ro13-9904 and Seizures

Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci.. A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy.. A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs. 81%); deaths (2% vs. 3%); seizures after enrollment (22% vs. 21%); and severe sequelae (14% vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months.. We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.

Topics: Anti-Infective Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Infant; Infusions, Intravenous; Liver; Male; Meningitis, Bacterial; Naphthyridines; Seizures; Treatment Outcome

Epilepsy is one of the most serious worldwide neurological disorders that lead to the cognitive-psychosocial insults in recurrent seizures. About one third of the patients are drug-resistant, so innovative drugs are needed to manage seizures to improve the quality of life. Ceftriaxone is a cephalosporin antibiotic that increases the expression of glutamate transporters-1 and improves the neurobehavioral effects caused by increased glutamate level in the CNS. Selenium is well known antioxidant. The present study aimed to investigate ceftriaxone and selenium therapeutic effects against epilepsy in rats. Epilepsy was induced by PTZ given at a dose (50 mg/kg I.P) on alternative days for 13 days. Eighty rats were randomly divided into 8 groups: Group1-2; normal and vehicle control, Group 3; PTZ group, Group 4-8; kindled rats received selenium, ceftriaxone100, ceftriaxone200, selenium + ceftriaxone100 and selenium + ceftriaxone200 mg/kg/day respectively for a week. At the end of the study, behavioral tests were performed. Oxidative stress, inflammatory markers, neurotransmitters and GLT-1 were measured in brain tissue homogenate. Brain histopathological investigation was also done. PTZ-kindled rats exhibited increased Racine score, besides behavioral tests and histopathological changes, significant elevation in oxidative stress and inflammatory markers, with decrease in serotonin, dopamine, GABA levels and GLT-1 expressions. Selenium and Ceftriaxone alone or combined treatment decreased Racine score with remarkable improvement in behavioral and histopathological changes. The antioxidant enzymes, neurotransmitters and GLT-1 expressions were increased, along with reduced TNF-α, IL-1 levels. Current study showed that selenium + ceftriaxone100 group represents a possible approach to improve epilepsy particularly through inhibiting oxidative stress and inflammation.

Topics: Animals; Anticonvulsants; Antioxidants; Ceftriaxone; Epilepsy; Glutamates; Neurotransmitter Agents; Oxidative Stress; Pentylenetetrazole; Quality of Life; Rats; Seizures; Selenium

The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit an abnormal excitatory / inhibitory balance. In this study, we examine how brain injury alters susceptibility to chemically-induced seizures in C57Bl/6J mice, and if pharmacological enhancement of glutamate transporters can reduce chronic post-traumatic seizures. We found that controlled cortical impact (CCI) mice display delayed susceptibility to pentylenetetrazol (PTZ)-induced seizures. While CCI mice have no change in seizure susceptibility at 7d post-injury (dpi), at 70dpi they have reduced latency to PTZ-induced seizure onset, higher seizure frequency and longer seizure duration. Quantification of glutamate transporter mRNA showed that levels of Scl1a2 and Scl1a3 mRNA were increased at 7dpi, but significantly decreased at 70dpi. To test if increased levels of glutamate transporters can ameliorate delayed-onset seizure susceptibility in TBI mice, we exposed a new cohort of mice to CCI and administered ceftriaxone (200mg/kg/day) for 14d from 55-70dpi. We found that ceftriaxone significantly increased Scl1a2 and Scl1a3 in CCI mouse brain at 70dpi, and prevented the susceptibility of CCI mice to PTZ-induced seizures. This study demonstrates cortical impact can induce a delayed-onset seizure phenotype in mice. Delayed (55dpi) ceftriaxone treatment enhances glutamate transporter mRNA in the CCI brain, and reduces PTZ-induced seizures in CCI mice.

Topics: Animals; Brain Injuries, Traumatic; Ceftriaxone; Disease Models, Animal; Epilepsy, Post-Traumatic; Glutamates; Humans; Mice; Mice, Inbred C57BL; Pentylenetetrazole; Seizures; Time-to-Treatment

To describe a term newborn with acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and multisystem involvement including seizures associated to ischemic lesions in the brain.. Coronavirus disease 2019 (COVID-19) is predominantly a respiratory infection, but it may affect many other systems. Most pediatric COVID-19 cases range from asymptomatic to mild-moderate disease. There are no specific clinical signs described for neonatal COVID-19 infections. In children, severe central nervous system compromise has been rarely reported.. We describe a 17-day-old newborn who acquired a SARS-CoV-2 infection in a family meeting that was admitted for fever, seizures and lethargy and in whom consumption coagulopathy, ischemic lesions in the brain and cardiac involvement were documented.. SARS-CoV-2 neonatal infection can be associated with multi-organic involvement. In our patient, significant central nervous system compromise associated to ischemic lesions and laboratory findings of consumption coagulopathy were found.. Although neonatal SARS-CoV-2 infections are infrequent, they can be associated with multi-organic involvement. Neonatologists and pediatricians should be aware of this unusual way of presentation of COVID-19 in newborn infants.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain; Brain Ischemia; Ceftriaxone; COVID-19; COVID-19 Drug Treatment; Fever; Frontal Lobe; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lethargy; Magnetic Resonance Imaging; Male; Nasopharynx; SARS-CoV-2; Seizures

β-Lactam antibiotics such as ceftriaxone, are potent stimulators of the expression of l-glutamate transporter GLT-1 and may exert neuroprotective effects when chronically used in rats and mice. In this study, we used two animal models to test the neurological effect of subchronic treatment with ceftriaxone: experimental acute glaucoma in Wistar rats and induction of acute seizures with pentylenetetrazole in mice. We also assessed the performance of mice in the rotarod to calculate therapeutic indexes and exploratory activity in the open field. Our results showed that subchronic use of ceftriaxone was neuroprotective in both models, reducing injury in acute ischemia and ischemia/reperfusion in specific layers of retina and leading to a decrease in the seizure severity score. In behavioral experiments, we observed that ceftriaxone increased hyperactivity followed by a decrease in exploratory behavior in the open field, and there was no motor impairment in the rotarod test. We conclude that ceftriaxone may be useful as a tool in the development of new neuroprotective drugs targeting diseases which present a possible dysfunction in the balance of glutamatergic neurotransmission.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Behavior, Animal; Ceftriaxone; Convulsants; Glaucoma; Male; Mice; Neuroprotective Agents; Rats; Rats, Wistar; Seizures; Tetrazoles

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Ceftriaxone; Diabetes Mellitus, Type 2; Electroencephalography; Female; Humans; Levetiracetam; Meningitis, Bacterial; Seizures; Streptococcal Infections; Streptococcus agalactiae

Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20-30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.

Topics: Animals; Anticonvulsants; Ceftriaxone; Epilepsy; Excitatory Amino Acid Transporter 2; Excitatory Postsynaptic Potentials; Gene Expression; Glutamic Acid; Hippocampus; Male; Rats, Wistar; Seizures; Synaptic Transmission; Temporal Lobe

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

Topics: Aged; Animals; Anti-Bacterial Agents; Borrelia burgdorferi; Ceftriaxone; Female; Humans; Lyme Neuroborreliosis; Male; Middle Aged; Seizures

Many drugs have been associated with seizures as a side effect. Although they are defined as safe for nervous system. The effect on proconvulsant activity of beta lactam antibiotics have been also reported. We aimed to investigate whether ceftriaxone has an anticonvulsant effect on PTZ-induced seizures in rats.. 36 male Sprague-Dawley rats, 18 of them for EEG recording and 18 of them are for behavioral studies, were randomly divided in two groups: group A for EEG recordings and group B for behavioral assesment. About 70 mg/kg PTZ was used for behavioral studies after Ceftriaxone administiration. About 35 mg/kg PTZ were used for EEG recording after ceftriaxone administiration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale, first myoclonic jerk onset time, spike percentages, brain MDA and SOD levels were evaluated between the groups.. First myoclonic jerk onset time was significantly shorter in saline group than both 200 and 400 mg/kg ceftriaxone groups (p < 0.05). Racine's convulsion scale was significantly lower in 200 and 400 mg/kg ceftriaxone groups than saline group (p < 0.01, p < 0.0001). Both of two ceftriaxone groups have lower spike percentages than the saline group (p < 0.05). Significantly lower MDA levels and higher SOD activity were determined in 200 mg/kg ceftriaxone group compared with the saline group (p < 0.05).. Our study demonstrated that ceftriaxone has protective effects on PTZ-induced convulsions and on oxidative damage associated with PTZ.

Topics: Animals; Anticonvulsants; Brain; Ceftriaxone; Convulsants; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electrodes, Implanted; Electroencephalography; GABA Antagonists; Lipid Peroxidation; Male; Malondialdehyde; Myoclonus; Pentylenetetrazole; Random Allocation; Rats; Rats, Sprague-Dawley; Seizures; Superoxide Dismutase

Topics: Anti-Bacterial Agents; Ceftriaxone; Emergency Service, Hospital; Female; Fever; Humans; Infant; Lethargy; Male; Meningitis, Pneumococcal; Pneumococcal Vaccines; Seizures; Serotyping; Sinus Thrombosis, Intracranial; Streptococcus pneumoniae; Stroke; Treatment Outcome; Vancomycin

Multiple lines of investigation have explored the role of glutamatergic and purinergic systems in epilepsy, related cognitive impairment, and oxidative stress. Glutamate transporters, particularly GLT-1 expression, were found to be decreased, and purinergic receptor, P2X7 expression, was found to be increased in brain tissue associated with epilepsy. The present study was carried out to investigate the effect of ceftriaxone (GLT-1 upregulator) and Brilliant Blue G (P2X7 antagonist) against PTZ-induced kindling in rats. The study was further extended to elucidate the cross-link between glutamatergic and purinergic pathways in epilepsy.. Systemic administration of subconvulsant dose of PTZ (30 mg/kg) every other day for 27days (14 injections) significantly increased the mean kindling, and developed generalized tonic-clonic seizures, and reduced motor co-ordination, cognitive skills, oxidative defense (increases lipid peroxidation, nitrite levels and decreases GSH level) and acetylcholinesterase enzyme activities in the cortex and subcortical region. Treatments with CEF (100 and 200mg/kg) and BBG (15 and 30 mg/kg) alone and in combination (CEF 100mg/kg and BBG 15 mg/kg) significantly decreased the mean kindling score and restored behavioral and oxidative defense activities compared with treatment with PTZ.. The combination of both the drugs was shown to have better effect in preventing kindled seizures and a significantly synergistic effect compared with their effect alone in PTZ-kindled rats. The present study elucidated the mechanistic role of GLT-1 modulator and selective P2X7 antagonist and their combination against PTZ-induced kindling. The study for the first time demonstrated the cross-link between glutamatergic and purinergic pathways in epilepsy treatment.

Topics: Animals; Brain; Ceftriaxone; Cognition Disorders; Convulsants; Dose-Response Relationship, Drug; Epilepsy; Excitatory Amino Acid Transporter 2; Kindling, Neurologic; Lipid Peroxidation; Male; Oxidative Stress; Pentylenetetrazole; Purinergic P2X Receptor Antagonists; Rats; Rosaniline Dyes; Seizures

Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely to post-traumatic epilepsy. Glutamate transport is the only known mechanism of extracellular glutamate clearance, and glutamate transporter 1 (GLT-1) is the major glutamate transporter of the mammalian brain. We tested, by immunoblot, in the rat lateral fluid percussion injury TBI model whether GLT-1 expression is depressed in the cortex after TBI, and whether GLT-1 expression after TBI is restored after treatment with ceftriaxone, a well-tolerated β-lactam antibiotic previously shown to enhance GLT-1 expression in noninjured animals. We then tested whether treatment with ceftriaxone mitigates the associated regional astrogliosis, as reflected by glial fibrillary acid protein (GFAP) expression, and also whether ceftriaxone treatment mitigates the severity of post-traumatic epilepsy. We found that 7 days after TBI, GLT-1 expression in the ipsilesional cortex was reduced by 29% (n=7/group; p<0.01), relative to the contralesional cortex. However, the loss of GLT-1 expression was reversed by treatment with ceftriaxone (200 mg/kg, daily, intraperitoneally). We found that ceftriaxone treatment also decreased the level of regional GFAP expression by 43% in the lesioned cortex, relative to control treatment with saline (n=7 per group; p<0.05), and, 12 weeks after injury, reduced cumulative post-traumatic seizure duration (n=6 rats in the ceftriaxone treatment group and n=5 rats in the saline control group; p<0.001). We cautiously conclude that our data suggest a potential role for ceftriaxone in treatment of epileptogenic TBI.

Topics: Animals; Brain Injuries; Ceftriaxone; Cerebral Cortex; Excitatory Amino Acid Transporter 2; Gliosis; Male; Rats; Rats, Long-Evans; Seizures; Treatment Outcome

Topics: Adrenal Cortex Hormones; Allergens; Carbamazepine; Ceftriaxone; Child; Child, Preschool; Drug Eruptions; Female; Humans; Hypersensitivity, Delayed; Ibuprofen; Immunoglobulins, Intravenous; Male; Patch Tests; Penicillin G Procaine; Respiratory Tract Infections; Seizures; Stevens-Johnson Syndrome

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

We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.

Topics: Brain Damage, Chronic; Cefotaxime; Ceftriaxone; Child, Preschool; Coma; Diazepam; Encephalomyelitis, Acute Disseminated; Facial Paralysis; Humans; Immunoglobulins, Intravenous; Lyme Neuroborreliosis; Magnetic Resonance Imaging; Male; Mastoiditis; Methylprednisolone; Portugal; Respiration, Artificial; Respiratory Insufficiency; Respiratory Tract Infections; Seizures; Sinusitis; Vancomycin

In children, neuroborreliosis often manifests itself as cranial neuritis (particularly facial palsy) or aseptic meningitis. Presentation with torticollis and simple partial seizures resulting from diffuse leptomeningeal inflammation is rare.. A seven-year-old boy who had developed torticollis and partial seizures, lost weight and was complaining of tiredness was seen by a paediatric neurologist. A brain and spinal cord MRI showed diffuse leptomeningeal enhancement, in combination with a hyperintense cervical cord lesion. Laboratory testing of serum and cerebrospinal fluid confirmed the diagnosis of neuroborreliosis. The boy was treated with intravenous ceftriaxone for 30 days and made a full recovery.. As illustrated by this case neuroborreliosis can manifest itself atypically with torticollis, seizures and diffuse leptomeningeal enhancement due to inflammation. If there is leptomeningeal enhancement on MRI then neuroborreliosis should be included in the differential diagnosis. In childhood neuroborreliosis can be successfully treated and the prognosis is good.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Diagnosis, Differential; Facial Paralysis; Humans; Lyme Neuroborreliosis; Male; Seizures; Torticollis; Treatment Outcome

Following initial signs of dural infection, or as prophylactic postoperative therapy, three cynomologus macaques were given an intramuscular or a subcutaneous injection of ceftriaxone dissolved in a 1% lidocaine diluent (CL). Two to 15 min later, all three monkeys experienced a long-lasting generalized apnoeic clonic convulsive seizure. The injected doses of lidocaine (0.7-2 mg/kg) were as low as 7-20-fold less than the experimental intravenous dosage (14.2 +/- 3.2 mg/kg) previously reported to induce seizure in healthy rhesus monkeys. Under different clinical conditions, the same three animals were either once (1 animal) or repeatedly given CL without any resultant neurological alterations. The monkeys had a cranial device implanted and two of them were craniotomized. This first report of accidental lidocaine-induced seizure in laboratory non-human primates following CL injection strongly suggests increased susceptibility when lidocaine administration is associated with central nervous system alteration. A novel hypothesis, the possible role of cytokine in lowering the lidocaine seizure threshold, is suggested.

Topics: Anesthetics, Local; Animals; Anti-Bacterial Agents; Ceftriaxone; Injections, Intramuscular; Injections, Subcutaneous; Lidocaine; Macaca fascicularis; Male; Monkey Diseases; Pharmaceutical Vehicles; Seizures; Skull

Topics: Anti-Infective Agents; Atrial Fibrillation; Ceftriaxone; Cell Transformation, Neoplastic; Coronary Artery Disease; Diagnosis, Differential; Humans; Hyperlipidemias; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Male; Middle Aged; Neoplasm Recurrence, Local; Nocardia Infections; Seizures; Smoking; Trimethoprim, Sulfamethoxazole Drug Combination

We report a very unusual case of meningoencephalitis due to Listeria monocytogenes in a 7-month-old immunocompetent boy. Cerebrospinal fluid (CSF) culture was initially negative, but was positive on the seventh day. The disease was complicated by seizures and hydrocephalus managed with temporary ventriculostomy. The infant was discharged without obvious neurological sequelae after 30 days and developed without neurological or developmental sequelae at two years of age. Listeria is difficult to isolate and is not susceptible to third-generation cephalosporins commonly used for the empirical treatment of bacterial meningitis.

Topics: Ampicillin; Anti-Bacterial Agents; Anticonvulsants; Ceftriaxone; Drug Therapy, Combination; Gentamicins; Humans; Hydrocephalus; Immunocompetence; Infant; Male; Meningitis, Listeria; Phenytoin; Seizures; Tomography, X-Ray Computed; Vancomycin

Although considered to be generally safe, a number of beta-lactam antibiotics have been associated with epileptic seizures in humans. Furthermore, some beta-lactam antibiotics, including ceftriaxone, are used to evoke convulsions under experimental conditions. Recently it was demonstrated that ceftriaxone increased expression of the glutamate transporter (GLT1) and its biochemical and functional activity in the brain of rodents. GLT1 regulates extracellular concentrations of glutamate, an excitatory amino acid involved in the pathogenesis of seizures and epilepsy. Because of its rapid transfer of glutamate into neurons and adjacent glial cells, GLT1 diminishes glutamate toxicity. We investigated whether ceftriaxone (200 mg/kg body wt) administered intraperitoneally (ip) for 6 days could modify the convulsant effects of pentylenetetrazole (PTZ, 100 mg/kg ip) in inbred male BALBcAnNCR and C57 black (BL)/6 mice aged 4 and 12 weeks. Ceftriaxone pretreatment provided significant protective effects against PTZ-evoked generalized clonic convulsions (GCCs), generalized clonic-tonic convulsions (GCTCs), and convulsion-induced mortality during a period of 30 mins after PTZ administration. The incidence of GCCs, GCTCs, and death was statistically significantly lower for BALBcAnNCR mice of both ages, particularly younger mice. The latency time for each of the three parameters was significantly greater, with the exception of GCCs in adult mice. Protective effects of ceftriaxone were also noticed in adult C57BL/6 mice but not in prepubertal C57BL/6 mice. This is the first demonstration of anticonvulsant effects of ceftriaxone or any other beta-lactam antibiotic, which are not uniform across the mouse population. Our results provide new insight into the effects of ceftriaxone, which need further investigation.

Topics: Animals; Ceftriaxone; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred Strains; Pentylenetetrazole; Protective Agents; Seizures; Time Factors

Salmonella panama is group-D nontyphi salmonella strongly associated with invasive infection, including meningitis. So far, no case of S. panama meningitis has been reported from the United States, and none has ever been reported in babies >3.5 months of age. To the best of our knowledge, we are reporting the first such case in English-language literature.

Topics: Anti-Bacterial Agents; Ceftriaxone; Humans; Infant; Male; Meningitis, Bacterial; Salmonella; Salmonella Infections; Seizures

Topics: Anti-Bacterial Agents; Ceftriaxone; Expert Testimony; Humans; Infant; Malpractice; Medical Staff, Hospital; North Carolina; Nursing Staff, Hospital; Practice Guidelines as Topic; Seizures

A 44-month-old boy with chronic granulomatous disease has been suffering from fever and skin rash for 7 days prior to admission. The blood culture obtained on admission revealed Salmonella enterica subspecies houtenae. He received intravenous ceftriaxone therapy during his hospital stay and oral cefixime after discharge. Unfortunately, the same symptoms recurred 2 weeks after discontinuing cefixime and the culture from the aspirate of a skin nodule yielded the same microorganism again. He received intravenous ceftriaxone therapy after readmission and became afebrile 3 days later. However, focal seizure was noted on the 14th day of hospitalization. Brain magnetic resonance imaging revealed multiple brain abscesses, and electroencephalogram showed epileptiform activity. The intravenous antimicrobial agents were continued for a total of 84 days and interferon-gamma was administered as adjunctive therapy. Finally, he recovered from brain abscesses without any neurologic sequel. It is suggested that an extended course of antimicrobial treatment is necessary for chronic granulomatous disease with pyogenic infection because of the defective intracellular killing ability.

Topics: Anti-Bacterial Agents; Bacteremia; Brain Abscess; Ceftazidime; Ceftriaxone; Child, Preschool; Drug Therapy, Combination; Electroencephalography; Exanthema; Granulomatous Disease, Chronic; Humans; Interferon-gamma; Magnetic Resonance Imaging; Male; Salmonella enterica; Salmonella Infections; Seizures

The purpose of the present study was to retrospectively review the antibiotic therapy of aspiration or tracheostomy-associated pneumonia in 57 neurologically impaired children (NIC). The antimicrobials used were either ticarcillin-clavulanate or clindamycin, which are effective against penicillin-resistant anaerobic bacteria, or ceftriaxone, which is less effective against these organisms. In those with aspiration pneumonia, a satisfactory clinical and microbiological response was observed in 8/9 (89%) patients who received ticarcillin-clavulanate, and 10/11 (91%) who received clindamycin with or without ceftazidime, as compared to 7/14 (50%) who received ceftriaxone (P < 0.05). For those who experienced tracheostomy-associated pneumonia, a positive response to therapy was observed in 5/6 (83%) who received ticarcillin-clavulanate, and 7/7 (100%) who received clindamycin with or without ceftazidime, as opposed to 4/10 (40%) who were treated with ceftriaxone (P < 0.05). The duration of fever was longer in both cases for those who received ceftriaxone. To summarize, this study illustrates the superiority of antimicrobials effective against penicillin-resistant anaerobic bacteria, as compared to an antibiotic without such coverage, in the therapy of aspiration or tracheostomy-associated pneumonia in NIC.

Topics: Adolescent; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Ceftazidime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Clavulanic Acid; Clavulanic Acids; Clindamycin; Female; Fever; Humans; Male; Penicillins; Pneumonia, Aspiration; Pneumonia, Bacterial; Retrospective Studies; Seizures; Ticarcillin; Tracheostomy; Unconsciousness

We have characterized the pattern of brain injury in a rat model of meningitis caused by group B streptococci (GBS). Infant rats (12-14 days old; n = 69) were infected intracisternally with 10 microliters of GBS (log10(2.3) to 4.5 colony-forming units). Twenty hours later, illness was assessed clinically and cerebrospinal fluid was cultured. Animals were either immediately euthanized for brain histopathology or treated with antibiotics and examined later. Early GBS meningitis was characterized clinically by severe obtundation and seizures, and histopathologically by acute inflammation in the subarachnoid space and ventricles, a vasculopathy characterized by vascular engorgement, and neuronal injury that was most prominent in the cortex and often followed a vascular pattern. Incidence of seizures, vasculopathy and neuronal injury correlated with the inoculum size (p < 0.01). Early injury was almost completely prevented by treatment with dexamethasone. Within days after meningitis, injured areas became well demarcated and showed new cellular infiltrates. Thirty days post-infection, brain weights of infected animals treated with antibiotics were decreased compared to uninfected controls (1.39 +/- 0.18 vs 1.64 +/- 0.1 g; p < 0.05). Thus, GBS meningitis in this model caused extensive cortical neuronal injury resembling severe neonatal meningitis in humans.

Topics: Animals; Animals, Newborn; Brain Damage, Chronic; Ceftriaxone; Cerebral Cortex; Cerebral Ventricles; Consciousness Disorders; Dexamethasone; Granulocytes; Meningitis, Bacterial; Neurons; Organ Size; Rats; Rats, Sprague-Dawley; Seizures; Severity of Illness Index; Streptococcal Infections; Streptococcus agalactiae; Subarachnoid Space; Vasculitis

Topics: Anticonvulsants; Brain; Brain Edema; Ceftriaxone; Cephalosporins; Child, Preschool; Diarrhea; Dysentery, Bacillary; Feces; Female; Humans; Phenytoin; Seizures; Shigella flexneri; Tomography, X-Ray Computed