SVIBOR - Project code: 3-01-241

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
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Project code: 3-01-241


CONCENTRATION OF ANTIBIOTICS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH MENINGITIS


Main researcher: BEUS, IVAN (61520)


Assistants
Type of research: developmental
Duration from: 01/01/91. to 12/31/93.
Papers on project (total): 41
Papers on project quoted in Current Contents: 2
Institution name: Bolnica "Dr. Fran Mihaljević", Zagreb (143)
Department/Institute: UNIVERSITY HOSPITAL FOR INFECTIOUS DISEASES ZAGREB INTENSIVE CARE
Address: Mirogojska 8, Zagreb, Croatia
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 4557 222
Fax: 385 (0)1 425 907
Summary: A total number of 88 blood specimens and the same number of cerebrospinal fluid (CSF) specimens were analyzed in the course of prospective research of ceftazidime and chloramphenicol concentration in blood and CSF of patients with purulent meningitis. The specimens were taken 1st, 7th and 14th day of therapy. Ceftazidime concentrations in blood were 7-11 times higher than in CSF in the beginning of treatment, and in the end (14th day of therapy) they were 11-20 times higher. Chloramphenicol concentrations in blood were 3-4 times higher than in CSF in the beginning of treatment, and in the end of therapy they were 3-5 times higher. On the first day of therapy the attained ceftazidime concentrations in CSF were 14% of concentration attained in blood, and in the end of therapy the attained concentrations were 8.4% only. Chloramphenicol concentrations in CSF were 32.5% of values attained in blood in the beginning of therapy, and in the end of therapy the attained chloramphenicol concentrations in CSF were identical with those in blood. The attained concentrations of examined antibiotics in CSF were in the beginning of therapy high above the minimal bactericidal concentrations (MBC) to the causative agent of purulent meningitis what absolutely met the therapeutic criteria (bacteriological sterilization of CSF within 48 hours, improvement of cytologic and biochemical findings of CSF). In the end of treatment, ceftazidime concentration was below MBC, while the concentration of chloramphenicol remained multiple higher and thus the therapeutic criteria were achieved. As a conclusion: 1. Chloramphenicol was proved as ver good antimicrobial drug in the treatment of purulent meningitis caused by pathogens susceptible to Chloramphenicol. High concentrations of antibiotic in the cerebrospinal fluid even at the end of the treatment can ensure the good outcome of the disease; 2. Ceftazidime could not reach the higher concentrations in cerebrospinal fluid above MBC, so the final outcome of the treatment is uncertian; 3. The initial ceftazidime therapy for susceptible pathogens is available at the beginning of treatment, but it should be replaced with permanent and final chloramphenicol therapy specially in later stages of the disease (after 7 th day).

Keywords: Antibiotics, concentrations, cerebrospinal fluid, meningitis

Research goals: The purpose of the research was the evaluation of ceftazidime and chloramphenicol therapy efficiency in the treatment of purulent meningitis with special comment to the therapy duration. Already previously known fact that the inflammatory process of brain changes the penetration ability of blood-brain barrier has been proved by evaluation of ceftazidime and chloraphenicol concentrations in CSF in the beginning of treatment when in all CSF specimens multiply higher concentrations of antibiotics than minimal bactericidal concentration (MBC) was proved. The result was fast sterilization of CSF and improvement of cytologic and biochemical findings of CSF. The 7th day of therapy the ceftazidime concentrations fall to the MBC values, while the chloramphenicol concentrations remain multiply higher than MBC. In the end of therapy the concentrations of ceftazidime fall below MBC that give rise to suspicion in drug efficiency after 7th day of application, while the concentrations of chloramphenicol, remain high permanently, that refers to more efficacious therapeutic effect.

COOPERATION - INSTITUTIONS


  1. Name of institution: Zavod za ispitivanje i kontrolu lijekova
    Type of institution: State institute
    Type of cooperation: Joint project
    City: 10000 - Zagreb, Croatia
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