-89-like and EM-90-like interactions can modulate SRS disease dynamics in Atlantic salmon, causing a synergistic effect that increases the severity of the disease and the mortality rate of the fish. Overall, this study contributes to achieving a better understanding of P. salmonis population dynamics.
Assuntos
Coinfecção , Doenças dos Peixes , Piscirickettsia , Infecções por Piscirickettsiaceae , Salmo salar , Animais , Piscirickettsia/fisiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/imunologia , Infecções por Piscirickettsiaceae/veterinária , Infecções por Piscirickettsiaceae/microbiologia , Coinfecção/veterinária , Coinfecção/microbiologia , Coinfecção/imunologia , Chile , Sepse/veterinária , Sepse/microbiologia , Sepse/imunologiaRESUMO
Pseudomonas aeruginosa is a complex nosocomial infectious agent responsible for numerous illnesses, with its growing resistance variations complicating treatment development. Studies have emphasized the importance of virulence factors OprE and OprF in pathogenesis, highlighting their potential as vaccine candidates. In this study, B-cell, MHC-I, and MHC-II epitopes were identified, and molecular linkers were active to join these epitopes with an appropriate adjuvant to construct a vaccine. Computational tools were employed to forecast the tertiary framework, characteristics, and also to confirm the vaccine's composition. The potency was weighed through population coverage analysis and immune simulation. This project aims to create a multi-epitope vaccine to reduce P. aeruginosa-related illness and mortality using immunoinformatics resources. The ultimate complex has been determined to be stable, soluble, antigenic, and non-allergenic upon inspection of its physicochemical and immunological properties. Additionally, the protein exhibited acidic and hydrophilic characteristics. The Ramachandran plot, ProSA-web, ERRAT, and Verify3D were employed to ensure the final model's authenticity once the protein's three-dimensional structure had been established and refined. The vaccine model showed a significant binding score and stability when interacting with MHC receptors. Population coverage analysis indicated a global coverage rate of 83.40%, with the USA having the highest coverage rate, exceeding 90%. Moreover, the vaccine sequence underwent codon optimization before being cloned into the Escherichia coli plasmid vector pET-28a (+) at the EcoRI and EcoRV restriction sites. Our research has developed a vaccine against P. aeruginosa that has strong binding affinity and worldwide coverage, offering an acceptable way to mitigate nosocomial infections.
Assuntos
Biologia Computacional , Infecções por Pseudomonas , Pseudomonas aeruginosa , Sepse , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/genética , Humanos , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Sepse/prevenção & controle , Sepse/imunologia , Sepse/microbiologia , Biologia Computacional/métodos , Epitopos/imunologia , Epitopos/química , Pneumonia/prevenção & controle , Pneumonia/imunologia , Pneumonia/microbiologia , Vacinas contra Pseudomonas/imunologia , Vacinas Bacterianas/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genéticaRESUMO
Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.
Assuntos
Ceco , Emodina , Camundongos Endogâmicos C57BL , Sepse , Animais , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/microbiologia , Emodina/farmacologia , Emodina/uso terapêutico , Emodina/análogos & derivados , Ceco/cirurgia , Ceco/microbiologia , Camundongos , Masculino , Ligadura , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Punções , Modelos Animais de Doenças , Imipenem/uso terapêutico , Imipenem/farmacologia , Citocinas/metabolismo , Quimioterapia Combinada , Microbioma Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Microbiota/efeitos dos fármacos , Carga Bacteriana/efeitos dos fármacosRESUMO
Background: Gut microbiota is closely related to the occurrence and development of sepsis. However, the causal effects between the gut microbiota and sepsis, and whether circulating inflammatory proteins act as mediators, remain unclear. Methods: Gut microbiota, circulating inflammatory proteins, and four sepsis-related outcomes were identified from large-scale genome wide association studies (GWAS) summary data. Inverse Variance Weighted (IVW) was the primary statistical method. Additionally, we investigated whether circulating inflammatory proteins play a mediating role in the pathway from gut microbiota to the four sepsis-related outcomes. Results: There were 14 positive and 15 negative causal effects between genetic liability in the gut microbiota and four sepsis-related outcomes. Additionally, eight positive and four negative causal effects were observed between circulating inflammatory proteins and the four sepsis-related outcomes. Circulating inflammatory proteins do not act as mediators. Conclusions: Gut microbiota and circulating inflammatory proteins were causally associated with the four sepsis-related outcomes. However, circulating inflammatory proteins did not appear to mediate the pathway from gut microbiota to the four sepsis-related outcomes.