Sustained Bacteremia Research Articles

Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model.

Neisseria meningitidis (the meningococcus) remains a major cause of bacterial meningitis and fatal sepsis. This commensal bacterium of the human nasopharynx can cause invasive diseases when it leaves its niche and reaches the bloodstream. Blood-borne meningococci have the ability to adhere to human endothelial cells and rapidly colonize microvessels. This crucial step enables dissemination into tissues and promotes deregulated inflammation and coagulation, leading to extensive necrotic purpura in the most severe cases. Adhesion to blood vessels relies on type IV pili (TFP). These long filamentous structures are highly dynamic as they can rapidly elongate and retract by the antagonistic action of two ATPases, PilF and PilT. However, the consequences of TFP dynamics on the pathophysiology and the outcome of meningococcal sepsis in vivo have been poorly studied. Here, we show that human graft microvessels are replicative niches for meningococci, that seed the bloodstream and promote sustained bacteremia and lethality in a humanized mouse model. Intriguingly, although pilus-retraction deficient N. meningitidis strain (ΔpilT) efficiently colonizes human graft tissue, this mutant did not promote sustained bacteremia nor induce mouse lethality. This effect was not due to a decreased inflammatory response, nor defects in bacterial clearance by the innate immune system. Rather, TFP-retraction was necessary to promote the release of TFP-dependent contacts between bacteria and, in turn, the detachment from colonized microvessels. The resulting sustained bacteremia was directly correlated with lethality. Altogether, these results demonstrate that pilus retraction plays a key role in the occurrence and outcome of meningococcal sepsis by supporting sustained bacteremia. These findings open new perspectives on the role of circulating bacteria in the pathological alterations leading to lethal sepsis.

SEPTIC PULMOMARY EMBOLI SECONDARY TO UNREPORTED PARTIALLY TREATED DENTAL INFECTION

SESSION TITLE: Fellows Chest Infections Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Septic pulmonary emboli are usually caused by infected intravenous catheters and endocarditis. Dental infection is an extremely rare cause. We present a case of septic pulmonary emboli attributed to dental infection. Antibiotics, proper oral care and extraction of the causative teeth are key components of treatment. CASE PRESENTATION: Patient is a 60 year old male with no significant past medical history presented with complaints of fever, chills, myalgia. Patient states that about 2 weeks prior to presentation to the emergency department he had toothache and took antibiotics for two days with resolution of the pain. At the time of presentation, patient was afebrile, normotensive and was saturating 97 percent on room air. Patient underwent portable chest x-ray and Computerized tomography scan that revealed multiple bilateral patchy infiltrates with a lucent center suggestive of septic emboli. Physical examination was consistent with clear breath sounds bilaterally, no murmurs on cardiovascular examination. Oral examination revealed dental caries with no apparent gingivitis. Labs on admission showed hemoglobin of 13 gm/dL, white blood cell count of 12,000/mL, platelet count of 281,000/mm3, BUN of 13 mg/dL, creatinine of 0.58 mg/dL, sodium of 132 mEq/L, potassium of 3.8 mEq/L, sedimentation rate of 52 mm. TB Quantiferon test, HIV, ANCA panel were negative. Blood cultures were negative. Patient underwent a trans-esophageal echocardiogram that did not show endocarditis. He also underwent a whole body Gallium scan that showed increased uptake in the thorax and no other sites of infection. Consultation with oral maxillofacial surgery was sought due to the concern for dental source of infection. Patient underwent Orthopantogram that demonstrated lucency over the right maxillary suspicious for a fracture, partially edentulous oral cavity and extensive dental disease. Patient was started on broad spectrum antibiotic coverage with Vancomycin and Piperacillin- Tazobactam on which he developed acute interstitial nephritis presumed secondary to beta lactam antibiotics. Antibiotics were changed to Clindamycin and Doxycycline. Patient was subsequently discharged on oral antibiotics. He was followed in the pulmonary clinic with a repeat CAT scan that showed radiographic improvement in the septic emboli. DISCUSSION: Sustained Bacteremia and seeding in the lungs can occur in patients with periodontal infection. Indigenous oral florae include various Streptococci, Lactobacillus, Corynebacterium, and Actinomyces species. Antibiotics to cover oral flora is the main stay of treatment. Complications include pleural effusion and empyema. CONCLUSIONS: Dental infections are a rare cause of septic pulmonary emboli and are usually under reported by the patient. Antibiotics are the main stay of treatment. History and thorough physical examination are crucial in pointing towards the possible source of infection. Reference #1: Watanabe, Tsuyoshi et al. “Septic pulmonary embolism associated with periodontal disease: a case report and literature review.” BMC infectious diseases vol. 19,1 74. 21 Jan. 2019, doi:10.1186/s12879-019-3710-3 DISCLOSURES: No relevant relationships by Medhat Ismail, source=Web Response No relevant relationships by Rishitha Yelisetti, source=Web Response

Is Echocardiography Mandatory for All Streptococcus gallolyticus Subsp. pasteurianus Bacteremia?

BackgroundStreptococcus gallolyticus, formerly known as one of the Streptococcus bovis group, is frequently associated with endocarditis. Current guidelines recommended diagnostic work-up for endocarditis among patients with S. gallolyticus bacteremia. However, S. gallolyticus subsp. pasteurianus, was found to be associated with neonatal sepsis and liver diseases and is less commonly associated with endocarditis compared with S. gallolyticus subsp. gallolyticus. Our study aimed to identify the risk factors for S. gallolyticus subsp. pasteurianus endocarditis to help select the patients for echocardiography.MethodsIn this retrospective cohort study, medical records from all adult patients with S. gallolyticus subsp. pasteurianus isolated from blood cultures at Phramongkutklao Hospital from 2009 to 2015 were reviewed. Patients who had mixed bacteremia or missing records were excluded from the study.ResultsDuring the study period, S. gallolyticus subsp. pasteurianus was isolated among 106 individuals. Mean age was 66.9±15.6 years. Most patients (61.3%) were male, with cirrhosis as the most common underlying diseases (46.2%), followed by malignancy and chronic kidney disease. Most common manifestations included primary bacteremia (44.3%), followed by spontaneous bacterial peritonitis (23.6%). Infective endocarditis was found among 9 patients. No patients with cirrhosis or single blood specimen of bacteremia had endocarditis (RR 0; p-value 0.003, and RR 1.35; p-value 0.079). The common complications associated with endocarditis were acute respiratory failure (RR 4.32; p-value 0.05), whereas acute kidney injury was a protective factor (RR 0; p-value 0.01). Among 76 patients who had records of 2-year follow-up, no new diagnosis of endocarditis or malignancy was observed.ConclusionAmong patients with S. gallolyticus subsp. pasteurianus bacteremia, echocardiography might not be needed among patients with cirrhosis and without sustained bacteremia.

Surgical management of infective endocarditis: risk factors affecting early outcome

Objective To evaluate the risk factors affecting the early outcome of surgical treatment of infective endocarditis (IE). Background IE represents a series of clinical conditions with high in-hospital mortality, so early diagnosis and treatment can improve outcomes. Diagnosis depends on constant history and classic manifestations like sustained bacteremia or fungemia or active valvulitis. IE is a medical-surgical disease in which surgical treatment is a part of the therapeutic process rather than a result of the failure of medical treatment. Patients and methods A prospective cohort study was conducted on 50 consecutive patients diagnosed with definite IE and underwent cardiac surgery after being admitted to the Cardiothoracic Surgical Department, National Heart Institute, Giza, Egypt, during the period from December 2015 till March 2017. Preoperative, intraoperative, and postoperative data as potential predictors of mortality were tested. Results Our results showed that rheumatic heart disease was the most common underlying cardiac disease. Native valve endocarditis was present in 31 (62%) and prosthetic valve endocarditis in 19 (38%) patients. Mean Euro SCORE II was 5.71%. The hospital mortality was 22%, whereas the 6-month mortality was 10%. Congestive heart failure, embolization, and periannular extension of infection are the most powerful predictors of hospital mortality and also 6-month mortality. Conclusion Surgery for IE continues to be challenging. Euro SCORE II has a good discrimination ability to predict in-hospital mortality in IE surgery. Satisfactory results can be obtained with valve repair in IE.

Peripheral blood vessels are a niche for blood-borne meningococci

ABSTRACT Neisseria meningitidis is the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known as purpura fulminans. Meningococcemia is characterized by bacterial adhesion to human endothelial cells of the microvessels. Host specificity has hampered studies on the role of blood vessels colonization in N. meningitidis associated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in an in vivo context we demonstrate that meningococcal colonization of human blood vessels is a prerequisite to the establishment of sepsis and lethality. To identify the molecular pathways involved in bacterial virulence, we performed transposon insertion site sequencing (Tn-seq) in vivo. Our results demonstrate that 36% of the genes that are important for growth in the blood of mice are dispensable when bacteria colonize human blood vessels, suggesting that human endothelial cells lining the blood vessels are feeding niches for N. meningitidis in vivo. Altogether, our work proposes a new paradigm for meningococcal virulence in which colonization of blood vessels is associated with metabolic adaptation and sustained bacteremia responsible for sepsis and subsequent lethality.

135 Sources of streptococcal bacteraemia and their implications for the diagnosis of infective endocarditis

IntroductionThe diagnosis of infective endocarditis (IE) is dependent on the detection of a sustained bacteraemia with multiple positive blood cultures being major criteria in the Duke nosology for IE. The...

Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association.

### Background The use of synthetic material for reconstructive vascular surgery was first reported during the early 1950s. Infection involving vascular graft prostheses is an infrequent but devastating complication of reconstructive vascular graft surgery and is associated with a high morbidity and, in some situations, mortality. Improvements in surgical techniques and graft design, including the use of native venous or arterial tissue, have reduced the frequency of infection and severity of complications from vascular graft infection (VGI). However, these advances have also led to more frequent vascular graft procedures occurring in a patient population with multiple underlying comorbidities that would have previously disqualified them as candidates for vascular reconstructive surgery. Underlying comorbidities, such as diabetes mellitus or immune compromise, increase the risk of infection and serious infection-related complications. The major complications of VGI include sepsis, amputation, disruption of infected anastomotic suture line with rupture or pseudoaneurysm formation, embolization of infected thrombi, reinfection of reconstructed vascular grafts, enteric fistulae to the small or large bowel, bacteremic spread of infection to other sites, and death. VGIs can be categorized broadly into those that occur in an extracavitary location, primarily in the groin or lower extremities, or in an intracavitary location, primarily within the abdomen or less commonly within the thorax. ### Frequency The frequency of VGI depends on the anatomic location of the graft. The infection rate is 1.5% to 2% for most extracavitary grafts and as high as 6% with vascular grafts in the groin.1–9 For intracavitary grafts, the infection rate is ≈1% to 5%.1–6 Graft infection is most common after emergency procedures and after reoperation.1–4,10 Aortic graft erosion or fistulous communication into the duodenum or other areas of the bowel reportedly occurs in 1% to 2% of patients after aortic reconstruction.11, …

Sustained Clostridium tertium Bacteremia in a Nonneutropenic Patient

Abstract We report a case of sustained Clostridium tertium bacteremia mimicking an endovascular infection in a nonneutropenic patient with metastatic pancreatic neuroendocrine cancer. Clostridium tertium infection has been increasingly recognized in immunocompromised patients. The significance of this organism in nonneutropenic host, however, is unclear. The diagnosis and treatment can be challenging owing to morphology and antibiotic resistance patterns. Newer rapid identification testing with mass spectrometry enables for early diagnosis and treatment. We discuss the clinical significance of C. tertium as an emerging pathogen with review of the literature.

Prospective evaluation of bacteremia rates and infectious complications among patients undergoing single-operator choledochoscopy during ERCP

Choledochoscopy is increasingly performed during endoscopic retrograde cholangiopancreatography (ERCP) for direct bile duct visualization. Choledochoscopy necessitates irrigation of the bile duct with water or saline, which may increase intrabiliary pressure and consequently the risks of bacteremia and cholangitis. The aim of this study was to prospectively evaluate the risk of bacteremia and infectious complications in patients undergoing single-operator choledochoscopy (SOC). Patients requiring ERCP with SOC at two tertiary care centers were enrolled prospectively. Blood cultures were obtained immediately before the ERCP, after completion of the ERCP portion of the procedure (to determine ERCP-related bacteremia), and 15 minutes after completion of SOC. A total of 72 patients (mean age 64 years; 51.4 % male) underwent ERCP with SOC. True positive blood cultures were noted in 20 patients (27.8 %; 95 % confidence interval [CI] 17.86 % - 39.59 %), of whom 6 patients (8.3 %; 95 %CI 3.12% - 17.26 %) had transient bacteremia following ERCP. Of 14 patients (19.4 %; 95 %CI 11.05 % - 30.46 %) with sustained bacteremia following ERCP or SOC, 10 patients (13.9 %; 95 %CI 6.86 % - 24.06 %) had sustained bacteremia related to SOC. Despite the use of post-procedure intravenous antibiotic administration, seven patients (9.7 %; 95 %CI 3.99 - 19.01 %) required further antibiotic treatment for infectious complications, three of whom (4.2 %; 95 %CI 0.86 % - 11.69 %) were hospitalized in order to receive intravenous antibiotic therapy. The bacteremia associated with ERCP with SOC and the subsequent risk of hospitalization for infectious complications suggest that preprocedure antibiotic prophylaxis should be considered for patients undergoing SOC, particularly in older patients and those with prior stent placement or undergoing intraductal stone lithotripsy. clinical trials.gov (NCT01414400).

Intravenous Drug Abuse by Patients Inside the Hospital: A Cause for Sustained Bacteremia.

Patients with history of intravenous drug abuse are noted to be at risk of several infections including HIV, endocarditis, and other opportunistic infections. We report the case of a patient with sustained Bacillus cereus bacteremia despite use of multiple antibiotic regimens during his inpatient stay. Our case highlights the importance of high suspicion for active drug use inside the hospital in such patients. This is important in order to minimize unnecessary diagnostic workup and provide adequate treatment and safe hospital stay for these patients.

Treatment of central line associated Rhodococcus equi bacteremia with an oral antibiotic regimen in a pediatric oncology patient

Rhodococcus equi is an emerging pathogen among immunocompromised hosts. Increased incidence has been described in the human immunodeficiency virus/acquired immune deficiency syndrome population, patients immunocompromised due to organ transplantation and in those receiving chemotherapy. Features associated with this case included a sustained bacteremia and delay in recognition of the clinical syndrome due to the intermittent positivity of the blood cultures and initial mis-identification of the organism as a coryneform contaminant. The patient was successfully treated with an oral antibiotic regimen after removal of the central catheter.

Host fate is rapidly determined by innate effector-microbial interactions during Acinetobacter baumannii bacteremia.

Acinetobacter baumannii is one of the most antibiotic-resistant pathogens. Defining mechanisms driving pathogenesis is critical to enable new therapeutic approaches. We studied virulence differences across a diverse panel of A. baumannii clinical isolates during murine bacteremia to elucidate host-microbe interactions that drive outcome. We identified hypervirulent strains that were lethal at low intravenous inocula and achieved very high early, and persistent, blood bacterial densities. Virulent strains were nonlethal at low inocula but lethal at 2.5-fold higher inocula. Finally, relatively avirulent (hypovirulent) strains were nonlethal at 20-fold higher inocula and were efficiently cleared by early time points. In vivo virulence correlated with in vitro resistance to complement and macrophage uptake. Depletion of complement, macrophages, and neutrophils each independently increased bacterial density of the hypovirulent strain but insufficiently to change lethality. However, disruption of all 3 effector mechanisms enabled early bacterial densities similar to hypervirulent strains, rendering infection 100% fatal. The lethality of A. baumannii strains depends on distinct stages. Strains resistant to early innate effectors are able to establish very high early bacterial blood density, and subsequent sustained bacteremia leads to Toll-like receptor 4-mediated hyperinflammation and lethality. These results have important implications for translational efforts to develop therapies that modulate host-microbe interactions.

Lethal Factor, but Not Edema Factor, Is Required to Cause Fatal Anthrax in Cynomolgus Macaques after Pulmonary Spore Challenge

Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. To better understand the contribution of these toxins to the disease pathophysiology in vivo, we used B. anthracis Ames strain and isogenic toxin deletion mutants derived from the Ames strain to examine the role of lethal toxin and edema toxin after pulmonary spore challenge of cynomolgus macaques. Lethal toxin, but not edema toxin, was required to induce sustained bacteremia and death after pulmonary challenge with spores delivered via bronchoscopy. After intravenous challenge with bacilli to model the systemic phase of infection, lethal toxin contributed to bacterial proliferation and subsequent host death to a greater extent than edema toxin. Deletion of protective antigen resulted in greater loss of virulence after intravenous challenge with bacilli than deletion of lethal toxin or edema toxin alone. These findings are consistent with the ability of anti-protective antigen antibodies to prevent anthrax and suggest that lethal factor is the dominant toxin that contributes to the escape of significant numbers of bacilli from the thoracic cavity to cause anthrax after inhalation challenge with spores.

Infected Pancreatic Necrosis Increases the Severity of Experimental Necrotizing Pancreatitis in Mice

Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice. Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 10 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed. Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis. Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice.

An epidemiological surveillance of asymptomatic typhoid carriers associated in respect to socioeconomic status in India

The term ‘enteric fever’ was coined to embrace both typhoid and paratyphoid. It was known as a generalized infection of the reticuloendothelial system and intestinal lymphoid tissue accompanied by sustained fever and bacteraemia. Typhoid has remained a major public health issue in many tropical countries and the highest burden of the disease is in Asia (Pang et al. 1998). The global burden of typhoid was estimated as 16,000,000 cases and 600,000 deaths per year (Pang and Puthucheary 1983; Pang and Bhutta 1995). Currently global pandemics are being caused by the less common serovar of S. typhi (Miko et al. 2002). The asymptomatic carrier state in humans has had serious consequences on public health and the exclusive source for typhoid bacillus was asymptomatic typhoid carriers. An individual could asymptomatically carry the typhoid bacilli for days to years without any symptoms of typhoid fever (Bigelow and Anderson 1933: White and Parry 1996; Senthilkumar and Prabakaran 2005). They usually excrete as many as 10 virulent typhoid bacilli per gram of faeces. These organisms reside in the scarred foci of the biliary tract, migrate through the bile ducts and over the vast surface area of intestinal epithelium; however, they did not cause typhoid fever in the carrier (Hornick et al. 1970). S. typhi usually possesses a polysaccharide Vi (virulence) surface antigen that was associated with enhanced capacity to invade the host. Vi antigen of S. typhi and its relation with high serum titres of S. typhi carrier state, reports about the usefulness of Vi serology in the detection of the carrier state (Felix and Pitt 1934; Felix 1938; Lanata et al. 1983) and establishes a chronic asymptomatic infection in the gall bladder (Kauffmann 1954; Prouty et al. 2002). Asymptomatic typhoid carriers were deficient in IgM and anatomical alterations in the biliary tract lead to prolong bacterial persistence (Cheronokhvostova et al. 1969). The carrier state occurred disproportionately often following infection not only in women but also in older patients, with biliary carriage rather than the urinary carriage (Hornick 1985). Identification of asymptomatic typhoid carriers as the source of an outbreak usually required multiple cultures for several weeks (Engleberg et al. 1983). Positive asymptomatic carriers from food handlers significantly contributed to the spread of S. typhi, S. paratyphi A and S. paratyphi B. Therefore, a periodic assay of Salmonella spp in foodstuffs and food handlers could help in the control of food borne diseases (Sasikumar et al. 2005).

Infection of pancreatic necrosis in experimental necrotizing pancreatitis induces sustained bacteremia and increases pancreatitis severity which is only partially reversed by antibiotic therapy

Infection of pancreatic necrosis in experimental necrotizing pancreatitis induces sustained bacteremia and increases pancreatitis severity which is only partially reversed by antibiotic therapy

Diagnosing infected necrotizing pancreatitis: Clinical signs, gas bubbles or routine fine-needle aspiration?

Introduction: Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality. Aims/objectives: To examine the mechanisms underlying this clinical circumstance we used a model of primary infected pancreatic necrosis in taurocholate induced pancreatitis in mice. Materials and methods: Acute necrotizing pancreatitis with sterile necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice, infected pancreatic necrosis (IN) was induced by co-injecting 108 CFU E. coli. For antibiotic therapy 10 mg/kg bodyweight moxifloxacin were administered intravenously (AIN). After 6, 12, 24, 48 and 120 hours animals were sacrificed and serum as well as SIRS related organs were examined. Results: Prolonged bacteremia occurred when infected acinar cell necrosis was induced (24h CFU E. coli in blood; bacteria only not detected, IN 121 63). Infection of pancreatic necrosis with E. coli further increased the pancreatic damage (histology score 24h: SN 17.8 2.6 vs. IN 23.7 2.2; p<0.001) and the systemic complications such as the pulmonary vascular leak (albumin in bronchoalveolary lavage 6h: SN 151.0 57.7 mg/ml vs. IN 219.5 76.2 mg/ml; p<0.05). Additionally, infected necrosis induced impaired hepatic function with reduced serum glucose concentrations (24h: SN 167.0 35.6 mg/dl vs. IN 106.9 12.7 mg/dl; p<0.001). Moxifloxacin treatment reduced the systemic inflammatory response (serum IL-6: IN 330.5 336.6 vs. AIN 38.7 25.5 pg/ml; p<0.001) and restored liver function (serum glucose: IN 105.8 12.7 vs. AIN 155.7 39.5 mg/dl; p<0.001). Conclusion: Infection of pancreatic necrosis induces sustained bacteremia and increases the systemic complications in acute necrotizing pancreatitis. Initial antibiotic therapy reduces the inflammatory response and restores liver function.

Escherichia coli K1-induced cytopathogenicity of human brain microvascular endothelial cells

Pathophysiology of Escherichia coli sepsis is complex involving circulating bacterial products, cytokine release, and sustained bacteremia resulting in the damage of vascular endothelium. Here, it is shown that E. coli K1 produced cytopathogenicity of human brain microvascular endothelial cells (HBMEC), that constitute the blood–brain barrier. Whole bacteria or their conditioned medium produced severe HBMEC damage suggesting E. coli K1-cytopathogenicity is a contact-independent process. Using lipopolysaccharide (LPS) inhibitor, polymyxin B, purified LPS extracted from E. coli K1 as well as LPS mutant derived from E. coli K1, we showed that LPS is not the sole determinant of E. coli K1-mediated HBMEC death. Bacterial product(s) for HBMEC cytopathogenicity was heat-labile suggesting LPS-associated proteins. Several isogenic gene-deletion mutants (ΔompA, ΔibeA, ΔibeB, Δcnf1) exhibited HBMEC cytopathogenicity similar to that produced by wild type E. coli K1. E. coli K1-mediated HBMEC death was independent of phosphatidylinositol 3-kinase (PI3K) but dependent partially on focal adhesion kinase (FAK) using HBMEC expressing dominant negative FAK and PI3K.

Severe cochlear inflammation and vestibular syndrome in an experimental model of Streptococcus suis infection in mice

Hearing impairment is a common and frequently permanent sequel of Streptococcus suis meningitis in humans. Nevertheless, mechanisms underlying the development of cochlear damage have not been addressed so far. In the present work, we characterized a mouse model of suppurative labyrinthitis and meningitis induced by a systemic infection with S. suis and studied the impact of the injected bacterial dosage on the progression of such inflammatory events. We observed that high infection doses of bacteria lead to sustained bacteremia, with an increase in the permeability of the blood-labyrinth and blood-brain barriers, causing suppurative labyrinthitis and meningitis, respectively. However, in mice infected with a low dose of S. suis, bacteria disappeared quickly from blood, hence, cochlear inflammation and meningitis were not consistent features. This model of S. suis infection seems ideal to evaluate novel drugs that may help alleviate the negative consequences of such important sequelae of S. suis-induced meningitis and labyrinthitis.

Prolonged venovenous extracorporeal membrane oxygenation in a child with leukemia and persistent bacteremia*

In patients who require extracorporeal membrane oxygenation for prolonged periods, it is uncertain whether nosocomial bacteremia that persists throughout an entire extracorporeal membrane oxygenation run can be associated with good outcomes. Case report. Tertiary pediatric intensive care unit. A 6-yr-old boy with acute myeloid leukemia and prolonged mechanical ventilatory support. Venovenous extracorporeal membrane oxygenation. The patient required extracorporeal membrane oxygenation for refractory hypoxia secondary to nosocomial pneumonia. On day 2 of the extracorporeal membrane oxygenation run and every day thereafter, blood cultures were consistently positive for Stenotrophomonas maltophilia despite combination therapy with intravenous polymyxin B and cotrimoxazole. Excluding the cannulae, the extracorporeal membrane oxygenation circuit was electively changed once during the run but without any effect on bacteremia. After 38 days of extracorporeal membrane oxygenation, the patient was successfully decannulated and the bacteremia ceased. He remains completely well and disease-free at 6-month follow-up. Sustained bacteremia during an extracorporeal membrane oxygenation run should not be regarded as a reason to withdraw extracorporeal support, although efforts are clearly warranted to identify possible sources of sepsis and wean off extracorporeal membrane oxygenation at the earliest opportunity.