rifampin and Seizures

Topics: Ampicillin; Bacterial Infections; Brain Edema; Child, Preschool; Chloramphenicol; Cloxacillin; Gentamicins; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Injections, Spinal; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Methicillin; Minocycline; Neisseria meningitidis; Penicillin G; Rifampin; Seizures; Shock; Streptococcus pneumoniae; Sulfonamides

Levofloxacin is an effective bactericidal category III antitubercular drug. There is paucity of studies comparing the role of additional levofloxacin to standard antitubercular regimen in the patients with tuberculous meningitis (TBM).. To compare the safety and efficacy of adding levofloxacin to standard four drug ATT regimen (RHZE).. The patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF) and MRI criteria were included. Children below 15 years, patients with pregnancy, seizures, liver failure, kidney failure and malignancy were excluded. The baseline clinical, CSF and MRI characteristics were noted and consciousness was evaluated by Glasgow Coma Scale (GCS). The patients were randomized to RHZE (rifampicin, isoniazid, pyrazinamide and ethambutol) and RHZEL (RHZE and levofloxacin) groups. Outcome was defined at 6 months. Primary outcome was death and secondary outcomes were disability as assess by Barthel Index score and adverse events.. Out of 110 TBM patients screened, 57 fulfilled the inclusion criteria. Their median age was 35 (15-75) years. 29 patients received RHZEL and 28 RHZE. The baseline clinical, biochemical and MRI characteristics were similar in the two groups. At 6 months, 11 (19.3%) patients died, 38 (66.7%) had good and 7 (12.3%) poor outcome. There was insignificant survival benefit in RHZEL group compared to RHZE (HR-2.61, 95% CI 0.73-9.36, P = 0.14), 25% patients died in RHZE where as 13.8% in RHZEL group. The disability was not significantly different between the two groups. The composite side effects were also similar between the two groups except for a higher frequency of seizure in RHZEL group (5 Vs 0) which resulted in withdrawal of levofloxacin.. There was insignificant survival benefit in RHZEL which was associated with high frequency of seizures.

Topics: Adolescent; Adult; Aged; Antitubercular Agents; Disability Evaluation; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Levofloxacin; Male; Middle Aged; Pilot Projects; Proportional Hazards Models; Pyrazinamide; Rifampin; Seizures; Time Factors; Treatment Outcome; Tuberculosis, Meningeal; Young Adult

Patients with tuberculous meningitis (TBM) in any stage of the British Medical Research Council (BMRC) scale, if requiring mechanical ventilation (MV), are likely to have a poor outcome. We report the usefulness of BMRC, BMRC-MV, and BMRC-hydrocephalus (BMRC-HC) staging, and Haydarpasa Meningitis Severity Index (HAMSI) scoring in predicting the outcome of TBM. One hundred ninety-seven TBM patients were analyzed from a prospectively maintained TBM registry. The severity of meningitis was categorized using BMRC (stages I-III), BMRC-MV (I-IV [MV patients were grouped as stage IV]), and BMRC-HC (I-IV [BMRC stage III patients with hydrocephalus were grouped as stage IV]). Haydarpasa Meningitis Severity Index scoring was categorized as < 6 and ≥ 6. The outcome was defined at 6 months using the modified Rankin Scale (mRS) as death, poor (mRS score > 2), or good (mRS score ≤ 2). Forty-nine (25%) patients died. BMRC-mechanical ventilation stage IV had the highest predictive value for defining death, with a sensitivity of 88% and a specificity of 86%. About 81.7% of surviving patients had a good outcome at 6 months. BMRC-mechanical ventilation stages I-III had the highest predictive value for defining good outcome, with a sensitivity of 93% and a specificity of 61%. In TBM, BMRC-MV staging has the best predictive value for defining death and disability.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antitubercular Agents; Child; Child, Preschool; Consciousness Disorders; Ethambutol; Female; Humans; Hydrocephalus; India; Isoniazid; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Pyrazinamide; Registries; Respiration, Artificial; Rifampin; Seizures; Severity of Illness Index; Tomography, X-Ray Computed; Tuberculosis, Meningeal; Ventriculoperitoneal Shunt; Young Adult

Epilepsy is one of the serious neurological sequelae of bacterial meningitis. Rifampicin, the well-known broad spectrum antibiotic, is clinically used for chemoprophylaxis of meningitis. Besides its antibiotic effects, rifampicin has been proven to be an effective neuroprotective candidate in various experimental models of neurological diseases. In addition, rifampicin was found to have promising antioxidant, anti-inflammatory and anti-apoptotic effects. Herein, we investigated the anticonvulsant effect of rifampicin at experimental meningitis dose (20 mg/kg, i.p.) using lithium-pilocarpine model of status epilepticus (SE) in rats. Additionally, we studied the effect of rifampicin on seizure induced histopathological, neurochemical and behavioral abnormalities. Our study showed that rifampicin pretreatment attenuated seizure activity and the resulting hippocampal insults marked by hematoxylin and eosin. Markers of oxidative stress, neuroinflammation and apoptosis were evaluated, in the hippocampus, 24 h after SE induction. We found that rifampicin pretreatment suppressed oxidative stress as indicated by normalized malondialdehyde and glutathione levels. Rifampicin pretreatment attenuated SE-induced neuroinflammation and decreased the hippocampal expression of interleukin-1β, tumor necrosis factor-α, nuclear factor kappa-B, and cyclooxygenase-2. Moreover, rifampicin mitigated SE-induced neuronal apoptosis as indicated by fewer positive cytochrome c immunostained cells and lower caspase-3 activity in the hippocampus. Furthermore, Morris water maze testing at 7 days after SE induction showed that rifampicin pretreatment can improve cognitive dysfunction. Therefore, rifampicin, currently used in the management of meningitis, has a potential additional advantage of ameliorating its epileptic sequelae.

Topics: Animals; Apoptosis; Hippocampus; Inflammation; Lithium Chloride; Male; Memory Disorders; Oxidative Stress; Pilocarpine; Rats; Rats, Wistar; Rifampin; Seizures

Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka.. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge.. Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting.

Topics: Administration, Oral; Antidotes; Antitubercular Agents; Diazepam; Drug Combinations; Female; Humans; Isoniazid; Pyridoxine; Rifampin; Seizures; Sri Lanka; Suicide, Attempted; Tablets; Treatment Outcome; Unconsciousness; Young Adult

This study aims to examine the use and safety of rifampin in the hospitalized infants.. Observational study of clinical and laboratory adverse events among infants exposed to rifampin from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012.. Overall, 2,500 infants received 4,279 courses of rifampin; mean gestational age was 27 weeks (5th, 95th percentile; 23, 36) and mean birth weight was 1,125 g (515; 2,830). Thrombocytopenia (121/1,000 infant days) and conjugated hyperbilirubinemia (25/1,000 infant days) were the most common laboratory adverse events. The most common clinical adverse events were medical necrotizing enterocolitis (64/2,500 infants, 3%) and seizure (60/2,500 infants, 2%).. The overall incidence of adverse events among infants receiving rifampin appears low; however, additional studies to further evaluate safety and dosing of rifampin in this population are needed.

Topics: Antibiotics, Antitubercular; Birth Weight; Enterocolitis, Necrotizing; Female; Gestational Age; Hospitalization; Humans; Hyperbilirubinemia; Infant; Infant, Extremely Premature; Infant, Newborn; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Male; Rifampin; Seizures; Thrombocytopenia

Anti-epileptic drugs (AEDs) have a small therapeutic window, so it is important to monitor plasma levels. Inadequate plasma levels may lead to convulsions. Many AEDs are cleared hepatically, and there are many drug interactions that are known to lead to changes in plasma levels.. A 54-year-old woman with known epilepsy developed convulsions after using rifampicin and flucloxacillin, despite the use of maintenance treatment in the form of carbamazepine, valproic acid and clonazepam. Since rifampicin is known to induce several cytochrome P450 enzymes and clearance of the anti-epileptic drug used may be affected by this, it can be assumed that the convulsions were caused by rifampicin. This interaction is however not mentioned in the Dutch 'G-standard' database.. Rifampicin is known to be a strong inducer of various cytochrome P450 enzymes. This case description shows that the use of rifampicin may lead to convulsions. For this reason, these interactions should be included in the Dutch G-standard database.

Topics: Anticonvulsants; Carbamazepine; Clonazepam; Cytochrome P-450 Enzyme System; Drug Interactions; Epilepsy; Female; Floxacillin; Humans; Middle Aged; Rifampin; Seizures; Valproic Acid

Phenytoin, a commonly used antiepileptic, is difficult to dose optimally due to its narrow therapeutic window, nonlinear pharmacokinetics, extensive protein binding, and participation in clinically significant drug interactions. Although clinicians are aware of the interaction with two widely used antituberculosis agents, rifampin and isoniazid, few reports have described the implications for managing phenytoin dosing in this situation. To our knowledge, only two reports of the clinical experience with this interaction have been published, and only one of these reports involved the addition of isoniazid. We present a case of a 60-year-old man treated with triple antiepileptic therapy, including phenytoin, who experienced seizures shortly after hospital admission. Dosing of phenytoin proved difficult in this patient due to an acute kidney injury and severe hypoalbuminemia requiring hemodialysis. A further complexity was the addition of antituberculosis therapy (rifampin, isoniazid, pyrazinamide, and ethambutol [RIPE]) for suspected tuberculosis meningitis after the patient experienced persistent encephalopathy. Phenytoin concentrations decreased steadily after rifampin and isoniazid initiation despite dose increases, and the free concentration of phenytoin reached a low of less than 0.5 µg/ml on day 8 of RIPE therapy. The patient continued on a stable dose of phenytoin and RIPE therapy for unconfirmed tuberculosis meningitis until discharge. This report is the first description of this drug interaction in 20 years and highlights the need for appropriate management of phenytoin in a patient with complicated needs for pharmacotherapy.

Topics: Acute Kidney Injury; Anticonvulsants; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Interactions; Humans; Hypoalbuminemia; Male; Middle Aged; Phenytoin; Renal Dialysis; Rifampin; Seizures; Severity of Illness Index; Tuberculosis, Meningeal

A young goat was presented with a left spastic hemiparesis and general proprioceptive ataxia with postural reaction deficits, a right head tilt and positional nystagmus. Seizure-like activity was elicited by rapid changes in the position of the animal's head. The neurological signs and quality of the seizure activity suggested a lesion involving the medulla and possibly the cerebellum. A focal lesion at the level of the left cerebellar peduncles could explain the left hemiparesis and right paradoxical vestibular signs. A large encapsulated abscess was found at the confluence of the left cerebellar peduncles. The morphology and staining characteristics of the organisms within the abscess were consistent with Corynebacterium pseudotuberculosis.

Topics: Animals; Ataxia; Brain; Brain Abscess; Cerebellar Diseases; Corynebacterium Infections; Corynebacterium pseudotuberculosis; Diagnosis, Differential; Diazepam; Goat Diseases; Goats; Hemiplegia; Male; Neurologic Examination; Penicillin G Procaine; Rifampin; Seizures

Topics: Accidents, Home; Female; Humans; Infant; Isoniazid; Peritoneal Dialysis; Rifampin; Seizures

Topics: Acute Kidney Injury; Adult; Chemical and Drug Induced Liver Injury; Humans; Male; Rifampin; Seizures

Topics: Acidosis; Adult; Alanine Transaminase; Aspartate Aminotransferases; Ethambutol; Female; Humans; Isoniazid; Renal Dialysis; Rifampin; Seizures