Vancomycin Concentration Of CSF And Serum In Different Administration Approaches And Comparison Of The Effect

Background and purposes of the researchGram-positive bacteria is the important pathogen of hospital-acquired infections and community-acquired infections. Vancomycin is a glycopeptide antibiotic that was isolated in 1956 from the actinomycetes Streptomyces orientalis and is used to treat gram-positive bacteria, especially to methicillin-resistant Staphylococcus (MRS) infections that is increasing recent years. Vancomycin when administered intravenously cerebrospinal fluid (CSF) permeation can be finded only in the situation of meningitis, but the level of concentrations can not be predicted. So it often is used for intrathecal or intraventricular administration to cure the meningitis clinically. But, what about the dosage, course of treatment, toxicity et al of Vancomycin administration into the cerebrospinal fluidis poorly reported previously. A Prospective randomized controlled trial was performed to reach the aim:1. to obtain the data of vancomycin intrathecal administration drug peak and trough concentrations in CSF and serum to gram- positive bacterial meningitis;2. to compare the effect of vancomycin administration intravenously sololy and intravenously conbining with intrathecally;3. We will evaluate the safety of intrathecal administration through clinical observation of adverse effect and the following-up.Materials and Methodstwenty six adult patients with gram-positive bacterial meningitis or diagnosed empirically were randomly divided into two groups: therapied group ( 13 cases) and controlled group (13 cases), range 24—67 years, 17 men and 9 women. All patients had the symptom of fever, with headache and emesis in 11 cases, and meningeal irritation sign in nine. Etiopathogenisis include ventriculoperitoneal shunt in 11 cases, cerebral trauma in 11cases (craniotomy in 7cases), and craniotomy in 4cases with tumors. All the routine examination of CSF has the result of leucocyte count rising, mean count is 386.63/μL and the highest is 3200/μL. The result of CSF bacterial stain smear is Gram-positive bacteria in 21 cases, diagnosed empirically in else 5 cases.The result of CSF culture and drug sensitivity test is 5 strains of methicillin resistant staphylococcus (MRS) , including three methicillin resistant staphylococcus aureus (MRSA) and two methicillin resistant staphylococcus epidermidis (MRSE). All the MRS strains are sensitive to vancomycin and the results of CSF culture are negative of else 16 cases. All the 26 patients'function of heart, liver and kidney was normal before our treatment. Vancomycin was administered intravenously and intrathecally in therapied group and only intravenously in controlled group daily. Vancomycin intravenously was administered at a daily dose of 2g in four administration (500 mg intravenously over 60 min every 6 h), and intrathecally at a daily dose of 20mg once. The samples of blood and CSF were collected, the concentration of vancomycin in serum and CSF was determined by fluorescence polarization immunoassay (FPIA) method. Statistical analysis was done with the software program SPSS 11.5, quantitative results presented are the mean±standard deviation (SD) ((?)±s), comparison means was used with Independent-Samples T Test and the Clustered Error Bar, comparison numeration data was done with Chi-Square Test, a probability value (p value ) of less than 0.05 was considered significant.ResultsThe administration time of therapied group was 11.92±3.75 days, and controlled group was 17.08±4.92 days, there was significant difference between the two groups (P=0.006) , therapied group was shorter than controlled group. The effective power of therapied group was 100%, and controlled group was 84.62% ( 11/13 ). There was no significant difference between the two groups at the peak and trough concentrations of vancomycin in serum. The peak concentration of vancomycin in therapied group was 135.99±106.84mg/L , trough concentration was 28.01±14.12mg/L, The peak concentration of vancomycin in controlled group was 4.21±2.28mg/L, trough concentration was1.27±0.76mg/L, there was significant difference between the two groups (P=0.000, 0.000) , Both the peak and trough concentrations of vancomycin in CSF of therapied group were higher than those of controlled group. There was no adverse effect except one patient with "Red man syndrome" in the period of administration of all patients, and no evidence of functional lesion of liver and kidney, hearing functional lesion, abnormal changing in hematocyte, abdominal pain, diarrhoea, epilepsy and subarachnoid cavity adherence. In the following-up 3 to 12 months, combination with the examinations of CT, MRI, laboratory and physical was no evidence of vancomycin toxical injury.ConclusionsI The results of our study demonstrate that vancomycin intrathecal administration can reach the level of drug concentrations that is several times than minimum inhibitory concentration (MIC) within the CSF.2 The results of our study demonstrate that vancomycin intrathecal administration is a safe and efficacious treatment modality in gram-positive bacterial meningitis.3 The results of our study demonstrate that vancomycin intrathecal administration can cure gram-positive bacterial meningitis with much shorter treatment time and lower costs.