hr-810 and Meningitis--Bacterial

Cefepime and cefpirome are new beta-lactamase resistant parenteral cephalosporin derivatives whose spectrum of activity makes them suitable for use in the treatment of severe infections such as bacterial meningitis. However, the published information on the penetration of these new agents into human CSF and on their use in the treatment of bacterial meningitis are really scarce. Experimental studies have shown that cefepime and cefpirome penetrated remarkably well into the CSF of animals infected with Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae type b or Pseudomonas aeruginosa. The mean changes in bacterial colony count in CSF after cefpirome or cefepime administration express the antibacterial activity of these drugs. Studies in patients show that cefepime and cefpirome crossed the blood-brain barrier and reached concentrations in the CSF that are bactericidal against most potential pathogens. Higher levels are likely to be achieved with multiple dosing and in the presence of inflamed meninges. No study has been performed to investigate the efficacy of cefpirome in the treatment of bacterial meningitis. Cefepime was as effective and safe as cefotaxime for treatment of patients with bacterial meningitis as shown in the only clinical trial.

Topics: Animals; Blood-Brain Barrier; Cefepime; Cefpirome; Cephalosporins; Clinical Trials as Topic; Humans; Meningitis, Bacterial; Microbial Sensitivity Tests

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) microg/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.

Topics: Cefpirome; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Injections, Intravenous; Male; Meningitis, Bacterial

A patient with intracerebral hematoma suffered from postoperative bacterial meningitis. Staphylococcus aureus was found from CSF. The organism was multiple drug resistant and refractory to antibiotics including piperacillin (PIPC), cephalexin (CEX), cefotaxime (CTX), ceftazidime (CAZ) and latamoxef (LMOX). It was susceptible to cefpirome (CPR). Treatment with CPR resulted in clinical improvement associated with clearing of the organism from CSF. Serum level of CPR was high enough and CPR penetration into the CSF was satisfactory. The results suggest that CPR is an extremely effective antibiotic for meningitis caused by CPR-susceptible bacteria. Evaluation of the CPR penetration into the CSF of adult meningitis was rarely reported. The result we obtained was important in the treatment for the adult meningitis.

Topics: Adult; Cefpirome; Cephalosporins; Female; Humans; Meningitis, Bacterial; Staphylococcal Infections; Time Factors

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefpirome; Cephalosporins; Chloramphenicol; Endotoxins; Escherichia coli Infections; Gentamicins; Inflammation; Male; Meningitis, Bacterial; Meropenem; Rabbits; Thienamycins