Activity of sub-minimal inhibitory concentrations of aspoxicillin in prolonging the postantibiotic effect against Staphylococcus aureus.
Aspoxicillin, a newly developed acylureido-penicillin with a long half-life in mouse serum of 55 min, induced postantibiotic effects (PAEs) against Staphylococcus aureus Smith of 1.7 h in vitro and 5.2 h in vivo in a thigh infection model in neutropenic mice. The long serum half-life meant that in order to evaluate the in-vivo PAE, it was necessary to examine the contribution of the drug at a sub-minimal inhibitory concentration (sub-MIC). Growth suppression by sub-MICs of aspoxicillin was examined in vitro using either previously unexposed bacterial cells or cells which had been pre-exposed to twice the MIC of aspoxicillin for 2 h. At each sub-MIC tested, the duration of growth suppression for pre-exposed cells was longer than that for unexposed cells. In an attempt to eliminate the sub-MIC effect in vivo, penicillinase was injected into mice at the time after administration when the aspoxicillin serum concentration approached the MIC. The in-vivo PAE decreased to 2.7 h when penicillinase was injected. It was concluded that aspoxicillin induced a PAE in vivo which was additional to the effect of sub-inhibitory residual drug, but that sub-MIC levels of the drug were simultaneously involved in suppressing bacterial regrowth after the drug concentration decreased below the MIC. Similar postantibiotic sub-MIC effects may also occur with other long half-life antibiotics.
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
T
T
Oshida
T
T
Onta
N
N
Nakanishi
T
T
Matsushita
T
T
Yamaguchi
D000658:Amoxicillin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D006207:Half-Life; D051379:Mice; D008826:Microbial Sensitivity Tests; D010405:Penicillinase / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects*
C037485:aspoxicillin; D000658:Amoxicillin; D010405:Penicillinase; D010878:Piperacillin