Septic Infection Research Articles

Monitoring Immune Dysfunction in Critically Ill Patients with Carbapenem-Resistant Acinetobacter baumannii Sepsis Treated with Regimens Including Cefiderocol: A Pilot Study to Identify Accessible Biomarkers to Stratify Patients’ Prognosis

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care.

The priority of bacteria <i>Staphylococcus</i> spp. in the etiology of purulent septic infections through the prism of new diagnostic capabilities: A literature review

Representatives of the genus Staphylococcus spp. occupy a leading place in the etiology of infections caused by opportunistic bacteria. Staphylococcus spp., being symbionts of humans and/or animals, are constantly located on the surface of the skin and mucous membranes, which are their natural habitats. The importance of bacteria of the genus Staphylococcus spp. It is determined by their significant distribution in the population, as well as among patients and medical personnel, due to their transient and resident carrier, as well as their high adaptive potential, due to their ability to form biofilms and produce enzymes that provide them with protection from antimicrobial drugs. Modern molecular genetic methods for identifying Staphylococcus spp. and assessing their epidemic potential allow us to rethink their importance in the etiology of nosocomial purulent septic infections in a new way. It is no coincidence that they entered the group of ESCAPE pathogens with a high level of priority. The ability of staphylococci to form biofilms ensures their survival in various hospital/environmental facilities, which in the conditions of a medical organization become additional, or so-called “inanimate” sources of infection. In recent years, despite the increasing role of coagulase-negative staphylococci in the etiology of purulent septic infections, Staphylococcus aureus remains the most significant causative agent of purulent septic infections.

Klebsiella Pneumoniae – Taxonomy, Occurrence, Identification, Virulence Factors and Pathogenicity

Abstract Gram-negative bacilli Klebsiella pneumoniae are among the most important pathogens responsible for healthcare-associated infections (HAIs). These bacteria often have high pathogenic and epidemic potential, contributing to infection outbreaks worldwide. K. pneumoniae is part of the natural microbiota of humans. At the same time, as an opportunistic microorganism, when the host organism is weakened, it can cause serious infections such as pneumonia, urinary tract infections, septic infections and intra-organ abscesses. Widespread distribution in nature and exceptional adaptability provide K. pneumoniae with the opportunity to master new niches in the hospital environment, which poses a threat to hospitalized patients. Also, the bacteria are increasingly causing life-threatening infections in the non-hospital environment. The pathogenicity of K. pneumoniae is determined by the presence of many virulence factors such as capsular polysaccharide (CPS, K antigen), lipopolysaccharid (LPS, O antigen), fimbrial and non-fimbrial adhesins, siderophores (aero-bactin, enterobactin, salmochelin and yersiniabactin), heat-stabile and heat-labile enterotoxins, cytotoxins and biofilm-forming ability. Currently, hypervirulent strains of K. pneumoniae (hvKp) equipped with new virulence traits constitute a significant danger. The paper presents these bacteria concerning the global threat arising from the dynamic spread of hvKp strains in hospitals in Poland and worldwide.

Epidemiological and clinical profiles of septic arthritis in children of 0-2 years of age in Eastern Uttar Pradesh, India

Background: Septic arthritis identified as infectious arthritis is a serious joint infection following the invasion of joint cavities by infectious agents usually bacteria. Due to speediness of joint destruction untreated septic arthritis may result in morbidity and mortality. Methods: Out of 71 sick children attending pediatric OPD/IPD of BRDMC Gorakhpur with musculoskeletal infection during November 2019 to October 2020, 52 patients of 0-2 years of age were enrolled for study. The computerized charts containing various parameters related to the epidemiological and clinical profiles of the patients were recorded and analyzed following statistical package for the social sciences (SPSS) version 23. Results: Out of 52 children 28.8% were neonates under the age of 28 days, 73.1% were full-term infants and 23.1% were premature. Likewise, 17.3% of the cases were with low birth weight whereas 7.7% had a history of septic infection. Hip joints in 65.4%, knee joints in 23.1% and elbow and shoulder joints in 5.8% of patients were infected. 44.2% of cases had right side involvement, 36.5% left side, 19.2% e bilateral joints, 80.8% Mono-articular and 19.2% showed poly-articular involvement. 84.6% of cases showed joint pain whereas 92.3% showed joint swelling. In 20% patients microbial culture of joint fluid revealed the growth of Staphylococcus aureus, Candida spp, E. coli and Pseudomonas spp. In 78.8% cases no growth of any pathogen was recorded in their blood culture. Ultrasonography (USG) diagnosis revealed fluid collection at joints in 94.2% cases while 5.8% exhibited pus collection. Conclusions: Septic arthritis was more common in males than females, monoarticular involvement was more common on the right side, hip joints were most affected joints and Staphylococcus aureus was the most common pathogen affecting the patients.

Tolerability of N-chlorotaurine in comparison with routinely used antiseptics: an in vitro study on chondrocytes

BackgroundCurrently, povidone-iodine (PVP-I) and hydrogen peroxide (H2O2) are frequently used antiseptics in joint infections, but the cytotoxic effects of these solutions are already reported. N-chlorotaurine (NCT) shows a broad-spectrum bactericidal activity and is well tolerated in various tissues, but its effect on human chondrocytes is unknown. The purpose of this study was to assess the cytotoxic effect of NCT, PVP-I, and H2O2 on human chondrocytes compared to a control group in an in vitro setting to get first indications if NCT might be a promising antiseptic in the treatment of septic joint infections for the future.Material and methodsChondrocytes extracted from human cartilage were incubated with various concentrations of NCT, PVP-I, and H2O2 for 5 and 30 min respectively. EZ4U cell viability kit was used according to the manufacturer’s recommendations determining cell viability. To assess cell viability based on their nuclear morphology, cells were stained with acridine-orange and identified under the fluorescence microscope.ResultsEZ4U kit showed after 5 and 30 min of incubation a significant decrease in cell viability at NCT 1%, NCT 0.1%, PVP-I, and H2O2, but not for NCT 0.001% and NCT 0.01%. Acridine-orange staining likewise presented a significant decrease in vital cells for all tested solutions except NCT 0.001% and NCT 0.01% after 5 and 30 min of incubation.ConclusionOur results demonstrate that NCT is well tolerated by chondrocytes in vitro at the tested lower NCT concentrations 0.01% and 0.001% in contrast to the higher NCT concentrations 1% and 0.1%, PVP-I (1.1%), and H2O2 (3%), for which a significant decrease in cell viability was detected. Considering that the in vivo tolerability is usually significantly higher, our findings could be an indication that cartilage tissue in vivo would tolerate the already clinically used 1% NCT solution. In combination with the broad-spectrum bactericidal activity, NCT may be a promising antiseptic for the treatment of septic joint infections.Graphical abstract

Exosomal Tenascin-C primes macrophage pyroptosis amplifying aberrant inflammation during sepsis-induced acute lung injury

Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression. By integrating exosomal proteomics with transcriptome sequencing and experimental validation, we elucidated that LPS induce unresolved endoplasmic reticulum stress (ERs) in alveolar epithelial cells (AECs), ultimately leading to the release of exosomal TNC through the activation of PERK-eIF2α and the transcription factor CHOP. In the sepsis mouse model with TNC knockout, we noted a marked reduction in macrophage pyroptosis. Our detailed investigations found that exosomal TNC binds to TLR4 on macrophages, resulting in an augmented production of ROS, subsequent mitochondrial damage, activation of the NF-κB signaling pathway, and induction of DNA damage response. These interconnected events culminate in macrophage pyroptosis, thereby amplifying the release of inflammatory cytokines. Our findings demonstrate that exosomal Tenascin-C, released from AECs under unresolved ER stress, exacerbates acute lung injury by intensifying sepsis-associated inflammatory responses. This research provides new insights into the complex cellular interactions underlying sepsis-induced ALI.

The bone marrow endothelial progenitor cell response to septic infection.

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)-, lin-c-kit+, and lin- cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin-c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin-c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin-c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.

Characterisation of a capsular polysaccharide from Moraxella nonliquefaciens CCUG 348T

Moraxella nonliquefaciens is a commensal of the human upper respiratory tract (URT) but on rare occasions is recovered in cases of ocular, septic and pulmonary infections. Hence there is interest in the pathogenic determinants of M. nonliquefaciens, of which outer membrane (OM) structures such as fimbriae and two capsular polysaccharide (CPS) structures, →3)-β-D-GalpNAc-(1→5)-β-Kdop-(2→ and →8)-α-NeuAc-(2→, have been reported in the literature. To further characterise its surface virulence factors, we isolated a novel CPS from M. nonliquefaciens type strain CCUG 348T. This structure was elucidated using NMR data obtained from CPS samples that were subjected to various degrees of mild acid hydrolysis. Together with GLC-MS data, the structure was resolved as a linear polymer composed of two GalfNAc residues consecutively added to Kdo, →3)-β-D-GalfNAc-(1→3)-α-D-GalfNAc-(1→5)-α-(8-OAc)Kdop-(2→.Supporting evidence for this material being CPS was drawn from the proposed CPS biosynthetic locus which encoded a potential GalfNAc transferase, a UDP-GalpNAc mutase for UDP-GalfNAc production and a putative CPS polymerase with predicted GalfNAc and Kdo transferase domains. This study describes a unique CPS composition reported in Moraxella spp. and offers genetic insights into the synthesis and expression of GalfNAc residues, which are rare in bacterial OM glycans.

Substantiation of ways to reduce contamination by bacteria of the genus Cronobacter of dry specialized products for baby food during their production

Prevention of morbidity in the child population from septic foodborne infections caused by the new bacterial pathogen Enterobacter sakazakii (according to the new classification - Cronobacter spp.) is becoming increasingly relevant due to an expanding contingent of susceptible individuals and the proven ability of low doses of the pathogen to quickly increase a population in dry specialized products for formula feeding after rehydration. In this regard, it is important to assess the risk of accumulation of thermoresistant coliform enterobacteria, including Cronobacter spp., in residual microflora of such products during their production in order to determine ways to minimize it. To identify a hazardous factor in specialized infant formula of domestic production, we summarized and analyzed expert data on contamination of 245 samples of infant formula and 182 cereals with the entire spectrum of coliform enterobacteria, which were previously identified as Enterobacter sakazakii (Cronobacter spp.). Cronobacter spp. was detected in 4 samples of instant formula (1.6 %) in amounts ranging from 0.04 to 0.5 CFU/g, which is above the hazardous level (≥ 0.003 CFU/g) for susceptible children. No pathogen was isolated from dry mixtures for cooking and instant porridges produced by dry mixing but the content of heat-resistant Enterobacter spp. was 10 times higher than those produced during the full cycle. Using a risk process model and assuming the content of coliforms in raw milk at the level of the regulated microbial number, probability of pathogen survival in dry mixtures was assessed under standard parameters of spray drying technology. The calculation results showed that under this scenario of raw material contamination, 0.3–0.5 CFU of heat-resistant E.sakazakii (Cronobacter spp.) can be retained in 1 g of a finished product. This substantiates the necessity to introduce the strongest possible requirements for the microbiological quality of raw milk.

Construction of an aerolysin-based multi-epitope vaccine against Aeromonas hydrophila: an in silico machine learning and artificial intelligence-supported approach.

Aeromonas hydrophila, a gram-negative coccobacillus bacterium, can cause various infections in humans, including septic arthritis, diarrhea (traveler's diarrhea), gastroenteritis, skin and wound infections, meningitis, fulminating septicemia, enterocolitis, peritonitis, and endocarditis. It frequently occurs in aquatic environments and readily contacts humans, leading to high infection rates. This bacterium has exhibited resistance to numerous commercial antibiotics, and no vaccine has yet been developed. Aiming to combat the alarmingly high infection rate, this study utilizes in silico techniques to design a multi-epitope vaccine (MEV) candidate against this bacterium based on its aerolysin toxin, which is the most toxic and highly conserved virulence factor among the Aeromonas species. After retrieval, aerolysin was processed for B-cell and T-cell epitope mapping. Once filtered for toxicity, antigenicity, allergenicity, and solubility, the chosen epitopes were combined with an adjuvant and specific linkers to create a vaccine construct. These linkers and the adjuvant enhance the MEV's ability to elicit robust immune responses. Analyses of the predicted and improved vaccine structure revealed that 75.5%, 19.8%, and 1.3% of its amino acids occupy the most favored, additional allowed, and generously allowed regions, respectively, while its ERRAT score reached nearly 70%. Docking simulations showed the MEV exhibiting the highest interaction and binding energies (-1,023.4 kcal/mol, -923.2 kcal/mol, and -988.3 kcal/mol) with TLR-4, MHC-I, and MHC-II receptors. Further molecular dynamics simulations demonstrated the docked complexes' remarkable stability and maximum interactions, i.e., uniform RMSD, fluctuated RMSF, and lowest binding net energy. In silico models also predict the vaccine will stimulate a variety of immunological pathways following administration. These analyses suggest the vaccine's efficacy in inducing robust immune responses against A. hydrophila. With high solubility and no predicted allergic responses or toxicity, it appears safe for administration in both healthy and A. hydrophila-infected individuals.

Обоснование путей снижения контаминации бактериями рода Cronobacter сухих специализированных продуктов для детского питания на этапе их производства

Prevention of morbidity in the child population from septic foodborne infections caused by the new bacterial pathogen Enterobacter sakazakii (according to the new classification - Cronobacter spp.) is becoming increasingly relevant due to an expanding contingent of susceptible individuals and the proven ability of low doses of the pathogen to quickly increase a population in dry specialized products for formula feeding after rehydration. In this regard, it is important to assess the risk of accumulation of thermoresistant coliform enterobacteria, including Cronobacter spp., in residual microflora of such products during their production in order to determine ways to minimize it. To identify a hazardous factor in specialized infant formula of domestic production, we summarized and analyzed expert data on contamination of 245 samples of infant formula and 182 cereals with the entire spectrum of coliform enterobacteria, which were previously identified as Enterobacter sakazakii (Cronobacter spp.). Cronobacter spp. was detected in 4 samples of instant formula (1.6 %) in amounts ranging from 0.04 to 0.5 CFU/g, which is above the hazardous level (≥ 0.003 CFU/g) for susceptible children. No pathogen was isolated from dry mixtures for cooking and instant porridges produced by dry mixing but the content of heat-resistant Enterobacter spp. was 10 times higher than those produced during the full cycle. Using a risk process model and assuming the content of coliforms in raw milk at the level of the regulated microbial number, probability of pathogen survival in dry mixtures was assessed under standard parameters of spray drying technology. The calculation results showed that under this scenario of raw material contamination, 0.3–0.5 CFU of heat-resistant E.sakazakii (Cronobacter spp.) can be retained in 1 g of a finished product. This substantiates the necessity to introduce the strongest possible requirements for the microbiological quality of raw milk.

Subcutaneous cardioverter defibrillator implanted intermuscularly in patients with end-stage renal disease requiring hemodialysis: 5-year follow-up.

The aim of the present study was to evaluate the long-term safety and effectiveness of the subcutaneous implantable cardioverter defibrillator (S-ICD) when implanted intermuscularly in patients with end-stage renal disease and hemodialysis. This study is a retrospective analysis of 21 consecutive patients implanted with S-ICDs at three experienced centers in Germany with comorbid renal insufficiency requiring hemodialysis, as well as being at risk of sudden cardiac death. The S-ICD was placed intermuscularly in all patients. Follow-ups (FUs) were performed every 6months. The mean ± standard deviation FU duration was 60.0 ± 11.4months, with a range of 39 to 78months. There were no deaths due to arrhythmia, or device-associatedinfections and complications. Four patients (19.1%) died during FU due to respiratory insufficiency during dialysis, systolic heart failure, septic infection of the urogenital tract, and colorectal cancer, respectively. There were six non-device-related hospitalizations with a duration of 12.7 ± 5.1days and a hospitalization rate of 4.1 per 100 patient years. In the long-term FU of this small population of seriously compromised hemodialysis patients at risk of sudden cardiac death, the intermuscularly implanted S-ICD system was safe and effective. No arrhythmic complications, device-associated infections, or complications compromised survival. These data are encouraging and support testing in a larger group of similarly compromised patients.

Análisis de las variantes genéticas IL-6 – 174G/C y FNT-α -308 G/A en pacientes con diagnóstico de sepsis bacteriana

The objective of this study was to evaluate the IL-6 -174G/C and TNF-α -308G/A variants in patients diagnosed with bacterial sepsis in an Intensive Care Unit (ICU).
 Materials and methods. A prospective observational study was conducted that included one hundred patients with sepsis and thirty control subjects. Blood samples were collected to measure the concentrations of cytokines IL-6 and TNF-α and to detect the genetic variants IL-6-174G/C and TNF-α-308A/G. A multivariate analysis was performed with cytokine levels, sepsis progression, comorbidities and mortality as dependent variables and genetic variants analyzed as independent variables. Survival analysis was performed according to the Kaplan and Meyer model.
 Results. Multivariate analysis showed that the G allele of IL-6-174 G/C was a risk factor for developing sepsis due to infection by Gram-negative bacteria (62,3%; OR:2,619; IC95%1,095-6,259; p=0,030) and the GA genotype of TNF-α-308G/A was significantly associated with the development of septic shock (50%; OR:4,053; IC95%1,546- 10,623; p=0,004), arterial hypertension (53%; OR:3,359; IC 95% 1,253-9,008; p=0,016) and infection by Gram-positive bacteria (17,6%; OR:9,525; IC95%1,854-48,928; p=0,007). Conclusion. The GA genotype of TNF-α-308G/A was found to be a risk factor for the development of septic shock

Diagnostic considerations in the clinical management of sudden swelling of the knee: a case report and review of the literature

BackgroundReactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee.Case presentationWe report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease.ConclusionsIt is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms.

In vivo functional immunoprotection correlates for vaccines against invasive bacteria

Vaccination has significantly reduced the incidence of invasive infections caused by several bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. However, no vaccines are available for many other invasive pathogens. A major hurdle in vaccine development is the lack of functional markers to quantify vaccine immunity in eliminating pathogens during the process of infection. Based on our recent discovery of the liver as the major organ of vaccine-induced clearance of blood-borne virulent bacteria, we here describe a new vaccine evaluation system that quantitatively characterizes the key features of effective vaccines in shuffling virulent bacteria from the blood circulation to the liver resident macrophage Kupffer cells (KCs) and sinusoidal endothelial cells (LSECs) in mouse septic infection model. This system consists of three related correlates or assays: pathogen clearance from the bloodstream, pathogen trapping in the liver, and pathogen capture by KCs/LSECs. These readouts were consistently associated with the serotype-specific immunoprotection levels of the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) against lethal infection of S. pneumoniae, a major invasive Gram-positive pathogen of community-acquired infections in humans. Furthermore, the reliability and sensitivity of these correlates in reflecting vaccine efficacy were verified with whole cell vaccines of Klebsiella pneumoniae and Escherichia coli, two major Gram-negative pathogens in hospital-acquired invasive infections. This system may be used as effective readouts to evaluate the immunoprotective potential of vaccine candidates in the preclinical phase by filling the current technical gap in vaccine evaluation between the conventional in vitro approaches (e.g. antibody production and pathogen neutralization/opsonophagocytosis) and survival of immunized animals.

Purpura fulminans – meningococcal infection or postsplenectomy sepsis

The article presents two clinical cases with description of peculiarities of septic infection occurred after splenectomy and due to congenital splenic hypoplasia.Decreased immune defense resulted from splenectomy leads to severe infections with a high risk of death. The most severe sequela is overwhelming postsplenectomy infection (OPSI-syndrome) which is characterized by high mortality rate (50-70%) within 12-24 hours from the onset of the first symptoms. The main risk factors of postsplenectomy sepsis are a condition which became an indication for splenectomy, the immune status of the patient, age and the time period after splenectomyStreptococcus pneumoniae, Haemophilus infuenzae type b, Neisseria meningitidis are commonly identified etiological factors of OPSI-syndrome. The diagnosis could be delayed due to nonspecific flu-like prodromal symptoms of the OPSI-syndrome. Delay in the diagnosis and treatment of sepsis may increase the risk of death.One of the syndromes associated with post-splenectomy sepsis is fulminant purpura (purpura fulminans), which requires differential diagnosis with meningococcal infection. However, half of the cases of fulminant pneumococcal purpura occur in patients with asplenia or hyposplenia. In the first clinical case, a preliminary diagnosis of generalized meningococcal infection was made on admission, but the diagnosis of pneumococcal infection could not be excluded in asplenic patient and was subsequently confirmed by laboratory tests.Given the high risk of fulminant postsplenectomy sepsis, and the difficulties of timely diagnosis, the preventive strategy of infections after splenectomy falls into three major categories- vaccination, antibiotic prophylaxis, and patient (patient’s parents) education.Improving healthcare workers’ knowledge is required to ensure prompt diagnosis of hyposplenism, adequate risk assessment of postplenectomy infection and prevention of OPSI-syndrome.

18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

Urinary tract infections in children in the era of growing antimicrobial resistance – recommendations of the Polish Society of Paediatric Nephrology

Introduction and objective: Urinary tract infections can recur in children, and due to their potential long-term consequences, they require appropriate diagnosis and prompt treatment. Although Escherichia coli is the most common aetiology, an increase in infections with drug-resistant strains has been observed. The aim of this study was to develop current diagnostic and treatment recommendations in the era of increasing microbial resistance. Materials and methods: The recommendations are based on updated guidelines developed by the experts of the Polish Society of Paediatric Nephrology and a literature review. Results: Because the symptoms of urinary tract infection are often non-specific, urinalysis and urine culture should be performed in children presenting with fever without an identifiable cause. Correct method of urine collection and interpretation of the results are crucial for therapeutic decisions. Treatment should be continued for 7–14 days for upper and 3–5 days for lower urinary tract infections; the choice of the narrowest-spectrum antimicrobial should be based on bacterial susceptibility. Antibiotic prophylaxis is limited and recommended in children with grade III–V vesicoureteral reflux. Non-pharmacological management should include treatment of bladder and bowel dysfunction. Ultrasound is recommended for all children up to 24 months of age. Indications for voiding cystourethrography are limited to cases with ultrasound abnormalities, recurrent and septic infections. Conclusion: The paper provides up-to-date, practical recommendations for the diagnosis and management of urinary tract infections in children in the era of increasing microbial resistance and restricted indications for invasive radiological investigations.

Alteration of lipopolysaccharide O antigen leads to avirulence of gut-colonizing Serratia marcescens.

The reason why the potent entomopathogen Serratia marcescens fails to kill insects through oral infection is unknown. To compare effects of septic injection and oral administration of S. marcescens, we used a model bean bug, Riptortus pedestris. Most R. pedestris insects survived oral infections, but not septic infections. Although the number of S. marcescens cells in hemolymph after oral infection, which were originated from gut-colonizing S. marcescens, was higher than the fatal number of cells used in septic injection, they did not kill host insects, suggesting a loss of virulence in gut-colonizing S. marcescens cells. When gut-colonizing S. marcescens cells were septically injected into insects, they failed to kill R. pedestris and survive in hemolymph. To understand the avirulence mechanisms in gut-colonizing bacteria, lipopolysaccharides of S. marcescens were analyzed and revealed that the O antigen was lost during gut colonization. Gut-colonizing S. marcescens cells were resistant to humoral immune responses but susceptible to cellular immune responses, easily succumbing to phagocytosis of hemocytes. When cellular immunity was suppressed, the gut-colonizing S. marcescens cells recovered their virulence and killed insects through septic injection. These results suggest that a key mechanism of avirulence in orally infected S. marcescens is the loss of the O antigen, resulting in susceptibility to host's cellular immune responses.

Impact of 1-hour and 3-hour sepsis time bundles on antibiotic use in emergency departments in Queensland, Australia: a before-and-after cohort study

ObjectiveTo determine if the introduction of an emergency department (ED) sepsis screening tool and management bundle affects antibiotic prescribing and use.DesignMulticentre, cohort, before-and-after study design.SettingThree tertiary hospitals in Queensland, Australia...