title: [Concentration of tazobactam/piperacillin in the cerebrospinal fluid of patients with Haemophilus influenzae type B meningitis].
abstract: While the incidence of Haemophilus influenzae type b (Hib) meningitis is expected to decrease with the widespread use of the Hib vaccine, the resistance of Hib has actually increased. Therefore, selection of the initial antibiotics used for treatment must be performed with resistant bacteria, including beta-lactamase negative ampicillin resistant H. influenzae (BLNAR), in mind. Tazobactam/piperacillin (TAZ/PIPC) has a satisfactory minimum inhibitory concentration (MIC) against BLNAR and is a beta-lactamase inhibitor. Although there is no insurance coverage for its use in patients with meningitis, the penetration of TAZ/PIPC into cerebrospinal fluid (CSF) in animal experiments promises a satisfactory result, and we have been using a combination of ceftriaxone (CTRX) and TAZ/PIPC as an initial treatment and a resistant bacteria countermeasure in patients with Hib meningitis at our hospital since 2008. We examined the concentration of TAZ/PIPC in CSF to further investigate the possibility of using TAZ/PIPC as an antibiotic treatment against bacterial meningitis. In cases treated with a 1: 8 drug formulation of TAZ/PIPC against Hib meningitis at our hospital, we used the remaining portion of a CSF sample collected after the initiation of TAZ/PIPC administration and then measured the concentrations of TAZ and PIPC in the CSF. Six specimens from 5 patients between the ages of 6 and 59 months were examined. The dosage of TAZ/PIPC was 95.7-113.6 mg/kg/dose x 3 times/day, and the CSF concentrations at 0-105 minutes after the completion of the administration were 0.319-1.32 microg/mL for TAZ and 2.54-7.74 microg/mL for PIPC. With the approved dosage, the peak concentration level during the acute period indicated a sufficient CSF concentration level for the antibacterial and beta-lactamase inhibition effects against Hib. As an antibiotic treatment for H. influenzae meningitis, the combined usage of TAZ/PIPC is likely to be effective as a resistant bacteria countermeasure, in addition to third-generation cephem drugs and meropenem.
authors.affiliation: Division of Infectious Diseases, Chiba Children's Hospital.
authors.forename: Chie
authors.initials: C
authors.lastname: Fukasawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hoshino
authors.forename: Satoru
authors.initials: S
authors.lastname: Kutsuna
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sawada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sato
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Ishiwada
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D010878:Piperacillin / Q000134:cerebrospinal fluid; D000077725:Piperacillin, Tazobactam Drug Combination; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin