ro13-9904 and Dyspnea

Glutamate excitotoxicity might contribute to the pathophysiology of amyotrophic lateral sclerosis. In animal models, decreased excitatory aminoacid transporter 2 (EAAT2) overexpression delays disease onset and prolongs survival, and ceftriaxone increases EAAT2 activity. We aimed to assess the safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis in a combined phase 1, 2, and 3 clinical trial.. This three-stage randomised, double-blind, placebo-controlled study was done at 59 clinical sites in the USA and Canada between Sept 4, 2006, and July 30, 2012. Eligible adult patients had amyotrophic lateral sclerosis, a vital capacity of more than 60% of that predicted for age and height, and symptom duration of less than 3 years. In stages 1 (pharmacokinetics) and 2 (safety), participants were randomly allocated (2:1) to ceftriaxone (2 g or 4 g per day) or placebo. In stage 3 (efficacy), participants assigned to ceftriaxone in stage 2 received 4 g ceftriaxone, participants assigned to placebo in stage 2 received placebo, and new participants were randomly assigned (2:1) to 4 g ceftriaxone or placebo. Participants, family members, and site staff were masked to treatment assignment. Randomisation was done by a computerised randomisation sequence with permuted blocks of 3. Participants received 2 g ceftriaxone or placebo twice daily through a central venous catheter administered at home by a trained caregiver. To minimise biliary side-effects, participants assigned to ceftriaxone also received 300 mg ursodeoxycholic acid twice daily and those assigned to placebo received matched placebo capsules. The coprimary efficacy outcomes were survival and functional decline, measured as the slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00349622.. Stage 3 included 66 participants from stages 1 and 2 and 448 new participants. In total, 340 participants were randomly allocated to ceftriaxone and 173 to placebo. During stages 1 and 2, mean ALSFRS-R declined more slowly in participants who received 4 g ceftriaxone than in those on placebo (difference 0·51 units per month, 95% CI 0·02 to 1·00; p=0·0416), but in stage 3 functional decline between the treatment groups did not differ (0·09, -0·06 to 0·24; p=0·2370). No significant differences in survival between the groups were recorded in stage 3 (HR 0·90, 95% CI 0·71 to 1·15; p=0·4146). Gastrointestinal adverse events and hepatobiliary adverse events were more common in the ceftriaxone group than in the placebo group (gastrointestinal, 245 of 340 [72%] ceftriaxone vs 97 of 173 [56%] placebo, p=0·0004; hepatobiliary, 211 [62%] vs 19 [11%], p<0·0001). Significantly more participants who received ceftriaxone had serious hepatobiliary serious adverse events (41 participants [12%]) than did those who received placebo (0 participants).. Despite promising stage 2 data, stage 3 of this trial of ceftriaxone in amyotrophic lateral sclerosis did not show clinical efficacy. The adaptive design allowed for seamless transition from one phase to another, and central venous catheter use in the home setting was shown to be feasible.. National Institute of Neurological Disorders and Stroke.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Ceftriaxone; Double-Blind Method; Dyspnea; Female; Humans; Male; Middle Aged; Treatment Outcome

Topics: Abscess; Anti-Bacterial Agents; Ceftriaxone; Cough; Diagnosis, Differential; Drainage; Dyspnea; Female; Fever; Humans; Middle Aged; Point-of-Care Testing; Radiography, Thoracic; Salmonella; Salmonella Infections; Splenic Diseases; Ultrasonography

A 39-year-old male patient presented with dyspnea and palpitations. The electrocardiogram (ECG) showed a first degree atrioventricular (AV) block and frequent atrial extra systoles. Within the following 48 h the AV block gradually developed into a third degree intermittent complete AV block. The patient history included an untreated tick bite 2 months before presentation. The serological proof of antibodies confirmed the diagnosis of Lyme carditis and antibiotic treatment with ceftriaxon i.v. was initiated. Normal AV conduction finally resumed and the symptoms subsided completely without any further clinical consequences.. Das Elektrokardiogramm eines 39-Jährigen, der sich mit Kurzatmigkeit und Herzstolpern vorstellt, zeigt einen atrioventrikulären (AV) Block ersten Grades und häufige atriale Extrasystolen. Innerhalb von 2 Tagen kommt es zu einer schrittweisen Progredienz bis hin zum AV-Block dritten Grades. Ein Zeckenbiss des Patienten 2 Monate zuvor war unbehandelt geblieben. Erhöhte Borrelientiter bestätigen die Verdachtsdiagnose einer Lyme-Karditis. Unter antibiotischer Therapie entwickelt sich die AV-Blockierung vollständig zurück.

Topics: Adult; Atrioventricular Block; Ceftriaxone; Dyspnea; Electrocardiography; Humans; Lyme Disease; Male; Myocarditis

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, Viral; Capsid Proteins; Ceftriaxone; Chills; Diagnosis, Differential; Dyspnea; Fatal Outcome; Fever; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Bacterial; Prednisolone; Shock, Hemorrhagic

Topics: Anti-Bacterial Agents; Australia; Ceftriaxone; Deglutition Disorders; Dyspnea; Epiglottitis; Humans; Male; Meningococcal Infections; Middle Aged; Pharyngitis

Our patient's signs and symptoms developed one week after being bitten by a rat that she was feeding to her son's pet snake.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Arthralgia; Ceftriaxone; Dyspnea; Female; Fever; Humans; Middle Aged; Purpura; Rat-Bite Fever; Rats

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Cefdinir; Ceftriaxone; Cephalosporins; Child; Diagnosis, Differential; Dyspnea; Epiglottis; Epiglottitis; Humans; Intubation, Intratracheal; Male; Radiography; Vancomycin

Since microbial gene sequencing was utilized for etiologic diagnosis of culture-negative endocarditis, cases of Bartonella endocarditis have been reported in various countries. Herein we report the first case of Bartonella quintana endocarditis, which was confirmed for the first time in Korea by 16S rRNA gene sequencing from the excised valve. A 75-yr-old woman was hospitalized due to dyspnea. Echocardiography demonstrated large oscillating vegetation at the aortic valve. Blood culture was negative. She underwent valve replacement and sequencing of the 16S rRNA gene from excised valve identified Bartonella quintana. She was successfully treated with combined use of ceftriaxone and gentamicin.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Valve; Bartonella quintana; Ceftriaxone; Drug Therapy, Combination; Dyspnea; Echocardiography; Endocarditis, Bacterial; Female; Gentamicins; Humans; Republic of Korea; RNA, Ribosomal, 16S; Sequence Analysis, RNA

A 65-year-old previously healthy man was referred because of high fever, progressive dyspnea and retrosternal pain for 2 days. On admission, the patient was already in a reduced general condition, blood pressure was 120/70 mmHg, heart rate irregular at 75/min and temperature at 39.7 degrees C. Auscultation of the heart revealed distant heart sounds, murmurs were not present, but mild rales were heard over both lung bases. Jugular veins were congested.. ECG showed a generalized ST-segment elevation with preserved R-waves, slightly depressed PR-segment and atrial bigemini. Chest X-ray revealed an enlarged cardiac silhouette with signs of a pneumopericardium. Transthoracic echocardiography showed a circular pericardial effusion and haemodynamic impairment. Percutaneous pericardiocentesis revealed a purulent effusion with microbiological proof of pneumococci. The primary infectious focus was a maxillary sinusitis caused by pneumococci.. Bacterial pericarditis due to by haematogenous spread of pneumococci.. Antibiotic therapy consisted of intravenous ceftriaxon and gentamicin. To rinse the pericardial space and drain the thick, purulent effusion subxiphoidal, pericardiocentesis and insertion of a drainage tube were done. Physiological saline was put into the pericardial space several times a day, drained and analysed microbiologically. In the meantime rinsing of the infected maxillary sinus was performed. Transthoracic echocardiography was done repeatedly to rule out complications of bacterial pericarditis, especially constrictive pericarditis. The pericardial tube was removed after proof of a sterile drainage 9 days after insertion. The patient was discharged after 4 weeks of hospitalization without clinical or echocardiographic signs of diastolic dysfunction.. Suspected bacterial pericarditis must be treated as an emergency and confirmed or ruled out by percutaneous pericardiocentesis.

Topics: Aged; Ceftriaxone; Diagnosis, Differential; Diagnostic Imaging; Dyspnea; Fever of Unknown Origin; Follow-Up Studies; Gentamicins; Humans; Male; Maxillary Sinusitis; Microbial Sensitivity Tests; Pericarditis; Pneumococcal Infections; Suction; Therapeutic Irrigation

Although uncommon, lesions of Crohn's disease can involve the hypopharynx and lower respiratory tract. We describe a patient with partial airway obstruction secondary to Crohn's disease of the hypopharynx and larynx. This entity should be considered in the differential diagnosis of patients presenting to the Emergency Department with upper airway obstruction.

Topics: Adult; Airway Obstruction; Anti-Inflammatory Agents; Biopsy; Ceftriaxone; Cephalosporins; Combined Modality Therapy; Crohn Disease; Dexamethasone; Diagnosis, Differential; Dyspnea; Emergency Treatment; Humans; Hypopharynx; Laryngeal Diseases; Male; Oxygen Inhalation Therapy; Pharyngeal Diseases

This case report describes Nocardia pericarditis in a newly diagnosed human immunodeficiency virus (HIV) patient as an initial manifestation. Previously, two cases of Nocardia pericarditis were reported in patients with established HIV infection. To our knowledge this is the first case of Nocardia pericarditis as an initial manifestation of HIV infection. This case substantiates and emphasizes the importance of identifying Nocardia as an infectious cause of pericarditis in patients with acquired immunodeficiency. Long-term survival may be achieved with a combined medical and surgical approach.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Chest Pain; Combined Modality Therapy; Cough; Drug Therapy, Combination; Dyspnea; Humans; Male; Minocycline; Nocardia asteroides; Nocardia Infections; Pericardial Effusion; Pericardial Window Techniques; Pericarditis

Topics: Airway Obstruction; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Clindamycin; Dyspnea; Emergencies; Epiglottis; Epiglottitis; Female; Foreign Bodies; Humans; Infant; Pharynx; Staphylococcal Infections; Staphylococcus aureus