New promising β-lactamase inhibitors for clinical use.

Abstract

Clavulanate, sulbactam, and tazobactam have been used extensively for the last 30years, together with β-lactam antibiotics, to inhibit the effect of β-lactamases. Although they have been useful as β-lactamase inhibitors in many cases, their effectiveness is restricted to class A β-lactamases. With the increasing frequency and breadth of β-lactamases now threatening public health throughout the world, we need a much broader spectrum of β-lactamase inhibitors efficient against all classes of β-lactamases. There are several β-lactamase inhibitors under development, but only a few of them are able to inhibit class D and even fewer class B metallo-β-lactamases (MβLs). The latter represent a real threat to the latest generations of β-lactam antibiotics, including cephalosporins and carbapenems. Only two β-lactamase inhibitors are, so far, under clinical evaluation, i.e., avibactam and MK-7655. The others are years from being clinically available. Although this has caused cautious optimism, the progress in this field is far too slow. This is particularly so because none of the substances provided are active against MβLs and because new β-lactamases invariably force their way into our therapeutic armamentarium. While waiting for new antibiotics and new β-lactamase inhibitors to become available, it is important to carry out accurate clinical and microbiological diagnosis, perform adequate hygiene, and use antibiotics properly. This may save lives and reduce resistance resulting from inappropriate antibiotic treatment.