Broad-spectrum beta-lactams for treating experimental peritonitis in mice due to Escherichia coli producing plasmid-encoded cephalosporinases.
OBJECTIVE
To investigate the correlation between in vitro activity and in vivo efficacy of broad-spectrum beta-lactams for treating experimental infections due to Escherichia coli expressing two types of plasmid-mediated AmpC-type beta-lactamases, LAT-1 and FOX-1.


METHODS
Susceptibility testing and time-kill curves were determined for piperacillin/tazobactam, ceftazidime, cefepime and imipenem. A mouse model of peritonitis was developed to determine 50% effective doses (ED(50)s) of beta-lactams against E. coli clinical strains producing recombinant plasmids pLAT-1 and pFOX-1.


RESULTS
MIC and MBC values correlated with the ED(50)s for ceftazidime, cefepime and imipenem. Among the beta-lactams tested, both cefepime and imipenem were effective for treating peritonitis caused by E. coli strains harbouring pLAT-1 or pFOX-1, whereas ceftazidime was effective only against E. coli (pLAT-1). Piperacillin/tazobactam was not effective for treating infections with either of these two strains.


CONCLUSIONS
Piperacillin/tazobactam was not efficacious for treating infections due to E. coli producing plasmid-mediated AmpC-type beta-lactamases, whereas cefepime and imipenem were efficacious.
Vimont
Sophie
S
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine de Paris-Sud, 94275 K.-Bicêtre, France.
Aubert
Daniel
D
Mazoit
Jean-Xavier
JX
Poirel
Laurent
L
Nordmann
Patrice
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002510:Cephalosporinase / Q000235:genetics* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D010957:Plasmids / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*