cefotaxime and Seizures

Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for convulsions. Since chloramphenicol inhibits the metabolism of phenytoin in vivo, we studied the effects of chloramphenicol on phenytoin pharmacokinetics in children with malaria.. Multiple intravenous (i.v.) doses of chloramphenicol succinate (CAP) (25 mg kg-1 6 hourly for 72 h) and a single intramuscular (i.m.) seizure prophylactic dose of fosphenytoin (18 mg kg-1 phenytoin sodium equivalents) were concomitantly administered to 15 African children with malaria. Control children (n = 13) with malaria received a similar dose of fosphenytoin and multiple i.v. doses (25 mg kg-1 8 hourly for 72 h) of cefotaxime (CEF). Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness and convulsion episodes were monitored. Cerebrospinal fluid (CSF) and plasma phenytoin concentrations were determined.. The area under the plasma unbound phenytoin concentration-time curve (AUC(0, infinity ); means (CAP, CEF): 58.5, 47.6 micro g ml-1 h; 95% CI for difference between means: -35.0, 11.4), the peak unbound phenytoin concentrations (Cmax; medians: 1.12, 1.29 micro g ml-1; 95% CI: -0.5, 0.04), the times to Cmax (tmax; medians: 4.0, 4.0 h; 95% CI: -2.0, 3.7), the CSF:plasma phenytoin ratios (means: 0.21, 0.22; 95% CI: -0.8, 0.10), the fraction of phenytoin unbound (means: 0.06, 0.09; 95% CI: -0.01, 0.07) and the cardiovascular parameters were not significantly different between CAP and CEF groups. However, mean terminal elimination half-life (t1/2,z) was significantly longer (23.7, 15.5 h; 95% CI: 1.71, 14.98) in the CAP group compared with the CEF group. Seventy per cent of the children had no convulsions during the study period.. Concomitant administration of chloramphenicol and a single i.m. dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria. Moreover, a single i.m. dose of fosphenytoin provides anticonvulsant prophylaxis in the majority of the children over 72 h. However, a larger study would be needed to investigate the effect of concomitant administration of multiple doses of the two drugs in this population of patients.

Topics: Anti-Bacterial Agents; Anticonvulsants; Area Under Curve; Cefotaxime; Child, Preschool; Chloramphenicol; Drug Therapy, Combination; Female; Half-Life; Humans; Infant; Injections, Intramuscular; Injections, Intravenous; Malaria; Male; Models, Biological; Phenytoin; Seizures

Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

Topics: Adolescent; Cefotaxime; Child; Child, Preschool; Dexamethasone; Female; Hearing Tests; Humans; Infant; Male; Meningitis, Bacterial; Meropenem; Nervous System Diseases; Prospective Studies; Seizures; Thienamycins; Treatment Outcome

Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.

Topics: Aged; Aged, 80 and over; Animals; Cefotaxime; Female; Humans; Imipenem; Male; Mice; Middle Aged; Multicenter Studies as Topic; Penicillin G; Seizures

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

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Cesarean Section; Clavulanic Acid; Female; Fever; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Male; Maternal Exposure; Meningitis, Meningococcal; Neisseria meningitidis, Serogroup B; Penicillin G; Pregnancy; Pregnancy Complications, Infectious; Respiratory Tract Infections; Seizures; Treatment Outcome

Topics: Acetabulum; Anti-Bacterial Agents; Cefotaxime; Cholecystitis, Acute; Follow-Up Studies; Fractures, Bone; Humans; Injections, Intravenous; Male; Middle Aged; Orthopedic Procedures; Risk Factors; Seizures; Tomography, X-Ray Computed

Over the last decade Streptococcus pneumoniae has emerged as the most common bacterial pathogen for meningitis in all age groups, beyond the neonatal period.. To determine the epidemiological and clinical characteristics; and risk factors for mortality of pneumoccocal meningitis in children in a developing transitional country.. A retrospective study that included patients<15 years of age admitted at the Instituto de Medicina Tropical of Paraguay, from January 1990 until December 2003 with the diagnosis of bacterial meningitis caused by S. pneumoniae. Clinical and laboratory data were collected and analysed in order to identify risk factors associated with morbidity and mortality outcomes of this infection.. Seventy-two patients (between the ages of 35 days and 14 years) were identified. Forty-two per cent of patients had seizures prior to or at the time of admission, 36% were admitted in a comatose state, and 19% with shock. Mortality was 33% (24/72), and 18% of the survivors (11/60) developed severe sequelae. Upon admission, the following variables were strongly correlated with mortality: age<12 months (P=0.007), the presence of seizures (P=0.0001) or development of seizures 48 h after admission (P=0.01), a cerebrospinal fluid (CSF) glucose level of <10 mg/dl (P=0.01), CSF albumin>200 mg/dl (P=0.0003), an absolute blood neutrophil count<2000/mm3 (P=0.006) and a haemoglobin value of <9 g/dl (P=0.0001).. This study confirms the high morbidity and mortality associated with S. pneumoniae meningitis in Paraguay. Certain clinical parameters and laboratory findings in blood and CSF at the time of admission could be used as predictors for mortality or severe sequelae among survivors.

Topics: Acute Disease; Adolescent; Age Distribution; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Coma; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Paraguay; Penicillins; Retrospective Studies; Risk Factors; Seizures; Streptococcus pneumoniae; Treatment Outcome

Medication errors may produce severe toxicity resulting in hospitalization. This can be compounded if the physician obtains the wrong concentration from a reference manual and a pharmacy miscalculates the conversion. We report a child presenting with ileus, hypothermia and lethargy after receiving supratherapeutic dosing of phenytoin after a concentration miscalculation.. A one-month-old infant presented to the Emergency Department with progressive worsening of abdominal distension, diminished activity, and a one day history of difficulty feeding secondary to a decreased level of consciousness. The past medical history was significant for neonatal Group B Strep meningitis with seizures. Among the child's discharge medications was a prescription for phenytoin (30 mg/5 mL) 2.5 cc by mouth three times daily. On exam, the child was hypothermic with pink mottled skin, poor responsiveness, prolonged capillary refill, abdominal distension with hypoactive bowel sounds, and a dysconjugate gaze. The Initial phenytoin serum concentration was 91.8 mcg/mL. She was admitted to the PICU and was started on ampicillin and cefotaxime for R/O sepsis. Phenytoin was withheld and subsequent serum concentrations revealed an extremely slow elimination (mcg/mL vs. time pair coordinates were 78.2/13.3h; 74.3/62.3h; 43.7/109.6h; 10.8/160.9h) reflecting zero-order kinetics. Post discontinuing antibiotics, phenytoin levels decreased at rates expected. She was discharged after resolution of symptoms. The MD who had written the phenytoin prescription had based it on the Harriet Lane Handbook, 2000 Ed. The 30 mg/5 mL formulation has been unavailable in the US for several years. A community pharmacy substituted the 125 mg/5 mL formulation, but miscalculated the dosage to be 1.6 cc (40 mg) tid.. Abdominal distension and ileus may be presenting symptoms in children at toxic phenytoin levels. Ampicillin and cefotaxime may effect the elimination rate of phenytoin at such levels. We report one of the highest phenytoin levels recorded after therapeutic misadventure. Physicians must be aware of inaccuracies in reference manuals that may result in dosing errors.

Topics: Abdomen; Administration, Oral; Ampicillin; Anti-Bacterial Agents; Anticonvulsants; Cefotaxime; Drug Interactions; Drug Overdose; Female; Humans; Ileus; Infant, Newborn; Medication Errors; Meningitis, Bacterial; Phenytoin; Seizures

A retrospective study of infants with bacterial meningitis admitted to our hospital during 1949-52, highlighted the lack of 'classical' signs of meningitis in these infants. We carried out a similar review of 44 infants aged less than three months, admitted during 1982-91. We also determined the causative organisms and their antibiotic sensitivities. Symptoms and signs were similar in the two series. Forty infants in the later series were either febrile, irritable or had seizures on the day of admission. Overall mortality fell from 30% to 11%. Between 1982 and 1991 Group B Streptocococcus and Neisseria meningitidis were the commonest causes of meningitis. All organisms, except one, were sensitive to ampicillin and/or cefotaxime. Bacterial meningitis should be suspected in young infants who are febrile, irritable or having seizures. Initial treatment with ampicillin and cefotaxime is appropriate.

Topics: Ampicillin; Cefotaxime; Fever; Humans; Infant; Infant, Newborn; Meningitis, Bacterial; Meningitis, Meningococcal; Retrospective Studies; Seizures; Streptococcal Infections; Streptococcus agalactiae