Importance of antibiotic resistance and resistance mechanisms

摘要

It is a frightening fact in the history of antimicrobial therapy that the phenomenon of antibiotic resistance was described well before the introduction of penicillin into clinical trials. As such, this chance observation, initially made in Bacillus (Escherichia) coli by Edward P Abraham and Ernst B Chain in 1939, was at first regarded as being 'irrelevant', since penicillin was only targeted for staphylococcal or streptococcal infections, not Gram-negative infections. Thereafter, antibiotic resistance mediated by enzymatic inactivation (e.g., by ?-lactamases and aminoglycoside-modifying enzymes), modification or protection of the target (e.g., through topoisomerase target modification by mutation or ribosomal target modification by Erm methylases), bypass of the antibiotic target (e.g., PBP2a in methicillin-resistant staphylococci), and reduced target attainment due to permeability barriers or efflux systems (e.g., Mef- or Mex-type efflux pumps) has threatened the efficacy of each novel antibiotic introduced into the clinical arena. It is unfortunate that no antibiotic has escaped resistance, even last-line agents, such as colistin and daptomycin that act on the cell's exterior membrane. The diversity and power of different resistance mechanisms reflects the extraordinary evolutionary potential of bacteria and the broad repertoire of mechanisms that can be combined and exploited to antagonize the toxic effects of antibiotics.