Resistance in Gram-negative Bacteria
Among Gram-negative bacteria, the emergence of resistance to expanded-spectrum cephalosporins has been a major concern. It appeared initially in a limited number of bacterial species (E. cloacae, C. freundii, S. marcescens, and P. aeruginosa ) that could mutate to hyperproduce their chromosomal class C β-lactamase. A few years later, resistance appeared in bacterial species not naturally-producing AmpC enzymes (K. pneumoniae, Salmonella spp., P. mirabilis) due to the production of TEM- or SHV-type ESBLs. Characteristically, such resistance has included oxyimino- (for example ceftizoxime, cefotaxime, ceftriaxone, and ceftazidime, as well as the oxyimino-monobactam aztreonam), but not 7-alpha-methoxy-cephalosporins (cephamycins); in other words, (cefoxitin and cefotetan) have been blocked by inhibitors such as clavulanate, sulbactam, or tazobactam, and did not involve carbapenems. Chromosomal-mediated AmpC β-lactamases represent a new threat, since they confer resistance to 7-alpha-methoxy-cephalosporins (cephamycins) such as cefoxitin or cefotetan are not affected by commercially-available β-lactamase inhibitors, and can, in strains with loss of outer membrane porins, provide resistance to carbapenems.
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