ro13-9904 and Nervous-System-Diseases

Several neurodegenerative disorders, namely Parkinson's disease dementia, dementia with Lewy bodies, and Alzheimer's disease, share common pathophysiological features, such as (1) cognitive deficits, (2) glutamatergic hyperactivity-related excitotoxicity, and (3) deposition of α-synuclein (α-syn) and β-amyloid (Aβ). Ceftriaxone (CEF) is a well-tested and safe drug that has been used as an antibiotic for several decades. Recent studies have demonstrated the following effects of CEF: (1) increasing glutamate transporter-1 expression and glutamate reuptake and suppressing excitotoxicity, (2) binding well with α-syn and inhibition of α-syn polymerization, (3) modulating expression of genes related to Aβ metabolism, and (4) enhancing neurogenesis and recovery of neuronal density. In addition, our data revealed that CEF ameliorates seizure and abnormal neuronal firing in the brain. These results suggest the potential of CEF in treating neuronal disorders. This paper addresses the effects and pharmacology of CEF.

Topics: Alzheimer Disease; Brain; Ceftriaxone; Humans; Lewy Body Disease; Nervous System Diseases; Neurodegenerative Diseases; Neurogenesis; Neurons; Neuroprotective Agents; Parkinson Disease

A 20-year-old man suffered two thalamic infarctions during the course of neuroborreliosis and was successfully treated with intravenous ceftriaxone. Review of 11 additional cases of stroke and cerebral vasculitis in neuroborreliosis suggests that there is a meningovascular form of the infection with predilection for the posterior circulation and an association with the European strains of Borrelia burgdorferi.

Topics: Adult; Borrelia Infections; Ceftriaxone; Cerebrovascular Disorders; Humans; Magnetic Resonance Imaging; Male; Nervous System Diseases; Tomography, X-Ray Computed

There are still no definite patterns for antibiotic therapy of Lyme borreliosis. Recent studies have shown that ceftriaxone or tetracyclines are superior to the conventional penicillin. Against erythema chronica migrans (stage I) oral therapy, preferably with tetracycline, is sufficient. In cases with stage II symptoms, such as arthritis or neurological affections, high dose parenteral treatment, preferably with ceftriaxone, is recommended, although its effect on the neurologic symptoms is not yet proven. Carditis also calls for high dose parenteral administration of antibiotics, even though there are no published studies on this treatment as yet. Opinion is divided on the cutaneous symptoms such as acrodermatitis chronica atrophicans, morphea, lichen sclerosus et atrophicus (acute inflammatory stage) and lymphadenitis cutis benigna. Even if oral penicillin or tetracycline can cure existing symptoms, in the absence of longterm observations, it remains an open question whether oral treatment can prevent further complications or evolution to chronicity (stage III). For these clinical pictures there is also a tendency to give high dose parenteral antibiotics, and ceftriaxone is likely to win favour. In stage II Lyme borreliosis, autoimmune processes occur which scarcely respond to antibiotics any longer. Nevertheless, parenteral administration of high dose antibiotics remains sensible as a means of eradicating pathogens from the tissues, CSF or synovial fluids, and to avoid further complications. Evaluation of the therapeutic effects of corticosteroids or other immunosuppressive agents would require prospective studies.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Ceftriaxone; Erythema Chronicum Migrans; Humans; Lyme Disease; Nervous System Diseases; Skin Diseases; Tetracyclines

Topics: Arthritis, Infectious; Ceftriaxone; Drug Administration Schedule; Erythema; Humans; Lyme Disease; Nervous System Diseases; Penicillins; Skin Diseases; Tetracycline

Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually.. We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models.. H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13-0.76; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09-0.77; P=.014).. Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ceftriaxone; Chemotherapy, Adjuvant; Child; Child, Preschool; Deafness; Death; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Glycerol; Humans; Latin America; Male; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Nervous System Diseases; Placebos; Prospective Studies; Treatment Outcome

The aim of this study was to determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG).. An open prospective, randomised, multicenter study was conducted in 141 patients; 72 received ceftriaxone 1 g i.v. 30 min preintervention, and 69 received no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15-Fr gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score >3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined.. In no-prophylaxis patients, wound infection rates were 25% on day 4 and 26.4% on day 10, versus 10.1% (p = 0.03) and 14.5% (p = 0.10), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients: systemic infection rates were 16.7% versus 5.8% in no-prophylaxis versus prophylaxis patients (p = 0.045), and overall infection rates 38.9% versus 17.4%, respectively (p = 0.046). Pneumonia was more frequent in patients with underlying neurological disease. Antibiotic costs were the same in both groups (p = 0.792).. Single dose ceftriaxone 1 g is an effective prophylaxis against local and systemic infection after PEG.

Topics: Aged; Antibiotic Prophylaxis; Bacteremia; Ceftriaxone; Cephalosporins; Drug Costs; Economics, Pharmaceutical; Enteral Nutrition; Erythema; Exudates and Transudates; Female; Follow-Up Studies; Gastroscopy; Gastrostomy; Humans; Male; Neoplasms; Nervous System Diseases; Pneumonia; Prospective Studies; Sepsis; Suppuration; Surgical Wound Infection

To assess the value of adjunctive intravenous dexamethasone (DXM) and oral glycerol (GLY) for the treatment of bacteriologically proved bacterial meningitis, 122 infants and children with bacterial meningitis were randomly assigned to receive DXM intravenously (n = 32), GLY orally (n = 30), DXM plus GLY (n = 34) or neither (n = 26) of these drugs. All patients were treated with the same antimicrobial agent, ceftriaxone. The patients were followed neurologically for as long as 6 months. A thorough hearing evaluation was performed routinely 2 months or more after discharge from hospital. Overall 4 (7%) of the GLY-treated patients, compared with 11 (19%) of those not given GLY, developed audiologic or neurologic sequelae (P = 0.052), the relative risk of sequelae being 2.94 (95% confidence interval, 0.99 to 8.72). The patients who had received GLY showed less severe or profound bilateral hearing impairment than those not given GLY (0 vs. 7%, P = 0.049), and none of them had other neurologic abnormalities 3 or 6 months after discharge, compared with 5 (9%) of those not treated with GLY (P = 0.024). The DXM recipients showed only a tendency to less severe hearing impairment than those not given DXM. In conclusion oral GLY prevented neurologic sequelae in infants and children with bacterial meningitis more effectively than intravenous DXM.

Topics: Administration, Oral; Adolescent; Ceftriaxone; Child; Child, Preschool; Confidence Intervals; Dexamethasone; Drug Therapy, Combination; Female; Glycerol; Hearing Disorders; Humans; Infant; Injections, Intravenous; Male; Meningitis, Bacterial; Nervous System Diseases; Treatment Outcome

To determine whether treatment with dexamethasone and ceftriaxone for children with bacterial meningitis reduces the frequency of either sensorineural hearing loss or other neurologic sequelae.. This was a prospective, multicentered, placebo-controlled clinical trial. Subjects were followed for 1 year.. The study was conducted in six children's hospitals located in Pittsburgh, Houston, Los Angeles, Chicago, Washington, D.C., and Columbus, Ohio.. Enrolled were 173 children, 8 weeks to 12 years of age, with suspected bacterial meningitis; 143 children were evaluable. Eighty-seven percent of patients were followed for at least 6 weeks to 3 months, and 67% were followed for 1 year.. Subjects were randomized to receive ceftriaxone with or without dexamethasone (0.15 mg/kg every 6 hours for 4 days). Auditory brainstem responses (ABR) were measured within 24 hours of admission.. Hearing, development, and neurologic sequelae were assessed at the time of discharge and 6 weeks and 1 year later.. One hundred forty-three patients (69 received dexamethasone and 74 received placebo) with bacterial meningitis were evaluable: Haemophilus influenzae type b (83), Streptococcus pneumoniae (33), Neisseria meningitidis (24), and three others. Overall, there was no significant difference in auditory outcome between dexamethasone and placebo recipients. Twenty-two children had bilateral moderate or more severe hearing loss at the time of the first ABR. At follow-up, the resolution of hearing impairment was nearly identical for each group. Nine of ten children who remained persistently deaf were deaf at the time of the first ABR. There were no differences in neurologic or developmental outcome between groups.. All but one child with persistent bilateral moderate or more severe hearing loss had demonstrable deafness at the time of the first ABR. Dexamethasone did not significantly improve audiologic, neurologic, or developmental outcome in children with bacterial meningitis.

Topics: Ceftriaxone; Child; Child Development; Child, Preschool; Deafness; Dexamethasone; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Humans; Infant; Male; Meningitis, Bacterial; Nervous System Diseases; Prospective Studies

In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16). Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.

Topics: Adult; Aged; Antibodies, Bacterial; Borrelia burgdorferi Group; Cefotaxime; Ceftriaxone; Child; Female; Follow-Up Studies; Humans; Lyme Disease; Male; Middle Aged; Nervous System Diseases

The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China.. This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

Topics: Adenosine Deaminase; Adult; Animals; Antigens, Bacterial; Ceftriaxone; China; DNA, Bacterial; Doxycycline; Humans; Leukocyte Count; Male; Nervous System Diseases; Phylogeny; Rickettsia; Rickettsia Infections; RNA, Ribosomal, 16S; Tick Bites; Ticks

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Diagnosis, Differential; Encephalomyelitis, Eastern Equine; Fever; Humans; Infant; Male; Nervous System Diseases; Seizures

Early-onset pneumonia (EOP) after endotracheal intubation is common among critically ill patients with a neurologic injury and is associated with worse clinical outcomes.. This retrospective cohort study observed outcomes pre- and post-implementation of an EOP prophylaxis protocol which involved the administration of a single dose of ceftriaxone 2 g around the time of intubation. The study included patients ≥ 18 years who were admitted to the University of North Carolina Medical Center (UNCMC) neuroscience intensive care unit (NSICU) between April 1, 2014, and October 26, 2016, and intubated for ≥ 72 h.. Among the 172 patients included, use of an EOP prophylaxis protocol resulted in a significant reduction in the rate of microbiologically confirmed EOP compared to those without prophylaxis (7.4 vs 19.8%, p = 0.026). However, EOP prophylaxis did not decrease the combined incidence of microbiologically confirmed or clinically suspected EOP (32.2 vs 37.4%, p = 0.523). No difference in the rate of late-onset pneumonia (34.6 vs 26.4%, p = 0.25) or virulent organism growth (19.8 vs 14.3%, p = 0.416) was observed. No difference was observed in the duration of intubation, duration of intensive care unit (ICU) stay, duration of hospitalization, or ICU antibiotic days within 30 days of intubation. In hospital mortality was found to be higher in those who received EOP prophylaxis compared to those who did not receive prophylaxis (45.7 vs 29.7%, p = 0.04).. The administration of a single antibiotic dose following intubation may reduce the incidence of microbiologically confirmed EOP in patients with neurologic injury who are intubated ≥ 72 h. A prophylaxis strategy does not appear to increase the rate of virulent organism growth or the rate of late-onset pneumonia. However, this practice is not associated with a decrease in days of antibiotic use in the ICU or any clinical outcomes benefit.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Ceftriaxone; Critical Care; Female; Humans; Intubation, Intratracheal; Male; Middle Aged; Nervous System Diseases; Outcome and Process Assessment, Health Care; Pneumonia, Ventilator-Associated; Retrospective Studies; Risk

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.

Topics: Artesunate; Azithromycin; Ceftriaxone; Child; Communicable Diseases; Critical Care; Dengue; Diagnosis, Differential; Doxycycline; Exanthema; Female; Fever; Geography; Humans; Intensive Care Units; Leptospirosis; Malaria; Male; Nervous System Diseases; Pregnancy; Shock, Hemorrhagic; Syndrome; Travel; Tropical Medicine; Typhoid Fever

Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia.

Topics: Acetylcysteine; Analysis of Variance; Animals; Brain; Brain Edema; Brain Infarction; Ceftriaxone; Disease Models, Animal; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Excitatory Amino Acid Transporter 2; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Wistar; RNA, Messenger

HaNDL (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is an infrequent condition included at group 7 "headache attributed to non-vascular intracranial disorder" in the recent International Classification of Headache Disorders (ICHD-3), code 7.3.5. The description states "migraine-like headache episodes (typically 1-12) accompanied by neurological deficits including hemiparaesthesia, hemiparesis and/or dysphasia, but positive visual symptoms only uncommonly, lasting several hours. There is lymphocytic pleocytosis. The disorder resolves spontaneously within 3 months". In this description confusional state is not considered as a main symptom, even if in the literature this aspect is frequently reported. Here, we report the cases of two young boys presenting with confusional state as the main complaint. The possible pathogenesis of the different clinical presentation is discussed.

Topics: Acyclovir; Adolescent; Ceftriaxone; Confusion; Headache; Humans; Lymphocytosis; Male; Nervous System Diseases; Young Adult

Ceftriaxone is widely used in patients for the treatment of serious gram-negative infections. Ceftriaxone can induce some potential side effects, including neurotoxicity, however, nonconvulsive status epilepticus has rarely been reported. We report a case of acute reversible neurotoxicity associated with ceftriaxone. A 65-yr-old woman with chronic kidney disease developed altered consciousness during ceftriaxone treatment for urinary tract infection. The electroencephalogram demonstrated continuous bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity. Neurologic symptoms disappeared following withdrawal of ceftriaxone. The possibility of ceftriaxone-induced neurotoxicity should be considered in patients developing neurological impairment during ceftriaxone use, and the discontinuation of the drug could lead to complete neurological improvement.

Topics: Aged; Anti-Bacterial Agents; Anticoagulants; Ceftriaxone; Electroencephalography; Female; Humans; Nervous System Diseases; Renal Dialysis; Renal Insufficiency, Chronic; Seizures; Thrombosis; Tomography, X-Ray Computed; Urinalysis; Urinary Tract Infections

Topics: Amoxicillin; Anti-Bacterial Agents; Arthritis; Ceftriaxone; Doxycycline; Heart Diseases; Humans; Lyme Disease; Nervous System Diseases

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Ceftriaxone; Excitatory Amino Acid Transporter 2; Mice; Nervous System Diseases; Neuroprotective Agents; Spinal Cord

The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.

Topics: Antibodies, Bacterial; Antibody Formation; Borrelia burgdorferi Group; Ceftriaxone; Cephalosporins; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Immunoglobulin G; Immunoglobulin M; Lyme Disease; Nervous System Diseases; Retrospective Studies; Time Factors

Topics: Administration, Oral; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Cost-Benefit Analysis; Decision Trees; Doxycycline; Humans; Infusions, Intravenous; Injections, Intravenous; Lyme Disease; Nervous System Diseases; Quality of Life; Quality-Adjusted Life Years; Risk

Topics: Adult; Arrhythmias, Cardiac; Arthritis, Infectious; Ceftriaxone; Child; Doxycycline; Female; Humans; Lyme Disease; Male; Microbial Sensitivity Tests; Nervous System Diseases; Penicillins; Pregnancy; Tetracycline