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A lack of drugs for antibiotic-resistant Gram-negative bacteria

Nature Reviews Drug Discovery volume 6, page 938 (2007)Cite this article

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Payne et al. recently reported an excellent overview of a target-based approach to new antibacterial development and the lack of new antibacterial drugs in late-stage development several years ago1. This observation has also been made by the participants in the recent forum2 of anti-infective research and development. Also, the Infectious Diseases Society of America recently identified six top-priority dangerous pathogens — extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Aspergillus species — for which there are few or no drugs in late-stage development. This could further limit future safe and effective choices for treating these infections3.

Three of these six pathogens are antibiotic-resistant Gram-negative bacteria. Recently, antibacterial drugs against ESBL-producing Gram-negative bacteria accounted for ∼15% (2 out of 13) of all antibacterial drugs undergoing development in Phase II trials or later clinical studies3. However, there are no drugs being developed against class C ESBL-producing Gram-negative bacteria. Here, we draw attention to important aspects of urgently needed antibacterial drugs against class C ESBL-producing Gram-negative bacteria, which have been overlooked by these reports. We also suggest that the category of ESBLs should be expanded.

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Figure 1: A sequence alignment of amino-acid residues near the H-9 (α9) and H-10 (α10) helix of class C β-lactamases with extended substrate spectrum.

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Authors and Affiliations

  1. Jung Hun Lee is a research scientist of Biological Sciences at Myongji University, San 38-2 Namdong, Yongin, Gyeonggido 449-728, Republic of Korea.,

    Jung Hun Lee

  2. Seok Hoon Jeong is professor of laboratory medicine at the College of Medicine, Kosin University, Busan, Republic of Korea.,

    Seok Hoon Jeong

  3. Sun-Shin Cha is Director of structural biology at the Marine Biotechnology Center, Korea Ocean Research & Development Institute, Ansan, Republic of Korea.,

    Sun-Shin Cha

  4. Sang Hee Lee is Chair and professor of biological sciences, Director of Center for Antibiotic Resistance at Myongji University, San 38-2 Namdong, Yongin, Gyeonggido 449-728, Republic of Korea.,

    Sang Hee Lee

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Correspondence to Sang Hee Lee.

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Competing interests

S.H.L. has received research grants from the National Institute of Health of KCDC in Republic of Korea, the beamline 6B and 6C of PLS supported by MOST and POSCO, the Driving Force Project for the Next Generation of Gyeonggi Provincial Government in Republic of Korea and the Second-Phase of Brain Korea 21 Project. S.S.C. has received a research grant from the 21C Frontier Functional Proteomics Center in Republic of Korea. S.H.J. has received a research grant from the Korea Research Foundation (KRF-2006-331-E00455). J.H.L. declares that he has no conflicts of interest.

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Lee, J., Jeong, S., Cha, SS. et al. A lack of drugs for antibiotic-resistant Gram-negative bacteria. Nat Rev Drug Discov 6, 938 (2007). https://doi.org/10.1038/nrd2201-c1

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