The Comparative Activity of Carbapenems Testing (COMPACT) Study was designed to determine the in vitro potency of doripenem compared with imipenem and meropenem against a large number of contemporary Gram-negative pathogens from more than 100 centres across Europe and the Asia-Pacific region and to assess the reliability of Etest methodology for doripenem minimum inhibitory concentration (MIC) determination against these pathogens. Data from eight countries within the Asia-Pacific region, which collected 1612 bacterial isolates, are presented here. Etest methodology was found to be a reliable method for MIC determination. Doripenem showed in vitro activity similar to or better than meropenem and at least four-fold better than imipenem against Enterobacteriaceae. Against Pseudomonas aeruginosa, doripenem was also the most active of the three carbapenems in vitro. However, in vitro results do not necessarily correlate with clinical outcome.
Previous studies have shown that the bacteremias which occur in mice during the 2nd week following a moderate dose (600 or 450 r) of total body x-irradiation are caused by members of their normal enteric flora (1). Of the enteric microorganisms, Pseudomonas a~uginosa was shown by serial blood cultures to be the most rapidly lethal once it had invaded the blood stream (2). These observations pointed to the intestinal tract as the site of origin of postirmdiafion bacteremias. They also suggested that Ps. aeruginosa might be a particularly suitablemicroorganism for measuring changes in susceptibility to infection. These indications were substantiated by the observation that Pseudomonas introduced by stomach tube into the gastrointestinal tract of irradiated mice gave rise within a very few days to a high incidence of fatal bacteremlas if inoculation had been made on the 5th or l l t h day post irradiation (3). In normal animals even larger numbers of the same strain of Pse~o-monas, inoculated by the same route, produced no ill effects. This striking difference between normal and irradiated animals in their response to oral inoculation with P s e u J~ seemed to warrant a study of the fate of this microorganism after its introduction into the gastrointestinal tract. Mice were accordingly inoculated on the 5th day post irradiation (550 r) with approximately l0 T Ps. aeruginosa and killed at daily intervals thereafter to determine the numbers of this microorganism in the small and large intestine. It was found that these bacteria were much more likely to become implanted and to multiply in the intestine, particularly in the small intestine, of the irradiated than of the normal mouse. This observation has led to a series of additional experiments undertaken in an attempt to explain this effect of irradiation.
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