New promising β-lactamase inhibitors for clinical use
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Clavulanate, sulbactam, and tazobactam have been used extensively for the last 30 years, 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.
KeywordsCeftazidime Imipenem Carbapenems Clavulanic Acid Aztreonam
The author was funded through a grant from the European Commission (FP7-HEALTH-30609 “TRIGGER”).
Conflict of interest
The author has no commercial relationships and no potential conflicts of interest. The article does not contain any studies with human participants or animals performed by the author. The article does not contain patient data.
- 1.Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD (2013) Structural insight into potent broad-spectrum inhibition with reversible recyclization mechanism: avibactam in complex with CTX-M-15 and Pseudomonas aeruginosa AmpC β-lactamases. Antimicrob Agents Chemother 57(6):2496–2505PubMedCentralPubMedCrossRefGoogle Scholar
- 11.Søraas A, Olsen I, Sundsfjord A, Handal T, Bjørang O, Jenum PA (2014) Extended-spectrum beta-lactamase-producing bacteria are not detected in supragingival plaque samples from human fecal carriers of ESBL-producing Enterobacteriaceae. J Oral Microbiol 6:24026. doi: 10.3402/jom.v6.24026 CrossRefGoogle Scholar
- 18.Pucci MJ, Page MGP, Bush K (2014) Cautious optimism for the antibacterial pipeline. Microbe 9(4):147–152Google Scholar
- 25.Goldstein EJC, Citron DM, Merriam CV, Tyrrell KL (2013) Comparative in vitro activity of ceftaroline, ceftaroline–avibactam, and other antimicrobial agents against aerobic and anaerobic bacteria cultured from infected diabetic foot wounds. Diagn Microbiol Infect Dis 76(3):347–351PubMedCrossRefGoogle Scholar
- 29.Blizzard TA, Chen H, Kim S, Wu J, Young K, Park YW, Ogawa A, Raghoobar S, Painter RE, Hairston N, Lee SH, Misura A, Felcetto T, Fitzgerald P, Sharma N, Lu J, Ha S, Hickey E, Hermes J, Hammond ML (2010) Side chain SAR of bicyclic β-lactamase inhibitors (BLIs). 1. Discovery of a class C BLI for combination with imipinem. Bioorg Med Chem Lett 20(3):918–921PubMedCrossRefGoogle Scholar