Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Dec 24:4:392.
doi: 10.3389/fmicb.2013.00392.

Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance

Richard R Watkins  1 , Krisztina M Papp-Wallace  2 , Sarah M Drawz  3 , Robert A Bonomo  4
Affiliations

Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance

Richard R Watkins et al. Front Microbiol. .

Abstract

The increasing incidence and prevalence of multi-drug resistance (MDR) among contemporary Gram-negative bacteria represents a significant threat to human health. Since their discovery, β-lactam antibiotics have been a major component of the armamentarium against these serious pathogens. Unfortunately, a wide range of β-lactamase enzymes have emerged that are capable of inactivating these powerful drugs. In the past 30 years, a major advancement in the battle against microbes has been the development of β-lactamase inhibitors, which restore the efficacy of β-lactam antibiotics (e.g., ampicillin/sulbactam, amoxicillin/clavulanate, ticarcillin/clavulanate, and piperacillin/tazobactam). Unfortunately, many newly discovered β-lactamases are not inactivated by currently available inhibitors. Is there hope? For the first time in many years, we can anticipate the development and introduction into clinical practice of novel inhibitors. Although these inhibitors may still not be effective for all β-lactamases, their introduction is still welcome. This review focuses on the novel β-lactamase inhibitors that are closest to being introduced in the clinic.

Keywords: antibiotic resistance; β-lactamase inhibitors.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Chemical structures of the clinically available β-lactamase inhibitors.
FIGURE 2
FIGURE 2
Chemical structures of diazabicyclooctanes.
FIGURE 3
FIGURE 3
Chemical structures of a novel combination: a carbapenem (left) with a new boron-based β-lactamase inhibitor (right).
FIGURE 4
FIGURE 4
Chemical structure of a novel siderophore monosulfactam.
FIGURE 5
FIGURE 5
Chemical structures of novel β-lactams with β-lactamase inhibitor activity.
See this image and copyright information in PMC

References

    1. Ambler R. P. (1980). The structure of β-lactamases. Philos. Trans. R. Soc. Lond. B Biol. Sci. 289 321–331 10.1098/rstb.1980.0049 - DOI - PubMed
    1. Babini G. S., Yuan M., Livermore D. M. (1998). Interactions of β-lactamases with sanfetrinem (GV 104326) compared to those with imipenem and with oral β-lactams. Antimicrob. Agents Chemother. 42 1168–1175 - PMC - PubMed
    1. Bassetti M., Ginocchio F., Mikulska M. (2011). New treatment options against Gram-negative organisms. Crit. Care 15 215 10.1186/cc9997 - DOI - PMC - PubMed
    1. Bou G., Santillana E., Sheri A., Beceiro A., Sampson J. M., Kalp M., et al. (2010). Design, synthesis, and crystal structures of 6-alkylidene-2’-substituted penicillanic acid sulfones as potent inhibitors of Acinetobacter baumannii OXA-24 carbapenemase. J. Am. Chem. Soc. 132 13320–13331 10.1021/ja104092z - DOI - PMC - PubMed
    1. Boucher H. W., Talbot G. H., Benjamin D. K., Jr., Bradley J., Guidos R. J., Jones R. N., et al. (2013). 10 x ’20 Progress–development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin. Infect. Dis. 56 1685–1694 10.1093/cid/cit152 - DOI - PMC - PubMed