ANTIBACTERIAL ACTIVITY OF 4 CEPHALOSPORINS IN AN EXPERIMENTAL-INFECTION IN RELATION TO INVITRO EFFECT AND PHARMACOKINETICS

被引:26
作者
MATTIE, H
VANDOKKUM, AM
BRUSWEIJER, L
KRUL, AM
VANSTRIJEN, E
机构
[1] Department of Infectious Diseases, University Hospital Leiden
关键词
D O I
10.1093/infdis/162.3.717
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parametERs ofthe plasmaconcentrations in vivo and those ofthe Hill equation thecorresponding time course of ER was calculated and by integration with respect to time (∫0tERdt), an estimate was obtained of the effect on bactERia. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h. © 1990, by The University of Chicago.
引用
收藏
页码:717 / 722
页数:6
相关论文
共 14 条
[1]   ROLE OF PHARMACOKINETICS IN THE OUTCOME OF INFECTIONS [J].
DRUSANO, GL .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1988, 32 (03) :289-297
[2]  
FLANDERS H, 1985, CALCULUS
[3]   CLINICAL PHARMACOLOGY OF CEFAMANDOLE AS COMPARED WITH CEPHALOTHIN [J].
FONG, IW ;
RALPH, ED ;
ENGELKING, ER ;
KIRBY, WMM .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1976, 9 (01) :65-69
[4]   EXPERIMENTAL-INFECTION WITH STREPTOCOCCUS-PNEUMONIAE IN MICE - CORRELATION OF INVITRO ACTIVITY AND PHARMACOKINETIC PARAMETERS WITH INVIVO EFFECT FOR 14 CEPHALOSPORINS [J].
FRIMODTMOLLER, N ;
BENTZON, MW ;
THOMSEN, VF .
JOURNAL OF INFECTIOUS DISEASES, 1986, 154 (03) :511-517
[5]   ANTIBIOTIC-THERAPY OF INFECTIONS DUE TO PSEUDOMONAS-AERUGINOSA IN NORMAL AND GRANULOCYTOPENIC MICE - COMPARISON OF MURINE AND HUMAN PHARMACOKINETICS [J].
GERBER, AU ;
BRUGGER, HP ;
FELLER, C ;
STRITZKO, T ;
STALDER, B .
JOURNAL OF INFECTIOUS DISEASES, 1986, 153 (01) :90-97
[6]   UNDERSTANDING THE DOSE-EFFECT RELATIONSHIP - CLINICAL-APPLICATION OF PHARMACOKINETIC-PHARMACODYNAMIC MODELS [J].
HOLFORD, NHG ;
SHEINER, LB .
CLINICAL PHARMACOKINETICS, 1981, 6 (06) :429-453
[7]   THE EFFICACY OF RIFAMPICIN AGAINST STAPHYLOCOCCUS-AUREUS INVITRO AND IN AN EXPERIMENTAL-INFECTION IN NORMAL AND GRANULOCYTOPENIC MICE [J].
HOOGETERP, JJ ;
MATTIE, H ;
KRUL, AM ;
VANFURTH, R .
SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 1988, 20 (06) :649-656
[8]   CEFAZOLIN AND CEPHRADINE - RELATIONSHIP BETWEEN ANTIBACTERIAL ACTIVITY INVITRO AND IN MICE EXPERIMENTALLY INFECTED WITH ESCHERICHIA-COLI [J].
KUNST, MW ;
MATTIE, H .
JOURNAL OF INFECTIOUS DISEASES, 1978, 137 (04) :391-402
[9]   PULSE DOSING VERSUS CONTINUOUS INFUSION OF ANTIBIOTICS - PHARMACOKINETIC-PHARMACODYNAMIC CONSIDERATIONS [J].
LEBEL, M ;
SPINO, M .
CLINICAL PHARMACOKINETICS, 1988, 14 (02) :71-95