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Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19., Competing Interests: The authors declare no conflicts of interest.

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001-1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023-1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms., (© 2024. The Author(s).)

Nosocomial infections by multidrug-resistant (MDR) bacteria are among the main causes of morbidity and death in patients hospitalized in intensive care units (ICUs) worldwide. Antibiotic resistance has become a major concern for treating the patients with nosocomial infections. The aim of this study was to describe the antibiotic resistance patterns of pathogens causing infections in adult and pediatric patients in the ICUs of a tertiary care hospital in Kolkata, India. A cross-sectional, retrospective study was conducted from January 2022 to October 2022 on a total of 139 adult and 146 pediatric patients. Depending on clinical symptoms of the patients, samples were collected and subjected to antibiotic sensitivity testing. The culture and sensitivity pattern of clinical isolates from blood, urine, sputum, endotracheal tube (ET) aspirate, and central line catheter insertion site swabs were analyzed. A total of 695 and 556 specimens were obtained from adult and pediatric ICU, respectively. Culture positivity rate among adults and pediatric patients were 37% and 40%, respectively. The most commonly isolated organisms were Gram-negative Enterobacterales and non-fermenters. Most of the bacterial isolates showed very high resistance against multiple antibiotics. Escherichia coli from adult and pediatricpatients were found to be resistant to second generation cephalosporins (95% and 96%, respectively), beta-lactams (95% and 63%, respectively), fluoroquinolones (95% and 81%, respectively), and cotrimoxazole (85% and 78%, respectively). Klebsiella spp. from adult patients were found to be resistant to aminoglycosides (75%), second generation cephalosporins (100%), beta-lactams (94%), fluoroquinolones (92%), carbapenems (88%), and cotrimoxazole (83%). Proteus spp., Acinetobacter baumannii , and Pseudomonas spp. werefound to be resistant to multiple antibiotics. Enterococcus spp. from ICUs showed more than 90% resistance against ampicillin and more than 75% resistance against fluoroquinolones. MDR bacterial infections are increasing in both adult and pediatric ICUs, leading to significant therapeutic challenges. A frequent study of antimicrobial resistance patterns is imperative for antibiotic stewardshipin combatting the deadly effect of the MDR bacteria in critically ill patients.

Aim: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab)., Methods: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM)., Results: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem., Conclusions: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams' susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.

Implant-associated infections are characterized by microbial biofilm formation on implant surface, which renders the microbiological diagnosis challenging and requires, in the majority of cases, a complete device removal along with a prolonged antimicrobial therapy. Traditional cultures have shown unsatisfactory sensitivity and a significant advance in the field has been represented by both the application of the sonication technique for the detachment of live bacteria from biofilm and the implementation of metabolic and molecular assays. However, despite the recent progresses in the microbiological diagnosis have considerably reduced the rate of culture-negative infections, still their reported incidence is not negligible. Overall, several culture- and non-culture based methods have been developed for diagnosis optimization, which mostly relies on pre-operative and intra-operative (i.e., removed implants and surrounding tissues) samples. This review outlines the principal culture- and non-culture based methods for the diagnosis of the causative agents of implant-associated infections and gives an overview on their application in the clinical practice. Furthermore, advantages and disadvantages of each method are described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oliva, Miele, Al Ismail, Di Timoteo, De Angelis, Rosa, Cutone, Venditti, Mascellino, Valenti and Mastroianni.)

Introduction: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis., Methods: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed., Results: One hundred patients were included, with a median age (IQR) of 65 years (58-78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1-35). sE-selectin values did not differ between deceased and survivors ( p = 0.06) and among patients with or without a thrombotic event ( p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO 2 /FiO 2 < 200 and PaO 2 /FiO 2 200-300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 ( p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 ( p = 0.004))., Conclusions: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oliva, Miele, Di Timoteo, De Angelis, Mauro, Aronica, Al Ismail, Ceccarelli, Pinacchio, d’Ettorre, Mascellino and Mastroianni.)

Introduction: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications., Methods: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered., Results: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events., Discussion: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Objective: This study presents real-life experience with cefiderocol used on a compassionate basis for treatment of three patients with severe infections caused by extensively/pan-drug resistant (XDR/PDR) Acinetobacter baumannii (Ab)., Methods: Serum bactericidal activity was determined and considered as a surrogate of cefiderocol susceptibility., Results: Clinical improvement and microbiological eradication of A. baumannii were observed in all three patients, who were affected by extremely complex conditions either for type of infection, adverse effect or resistance profile of A. baumannii., Conclusion: Cefiderocol for XDR/PDR-Ab infections might be reconsidered, especially in light of the recent disappointing results of the CREDIBLE-CR study., (Copyright © 2020. Published by Elsevier Ltd.)

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the secondary resistance in Helicobacter pylori (Hp) infected patients who had failed a first-line therapy, and to compare the genotypic tests performed directly on gastric samples with phenotypic tests performed on culture media. The eradication rate of patients treated with bismuth quadruple therapy (BQT) is also evaluated. A total of 80 positive specimens were retrospectively examined. Antibiotic susceptibility testing of Hp strains was performed by E-test, whereas a molecular commercially available method was used for detecting the mutations involved in clarithromycin and levofloxacin resistance. High resistance levels to metronidazole and clarithromycin (61.6% and 35%, respectively) and worrying resistance levels to levofloxacin (15%) were found phenotypically. Multiple resistance to two or three antibiotics was observed as well. The polymorphism A2143G on clarithromycin 23S rRNA gene was found in 34/80 (42.5%) isolates including 10 mixed infections (29%), whereas 28/80 (35%) strains were resistant phenotypically. Levofloxacin resistance corresponded to 30% by PCR and 15% by E-test (statistically significant, p < 0.05). The knowledge of clarithromycin and levofloxacin resistance is crucial to establish an appropriate therapy in different geographical areas. The genetic methods were superior to phenotypic techniques in the absence of live bacteria or for identifying mixed infections that may lead to a resistance underestimation. The BQT eradication rate was effective (90%).

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae .

Introduction: Intestinal colonization with multi-drug resistant (MDR) microorganisms is a consequence of antimicrobial-induced gut dysbiosis. Given the effect of probiotics in modulating gut microbiota, the aim of the study was to investigate whether the ingestion of high concentration multi-strain probiotic formulation would change the antibacterial activity of the feces against clinical strains of MDR microorganisms. The corresponding in vitro antibacterial activity was also investigated. Materials/methods: The feces of healthy donors ( n = 6) were analyzed before and after a 7-day dietary supplementation with a multi-strain probiotic formulation and tested against MDR microorganisms of clinical concern (carbapenem-resistant (CR), Klebsiella pneumoniae (CR-Kp), CR- Acinetobacter baumannii (CR-Ab), CR- Pseudomonas aeruginosa (CR-Pa), and methicillin-resistant Staphylococcus aureus (MRSA)). The tested MDR pathogens were cultured with decreasing concentrations of fecal water obtained before and after the treatment period. Furthermore, to corroborate the results obtained from the feces of healthy donors, the in vitro antibacterial activity of probiotic formulation (both whole probiotic (WP) and probiotic surnatant (PS)) against the same collection of MDR microorganisms was evaluated at different incubation times throughout the minimum bactericidal dilution and the corresponding serial silution number. Results: While before probiotic administration, the fecal water samples did not inhibit MDR microorganism growth, after supplementation, a reduced bacterial growth was shown. Accordingly, a noticeable in vitro activity of WP and PS was observed. Conclusions: Although preliminary, these experiments demonstrated that a specific multi-strain probiotic formulation exhibits in vitro antibacterial activity against MDR microorganisms of clinical concern. If confirmed, these results may justify the administration of probiotics as a decolonization strategy against MDR microorganisms.

Background: Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI., Methods: Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively., Results: Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls ( P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values., Conclusions: CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)