RESUMEN
BACKGROUND: To identify changes in cefoperazone/sulbactam penetration into cerebrospinal fluid (CSF) after craniotomy and to investigate preliminarily whether cefoperazone/sulbactam CSF concentration can reach therapeutic level when administered intravenously after neurosurgical operation. METHODS: Neurosurgical patients with an indwelling ventricular drainage pipe who received prophylactic cefoperazone/sulbactam for the treatment of intracranial infection were received a cefoperazone/sulbactam 2:1, 3.0-g infusion for 3 hours every 6 hours for 24 h. Venous blood and CSF specimens were collected to determine cefoperazone/sulbactam concentrations. RESULTS: The cefoperazone and sulbactam concentrations in serum were highest at the second hour (237.54 ± 336.72 mg/L and 66.52 ± 80.38 mg/L, respectively) and then decreased. The cefoperazone and sulbactam concentrations in CSF were highest at the 4th hour (39.22 ± 75.55 mg/L and 6.24 ± 8.35 mg/L, respectively) and then decreased. CSF penetration measured by the ratio of peak concentrations (CSF/serum) was 8.6% ± 7.2% for cefoperazone and 13.5% ± 11.9% for sulbactam, CSF penetration measured by the ratio of trough concentrations (CSF/serum) was 13.4% ± 5.3% for cefoperazone and 106.5% ± 87.5% for sulbactam. CSF penetration represented by the ratio of area under the curve (AUC) of CSF and serum was 14.5% for cefoperazone and 22.6% for sulbactam. Neurosurgical impairment of the blood-brain barrier may improve the CSF penetration of these drugs, but it is difficult to reach the MIC90 of resistant bacteria. If single intravenous administration time was extended to 3 hours, the serum concentrations of drugs were able to meet the PK/PD standard (T> MIC%> 50%) for treating common, highly resistant bacteria. CONCLUSIONS: The CSF penetration of cefoperazone/sulbactam may be enhanced after neurosurgical impairment of the blood-brain barrier. This study is a pilot research of cefoperazone/sulbactam using in neurosurgical individuals, However, it needs to be confirmed by further large-scale studies.
Asunto(s)
Cefoperazona/sangre , Cefoperazona/líquido cefalorraquídeo , Craneotomía , Sulbactam/sangre , Sulbactam/líquido cefalorraquídeo , Adulto , Anciano , Antiinfecciosos Urinarios/administración & dosificación , Antiinfecciosos Urinarios/sangre , Antiinfecciosos Urinarios/líquido cefalorraquídeo , Cefoperazona/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prueba Bactericida de Suero , Sulbactam/administración & dosificación , Factores de TiempoRESUMEN
We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.
Asunto(s)
Ampicilina/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Meningitis Bacterianas/tratamiento farmacológico , Sulbactam/uso terapéutico , beta-Lactamasas/biosíntesis , Ampicilina/líquido cefalorraquídeo , Ampicilina/farmacocinética , Animales , Ceftriaxona/líquido cefalorraquídeo , Ceftriaxona/farmacocinética , Ceftriaxona/uso terapéutico , Quimioterapia Combinada/líquido cefalorraquídeo , Quimioterapia Combinada/farmacocinética , Quimioterapia Combinada/uso terapéutico , Infecciones por Escherichia coli/microbiología , Inyecciones Intravenosas , Meningitis Bacterianas/líquido cefalorraquídeo , Pruebas de Sensibilidad Microbiana , Conejos , Sulbactam/líquido cefalorraquídeo , Sulbactam/farmacocinéticaRESUMEN
Concentrations of sulbactam (SBT) and ampicillin (ABPC) in the blood and cerebrospinal fluid (CSF) following an intravenous administration of SBT/ABPC at a dose of 150 mg/kg (SBT/ABPC = 1:2) were determined in 12 rabbits with staphylococcal meningitis. Drug concentrations were measured 9 times, 6 times each with intervals of 15 minutes and thereafter with intervals of 30 minutes. The results were compared with those of a group of 9 rabbits given 100 mg/kg of ABPC alone. 1. The maximum concentration of SBT in the CSF and the percentages of both the maximum concentration and the area under the concentration-time curve (AUC) of SBT in CSF vs. those in serum of the SBT/ABPC group were higher than those of ABPC and the half-life of SBT in the CSF was also longer than that of ABPC, all with significant difference. When these parameters for SBT of SBT/ABPC groups were compared with those of ABPC of the ABPC group, not much differences existed between the 2 groups except that the CSF half-life of SBT was much longer than that of ABPC. 2. The percentages of both the maximum concentration and AUC of ABPC in CSF vs. those in serum of the SBT/ABPC group were significantly lower than those of ABPC of the ABPC group. The CSF half-life of ABPC of the former group was longer than that of the latter. 3. The above results suggest that when SBT and ABPC are administered simultaneously, the penetration of ABPC into the CSF is inhibited.
Asunto(s)
Ampicilina/líquido cefalorraquídeo , Meningitis/líquido cefalorraquídeo , Infecciones Estafilocócicas , Sulbactam/líquido cefalorraquídeo , Ampicilina/administración & dosificación , Ampicilina/sangre , Animales , Quimioterapia Combinada/administración & dosificación , Quimioterapia Combinada/sangre , Quimioterapia Combinada/líquido cefalorraquídeo , Inyecciones Intravenosas , Meningitis/sangre , Meningitis/etiología , Conejos , Sulbactam/administración & dosificación , Sulbactam/sangreRESUMEN
Infusions of 50 mg of sulbactam per kg per day and 400 mg of ampicillin per kg per day in divided doses to infants and children with bacterial meningitis produced levels in cerebrospinal fluid approximately one-third those in serum. Concentrations in cerebrospinal fluid of 5.5 micrograms of sulbactam per ml and 16.0 micrograms of ampicillin per ml declined within a few days of therapy to 1.9 microgram of sulbactam per ml and 5.2 micrograms of ampicillin per ml.