Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceftriaxone is a new third-generation cephalosporin with excellent activity against many gram-negative, and reasonable activity against most gram-positive microorganisms. Clinical studies have demonstrated its efficacy and safety in patients with bacterial meningitis; respiratory tract, urinary tract, soft tissue, bone and joint infections; and gonorrhea. Ceftriaxone has been well tolerated except for diarrhea, which in most cases has not required a change in therapy. The long elimination half-life of ceftriaxone has allowed twice- and once-daily administration, the latter potentially resulting in substantial cost savings. Because of its documented efficacy, safety, and convenient dosing schedule, ceftriaxone may become the preferred third-generation cephalosporin for the treatment of a variety of serious infections.
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PMID:Ceftriaxone: a third-generation cephalosporin. 391 Mar 86

Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.
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PMID:Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis. 407 58

In human subjects, ceftriaxone exhibits an exceptionally long elimination half-life (5.8 to 8.7 hours) and a small degree of nonlinearity in its pharmacokinetics which can be ignored in its clinical applications. Thirty-three to 67 percent of a dose is excreted in the urine as unchanged drug, and the remainder is secreted in the bile and ultimately is found in the feces as microbiologically inactive compounds. Ceftriaxone is rapidly and completely absorbed following intramuscular administration. Multiple dosing of ceftriaxone with doses ranging from 0.5 to 2 g at 12- or 24-hour intervals by intravenous and intramuscular routes resulted in 15 to 36 percent accumulation of ceftriaxone in plasma and no change in its elimination half-life. The volume of distribution and the plasma clearance of ceftriaxone in pediatric patients were threefold greater than those in adults, and ceftriaxone penetrated the inflamed meninges of infants and children with bacterial meningitis. Small changes in the pharmacokinetics of ceftriaxone in elderly subjects or patients with renal or hepatic dysfunction are such that dose adjustments should not be necessary with a ceftriaxone dosage up to 2 g per day. Ceftriaxone was not removed to any significant extent from plasma by hemodialysis. In a small percentage of patients, on dialysis, the elimination rate of ceftriaxone was significantly reduced, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary.
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PMID:Pharmacokinetic profile of ceftriaxone in man. 609 13

Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis. The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H. influenzae, and E. coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging. Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.
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PMID:Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis. 609 18

Thirty pediatric and young adult patients with bacterial meningitis were treated with ceftriaxone or "standard therapy" in a comparative trial; 41 other patients with severe bacterial infections were treated with ceftriaxone in an open protocol. Meningitis and brain abscesses were treated successfully with 50 mg/kg of ceftriaxone every 12 hours. In children, other infections were treated with 25 to 37.5 mg/kg of ceftriaxone every 12 hours. Young adults with pneumonia received 1 g of the antibiotic every 12 hours, whereas those with soft tissue infections were treated every 24 hours. All patients responded to therapy, and in all but one was the infectious process sterilized. No significant toxicity was observed. Ceftriaxone appears to be an excellent single agent for the treatment of most severe bacterial infections in pediatric and young adult patients and need not be administered more frequently than once every 12 hours.
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PMID:Ceftriaxone therapy of meningitis and serious infections. 609 19

Ceftriaxone (Ro 13-9904, CTRX) was evaluated for its safety and efficacy in 33 children with various bacterial infections including 10 cases of bacterial meningitis. CTRX was effective in all but 1 case who had acute mucositis due to a resistant strain of Enterobacter cloacae. The serum half-life (T1/2 beta) was 4.5 +/- 1.6 hours after an intravenous bolus injection in children. Cerebrospinal fluid levels of CTRX in the acute phase of bacterial meningitis were 7.69 +/- 4.75 mcg/ml. The only side effect was mild to moderate diarrhea observed in 10 of the 33 cases, but in no case was it necessary to discontinue the drug.
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PMID:[Clinical and pharmacokinetic study of ceftriaxone in pediatric bacterial infections]. 609 1

Forty-three children (ten neonates, 15 infants and 18 older children) were treated with single daily doses of ceftriaxone (50 to 100 mg/kg) intravenously or intramuscularly for serious bacterial infections. The infections included meningitis (31 patients), brain abscesses (four patients), septicaemia (three patients), pleuro-pneumonia (two patients), septic arthritis and soft tissue phlegmona (three patients). No other antibacterial agents were used except in four patients with brain abscesses, in whom ceftriaxone was combined with ornidazole. The overall bacteriological cure rate was 98%, and sterilisation of the cerebrospinal fluid occurred in 27 of 28 patients (96%) with proven bacterial meningitis. Two patients died, three survived with severe neurological sequelae; one neonate required partial gut resection. A complete clinical cure was achieved in the remaining 37 patients. Only one treatment failure was directly related to the drug therapy. The only side effect noted were sterilisation of the gut with overgrowth of Candida albicans in 35% of neonates and infants, an prolonged fever in 13% of all patients. Ceftriaxone given in a 24-hourly regimen is convenient and highly effective in serious bacterial infections in children and is without significant toxicity.
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PMID:Once-daily administration of ceftriaxone in the treatment of meningitis and other serious infections in children. 631 28

Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children.
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PMID:Comparison of ceftriaxone and traditional therapy of bacterial meningitis. 632 81

Third-generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations. No one cephalosporin is appropriate for all infectious disease problems. Cefotaxime and ceftizoxime have the best gram-positive coverage of the third-generation agents. Ceftazidime and cefoperazone are the only third-generation drugs that provide antipseudomonal coverage. Ceftriaxone's long half-life allows for once-daily dosing, making ceftriaxone an excellent drug for outpatient antibiotic therapy of community-acquired infections. Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases. The third-generation cephalosporins except for cefoperazone penetrate cerebrospinal fluid and are indicated for the treatment of bacterial meningitis. Their proven record of clinical efficacy, favorable pharmacokinetics, and low frequency of adverse effects make third-generation cephalosporins the preferred antibiotic in many clinical situations.
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PMID:Third-generation cephalosporins. 779 18

Treatment of pneumococcal meningitis has become problematic because of the emergence of penicillin- and cephalosporin-resistant strains and because of the concern that dexamethasone therapy might reduce penetration of antibiotics into the cerebrospinal fluid (CSF). We addressed these issues with our rabbit meningitis model by studying two pneumococcal isolates that were resistant to penicillin and ceftriaxone and susceptible to vancomycin and rifampin. Ceftriaxone, vancomycin, and rifampin were given alone or in combination, with or without coadministration of dexamethasone. Treatment was started 12 to 14 h after intracisternal inoculation of approximately 10(4) CFU of one of the organisms. Rifampin concentrations in serum and CSF were similar, regardless of whether dexamethasone was given, whereas those of ceftriaxone were somewhat lower at each time point in animals given dexamethasone. The penetration of vancomycin into CSF was consistently and substantially reduced with dexamethasone treatment, which resulted in a delay in CSF sterilization not observed in non-dexamethasone-treated animals. When rifampin was used with ceftriaxone for treatment of meningitis caused by the more resistant strain, bacteriologic cure occurred promptly, with or without dexamethasone therapy. In areas with high rates of occurrence of resistant pneumococcal strains, we believe initial empiric therapy of bacterial meningitis should include two antibiotics: ceftriaxone and either rifampin or vancomycin. When dexamethasone is used, the combination of ceftriaxone and rifampin is preferred for therapy.
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PMID:Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. 809 32


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