Sch 29482: Activity against susceptible and -lactam resistant variants of Enterobacteriaceae

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Abstract
The comparative activity of cefamandole, cefoxitin, cefotaxime, moxalactam thienamycin and Sch 29482 (SCH) was studied on homologous pairs of susceptible and resistant variants obtained by a single event in the same bacteria achieved by: modification of PBPs, multicopy plasmid, gene amplification and spontaneous susceptible variants. Resistance to all drugs of Serratia marcescens isolated from blood culture was related to modifications of PBPs. The introduction in Escherichia coli K12 of multicopy plasmids coding for TEM 1, SHV 1, OXA 3 β -lactamases did not change the 99 percent inhibitory concentration (IC 99 of this strain for all drugs except cefamandole. Variants of Enterobacter cloacae, Citrobacter freundii hyperproducing β -lactamases of different isoelectric points were 100- to 1000-fold more resistant than their susceptible counterpart to cefamandole, cefoxitin, cefotaxime and moxalactam. In contrast the activity of penem derivatives, thienamycin and SCH, remained unchanged towards susceptible and resistant variants.