[Antibacterial effect of cefixime in the presence of the type of beta-lactamases produced by Enterobacteriaceae].
The susceptibility of isolates or Enterobacteriaceae to orally absorbed beta-lactams (amoxicillin, cephalexin, cefaclor, cefuroxime, and cefixime), was maximum for the iminomethoxy-aminothiazolyl-cephalosporin but variable according to bacterial species. For E. coli, P. mirabilis, Salmonella, Shigella, K. pneumoniae, K. oxytoca (group 1) MIC50 were congruent to 0.06 mg/l, and MIC90 congruent to 0.12 mg/l. Finally for C. freundii, E. aerogenes, E. cloacae, S. marcescens, M. morganii, MIC50 were higher, congruent to 1, and MIC90 16 mg/l. The slight increase reported between MIC50 ans MIC90 of cefixime against isolates belonging to group 1 was related to stability towards beta-lactamases (TEM, SHV) unlike groups 2 and 3, where the drug was less stable to chromosomal type 1 enzyme. The discovery of extended-spectrum beta-lactamases (ESB) (e.g. SHV-2, CTX-1 or TEM-3), mainly in K. pneumoniae, led to further investigations of the behavior of cefixime. The in vitro activity of cefixime (CFM), amoxicillin (AMX) combined or not with clavulanate (AMC, 2 mg/l), ticarcillin (TIC), cephalothin (CF), cefotaxime (CTX), ceftazidime (CAZ) and aztreonam (AZM) was determined by the agar dilution method (inoculum 10(5) cfu/ml) against clinical isolates: E. coli (26), K. pneumoniae (42), K. oxytoca (9), Salmonella (3) producing several types of beta-lactamases, chromosomal (cephalosoporinase, broad-spectrum) or plasmid-encoded (TEM-1, TEM-2, CTX-1, SHV-2, SHV-3, SHV-4). The geometric mean MIC values of AMX, AMC, TIC, CF, CTX, CAZ, AZM and CFM were as follows: greater than 480, 21.6, greater than 285, 45.6, 0.53, 1.12, 0.51, and 0.77 respectively. An MIC increase of oxyimino beta-lactams (CTX, CAZ, AZM, CFM) was observed against over-producing isolates of K. oxytoca and isolates producing ESB (CTX-1, SHV-2, SHV-3, SHV-4). The comparative behavior of cefixime was determined after transfer by conjugation to E. coli K-12. Sixty-one derivatives were constructed producing TEM-1, TEM-2, SHV-1, CTX-1, TEM-4, CAZ-2, SHV-2, SHV-3, SHV-4, the MICs of cefixime were stable against derivatives producing a penicillinase (TEM-1, TEM-2, SHV-1), but not against those producing an ESB. The MIC increases of undigestible beta-lactams ranged from 1 to 135 fold (CFM), 40 to 200 fold (CTX) 12 to 232 fold (CAZ), and 4 to 240 fold (AZM).
Philippon
A
A
Unité d'Ecologie Bactérienne, Institut Pasteur, Paris.
Jarlier
V
V
Legrand
P
P
Fournier
G
G
Nicolas
M H
MH
Duval
J
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007709:Klebsiella / Q000187:drug effects / Q000201:enzymology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology; D010403:Penicillin Resistance; D010641:Phenotype; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D020682:Cefixime; D001618:beta-Lactamases; D002439:Cefotaxime
Activité antibactérienne du céfixime selon le type de bêta-lactamases des entérobactéries.