vancomycin cephem 1a 2 1 1 2 a : 15 4 15 15 9 5 1999 2 methicillin MRSA12 vancomycinvcm 4 cephem cefpiromecprcefoseliscfslcefepimecfpmcefozopranczop VCM CPR 12 77 75.5CFSL 82.4CFPM 81 79.4 CZOP 76 74.5 Fractional Inhibitory ConcentrationFICindex.67.75 VCM 4 cephem MRSA Key words: MRSAvancomycincefoselis Methicillin MRSA 1991 MRSA vancomycinvcm arbekacinabk teicoplaninteic 3 MRSA 1 MRSA ABK imipenemcilastatin levofloxacin Fractional Inhibitory ConcentrationFICindex.85.89 VCM VCM lactam 2 16 MRSA 96 VCM lactam 13 1999 2 12 MRSA VCM 4cephem cefpiromecprcefoselis CFSLcefepimeCFPMcefozopranCZOP in vitro I 1 VCM TEICCPR CFSL CFPM CZOP oxacillinmpipc Sigma 2 1999 2 MPIPC Minimum Inhibitory Concentration; MIC 4gmL 12 MRSA 3 Mueller Hinton BBL 37 1 Mac Farland.5 1 Mueller Hinton Difco 255gmL Ca 2 12.525gmL Mg 2 Cation adjusted Mueller Hinton CAMHB MIC 4 MIC 35 5 1 4 3311 1
cellswell 4 VCM cephem MIC FIC index FIC index FIC index FIC index.5.51. 1.2. 2. 5 35 5 1 4 cellswell FIC index A MIC B MIC A MIC B MIC II 1 12 MRSA MIC Table 1 VCM.51gmL MIC5 MIC9 1gmL TEIC.258gmL VCM MIC MIC5 MIC9 1gmL cephem MIC5 MIC9 CPR 64gmLCFSL 16 gmlcfpm 128gmL 128 gmlczop 32gmL 64g ml 4 CFSL MIC5 MIC9 2 VCM cephem VCM cephem FIC index Table 2 VCM CPR FIC index.5.51. 77 75.51.2. 25 24.5 FIC index.511.5.75±.3 VCM CFSL 3 2.9 79 77.5 19.6 FIC index.381.25.71±.2 VCM CFPM 1 1 78.4 21.6 FIC index.51.5.67±.2 VCM CZOP 4 3.9 72 7.6 26 25.5 FIC index.51.5.74±.2 FIC index 2. FIC index cephem VCM cephem Table 3 Fig. 1 Cephem Table 1 Summary of MIC distributions of antimicrobials in MRSA isolated from blood cultures MIC rangeµgml MIC5µgmL MIC9µgmL Vancomycin 5 1 1 1 Teicoplanin 25 8 1 1 Cefpirome 1 128 64 64 Cefoselis 2 64 16 16 Cefepime 2 128 128 128 Cefozopran 2 128 32 64 Oxacillin 4 128 128 128 Table 2 Combined effects of cephems and vancomycin against MRSA isolated from blood cultures FIC index meansd range synergy addition no relation antagonism Cefpirome 753 51 15 755 245 Cefoselis 712 38 125 29 775 196 Cefepime 672 5 15 1 784 6 Cefozopran 72 5 15 39 76 255
Table 3 Summary of MIC distributions for cefems combined with vancomycin against MRSA isolated from blood cultures MICs rangeµgml MIC5µgmL MIC9µgmL Cefpirome Cefoseils Cefepime Cefozopran alone 2 128 32 64 combination 125 32 2 16 alone 2 64 16 16 combination 125 16 2 8 alone 8 512 128 256 combination 1 128 8 64 alone 2 128 32 64 combination 125 64 4 16 Cummulative rate% acefpirome combination alone.625.125.25.5 1 2 4 8 16 32 64 128 128 MICg/mL Cummulative rate% bcefoselis 9 7 5 combination alone 3 1.625.125.25.5 1 2 4 8 16 32 64 128 128 MICg/mL Cummulative rate% ccefepime combination alone.625.125.25.5 1 2 4 8 16 32 64 128 128 MICg/mL Cummulative rate% dcefozopran combination alone.625.125.25.5 1 2 4 8 16 32 64 128 128 MICg/mL Fig. 1. MIC distributions of four vancomycin cephem combined treatments in MRSA isolated from blood cultures. MIC VCM cephem MIC VCM cephem MIC5 18MIC9 12 14 cephem MIC cephem VCM MIC 12 14 III VCM MRSA VCM MRSA 2 13 1999 2 12 MRSA VCM 4 cephem CPRCFSL CFPM CZOP in vitro VCM CPR 12 77 75.5 CFSL 82.4CFPM 81 79.4 CZOP 76 74.5 FIC index.67.75
6 VCM piperacillin in vitro 7 VCM CFSL in vitro in vivo MRSA in vivo MRSA VCM cephem VCM GlcNAc MurNAc pentapeptide pp lipid pp lipid 7 cephem penicillin binding proteins VCM cephem VCM MIC 1 2 14 VCM VCM 8 in vitro VCM cephem in vitro in vivo VCM TEIC cephem TEIC VCM lactam 911 TEIC 47 1 1 : MRSA ABK 49: 89941 2 : MRSA Jpn J Antibiotics 49: 7827991996 3 : MRSA cefotiamvancomycincefotiamarbekacin minocyclinevancomycin in vitro 44: 595931996 4 : MIC Chemotherapy 38: 1215199 5 Hewlett P S: Measurment of potencies of drug mixtures. Biometrics 25: 4774871969 6 : In vivo pharmacokinetic model methicillin Staphylococcus aureus vancomycin cefoselis 44: 2132191996 7 BarnaJCJWilliams D H: The structure and mode of action of glycopeptide antibiotics of the vancomycin group. Ann Rev Microbiol 38: 339357 1984 8 : MRSA MRSA 2 p.5758 9 : Methicillin resistant Staphylococcus aureus piperacillin vancomycinteicoplanin arbekacin in vitro 27: 22723 1 : MRSA Jpn J Antibiotics 52: 2682771999 11 : MRSA Jpn J Antibiotics 53: 643651
Combined antibacterial effects of between vancomycin and cephems in methicillin resistant Staphylococcus aureus Yasuhiro Shibuya 1a Takashi Ohno 2 and Kouichi Itoh 1 1 Department of Clinical Laboratory MedicineJichi Medical School3311 1 YakushijiMinamikawachi machikawachi guntochigijapan 2 Department of Clinical LaboratoryJichi Medical School Hospital a Present address: Department of Respiratory MedicineTokyo Metropolitan Hiroo General Hospital In vitro inetractions between vancomycinvcmand cefpiromecprcefoseliscfslcefepime CFPMor cefozopranczopwere studied using the micro dilution checkerboard technique in 12 clinical isolates of methicillin resistant Staphylococcus aureusmrsaall strains were isolated from blood samples obtained from patients admitted to Jichi Medical School between 1999 and. Out of 12 strainssynergism or an additive action was observed in 77 strains75.5treated with VCM plus CPR 82 strains.4treated with VCM plus CFSL81 strains79.4treated with VCM plus CFPMand 76 strains74.5treated with VCM plus CZOP. The fractional inhibitory concentrationficindexes for VCM plus each of the four cephems were between.67 and.75. Antagonism was not observed in any of the VCM plus any cephem combinations. Treatment with a combination of VCM and a fourth generation cephemsuch as CPRCFSLCFPM or CZOPproduces synergistic or additive effect and should be considered for the treatment of MRSA infections.