YOD1 protects against MRSA sepsis-induced DIC through Lys33-linked deubiquitination of NLRP3.

Disseminated intravascular coagulation (DIC) is considered to be the most common and lethal complication of sepsis. NLR-family pyrin domain-containing-3 (NLRP3) inflammasome plays an important role in host defense against microbial pathogens, and its deregulation may cause coagulation cascade and should be strictly managed. Here, we identified the deubiquitinase YOD1, which played a vital role in regulating coagulation in a NLRP3 inflammasome-dependent manner in sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA). YOD1 interacted with NLRP3 to remove K33-linked ubiquitination of NLRP3 based on its deubiquitinating enzyme activity and specifically inhibited expression of NLRP3 as well as activation of NLRP3 inflammasome. Deficiency of YOD1 expression enhanced NLRP3 inflammasome activation and coagulation both in vitro and in vivo. In addition, pharmacological inhibition of the NLRP3 effectively improved coagulation and alleviated organ injury in Yod1-/- mice infected with MRSA. Thus, our study reported that YOD1 is a key regulator of coagulation during MRSA infection, and provided YOD1 as a potential therapeutic target for the treatment of NLRP3 inflammasome-related diseases, especially MRSA sepsis-induced DIC.

Acute Cholecystitis, Sepsis, and Disseminated Intravascular Coagulation Caused by Edwardsiella tarda in an Elderly Woman.

Edwardsiella tarda is a gram-negative bacillus associated with gastrointestinal diseases. It is rarely responsible for sepsis; however, the fatality is very high. Only two cases of E. tarda infections in patients over 90 years of age have been reported; these are not cases of sepsis associated with acute cholecystitis. We report a case of acute cholecystitis, sepsis, and disseminated intravascular coagulation (DIC) caused by E. tarda in a super-elderly woman aged over 90 years. There could be a possibility for recovery from sepsis and DIC if antimicrobial treatment responsiveness is ensured in the super-elderly.

Bilateral acute renal cortical necrosis after a dog bite: case report.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats' normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a "reverse rim sign" in contrast-enhanced computed tomography on hospital admission. CASE PRESENTATION: We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. CONCLUSION: We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis - was visible as "reverse rim sign" on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

An uncommon cause of sepsis following dog exposure.

ABSTRACT: Capnocytophaga canimorsus is a bacteria commonly found in the normal oral cavity of dogs that can cause bacteremia in immunocompromised patients following a dog bite. This case describes sepsis and disseminated intravascular coagulation associated with C. canimorsus in a patient with a history of alcohol abuse. Clinicians must be alert to the risk factors for this infection and provide appropriate prophylaxis following dog bites.

A unique case of Lemierre's syndrome status post blunt cervical trauma.

BACKGROUND: Lemierre's syndrome is a rare but potentially fatal condition. The course is characterized by acute tonsillopharyngitis, bacteremia, internal jugular vein thrombosis, and septic embolization. There have been some cases secondary to penetrating trauma to the neck. Literature review has yielded no cases secondary to blunt neck trauma in the absence of oropharyngeal injury. We aim to shed light on this unique cause of Lemierre's syndrome, so as to raise the index of suspicion for clinicians working up patients with blunt cervical trauma. METHODS: We present a case of a 25-year-old male restrained driver who presented with left neck and shoulder pain with a superficial abrasion to the left neck from the seatbelt who was discharged same day by the Emergency Room physicians. He returned to the Emergency Department two days later with abdominal pain. As a part of his repeat evaluation, a set of blood cultures were sent and was sent home that day. The patient was called back to the hospital one day later as preliminary blood cultures were positive for Gram positive cocci and Gram negative anaerobes. Computerized tomography scan of the neck revealed extensive occlusive left internal jugular vein thrombosis and fluid collections concerning for abscesses, concerning for septic thrombophlebitis. The patient continued to decompensate, developing severe sepsis complicated by disseminated intravascular coagulation. RESULTS: The patient underwent a left neck exploration with en bloc resection of the left internal jugular vein, drainage of abscesses deep to the sternocleidomastoid, and washout/debridement of necrotic tissue. Direct laryngoscopy at the time of surgery revealed no injury to the aerodigestive tract. Wound cultures were consistent with blood cultures and grew Fusobacterium necrophorum, Staphylococcus epidermidis, and Methicillin-resistant staphylococcus aureus. The patient underwent two subsequent operative wound explorations without any evidence of residual infection. The patient was discharged home on postoperative day 13 on a course of antibiotics and aspirin. CONCLUSION: This case illustrates the importance of diagnosis of Lemierre's syndrome after an unconventional inciting event (blunt cervical trauma) and appropriate treatment.

An Immunocompetent Case of Capnocytophaga canimorsus Infection Complicated by Secondary Thrombotic Microangiopathy and Disseminated Intravascular Coagulation.

A 62-year-old woman with no previous history developed a Capnocytophaga canimorsus infection followed by thrombotic microangiopathy (TMA) and disseminated intravascular coagulation (DIC). She was treated with antibiotics and plasma exchange (PE) and recovered. C. canimorsus sepsis sometimes causes not only DIC but also TMA. The mortality of TMA is extremely high, so we should not hesitate to perform PE when a patient shows TMA symptoms.

Murine Typhus: A Life-Threatening Presentation of a Case in Galveston, Texas.

BACKGROUND Murine typhus is a rare bacterial infection caused by Rickettsia typhi, which is transmitted from rodents to humans through the infected Xenopsylla cheopis flea. The disease presentation is often non-specific, leading to unnecessary tests, and a delay in diagnosis and treatment. CASE REPORT A report is presented of a 22-year-old, previously healthy man, who presented with several symptoms and signs that increased in severity, requiring admission to the medical intensive care unit (MICU). After an extensive bacterial and viral laboratory workup, IgM and IgG titers confirmed the diagnosis of murine typhus due to infection by Rickettsia typhi. The patient was treated with doxycycline, which resulted in significant clinical improvement. CONCLUSIONS Murine typhus can present with a characteristic triad of fever, headache, and rash but also with other symptoms and signs and can vary in severity. Given its increasing prevalence in coastal cities, awareness of this infection and early diagnosis and treatment with doxycycline can reduce patient morbidity.

A Case Report and Literature Review of Scrub Typhus With Acute Abdomen and Septic Shock in a Child-The Role of Leukocytoclastic Vasculitis and Granulysin.

Scrub typhus is becoming a clinically important cause of acute undifferentiated febrile illness in Taiwan. The incubation period is between 6 and 21 days after exposure. It is transmitted by chiggers (larva of trombiculid mite) in long grasses and in dirt-floor homes, with infection characterized by a flu-like illness of fever, headache, and myalgia lasting approximately 1 week. It has various systemic manifestations, including GI symptoms. In some, the illness progresses to multiorgan dysfunction syndrome and death. We report on a 13-year-old boy who lived in Taipei City and who had initially tentative diagnosis of acute pyrexia of unknown origin with high fever up to 40.3°C for 1 week, but later had thrombocytopenia and diffuse abdominal pain with peritoneal sign suspected acute appendicitis. During the clinical course, septic shock and disseminated intravascular coagulopathy (DIC) were noted. There were skin rash in his trunk and extremities and an eschar with black crust surrounded by a scaling erythematous rim on his right buttock. In addition, we got the information of his travel history in Green Island and Orchid Island for 10 days.With the correct antibiotics, vancomycin, meropenem, and doxycycline, the patient was getting better and corresponding with high level of granulysin and tumor necrosis factor-alpha. The diagnosis of scrub typhus was confirmed by the biopsy of eschar and high quantitative real-time polymerase chain reaction values of Orientia tsutsugamushi (16sRNA and 56 kDa) tested by Centers for Disease Control and Prevention, Taiwan. Histopathological findings of the eschar revealed the leukocytoclastic vasculitis, crust and thrombus formation with many gram-negative microorganisms, O. tsutsugamushi demonstrated by 47 kDa monoclonal antibody immunohistochemical stain and electromicroscopy. OUTCOMES: After the careful selection of appropriate antibiotics including meropenem, vancomycin, and doxycycline, he recovered and was subsequently discharged 7 days after admission. LESSON SUBSECTIONS: This case highlights that scrub typhus infection can mimic acute abdomen and septic shock with DIC. This rare presentation of acute abdomen and septic shock with thrombocytopenia and DIC caused by scrub typhus should remind physicians to be alert to the possibility of acute abdomen and febrile illness resulting from scrub typhus.

Whole genome analysis of a multidrug-resistant Streptococcus pneumoniae isolate from a patient with invasive pneumococcal infection developing disseminated intravascular coagulation.

Multidrug-resistant Streptococcus pneumoniae strains were isolated from blood and sputum of a patient with disseminated intravascular coagulation in Sapporo city, Japan. These antibiograms were only susceptible to vancomycin, linezolid, daptomycin, some carbapenems, and some fluoroquinolones. Identical antibiograms, serotypes (19F), and sequence types (ST10017) suggested a shared origin of these isolates. Only one ST10017 strain has been isolated in the same city in Japan previously (2014), and the 2014 isolate is still susceptible to macrolides. The whole genome of the blood-derived isolate was sequenced. The strain harbored resistance mutations in parC, gyrA, pbp1a, pbp2a, pbp2b, and pbp2x, and harbored the resistance genes, ermB and tetM. The nucleotide sequences of parC and pbp2x genes of strain MDRSPN001 were clearly different from those of other S. pneumoniae strains and were similar to those of oral streptococci strains. These findings suggest that strain MDRSPN001 has been rapidly and drastically evolving multidrug resistance by gene replacement and accumulation of genes originating from other strains, such as oral streptococci, Streptococcus mitis.

Priapism as the Presenting Complaint in Fatal Group A Streptococcal Induced Disseminated Intravascular Coagulation.

A 60-year-old male presented to an emergency department (ED) with priapism following a sore throat illness. He did not have typical findings of sepsis. The patient then developed severe headache, mental status changes, and hypertension, then suffered a cardiopulmonary arrest. Autopsy showed group A streptococcal (GAS) sepsis, disseminated intravascular coagulation (DIC), and a septic thrombosis to the penile vein. This is the first known case of priapism being the presenting symptom of DIC.

Purpura Fulminans: A rare presentation of Streptococcus Pneumoniae infection.

A previously healthy man presented with fever for 2 days and rapidly progressive purpuric rash for 1 day. He progressed into hypotension, disseminated intravascular coagulation and refractory shock despite resuscitation and early antibiotic commencement. Blood culture grew Streptococcus pneumoniae This case report highlights the fact that purpura fulminans can be a rare presentation of S. pneumoniae infection as well.

Inactivation of human coagulation factor X by a protease of the pathogen Capnocytophaga canimorsus.

Essentials Capnocytophaga canimorsus causes severe dog bite related blood stream infections. We investigated if C. canimorsus contributes to bleeding abnormalities during infection. The C. canimorsus protease CcDPP7 causes factor X dysfunction by N-terminal cleavage. CcDPP7 inhibits coagulation in vivo, which could promote immune evasion and trigger hemorrhage. SUMMARY: Background Capnocytophaga canimorsus is a Gram-negative bacterium that is present in the oral flora of dogs and causes fulminant sepsis in humans who have been bitten, licked, or scratched. In patients, bleeding abnormalities, such as petechiae, purpura fulminans, or disseminated intravascular coagulation (DIC), occur frequently. Objective To investigate whether C. canimorsus could actively contribute to these bleeding abnormalities. Methods Calibrated automated thrombogram and clotting time assays were performed to assess the anticoagulant activity of C. canimorsus 5 (Cc5), a strain isolated from a fatal human infection. Clotting factor activities were measured with factor-deficient plasma. Factor X cleavage was monitored with the radiolabeled zymogen and western blotting. Mutagenesis of Cc5 genes encoding putative serine proteases was performed to identify the protease that cleaves FX. Protein purification was performed with affinity chromatography. Edman degradation allowed the detection of N-terminal cleavage of FX. Tail bleeding times were measured in mice. Results We found that Cc5 inhibited thrombin generation and increased the prothrombin time and the activated partial thromboplastin time of human plasma via FX cleavage. A mutant that was unable to synthesize a type 7 dipeptidyl peptidase (DPP7) of the S46 serine protease family failed to proteolyse FX. The purified protease (CcDPP7) cleaved FX heavy and light chains from the N-terminus, and was active in vivo after intravenous injection. Conclusions This is, to our knowledge, the first study demonstrating a detailed mechanism for FX inactivation by a bacterial protease, and it is the first functional study associating DPP7 proteases with a potentially pathogenic outcome.

Successful treatment of hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation secondary to histoplasmosis in a patient with HIV/AIDS.

Haemophagocytic lymphohistiocytosis is an uncommon syndrome that results from an uncontrolled activation of macrophages and lymphocytes resulting in the compromise of multiple organs that is potentially fatal without timely treatment. It can be hereditary or a secondary result of infectious processes, neoplasms or autoimmune conditions. We present the case of a patient with HIV/AIDS who developed hemophagocytic lymphohistiocytosis as well as disseminated intravascular coagulation associated with histoplasmosis and who was successfully treated with amphotericin B, steroids and transitory dialytic support.

Livedo Reticularis: A Presenting Sign of Escherichia Coli Sepsis in a Newborn.

UNLABELLED: Livedo reticularis is a red cutaneous netlike pattern that is caused by abnormalities of the microvascularization and can be associated with many other potential systemic etiologies. We describe a case of a newborn that presented with livedo reticularis on his first day of life without any obvious systemic signs. The livedo reticularis was associated with Escherichia Coli K1 meningitis as revealed by laboratory tests. Clinical infectious signs developed a few hours later. Despite appropriate antibiotics therapy, he died on his second day because of sepsis and disseminated intravascular coagulation. Cerebrospinal fluid culture, blood culture, and culture of samples from trachea showed the presence of Escherichia Coli serotype K1 with many virulence determinants. CONCLUSION: In newborn, livedo reticularis must not be considered as physiological, but as a potential sign of unknown severe bacterial infection. Thus, the presence of livedo reticularis must require urgent laboratory tests.

Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis.

The effectiveness of supplemental dose antithrombin administration (1,500 to 3,000 IU/ day) for patients with sepsis-associated disseminated intravascular coagulation (DIC), especially sepsis due to abdominal origin, remains uncertain. This was a retrospective cohort study of patients with mechanically ventilated septic shock and DIC after emergency surgery for perforation of the lower intestinal tract using a nationwide administrative database, Japanese Diagnosis Procedure Combination inpatient database. A total of 2,164 patients treated at 612 hospitals during the 33-month study period between 2010 and 2013 were divided into an antithrombin group (n=1,021) and a control group (n=1,143), from which 518 propensity score-matched pairs were generated. Although there was no significant 28-day mortality difference between the two groups in the unmatched groups (control vs antithrombin: 25.7 vs 22.9 %; difference, 2.8 %; 95 % confidence interval [CI], -0.8-6.4), a significant difference existed between the two groups in propensity-score weighted groups (26.3 vs 21.7 %; difference, 4.6 %; 95 % CI, 2.0-7.1) and propensity-score matched groups (27.6 vs 19.9 %; difference, 7.7 %; 95 % CI, 2.5-12.9). Logistic regression analyses showed a significant association between antithrombin use and lower 28-day mortality in propensity-matched groups (odds ratio, 0.65; 95 % CI, 0.49-0.87). Analysis using the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 6.5 % (95 % CI, 0.05-13.0) reduction in 28-day mortality. Supplemental dose of antithrombin administration may be associated with reduced 28-day mortality in sepsis-associated DIC patients after emergency laparotomy for intestinal perforation.

Staphylococcal Purpura Fulminans: Report of a Case.

Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1-producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1-producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome-associated PF may be highly underrecognized and much more common than reflected in the literature.

Antibiotic treatment following a dog bite in an immunocompromized patient in order to prevent Capnocytophaga canimorsus infection: a case report.

BACKGROUND: Capnocytophaga canimorsus is a commensal bacterium found in the saliva of dogs and cats. Clinically significant infections in humans after a bite are often associated with the presence of immune deficiency. Early recognition and appropriate treatment are crucial for patient survival. In addition, patients with immune deficiency are susceptible to serious life-threatening nosocomial infections, which may also influence the prognosis of patients with Capnocytophaga canimorsus infection. CASE PRESENTATION: A 62-year-old Caucasian female was admitted with septic shock, acute respiratory distress syndrome, acute renal failure, metabolic acidosis and disseminated intravascular coagulation after suffering two small bites from her dog. She had received a splenectomy during childhood. The patient survived after early empiric treatment with antibiotics and intensive supportive care, including ventilation support, a high dose of noradrenalin, and continuous venovenous hemodialysis applied prior to the definitive diagnosis of Capnocytophaga canimorsus sepsis. She improved within 2 weeks but, despite all efforts to prevent nosocomial infection, her hospital course was complicated by Enterococcus species and Candida albicans pleuropneumonia that prolonged her stay in the intensive care unit, and necessitated ventilation support for 2 months. CONCLUSION: Severe Capnocytophaga canimorsus sepsis may be complicated by life-threatening nosocomial infection in immunocompromized patients. The prophylactic application of antibiotics after a dog bite should be considered in high-risk individuals with immune deficiency in order to prevent both Capnocytophyga canimorsus sepsis and serious nosocomial complications.