Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.

Hemoadsorption as part of a multimodal therapy concept to treat Capnocytophaga sepsis with thrombocytopenia and multiple organ failure.

BACKGROUND: Capnocytophaga, a bacteria native to the oral flora of canines, in rare cases can lead to severe infections resulting in septic shock, respiratory tract infection, and multiple organ failure. In case of trauma following animal bites with rapidly progressing clinical courses, also adjunctive therapeutic measures such as extracorporeal blood purification therapies might be beneficial. CASE PRESENTATION: We report on a 68-year-old male who was hospitalized with fever, oliguria and repeated vomiting after suffering a minor bite by his dog. On admission, he was diagnosed with sepsis. In addition, his coagulation status was markedly deranged resulting in the administration of mass transfusions to stabilize his coagulative status. Following detection of Capnocytophaga canimorsus, anti-infective therapy was initiated. In the context of a progressive respiratory deterioration and an increasing vigilance disorder, he had to be intubated. Due to development of renal failure, dialysis was started in conjunction with CytoSorb hemoadsorption therapy to control the hyperinflammatory condition. All of the applied therapeutic measures led to a rapid clinical stabilization, a control of the hyperinflammatory situation, and an improvement in his neurological status. The therapy was well tolerated with no complications encountered. CONCLUSIONS: This case supports the clinical recognition of severe Capnocytophaga infection that can lead to critical conditions even in immunocompetent patients. Combined broad spectrum antibiotic therapy, mass transfusions, CRRT, and CytoSorb hemoadsorption therapy resulted in a control of the critical situation. However, further research is needed to fully elucidate the role of hemoadsorption in this rare but life-threatening setting.

Acute hemorrhagic necrotizing enterocolitis caused by non-O1/non-O139 Vibrio cholerae infection: A case report.

RATIONALE: Acute hemorrhagic necrotizing enterocolitis (AHNE) is a rapidly progressive and extremely dangerous disease. Here we report a rare case caused by Vibrio cholerae (V cholerae). PATIENT CONCERNS: A 70-year-old man was admitted to our emergency department because of a sudden loss of consciousness. DIAGNOSES: On admission with severe toxic shock, the patient presented with elevated body temperature, decreased blood pressure, abdominal tenderness and rebound pain, predominantly on the right side. Computed tomography showed swelling and thickening of the right colon and peritoneal effusion. Necrosis was found in the hepatic flexure of the colon. On the basis of these results, the patient was diagnosed with AHNE. INTERVENTIONS AND OUTCOMES: After fluid resuscitation, an exploratory laparotomy was performed immediately. The procedure was successful. Despite antibiotic therapy, the patient's clinical condition progressively deteriorated and he died of multi-organ failure on day 3 after admission. LESSONS: AHNE is a rapidly progressive and extremely dangerous disease. Here we report a case of AHNE caused by non-O1/non-O139 V cholerae infection. The clinical features, phenotypic analyses and the presence of a panel of known virulence genes in the isolated strain are described. To the best of our knowledge, this is the first report of V cholerae causing severe AHNE, which is of profound pedagogical significance.

Factor XII plays a pathogenic role in organ failure and death in baboons challenged with Staphylococcus aureus.

Activation of coagulation factor (F) XI promotes multiorgan failure in rodent models of sepsis and in a baboon model of lethal systemic inflammation induced by infusion of heat-inactivated Staphylococcus aureus. Here we used the anticoagulant FXII-neutralizing antibody 5C12 to verify the mechanistic role of FXII in this baboon model. Compared with untreated control animals, repeated 5C12 administration before and at 8 and 24 hours after bacterial challenge prevented the dramatic increase in circulating complexes of contact system enzymes FXIIa, FXIa, and kallikrein with antithrombin or C1 inhibitor, and prevented cleavage and consumption of high-molecular-weight kininogen. Activation of several coagulation factors and fibrinolytic enzymes was also prevented. D-dimer levels exhibited a profound increase in the untreated animals but not in the treated animals. The antibody also blocked the increase in plasma biomarkers of inflammation and cell damage, including tumor necrosis factor, interleukin (IL)-1ß, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, nucleosomes, and myeloperoxidase. Based on clinical presentation and circulating biomarkers, inhibition of FXII prevented fever, terminal hypotension, respiratory distress, and multiorgan failure. All animals receiving 5C12 had milder and transient clinical symptoms and were asymptomatic at day 7, whereas untreated control animals suffered irreversible multiorgan failure and had to be euthanized within 2 days after the bacterial challenge. This study confirms and extends our previous finding that at least 2 enzymes of the contact activation complex, FXIa and FXIIa, play critical roles in the development of an acute and terminal inflammatory response in baboons challenged with heat-inactivated S aureus.

Antibiotic strategies and clinical outcomes for patients with carbapenem-resistant Gram-negative bacterial bloodstream infection.

Carbapenem-resistant Gram-negative bacterial bloodstream infection (CRGNB-BSI) has become a rapidly growing global threat with limited antibiotic options and significant mortality. The aim of this study was to explore the antibiotic strategies and clinical outcomes of patients with CRGNB-BSI in Western China. We retrospectively investigated the demographic, microbiological and clinical characteristics of 355 patients with CRGNB-BSI from 2012-2017. Treatment failure and 28-day in-hospital mortality rates were 49.3% (175/355) and 23.7% (84/355), respectively. The most frequently isolated micro-organism was Acinetobacter baumannii (58.6%; 208/355). Patients with treatment failure had higher procalcitonin and interleukin-6 levels (P < 0.05). High-dosage tigecycline therapy (200 mg loading dose followed by 100 mg every 12 h) was not superior to standard tigecycline dosing (P > 0.05). Multivariable analysis revealed that multiple organ dysfunction syndrome (MODS) (OR = 2.226, 95% CI 1.376-3.602; P = 0.001) and intensive care unit (ICU) admission (OR = 3.116, 95% CI 1.905-5.097; P = 0.000) were independent risk factors for treatment failure, whereas monotherapy (OR = 0.386, 95% CI 0.203-0.735; P = 0.004) had a protective effect. Survival analysis revealed that inappropriate therapy, MODS and ICU admission were associated with a higher 28-day in-hospital mortality rate (P < 0.001). Combination antimicrobial therapy was not superior to monotherapy (P = 0.387). This study demonstrates that appropriate therapy is significantly associated with lower treatment failure and 28-day in-hospital mortality rates. Tigecycline might not be a suitable option for CRGBN-BSI. Patients with MODS and admitted to the ICU had poor clinical outcomes.

Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation.

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.

HSF1 Alleviates Microthrombosis and Multiple Organ Dysfunction in Mice with Sepsis by Upregulating the Transcription of Tissue-Type Plasminogen Activator.

Sepsis is a life-threatening complication of infection closely associated with coagulation abnormalities. Heat shock factor 1 (HSF1) is an important transcription factor involved in many biological processes, but its regulatory role in blood coagulation remained unclear. We generated a sepsis model in HSF1-knockout mice to evaluate the role of HSF1 in microthrombosis and multiple organ dysfunction. Compared with septic wild-type mice, septic HSF1-knockout mice exhibited a greater degree of lung, liver, and kidney tissue damage, increased fibrin/: fibrinogen deposition in the lungs and kidneys, and increased coagulation activity. RNA-seq analysis revealed that tissue-type plasminogen activator (t-PA) was upregulated in the lung tissues of septic mice, and the level of t-PA was significantly lower in HSF1-knockout mice than in wild-type mice in sepsis. The effects of HSF1 on t-PA expression were further validated in HSF1-knockout mice with sepsis and in vitro in mouse brain microvascular endothelial cells using HSF1 RNA interference or overexpression under lipopolysaccharide stimulation. Bioinformatics analysis, combined with electromobility shift and luciferase reporter assays, indicated that HSF1 directly upregulated t-PA at the transcriptional level. Our results reveal, for the first time, that HSF1 suppresses coagulation activity and microthrombosis by directly upregulating t-PA, thereby exerting protective effects against multiple organ dysfunction in sepsis.

Dual Antibacterial Activities and Biofilm Eradication of a Marine Peptide-N6NH2 and Its Analogs against Multidrug-Resistant Aeromonas veronii.

Aeromonas veronii is one of the main pathogens causing various diseases in humans and animals. It is currently difficult to eradicate drug-resistant A. veronii due to the biofilm formation by conventional antibiotic treatments. In this study, a marine peptide-N6NH2 and its analogs were generated by introducing Orn or replacing with D-amino acids, Val and Pro; their enzymic stability and antibacterial/antibiofilm ability against multi-drug resistant (MDR) A. veronii ACCC61732 were detected in vitro and in vivo, respectively. The results showed that DN6NH2 more rapidly killed A. veronii ACCC61732 and had higher stability in trypsin, simulated gastric/intestinal fluid, proteinase K, and mouse serum than the parent peptide-N6NH2. DN6NH2 and other analogs significantly improved the ability of N6NH2 to penetrate the outer membrane of A. veronii ACCC61732. DN6NH2, N6PNH2 and V112N6NH2 protected mice from catheter-associated biofilm infection with MDR A. veronii ACCC61732, superior to N6NH2 and CIP. DN6NH2 had more potent efficacy at a dose of 5 µmol/kg (100% survival) in a mouse peritonitis model than other analogs (50-66.67%) and CIP (83.33%), and it inhibited the bacterial translocation, downregulated pro-inflammatory cytokines, upregulated the anti-inflammatory cytokine, and ameliorated multiple-organ injuries (including the liver, spleen, lung, and kidney). These data suggest that the analogs of N6NH2 may be a candidate for novel antimicrobial and antibiofilm agents against MDR A. veronii infections.

Severe Leptospirosis in a Mexican Woman.

OBJECTIVE: To describe a severe case of infection by Leptospira in a woman in the northwest of Mexico. CASE REPORT: A 55-yearold woman from Sonora, México arrived at the Intensive Care Unit due to severe multiple organ failure primarily affecting the respiratory, renal and hepatic systems. Diagnostic tests were performed, and they were positive for anti-Leptospira antibodies, IgM and IgG; and spirochetes were observed on dark field microscopy and confirmed by Polymerase Chain Reaction (PCR). Doxycycline and platelet apheresis transfusion were used as treatment, which led to a very slow recovery. CONCLUSION: The information presented in this study may help in the identification of pathology caused by spirochetes. This case report is the first to present a case of severe leptospirosis in Sonora, México.

Non-typeable Haemophilus influenzae and purpura fulminans.

Haemophilus influenzae typically causes illness and infection in the paediatric population. We report a case of a 53-year-old man who developed invasive non-typeable H. influenzae infection associated with purpura fulminans and multiorgan failure. On review of the literature, this is the first reported case of non-typeable H. influenzae causing purpura fulminans. The patient was treated with intravenous ceftriaxone 2 g/day and was eventually discharged from the hospital almost 2 months after admission. We discuss the role that infection/sepsis plays in disturbances to the coagulation cascade leading to purpura fulminans and the virulence factors that make non-typeable H. influenzae unique. Finally, we review other cases of H. influenzae associated with purpura fulminans and discuss the similarities with our case.

Exoenzyme Y Contributes to End-Organ Dysfunction Caused by Pseudomonas aeruginosa Pneumonia in Critically Ill Patients: An Exploratory Study.

Pseudomonas aeruginosa is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, P. aeruginosa upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T and Y), ExoU has been shown in prior studies to associate with high mortality rates. Preclinical studies have shown that ExoY is an important edema factor in lung infection caused by P. aeruginosa, although its importance in clinical isolates of P. aeruginosa is unknown. We hypothesized that expression of ExoY would be highly prevalent in clinical isolates and would significantly contribute to patient morbidity secondary to P. aeruginosa pneumonia. A single-center, prospective observational study was conducted at the University of Alabama at Birmingham Hospital. Mechanically ventilated ICU patients with a bronchoalveolar lavage fluid culture positive for P. aeruginosa were included. Enrolled patients were followed from ICU admission to discharge and clinical P. aeruginosa isolates were genotyped for the presence of exoenzyme genes. Ninety-nine patients were enrolled in the study. ExoY was present in 93% of P. aeruginosa clinical isolates. Moreover, ExoY alone (ExoY+/ExoU-) was present in 75% of P. aeruginosa isolates, compared to 2% ExoU alone (ExoY-/ExoU+). We found that bacteria isolated from human samples expressed active ExoY and ExoU, and the presence of ExoY in clinical isolates was associated with end-organ dysfunction. This is the first study we are aware of that demonstrates that ExoY is important in clinical outcomes secondary to nosocomial pneumonia.

Multiorgan failure following gastroenteritis: a case report.

BACKGROUND: This report highlights the first published case of fatal septic shock associated with Clostridium perfringens and Enterococcus avium bacteremia due to infective gastroenteritis. CASE PRESENTATION: We report a case of hepatic infarction, abscess, and death following gastroenteritis in a 63-year-old Aboriginal man who initially presented to a rural hospital with suspected food poisoning. The patient had persistent fever and was commenced on empirical antibiotics. His blood culture results were positive for Clostridium perfringens and Enterococcus avium. He was transferred to a tertiary center but developed organ failure and refractory shock. Initial computed tomography of the abdomen was unremarkable, but repeat imaging showed small bowel enteritis, hepatic abscess, and infarction as a result of portal vein septic thromboembolism. Despite maximal intensive care treatment, including percutaneous drainage of hepatic abscess and broad antibiotic cover, the patient died 6 days after initial presentation. CONCLUSIONS: This case highlights the rare but commonly fatal course of sepsis associated with Clostridium perfringens bacteremia and demonstrates detrimental effects of coinfection with Enterococcus avium, including potential for rapidly seeding abscess formation. Lessons for rural practice are highlighted, including the need for urgent and early referral for intensive care support, particularly for patients with complex comorbidities.

Oncostatin M Plays a Critical Role in Survival after Acute Intestinal Ischemia: Reperfusion Injury.

Background: Acute intestinal ischemia-reperfusion injury (AIIRI) is a devastating clinical condition relevant to multiple diseases processes, including sepsis, trauma, transplantation, and burns. An AIIRI is a contributor to the development of multiple organ dysfunction syndrome (MODS). Oncostatin M (OSM)/oncostatin M receptor (OSMR) signaling is an unrecognized and novel candidate pathway for the mediation of MODS. In this study, we hypothesized that OSM mediates the injury mechanism of AIIRI leading to MODS. Methods: Wild-type (WT) and OSMR-knockout (OSMR-/-) C57BL/6 mice underwent AIIRI using a well-established model of selective occlusion of the superior mesenteric artery (SMA). Serum cytokine concentrations were measured using a multiplex detection system. Further tissue analysis was conducted with polymerase chain reaction, enzyme-linked immunosorbent assay, Western blots, and histologic review. Results: Survival was significantly higher in WT than in OSMR-/- groups at 30 minutes of ischemia with 2 hours of reperfusion (100% versus 42.9%; P = 0.015). No significant differences in the degree of local intestinal injury was seen in the two groups. In contrast, the degree of lung injury, as evidenced by myeloperixodase activity, was lower in OSMR-/- animals in the early AIIRI groups. There was a greater degree of renal dysfunction in OSMR-/- mice. Oncostatin M mediated interleukin (IL)-10 upregulation, with WT animals having significantly lower IL-10 concentrations (52.04 ± 23.06 pg/mL versus 324.37 ± 140.35 pg/mL; P = 0.046). Conclusion: Oncostatin M signalling is essential during acute intestinal ischemia-reperfusion injury. An OSMR deficiency results in decreased early lung injury but increased renal dysfunction. There was a significantly increased mortality rate after AIIRI in mice with OSMR deficiency. Augmentation of OSM may be a novel immunomodulatory strategy for AIIRI.

Gut Microbiota and Multiple Organ Dysfunction Syndrome (MODS).

Multiple organ dysfunction syndrome (MODS), also referred to as external challenge-induced multiple organ injury, is characterized by dysfunction of two or more organs during infection or following shock or trauma. The pathogenesis of MODS is multifactorial and involves systemic inflammation and cell stress responses including cell death; sepsis is defined as an infection with MODS. Gut microbiota contributes significantly to organ dysfunction and to the pathobiology of sepsis. However, the relationship between the development of sepsis and the composition of gut microbiota is equivocal and is only now starting to be elucidated. Recent studies by our group and others reveal that enteric microbial composition and function are disrupted during sepsis, and that microbial products can either promote or alleviate the progression of sepsis. Here, we summarize the current research on the functional link between gut microbiota and sepsis, and argue the point that gut microbiota is a potential therapeutic target in the management of sepsis.

Campylobacter colitis leads to toxic megacolon and multiple organ failure.

A 58-year-old woman presented to the emergency department in a district general hospital with severe abdominal pain and diarrhoea, after collapsing at home. She was admitted to the intensive care unit (ICU) in septic shock, and with acute kidney injury. An initial CT scan was suggestive of colitis. She was treated for suspected gastroenteritis and her microbiology results showed Campylobacter coli as the causative organism. She failed to respond to antibiotics, and underwent serial contrast CTs which showed no progression of colitis. Colonoscopy performed on day 10 of her admission, however, revealed fulminant colitis. After a multidisciplinary meeting among gastroenterologists, general surgeons and intensivists, the patient underwent total colectomy with ileostomy. She made a slow but steady recovery in ICU, and subsequently in the ward, and was discharged to a local community hospital for further rehabilitation.

The Inflammatory and Hemostatic Response in Sepsis and Meningococcemia.

Meningococcemia is notorious for evasion of the host immune system and its rapid progression to fulminant disease, and serves as a unique model for pediatric sepsis. Illness severity is determined by complex interplays among host, pathogen, and environment. The inflammatory host response, including proinflammatory and anti-inflammatory responses in innate and adaptive immunity, skews toward a proinflammatory state. This leads to endothelial dysfunction and activation of the hemostatic response, which may lead to disseminated intravascular coagulation. This article reviews the pathogenesis of sepsis, in particular the inflammatory and hemostatic response in meningococcal sepsis.

Invasive intestinal mucormycosis in a 40-year old immunocompetent patient - a rarely reported clinical phenomenon: a case report.

BACKGROUND: Mucormycosis is rare, life-threatening fungal infection. Frequently observed in those patients having underlying immunosuppression such as, diabetes, organ transplantation, Human immunodeficiency virus (HIV) infection, and elevated serum iron. However, invasive intestinal mucormycosis occurring in immunocompetent individuals without the traditional risk factors is extremely rare clinical phenomenon. CASE PRESENTATION: We report a 40-year-old male patient who presented with 1 week history of diffuse abdominal pain and high grade fever, associated with vomiting and frequent loose stools. Has history of chronic alcohol ingestion. Otherwise, no past history of chronic medical illness, nor he had contact with individuals with similar illness. He was in a septic shock with multiple organ failure up on presentation to emergency room. Physical examination revealed icterus sclera with abdominal tenderness. He was immediately resuscitated using crystalloids, supported with inotrope, and antibiotics. Histopathological examination of tissue sample from colonic ulcer biopsy revealed invasive intestinal mucormycosis. Patient showed full clinical and histopathological resolution after course of parenteral Liposomal Amphotercin B. CONCLUSION: This case highlights the fact that, despite its life-threatening nature, it's possible to treat patients with invasive intestinal mucormycosis with aggressive antifungal and supportive care without surgical intervention, provided that all the necessary supportive care were initiated early and the disease was diagnosed early and appropriate medical management was initiated timely. In addition, it's important to consider intestinal mucormycosis even in patients who are immunocompetent without traditional risk factors.

Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis.

BACKGROUND: Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-ß, the consequences of their activation, particularly during sepsis, remain unknown. METHODS: We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis. RESULTS: In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals. CONCLUSIONS: Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.