ro13-9904 and Cerebral-Infarction

Nosocomial infective endocarditis is a relatively rare, but critical disease. A Japanese man in his 80s with psoriatic arthritis that was being treated with prednisolone was admitted for dyspnea. The first diagnosis was healthcare-associated pneumonia, and piperacillin/tazobactam was started. The patient's blood culture was negative at the time of admission. During the treatment, acute kidney injury occurred due to the use of antibiotics. Hemodialysis was performed via a central venous catheter in the internal jugular vein. After treatment of pneumonia, the patient experienced a sudden onset of fever accompanied by a loss of consciousness. Blood cultures from the peripheral vein and the central venous catheter were positive for methicillin-susceptible Staphylococcus aureus. A transthoracic echocardiography revealed stringy strands of vegetation attached to the native mitral valve. Magnetic resonance imagings also showed a shower of emboli to the brain. Ceftriaxone and vancomycin were administered; however, the patient died following a massive cerebral infarction. Instances of in-hospital mortality from nosocomial endocarditis are higher than the rates of community-acquired endocarditis. Clinicians should pay close attention to risk factors for nosocomial infective endocarditis. These risk factors include long-term indwelling vascular devices, psoriatic arthritis and corticosteroid therapy.

Topics: Aged, 80 and over; Arthritis, Psoriatic; Ceftriaxone; Central Venous Catheters; Cerebral Infarction; Cross Infection; Endocarditis, Bacterial; Fatal Outcome; Humans; Magnetic Resonance Imaging; Male; Mitral Valve; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Topics: Aged; Anti-Bacterial Agents; Anticoagulants; Antimalarials; Azithromycin; Betacoronavirus; Ceftriaxone; Cerebral Infarction; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2

A 43-year-old male with a history of bioprosthetic aortic valve replacement and tricuspid valve annuloplasty presented with vertigo and was found to have an acute infarct in the left superior cerebellum, as well as a left-middle cerebral artery mycotic aneurysm. Blood cultures grew Cardiobacterium hominis and bioprosthetic aortic valve vegetation was found on transthoracic echocardiogram.

Topics: Adult; Aneurysm, Infected; Anti-Bacterial Agents; Aortic Valve; Bicuspid Aortic Valve Disease; Bioprosthesis; Cardiobacterium; Ceftriaxone; Cerebral Infarction; Endocarditis, Bacterial; Gram-Negative Bacterial Infections; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Intracranial Aneurysm; Male; Postoperative Complications; Tomography, X-Ray Computed; Treatment Outcome

Glutamate transporter-1 (GLT-1) maintains low concentrations of extracellular glutamate by removing glutamate from the extracellular space. It is controversial, however, whether upregulation of GLT-1 is neuroprotective under all ischemic/hypoxic conditions. Recently, a neuroprotective effect of preconditioning with a β-lactam antibiotic ceftriaxone (CTX) that increases expression of GLT-1 has been reported in animal models of focal ischemia. On the other hand, it is said that CTX does not play a neuroprotective role in an in vitro study. Thus, we examined the effect of CTX on ischemic injury in a rat model of two-vein occlusion (2VO). This model mimics venous ischemia during, e.g. tumor surgery, a clinical situation that is best suitable for pretreatment with CTX.. CTX (100mg/kg, 200mg/kg per day) or vehicle (0.9% NaCl) was intraperitoneally injected into Wistar rats for 5days before venous ischemia (n=57). Then, animals were prepared for occlusion of two adjacent cortical veins (2VO) by photothrombosis with rose bengal that was followed by KCl-induced cortical spreading depression (CSD). Infarct volume was evaluated with hematoxylin and eosin (H&E) staining 2days after venous occlusion. [(3)H]MK-801, [(3)H]AMPA and [(3)H]Muscimol ligand binding were examined autoradiographically in additional two groups without 2VO (n=5/group). Animals were injected either with NaCl (vehicle) or CTX 200mg/kg for 5days in order to evaluate whether NMDA, AMPA and GABAA ligand binding densities were affected.. CTX pretreatment reduced infarct volume compared to vehicle pretreatment (p<0.05). The effect of CTX pretreatment was attenuated by administration of the GLT-1 inhibitor, dihydrokainate (DHK) 30min before 2VO. CTX had no effect on the number of spontaneous spreading depressions after 2VO. Analysis of quantitative receptor autoradiography showed no statistically significant difference between rats after administration with CTX compared to control rats.. Pretreatment with CTX has neuroprotective potential without effect on NMDA, AMPA and GABAA receptor density and spontaneous spreading depression. This effect can be abolished by GLT-1 inhibition, indicating that upregulation of GLT-1 is an important mechanism for neuroprotective action in penumbra-like conditions, e.g. if neurosurgeons plan to occlude cerebral veins during tumor surgery.

Topics: Animals; Anti-Bacterial Agents; Brain Ischemia; Ceftriaxone; Cerebral Infarction; Cortical Spreading Depression; Drug Interactions; Excitatory Amino Acid Transporter 2; Kainic Acid; Male; Neuroprotective Agents; Potassium Chloride; Rats; Receptors, AMPA; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate

We present a case of endocarditis with embolic stroke and digital infarction due to the recently renamed Aggregatibacter aphrophilus. The isolation and identification of this organism can be problematic but was achieved in this case using both older phenotypic and newer genotypic methods. A benign tongue lesion is suggested as the likely portal of entry for this oropharyngeal organism. The patient made a good recovery with six weeks of intravenous ceftriaxone but will need cardiac valvular surgery at some point in the future.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cerebral Infarction; Endocarditis; Fingers; Haemophilus Infections; Haemophilus paraphrophilus; Humans; Infarction; Male; Middle Aged

Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100mg/kg. i.v) for five days resulted in a significant reduction (P<0.01) in neurological deficit as well as cerebral infarct volume after 1h of ischemia followed by 24h of reperfusion injury. It also caused a significant (P<0.05) upregulation of GLT-1 mRNA, protein and glutamine synthetase (GS) activity. Furthermore, inhibition of ceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (P<0.01) increase in [(3)H]-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.

Topics: Animals; Brain; Brain Ischemia; Ceftriaxone; Cerebral Infarction; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glutamate-Ammonia Ligase; Glutamic Acid; Kainic Acid; Male; Neuroglia; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Up-Regulation

The central nervous system (CNS) may be affected in up to 50% of patients with Whipple's disease and this can occur even with little or no gastrointestinal involvement. We describe a 63-year-old patient in whom CNS involvement with Whipple's disease had the clinical and imaging features of a brain infarction. Treatment with aspirin and ceftriaxone followed by trimethoprim-sulfamethoxazole resulted in a good neurological recovery and complete remission of the malabsorption syndrome. Cerebral Whipple's disease resembling a stroke syndrome has so far been reported in only two other patients and in both cases it represented the first presentation of the disease. Arterial or arteriolar fibrosis, thrombosis and thickening associated with the inflammation of adjacent brain parenchyma and leptomeninges, and cerebral vasculitis caused by the hematogenous spread of Tropheryma whippelii to the brain may all be important triggers of brain infarction in patients with Whipple's disease. Our case report highlights the important point that cerebral Whipple's disease with the features of a stroke syndrome, if recognized early and treated aggressively with antibiotics, could have a favorable course with no long-term disability sequelae.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Brain Diseases; Ceftriaxone; Cerebral Infarction; Drug Therapy, Combination; Humans; Male; Middle Aged; Stroke; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease