Polymyxins retain in vitro activity and in vivo efficacy against "resistant" Acinetobacter baumannii strains when tested in physiological conditions.

The emergence of plasmid-mediated resistance threatens the efficacy of polymyxins as the last line of defense against pan-drug-resistant infections. However, we have found that using Mueller-Hinton II (MHII), the standard minimum inhibitory concentration (MIC) medium, results in MIC data that are disconnected from in vivo treatment outcomes. We found that culturing putative colistin-resistant Acinetobacter baumannii clinical isolates, as defined by MICs of >2 mg/L in standard MHII testing conditions, in bicarbonate-containing media reduced MICs to the susceptible range by preventing colistin resistance-conferring lipopolysaccharide modifications from occurring. Furthermore, the lower MICs in bicarbonate-containing media accurately predicted in vivo efficacy of a human-simulated dosing strategy of colistin and polymyxin B in a lethal murine infection model for some polymyxin-resistant A. baumannii strains. Thus, current polymyxin susceptibility testing methods overestimate the contribution of polymyxin resistance-conferring mutations and incorrectly predict antibiotic activity in vivo. Polymyxins may remain a viable therapeutic option against Acinetobacter baumannii strains heretofore determined to be "pan-resistant."

The right hemisphere and the dark side of consciousness.

Self-awareness and Theory of Mind comprise the main elements of higher-order consciousness. In attempting to localize these abilities, it appears that regions of the right hemisphere including fronto-temporal regions are capable of sustaining a sense of self-awareness. The right hemisphere appears dominant for tasks involving Theory of Mind as well as deception, which may be important for understanding the brain and laterality in terms of evolution. These findings are critical for our understanding of hemispheric differences in terms of higher-order consciousness.