title: Clinical significance of cerebrospinal fluid inhibitory titers of antibiotics, based on pharmacokinetic/pharmacodynamic parameters, in the treatment of bacterial meningitis.
abstract: The cerebrospinal fluid (CSF) inhibitory titer (CSF-IT) of an antibiotic, which can be used to estimate the duration of time above the agent's MIC in the CSF, was introduced as one of the indices to evaluate the effectiveness of antibiotic selection in treating bacterial meningitis. The CSF-IT was determined via a microdilution method. A suspension of the causative organism was added to a tube containing twofold diluted CSF and double-concentrated Mueller-Hinton broth with supplement. The CSF-IT was determined by the maximum point without turbidity of medium after overnight incubation at 37 degrees C. Concerning the strain of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR), the killing rates of both meropenem and piperacillin were compared in an in vitro pharmacokinetic (PK) model, in which human pharmacokinetics in CSF were simulated. Organisms recovered from the CSF in 37 treated clinical cases of bacterial meningitis were H. influenzae, Streptococcus agalactiae, Streptococcus pneumoniae, Escherichia coli, and Neisseria meningitidis; in these cases, the CSF-IT ranged from 1: 8 to as high as 1: 4 096. In the in vitro PK model, the concentrations of both drugs were higher than the MICs over a period of 24 h; however, the killing rate of piperacillin was higher than that of meropenem, and bacterial regrowth was observed after the administration of meropenem. A CSF-IT value higher than 1: 32 indicates that the antibiotic concentration in the CSF exceeds the MIC for 24 h. The effect of piperacillin on BLNAR depends not only on the time above MIC of 24 h but also on the maximum concentration in the CSF.
authors.affiliation: Morikawa Pediatric Clinic, 2-16-6 Awaji, Higashi-Yodogawa-ku, Osaka, 533-0032, Japan. morikawa-ys@jttk.zaq.ne.jp
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Miyoshi
authors.initials: M
authors.lastname: Kitazato
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Shingo
authors.initials: S
authors.lastname: Mizunaga
authors.forename: Junichi
authors.initials: J
authors.lastname: Mitsuyama
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010878:Piperacillin / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013845:Thienamycins / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D010878:Piperacillin