β -Lactamases- the Threat Renews

ß-Lactamases are the greatest single source of resistance to ß-lactam antibiotics. For over 60 years, clinicians have seen a pattern whereby useful new ß-lactam analogues are introduced but then select for new ß-lactamases that cause resistance. Thus, penicillin G was undermined by swift accumulation of staphylococcal penicillinase, ampicillin by TEM- 1 enzyme and modern oxymino cephalosporins by “extended-spectrum” ß-lactamases. Tony Fink's work contributed greatly to our understanding of the mechanisms and active site function of ß-lactamases and this knowledge now informs the search for new ß-lactams and ß-lactamase inhibitors.