Synergistic Meropenem/Vaborbactam Plus Fosfomycin Treatment of KPC Producing K. pneumoniae Septic Thrombosis Unresponsive to Ceftazidime/Avibactam: From the Bench to the Bedside

Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) ST unresponsive to ceftazidime/avibactam (CZA) relapsed first with meropenem/vaborbactam (MVB) monotherapy and subsequently cured with MVB plus fosfomycin (FOS) combination. The present case highlights the possibility of CZA underexposure on the infected thrombus and the risk of in vivo emergence of CZA resistance in the setting of persistent bacteremia and sub-optimal anticoagulation. Pharmacokinetic analyses showed that both MVB and FOS were in the therapeutic range. In vitro studies demonstrated a high level of MVB + FOS synergism that possibly allowed definitive resolution of the endovascular infection.

Targeting Gα13-integrin interaction ameliorates systemic inflammation

Systemic inflammation as manifested in sepsis is an excessive, life-threatening inflammatory response to severe bacterial or viral infection or extensive injury. It is also a thrombo-inflammatory condition associated with vascular leakage/hemorrhage and thrombosis that is not effectively treated by current anti-inflammatory or anti-thrombotic drugs. Here, we show that MB2mP6 peptide nanoparticles, targeting the Gα13-mediated integrin “outside-in” signaling in leukocytes and platelets, inhibited both inflammation and thrombosis without causing hemorrhage/vascular leakage. MB2mP6 improved mouse survival when infused immediately or hours after onset of severe sepsis. Furthermore, platelet Gα13 knockout inhibited septic thrombosis whereas leukocyte Gα13 knockout diminished septic inflammation, each moderately improving survival. Dual platelet/leukocyte Gα13 knockout inhibited septic thrombosis and inflammation, further improving survival similar to MB2mP6. These results demonstrate that inflammation and thrombosis independently contribute to poor outcomes and exacerbate each other in systemic inflammation, and reveal a concept of dual anti-inflammatory/anti-thrombotic therapy without exacerbating vascular leakage.

Review: The Emerging Role of Neutrophil Extracellular Traps in Sepsis and Sepsis-Associated Thrombosis

Patients with sepsis commonly suffer from coagulation dysfunction and lead to the formation of thrombus. During the development of sepsis, neutrophils migrate from the circulating blood to infected tissues and mediate the formation of neutrophil extracellular traps (NETs) that kill pathogens. However, the overactivation of neutrophils can promote the formation of immunothrombosis and even cause disseminated intravascular coagulation (DIC), which damages microcirculation. The outcome of sepsis depends on early recognition and intervention, so clinical evaluation of NETs function may be a valuable biomarker for early diagnosis of sepsis. The interaction of NETs with platelets, complement, and endothelium mediates the formation of immunothrombosis in sepsis. Inhibiting the formation of NETs is also considered to be one of the potential treatments for sepsis. In this review, we will discuss the key role of neutrophils and NETs in sepsis and septic thrombosis, in order to reveal new mechanisms for thrombosis treatment of sepsis.

Cavernous sinus thrombosis as a serious complication of sphenoid sinusitis in children

Introduction:The cavernous sinus is a venous plexus delimited by the dura mater and sited at the base of skull, laterally to the sella turcica and to the sphenoid sinus. The cavernous sinus thrombosis (CST) is a serious illness that may result from infection of any tissue drained by the cavernous sinus (septic thrombosis). Septic thrombosis (ST) may occur through the suppurative process by the level of the orbit, of the upper half of the face or paranasal sinuses , constituting a critical complication of sinusitis. Objectives: To verify the association between cavernous sinus thrombosis and sphenoid sinusitis in children, in the bibliographic productions of the last 10 years. Methods:This is an integrative literature review, with a search carried out in the database of the Medical Literature and Retrieval System onLine (MEDLINE), using a combination of the following Health Sciences Descriptors (DECS): “Sphenoid Sinusitis” and “Thrombosis” And “ Cavernous sinus” in “ Children ”. Incomplete studies were excluded from the research, carried out before 2012, totaling 7 bibliographic studies for detailed analysis. Results:CST can result from infection of any tissue drained from the cavernous sinus. This includes the face, tonsils, soft palate, teeth and ears.Only 15% of cases of CST in patients up to 12 years of age, originated from the paranasal sinuses. However, more recent studies advance that sinusitis is currently the most common etiology. When the sinuses are the cause of CST, the sphenoid sinus emerged as the most common primary source of infection predisposing to CST, since it has important anatomical relationships with the cavernous sinus. Streptococcus has been reported as the most common organism associated with sphenoid sinusitis. Conclusion:Although CTS is a rare clinical condition, acute and persistent sphenoid sinusitis can progress to such a condition, despite medical treatment. The main support of treatment includes early diagnosis, aggressive intravenous antibiotics and appropriate surgical treatment.

Sphenoid sinusitis complicated by extensive septic thrombosis after coiling of a ruptured intracranial aneurism

We report here the case of a 40-year-old man who presented with sphenoid sinusitis complicated by jugular and cerebral venous thrombosis and intracranial infection 6 weeks after coiling of an anterior choroidal artery aneurysm. The pathogeny of this unusual and severe complication is discussed.

A Rare Cause of Hand Infection: Streptococcus Constellatus

Hand infections represent common medical and surgical challenges that endanger delicate structures with severe consequences if not promptly addressed. Early identification and management are essential to achieve optimal outcomes. To the best of our knowledge this is the first reported case caused by Streptococcus constellatus, in which a severe periungueal infection evolved rapidly with septic thrombosis of digital vessels and culminated in amputation. This microorganism belongs to a group of commensal bacteria, Streptococcus milleri, that causes dental, peritonsillar and sinus abscesses. When bacteriemia outbursts, distant abscesses may form or endocarditis may ensue. A missed diagnosis and treatment can induce important morbidities, often delayed by the difficult isolation of the agent in the laboratory and its complex mechanisms of antibacterial resistance. This article focus on the importance of identifying serious hand infections requiring urgent or emergent treatment, since delayed or inadequate identification and management can lead to important and permanent deficits.

Teeth roots displacement in the maxillary sinus: characteristics and management

Introduction: Teeth displacement in the maxillary sinus is one of the most frequently described peri-extraction complications in oral surgery. Roots or whole teeth accidentally displaced during an avulsion process are the most common cause of foreign bodies in the maxillary sinus. It exposes the patient to more or less serious complications that can go as far as development of pneumonia or septic thrombosis of the cavernous sinus in rare cases. Several therapeutic solutions can be proposed to manage this complication, ranging from therapeutic abstention to the removal of the dental component using various techniques. Corpus: The pedagogical objectives of this article are to explain the main characteristics of this complication as well as its treatment. Through a systematic review of the literature according to the PRISMA methodology, the risk factors, prevention, diagnosis, complications, and management of teeth displacement will be discussed. A treatment decision tree will be proposed to guide practitioners in the management of a tooth or dental root displaced into the sinus. Conclusion: This article summarizes the importance of pre-extraction radiographic examinations for preventive purposes and their analysis to guide the practitioner in the choice of an appropriate surgical technique. Furthermore, the surgical management in almost all cases must be carried out early to prevent later infectious complications.