Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two ...exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies.
Fosfomycin (FOS) administered intravenously has been recently rediscovered for the treatment of systemic infections due to multidrug-resistant bacteria. Its pharmacokinetic properties suggest a ...time-dependent dosing schedule with more clinical benefits from prolonged (PI) or continuous infusion (CI) than from intermittent infusion. We revised literature concerning PI and CI FOS to identify the best dosing regimen based on current evidence. We performed a MEDLINE/PubMed search. Ninety-one studies and their pertinent references were screened. Seventeen studies were included in the present review. The activity of FOS against Gram-negative and Gram-positive bacteria was evaluated in fourteen and five studies, respectively. Six studies evaluated FOS activity in combination with another antibiotic. Daily dosing of 12, 16, 18 or 24 g, administered with different schedules, were investigated. These regimens resulted active against the tested isolates in most cases. Emergence of resistant isolates has been shown to be preventable through the coadministration of another active antibiotic. FOS is a promising option to treat systemic infections caused by multidrug-resistant bacteria. Coadministration with another active molecule is required to prevent the emergence of resistant bacterial strains. The results of our review suggest that a therapeutic regimen including a loading dose of FOS 8 g followed by a daily dose of 16 g or 24 g CI could be the best therapeutic approach for patients with normal renal function. The dosing regimens in patients with renal insufficiency and CI or PI superiority compared with intermittent infusion in clinical settings should be further investigated.
Abstract Clostridium difficile infection (CDI) is an emerging problem worldwide associated with significant morbidity, mortality, recurrence rates and healthcare costs. Immunosuppressed patients, ...including HIV-seropositive individuals, solid organ transplant recipients, patients with malignancies, hematopoietic stem cell transplant recipients, and patients with inflammatory bowel disease are increasingly recognized as being at higher risk of developing CDI where it may be associated with significant complications, recurrence, and mortality. Fecal microbiota transplantation (FMT) has proven to be an effective and safe procedure for the treatment of recurrent or refractory CDI in immunocompetent patients by restoring the gut microbiota and resistance to further recurrences. During the last two years the first data on FMT in immunocompromised patients began to appear in the medical literature. Herein we summarize the use of FMT for the treatment of CDI with a focus on immunocompromised patients.
Highlights • ECMO patients have a higher infectious risk than other critically ill patients. • Infections during the ECMO run significantly affect mortality rates. • Colonisation of ECMO cannulae and ...oxygenator could have a role in causing bloodstream infections. • Enterobacteriaceae are the most frequent agents of ventilator-associated pneumonia in this setting. • There are no data supporting an antibiotic prophylaxis strategy during ECMO.
•Fosfomycin (FOF) is an antibiotic option against multidrug-resistant (MDR) Enterobacterales.•Zidovudine (ZDV) has unexploited antibacterial properties.•Study of ZDV in combination with FOF against ...MDR Enterobacterales.•In vitro, ZDV restored FOF susceptibility in ~90% of resistant strains.•In vivo, G. mellonella survival was higher (20–50%) with FOF + ZDV combination.
Multidrug-resistant (MDR) Enterobacterales are a priority health issue with few treatment options. Recently, fosfomycin has been reconsidered for MDR bacterial infections. Zidovudine, licensed for the treatment of human immunodeficiency virus (HIV), has unexploited antibacterial properties and has been considered for drug repurposing. The aim of this study was to assess the effect of the combination of fosfomycin plus zidovudine against clinical MDR Enterobacterales isolates. Minimum inhibitory concentration (MIC) determination and checkerboard assays for 36 MDR Enterobacterales strains were performed. In addition, fosfomycin-resistant strains were evaluated using time–kill assay and in an in vivo Galleria mellonella infection model. Zidovudine and fosfomycin MICs ranged between 0.06 to >64 mg/L and 0.125 to >512 mg/L, respectively. A synergistic effect fractional inhibitory concentration index (FICI) ≤0.5 was observed in 25 isolates and no antagonistic effect was observed in the remaining isolates. For 7 of 8 fosfomycin-resistant strains (MIC > 32 mg/L), zidovudine combination was able to restore fosfomycin susceptibility. These results were confirmed by time–kill assays. Fosfomycin + zidovudine presented greater larval survival (20–50%) than monotherapy. Synergistic activity was observed for fosfomycin + zidovudine in 69.4% of the tested strains. In vivo experiments confirmed the enhanced effectiveness of the combination. The zidovudine concentrations tested here can be reached in human serum using the actual licensed dosage, therefore this combination deserves further clinical investigation.
One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of ...approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population.
To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia.
Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2.
We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (
= 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg interquartile range (IQR) 21; 108; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (
< 0.001).
High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the 'leaky gut' syndrome.
OBJECTIVE:To study incidence, type, etiology, risk factors, and impact on outcome of nosocomial infections during extracorporeal membrane oxygenation.
DESIGN:Retrospective analysis of prospectively ...collected data.
SETTING:Italian tertiary referral center medical-surgical ICU.
PATIENTS:One hundred five consecutive patients who were treated with extracorporeal membrane oxygenation from January 2010 to November 2015.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Ninety-two patients were included in the analysis (48.5 37–56 years old, simplified acute physiology score II 37 32–47) who underwent peripheral extracorporeal membrane oxygenation (87% veno-venous) for medical indications (78% acute respiratory distress syndrome). Fifty-two patients (55%) were infected (50.4 infections/1,000 person-days of extracorporeal membrane oxygenation). We identified 32 ventilator-associated pneumonia, eight urinary tract infections, five blood stream infections, three catheter-related blood stream infections, two colitis, one extracorporeal membrane oxygenation cannula infection, and one pulmonary-catheter infection. G+ infections (35%) occurred earlier compared with G– (48%) (4 2–10 vs. 13 7–23 days from extracorporeal membrane oxygenation initiation; p < 0.001). Multidrug-resistant organisms caused 56% of bacterial infections. Younger age (2–35 years old) was independently associated with higher risk for nosocomial infections. Twenty-nine patients (31.5%) died (13.0 deaths/1,000 person-days of extracorporeal membrane oxygenation). Infected patients had higher risk for death (18 vs. 8 deaths/1,000 person-days of extracorporeal membrane oxygenation; p = 0.037) and longer ICU stay (32.5 19.5–78 vs. 19 10.5–27.5 days; p = 0.003), mechanical ventilation (36.5 20–80.5 vs. 16.5 9–25.5 days; p < 0.001), and extracorporeal membrane oxygenation (25.5 10.75–54 vs. 10 5–13 days; p < 0.001). Older age (> 50 years old), reason for connection different from acute respiratory distress syndrome, higher simplified acute physiology score II, diagnosis of ventilator-associated pneumonia, and infection by multidrug-resistant bacteria were independently associated to increased death rate.
CONCLUSIONS:Infections (especially ventilator-associated pneumonia) during extracorporeal membrane oxygenation therapy are common and frequently involve multidrug-resistant organisms. In addition, they have a negative impact on patients’ outcomes.
Dracunculiasis (Guinea Worm Disease) is a terrible disease limited, even historically, to the arid and poor areas of our planet and which in the West has always been seen as an exotic disease and ...therefore has never taken root in the collective imagination. This parasitosis is transmitted to humans by drinking water contaminated with crustacean harboring larvae of
Dracunculus
m
edinensis
, a nematode. The natural history of the disease is caused by adult worms invading connective tissues and causing blistering, ulceration and edema. Well known in Ancient Egypt where the disease was endemic in its southern area, was known in Europe mainly from the reports of medical writers starting from the Roman imperial period but without direct knowledge. In Middle age the descriptions of this disease that physicians and surgeons could read on medical books, at the end, were attributed to veterinary parasitic disease. In Modern age only during the colonialist era dracunculiasis was perceived as a problem, however sporadic. In 1986 Guinea Worm Eradication Program (GWEP) was launch without success. Thus, the disappearance of this parasitosis should still be postponed but not abandoned.
Abstract Background Early identification of sepsis in the emergency department (ED) triage is both valuable and challenging. Numerous studies have endeavored to pinpoint clinical and biochemical ...criteria to assist clinicians in the prompt diagnosis of sepsis, but few studies have assessed the efficacy of these criteria in the ED triage setting. The aim of the study was to explore the accuracy of clinical and laboratory markers evaluated at the triage level in identifying patients with sepsis. Methods A prospective study was conducted in a large academic urban hospital, implementing a triage protocol aimed at early identification of septic patients based on clinical and laboratory markers. A multidisciplinary panel of experts reviewed cases to ensure accurate identification of septic patients. Variables analyzed included: Charlson comorbidity index, mean arterial pressure (MAP), partial pressure of carbon dioxide (PetCO 2 ), white cell count, eosinophil count, C‐reactive protein to albumin ratio, procalcitonin, and lactate. Results A total of 235 patients were included. Multivariable analysis identified procalcitonin ≥1 ng/mL (OR 5.2; p < 0.001); CRP‐to‐albumin ratio ≥32 (OR 6.6; p < 0.001); PetCO 2 ≤ 28 mmHg (OR 2.7; p = 0.031), and MAP <85 mmHg (OR 7.5; p < 0.001) as independent predictors for sepsis. MAP ≥85 mmHg, CRP/albumin ratio <32, and procalcitonin <1 ng/mL demonstrated negative predictive values for sepsis of 90%, 89%, and 88%, respectively. Conclusions Our study underscores the significance of procalcitonin and mean arterial pressure, while introducing CRP/albumin ratio and PetCO 2 as important variables to consider in the very initial assessment of patients with suspected sepsis in the ED. Clinical Relevance Early identification of sepsis since the emergency department (ED) triage is challenging Implementing the ED triage protocol with simple clinical and laboratory markers allows to recognize patients with sepsis with a very good discriminatory power (AUC 0.88)
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