| Meropenem is a new carbarpenem antibiotic characterized by a broad antibacterial spectrum. It has been shown to have activity against both gram-positive and gram- negative pathogens (such as Enterobacteriaceae and P. aeruginosa) including anaerobes. Meropenem shows a good stability to many β -lactamas including those which hydrolyse third-generation cephaloporins. Unlike imipenem, meropenem also shows a good stability against human renal dehydropeptidase I. It is the first carbarpenem that can be used alone without coadministration of a dehydropeptidase I enzyme inhibitor.Meropenem can be penetrated and distributed into tissues widespreadly and rapidly indicated which can be used for infection of burn wound.The purpose of this study is to compare the antibacterial activity of meropenem in vitro with imipenem/cilastatin, tazocin-. ceftazidime and sulbactam sodium/ cefoperazone sodium. The method to determine the concentration of meropenem in plasma and urine was established and the pharmacokinetics of meropenem in patients with burn injury was investigated.1. Methods1.1 The antibacterial activity of meropenem in vitroThe minimal inhibition concentration (MIC) of meropenem against 136 clinical isolates was determined with double agar dilution method and was compared with that of imipenem/cilastatin, tazocin, ceftazidime and sulbactam sodium/cefoperazone sodium.The effects of the inoculum size, pH of medium and concentration of serum on the activity of meropenem were investigated. The minimal bactericidal concentration (MBC) of meropenem was determinedwith broth microdilution.1.2 The phannacokinetics of meropenem in patients with burn injury1.2.1 The concentrations of meropenem in plasma and urine were measured at UV wavelength of 299nm by high-performance liquid chromatography (HPLC) method using a Nova-pak-C18 column (3.9×150mm, 4 μ m) . The mobile phase were a mixture of CH3OH: KH2PO4(5mmol·L-1, pH 3.3) 5:95 (v/v) for plasma and CH3OH: KH2PO4 (pH 2.5) 13:87 (v/v) for urine .The flow rate were 1.4 ml·min-1 and 1.0ml·min-1, respectively.1.2.2 The recoveries of method , precisions and stabilities of meropenem were determined.1.2.3 Drug administration , blood sampling and urine collections. Each of 28 patients with burn injury was given a single dose of 500 mg of meropenem and ivgtt. during 30 min . Blood samples were collected at 0, 0.25, 0.5, 1.0, 1.5, 2.5, 3.5,4.5, 6h after the administration . Urine samples were collected during 0 to 2, 2 to 4, 4 to 6 and 6 to 12h of drug administration thereafter.1.2.4 Phannacokinetics parameters and statistical analysis: The software of 3P97 was used to estimate phannacokinetics parameters.The t test was used to analyze difference between phannacokinetics parameters of burn injury and normal volunteers reported by others.2. Results2.1 The antibacterial activity of meropenem in vitro.2.1.1 Meropenem showed a good activity against K.peneumoniae, S. pneumoniae and E.cloacae with a MIC90 of <0.0075-0.25g·ml-1. Meropenem was also active against S. aureus, P. aeruginosa, β -Hemolytic streptococcus, S. epidermidis and Micrococcus, with a MIC50 of <0.0075-0.25 μ g·ml-1.2.1.2 The activity of meropenem was-inferior to imipenem against β-Hemolytic streptococcus, similar to imipenem against Micrococcus andsuperior to imipenem against the other pathogens (S. aureus> P. aeruginosa, E.cloacae, E. coli, S. epidermidis, S. pneumoniae and K. pneumoniae).2.1.3 Meropenem was more active than tazocin, ceftazidime and sulbactam sodium/ cefoperazone sodium against all strains studied in this study.2.1.4 The activity of meropenem could be affected by the inoculum size, pH of medium and concentration of human serum. MIC90 were increase following the increased inoculum size, pH of medium and concentration of human serum.2.1.5 The MBC ( 0.06-4 μ g·m-1 ) of meropenem was 1-8 times of MIC. This indicated meropenem was a good bactericide.2.2 The pharmacokinetics o... |
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