Search Results (28)

Background/Objectives: Clinical experience indicates that the determination of interleukin 6 (IL-6) in human blood can vary depending on time span between sample collection and centrifugation. Here, we evaluated confounding effects in various blood specimens. Methods: The blood of healthy individuals and critically ill patients was collected in EDTA-, heparin-, and serum collection tubes. Tubes were facultatively incubated (20 °C, 24–48 h) before centrifugation, and IL-6 was measured in the supernatant. Results: The preincubation of the blood collection tubes increased the IL-6 values in heparin plasma (in 17/20 samples up to 50-fold) and serum (in 17/20 samples up to 12-fold). These changes were relevant since the normal values were thereby lifted above the upper confidence limit in 12/20 heparin plasma samples and 4/20 serum samples. These IL-6 increases were probably due to in vitro synthesis as opposed to the release of preformed IL-6 from blood cells because subjecting uncentrifuged collection tubes to mechanical cell lyses had negligible effects on IL-6, while incubation with microbial stimulators dramatically increased these values. In the case of EDTA blood, collection tube preincubation induced IL-6 decreases in 17/20 samples from healthy individuals and 20/23 samples from critically ill patients. Conclusions: IL-6 determination in heparin plasma and serum is compromised by delayed centrifugation. This effect is relevant for normal values. It increased the number of false high results by >50%. The delayed centrifugation of EDTA blood decreased the IL-6 values, which caused a single false-negative result in 1/43 healthy and critically ill people. The false-negative rate is possibly higher in EDTA blood from non-critically ill out-patients, exhibiting moderately increased IL-6 levels. Full article

Cefquinome is used to treat septicemia caused by Escherichia coli (E. coli) and respiratory infections caused by Streptococcus equi subsp. zooepidemicus in foals. However, studies reporting the use of cefquinome to target E. coli as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against E. coli using a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). The main pharmacokinetic parameters of cefquinome in foals were as follows: after intravenous administration, the elimination half-life (T_1/2β) was 2.35 h, the area under the curve (AUC_0–last) was 12.33 μg·h/mL, the mean residence time (MRT_0–last) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (C_max) was 0.89 μg/mL, the time to reach the maximum serum concentration (T_max) was 2.16 h, T_1/2β was 4.16 h, AUC_0–last was 5.41 μg·h/mL, MRT_0–last was 4.92 h, CL was 0.15 L/h/kg, and the absolute bioavailability (F) was 43.86%. An inhibitory sigmoid Emax model was used to integrate the PK/PD indices with ex vivo antimicrobial effects to identify pharmacodynamic targets (PDTs). According to the dose calculation formula, the doses of intramuscularly administered cefquinome required to achieve bacteriostatic effects, bactericidal effects, and bactericidal elimination were 1.10, 1.66, and 2.28 mg/kg, respectively. However, further studies are warranted to verify the therapeutic efficacy of cefquinome in clinical settings. Full article

Background and Clinical Significance: A brain abscess, defined as a localized intracranial infection that evolves into a purulent collection encased by a vascularized capsule, has higher prevalence among immunocompromised populations. Patients with sickle cell disease (SCD) are particularly vulnerable to bacterial infections due to their compromised immune systems, increasing their susceptibility to pathogens like Salmonella. While Salmonella is typically associated with gastroenteritis, osteomyelitis, and septicemia, its involvement in brain abscesses is exceedingly rare. There are few documented cases of Salmonella brain abscesses in the general population, and among patients with SCD, only one such case has been reported to date. In this report, we describe the second known case of a brain abscess caused by Salmonella infection in a patient with sickle cell disease, contributing to the limited literature on this rare and life-threatening condition. Case Presentation: A 32-year-old African American woman with sickle cell disease presented to the ER after a generalized seizure, reporting two weeks of worsening headaches, fevers, and left upper extremity weakness. Imaging revealed a right frontoparietal brain abscess, which was surgically drained, and cultures identified Salmonella enterica. After antibiotic treatment and a 23-day hospital stay, she was discharged. Four months later, she returned with another seizure during a sickle cell crisis, but follow-up MRI showed only minor scarring, and she was discharged on anticonvulsant therapy. Conclusions: This case emphasizes that Salmonella infections, though typically linked to osteomyelitis and sepsis, can also cause brain abscesses in immunocompromised patients like those with sickle cell disease. It highlights the need to consider infections alongside vascular causes in acute neurological cases and underscores the value of a multidisciplinary approach in managing such complex conditions. Full article

Objectives: The aim of the current report is to present three cases of necrotizing fasciitis and sepsis caused by Vibrio vulnificus on the Bulgarian Black Sea coast. Materials and Methods: Two of the patients are males, 70 and 86 years of age, respectively, and one is an 86-year-old female. Data were collected from the patients’ examination records. V. vulnificus was isolated on 5% sheep blood agar from wound and blood samples and identified by the automated system Phoenix M50 (BD, Franklin Lakes, NJ, USA). Antimicrobial susceptibility was tested with two well-known methods (disk diffusion and broth microdilution). Results: All of the patients were admitted to our hospital due to pain, swelling, ulceration, and bullae on the legs and were febrile. They underwent surgery and received intensive care support. One of the patients developed septicemia and septic shock; one of his legs was amputated, but the outcome was fatal. The other patient received immediate approptiate antibiotic and surgical treatment, and the outcome was favorable. The third patient underwent emergency fasciotomy but died a few hours after admission. Conclusions: Global climate change is affecting the distribution of Vibrio spp., and their incidence is expected to increase. It is important to highlight the need for awareness among immunocompromised and elderly patients of the potential threat posed by V. vulnificus infections. Full article

Pseudomonas aeruginosa is among the most ubiquitous bacteria in the natural world, exhibiting metabolic and physiological versatility, which makes it highly adaptable. Imipenem + cilastatin and tetracycline are antibiotic combinations commonly used to treat infections caused by P. aeruginosa, including serious infections such as sepsis. In the context of bacterial infections, biofilm, formed by bacterial cells surrounded by extracellular substances forming a matrix, plays a pivotal role in the resistance of P. aeruginosa to antibiotics. This study aimed to characterize a representative panel of P. aeruginosa isolates from septicemias, assessing their susceptibility to various antibiotics, specifically, imipenem + cilastatin and tetracycline, and the impact of these treatments on biofilm formation. Results from antibiotic susceptibility tests revealed sensitivity in most isolates to six antibiotics, with four showing near or equal to 100% sensitivity. However, resistance was observed in some antibiotics, albeit at minimal levels. Notably, tetracycline showed a 100% resistance phenotype, while imipenem + cilastatin predominantly displayed an intermediate phenotype (85.72%), with some resistance (38.1%). Microdilution susceptibility testing identified effective combinations against different isolates. Regarding biofilm formation, P. aeruginosa demonstrated the ability to produce biofilms. The staining of microtiter plates confirmed that specific concentrations of imipenem + cilastatin and tetracycline could inhibit biofilm production. A significant proportion of isolates exhibited resistance to aminoglycoside antibiotics because of the presence of modifying genes (aac(3)-II and aac(3)-III), reducing their effectiveness. This study also explored various resistance genes, unveiling diverse resistance mechanisms among P. aeruginosa isolates. Several virulence genes were detected, including the las quorum-sensing system genes (lasI and lasR) in a significant proportion of isolates, contributing to virulence factor activation. However, genes related to the type IV pili (T4P) system (pilB and pilA) were found in limited isolates. In conclusion, this comprehensive study sheds light on the intricate dynamics of P. aeruginosa, a remarkably adaptable bacterium with a widespread presence in the natural world. Our findings provide valuable insights into the ongoing battle against P. aeruginosa infections, highlighting the need for tailored antibiotic therapies and innovative approaches to combat biofilm-related resistance. Full article

Background and Objectives: Hearing loss after septicemia has been found in mice; the long-term risk increased 50-fold in young adults in a previous study. Hearing loss after septicemia has not received much attention. The aim of this study was to assess the relationship between septicemia and subsequent hearing loss. Materials and Methods: Inpatient data were obtained from the Taiwan Insurance Database. We defined patients with sensorineural hearing loss and excluded patients under 18 years of age. Patients without hearing loss were selected as controls at a frequency of 1:5. The date of admission was defined as the date of diagnosis. Comorbidities in the 3 years preceding the date of diagnosis were retrieved retrospectively. Associations with hearing loss were established by multiple logistic regression and forward stepwise selection. Results: The odds ratio (OR) for the association between sepsis and hearing loss was 3.052 (95% CI: 1.583–5.884). Autoimmune disease (OR: 5.828 (95% CI: 1.906–17.816)), brain injury (OR: 2.264 (95% CI: 1.212–4.229)) and ischemic stroke (OR: 1.47 (95% CI: 1.087–1.988)) were associated with hearing loss. Conclusions: Our study shows that hearing loss occurred after septicemia. Apoptosis caused by sepsis and ischemia can lead to hair cell damage, leading to hearing loss. Clinicians should be aware of possible subsequent complications of septicemia and provide appropriate treatment and prevention strategies for complications. Full article

Streptococcus pneumonia (S. pneumoniae, Pneumococcus) is a major cause of childhood morbidity and mortality worldwide. The most common presentations of invasive pneumococcal disease (IPD) in children include bacteremic pneumonia, meningitis, and septicemia. However, pneumococcal acute spontaneous peritonitis is a highly uncommon—and potentially life-threatening—presentation of invasive pneumococcal disease and should be considered in cases of abdominal sepsis. To our knowledge, we report the first case of intrafamilial transmission of pneumococcal peritonitis in two previously healthy children. Full article

Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a 4 mm catheter into the bladder using an ultrasound-guided method, previously developed by our group. The following day, Proteus mirabilis (PM) was introduced percutaneously in the bladder in three groups: g1—50 µL 1 × 10⁸ CFU/mL solution (n = 10); g2—50 µL 1 × 10⁷ CFU/mL solution (n = 10); and g3 (sham mice)—50 µL sterile saline (n = 3). On day 4, mice were sacrificed. The number of planktonic bacteria in urine, adherent to catheters, and adherent to/invaded into the bladder and spleen was assessed. Cell-free DNA, D-dimer, thrombin–antithrombin complex (TAT), and 32 pro-/anti-inflammatory cytokines/chemokines were quantified in the blood. All mice survived the 4 day postinterventional period. Mean weight loss was 11% in g1, 9% in g2, and 3% in the control mice. Mean urine CFU counts were highest in group 1. All catheters showed high catheter-adhered bacterial counts. Of the infected mice, 17/20 had CFU counts in the splenic tissue, indicating septicemia. Plasma levels of cell-free DNA, D-dimer, and the proinflammatory cytokines IFN-γ, IL-6, IP-10, MIG, and G-CSF were significantly elevated in infected mice versus controls. We present a reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death, and is useful for studying prolonged urosepsis. Full article

Acinetobacter baumannii is a Gram-negative, immobile, aerobic nosocomial opportunistic coccobacillus that causes pneumonia, septicemia, and urinary tract infections in immunosuppressed patients. There are no commercially available alternative antimicrobials, and multi-drug resistance is an urgent concern that requires emergency measures and new therapeutic strategies. This study evaluated a multi-drug-resistant A. baumannii whole-cell vaccine, inactivated and adsorbed on an aluminum hydroxide–chitosan (mAhC) matrix, in an A. baumannii sepsis model in immunosuppressed mice by cyclophosphamide (CY). CY-treated mice were divided into immunized, non-immunized, and adjuvant-inoculated groups. Three vaccine doses were given at 0D, 14D, and 28D, followed by a lethal dose of 4.0 × 10⁸ CFU/mL of A. baumannii. Immunized CY-treated mice underwent a significant humoral response, with the highest IgG levels and a higher survival rate (85%); this differed from the non-immunized CY-treated mice, none of whom survived (p < 0.001), and from the adjuvant group, with 45% survival (p < 0.05). Histological data revealed the evident expansion of white spleen pulp from immunized CY-treated mice, whereas, in non-immunized and adjuvanted CY-treated mice, there was more significant organ tissue damage. Our results confirmed the proof-of-concept of the immune response and vaccine protection in a sepsis model in CY-treated mice, contributing to the advancement of new alternatives for protection against A. baumannii infections. Full article

Bacterial sepsis induces the production of excessive pro-inflammatory cytokines and oxidative stress, resulting in tissue injury and hyperinflammation. Patients recovering from sepsis have increased rates of central nervous system (CNS) morbidities, which are linked to long-term cognitive impairment, such as neurodegenerative pathologies. This paper focuses on the tissue injury and hyperinflammation observed in the acute phase of sepsis and on the development of long-term neuroinflammation associated with septicemia. Here we evaluate the effects of Coriolus versicolor administration as a novel approach to treat polymicrobial sepsis. Rats underwent cecal ligation and perforation (CLP), and Coriolus versicolor (200 mg/kg in saline) was administered daily by gavage. Survival was monitored, and tissues from vital organs that easily succumb to infection were harvested after 72 h to evaluate the histological changes. Twenty-eight days after CLP, behavioral analyses were performed, and serum and brain (hippocampus) samples were harvested at four weeks from surgery. Coriolus versicolor increased survival and reduced acute tissue injury. Indeed, it reduced the release of pro-inflammatory cytokines in the bloodstream, leading to a reduced chronic inflammation. In the hippocampus, Coriolus versicolor administration restored tight junction expressions, reduce cytokines accumulation and glia activation. It also reduced toll-like receptor 4 (TLR4) and neuronal nitric oxide synthase (nNOS) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome components expression. Coriolus versicolor showed antioxidant activities, restoring glutathione (GSH) levels and catalase and superoxide dismutase (SOD) activities and reducing lipid peroxidation, nitrite and reactive oxygen species (ROS) levels. Importantly, Coriolus versicolor reduced amyloid precursor protein (APP), phosphorylated-Tau (p-Tau), pathologically phosphorylated tau (PHF1), phosphorylated tau (Ser202 and Thr205) (AT8), interferon-induced transmembrane protein 3 (IFITM3) expression, and β-amyloid accumulation induced by CLP. Indeed, Coriolus versicolor restored synaptic dysfunction and behavioral alterations. This research shows the effects of Coriolus versicolor administration on the long-term development of neuroinflammation and brain dysfunction induced by sepsis. Overall, our results demonstrated that Coriolus versicolor administration was able to counteract the degenerative process triggered by sepsis. Full article

Sepsis represents a common cause of morbidity in the Neonatal Intensive Care Unit (NICU). Our objective was to assess the value of clinical and laboratory parameters in predicting septicemia (positive blood culture) in NICU infants. In the first part of the present study (derivation cohort) we retrospectively reviewed the clinical files of 120 neonates with symptoms of suspected sepsis and identified clinical and laboratory parameters associated with proven sepsis on the day the blood culture was taken, as well as 24 h and 48 h earlier. These parameters were combined into a sepsis prediction score (SPS). Subsequently (validation study), we prospectively validated the performance of the SPS in a cohort of 145 neonates. The identified parameters were: temperature instability, platelet count < 150,000/mm³, feeding volume decrease > 20%, changes in blood glucose > 50%, CRP > 1 mg/dL, circulatory and respiratory deterioration. In the retrospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 82.54% sensitivity, 85.96% specificity, 5.88 PLR (Positive Likelihood Ratio), 0.20 NLR (Negative Likelihood Ratio), 86.67% PPV (Positive Predictive Value), 81.67% NPV (Negative Predictive Value) and 84.17% accuracy. In the prospective cohort, on the day the blood culture was obtained, a SPS ≥ 3 could predict sepsis with 76.60% sensitivity, 72.55% specificity, 2.79 PLR, 0.32 NLR, 83.72% PPV, 62.71% NPV and 75.17% accuracy. We concluded that this combination of clinical and laboratory parameters may assist in the prediction of septicemia in NICUs. Full article

Background: Late-onset neonatal sepsis (LOS) represents a significant cause of morbidity and mortality worldwide, and early diagnosis remains a challenge. Various ‘sepsis scores’ have been developed to improve early identification. The aim of the current review is to summarize the current knowledge on the utility of predictive scores in LOS as a tool for early sepsis recognition, as well as an antimicrobial stewardship tool. Methods: The following research question was developed: Can we diagnose LOS with accuracy in neonates using a predictive score? A systematic search was performed in the PubMed database from 1982 (first predictive score published) to December 2021. Results: Some (1352) articles were identified—out of which, 16 were included in the review. Eight were original scores, five were validations of already existing scores and two were mixed. Predictive models were developed by combining a variety of clinical, laboratory and other variables. The majority were found to assist in early diagnosis, but almost all had a limited diagnostic accuracy. Conclusions: There is an increasing need worldwide for a simple and accurate score to promptly predict LOS. Combinations of the selected parameters may be helpful, but until now, a single score has not been proven to be comprehensive. Full article

Background and Objectives: Sepsis increases cardiovascular disease and causes death. Ischemic heart disease (IHD) without acute myocardial infarction has been discussed less, and the relationship between risk factors and IHD in septicemia survivors within six months is worthy of in-depth study. Our study demonstrated the incidence of IHD and the possible risk factors for IHD in septicemia patients within six months. Materials and Methods: An inpatient dataset of the Taiwanese Longitudinal Health Insurance Database between 2001 and 2003 was used. The events were defined as rehospitalization of stroke and IHD after discharge or death within six months after the first septicemia hospitalization. The relative factors of major adverse cardiovascular events (MACEs) and IHD were identified by multivariate Cox proportional regression. Results: There were 4323 septicemia survivors and 404 (9.3%) IHD. New-onset atrial fibrillation had a hazard ratio (HR) of 1.705 (95% confidence interval (C.I.): 1.156–2.516) for MACEs and carried a 184% risk with HR 2.836 (95% C.I.: 1.725–4.665) for IHD by adjusted area and other risk factors. Conclusions: This study explored advanced-aged patients who experienced more severe septicemia with new-onset atrial fibrillation, which increases the incidence of IHD in MACEs within six months of septicemia. Therefore, healthcare providers must identify patients with a higher IHD risk and modify risk factors beforehand. Full article

The present work investigated the dynamic changes in stressed volume (Vs) and other determinants of venous return using a porcine model of hyperdynamic septic shock. Septicemia was induced in 10 anesthetized swine, and fluid challenges were started after the diagnosis of sepsis-induced arterial hypotension and/or tissue hypoperfusion. Norepinephrine infusion targeting a mean arterial pressure (MAP) of 65 mmHg was started after three consecutive fluid challenges. After septic shock was confirmed, norepinephrine infusion was discontinued, and the animals were left untreated until cardiac arrest occurred. Baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of septic shock. Mean circulatory filling pressure (Pmcf) analogue (Pmca), right atrial pressure, resistance to venous return, and efficiency of the heart decreased with time (p < 0.001 for all). Fluid challenges did not improve hemodynamics, but noradrenaline increased Vs from 107 mL to 257 mL (140%) and MAP from 45 mmHg to 66 mmHg (47%). Baseline Pmca and post-cardiac arrest Pmcf did not differ significantly (14.3 ± 1.23 mmHg vs. 14.75 ± 1.5 mmHg, p = 0.24), but the difference between pre-arrest Pmca and post-cardiac arrest Pmcf was statistically significant (9.5 ± 0.57 mmHg vs. 14.75 ± 1.5 mmHg, p < 0.001). In conclusion, the baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of hyperdynamic septic shock. Significant changes were also observed in other determinants of venous return. A new physiological intravascular volume existing at zero transmural distending pressure was identified, termed as the rest volume (Vr). Full article

Staphylococcus lugdunensis is a rare cause of late-onset sepsis in preterm infants. To our best knowledge, we report the fourth case of a male preterm infant who developed fulminant late-onset sepsis due to Staphylococcus lugdunensis with persistent bacteremia secondary to an infected aortic thrombus confirmed with two positive blood cultures. Our patient was an extremely low birth weight growth-restricted infant born at 27 weeks gestation and initially required an umbilical arterial catheter for blood pressure and blood gas monitoring. The course of this neonate was complicated by severe respiratory distress syndrome that evolved into chronic lung disease along with multiple episodes of tracheitis. Hemodynamically, the infant had a significant patent ductus arteriosus, and an episode of medical necrotizing enterocolitis followed by Staphylococcus lugdunensis septicemia. He was diagnosed with an infected aortic thrombus, probably the occult focus responsible for the persistent bacteremia. After a 6-week course of intravenous antibiotics and 4-week course of anticoagulant therapy, the infant responded and recovered without complications. Full article