The DOI matches its Crossref record; 266 of the 266 references it cites were found in a registry or an index.
Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?
Open accessAbstract
SUMMARY: The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades. We review some of these strategies, with emphasis on antibiotic hybrids either as stand-alone antibacterial agents or as adjuvants that potentiate a primary antibiotic in Gram-negative bacteria. Antibiotic hybrid is defined in this review as a synthetic construct of two or more pharmacophores belonging to an established agent known to elicit a desired antimicrobial effect. The concepts, advances, and challenges of antibiotic hybrids are elaborated in this article. Moreover, we discuss several antibiotic hybrids that were or are in clinical evaluation. Mechanistic insights into how tobramycin-based antibiotic hybrids are able to potentiate legacy antibiotics in multidrug-resistant Gram-negative bacilli are also highlighted. Antibiotic hybrids indeed have a promising future as a therapeutic strategy to overcome drug resistance in Gram-negative pathogens and/or expand the usefulness of our current antibiotic arsenal.
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Cited by
Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review
Mulani, M. S., Kamble, E. E., Kumkar, S. N., Tawre, M. S., & Pardesi, K. R. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00539 · Cited by 1,644
Zhanel, G. G., Golden, A. R., Zelenitsky, S., Wiebe, K., Lawrence, C. K., Adam, H. J., Idowu, T., Domalaon, R., Schweizer, F., Zhanel, M. A., et al. (2019) · Drugs · doi:10.1007/s40265-019-1055-2 · Cited by 446
Self-citationAntibiotic resistance: turning evolutionary principles into clinical reality
Andersson, D. I., Balaban, N. Q., Baquero, F., Courvalin, P., Glaser, P., Gophna, U., Kishony, R., Molin, S., & Tønjum, T. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa001 · Cited by 238
Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens
Saxena, D., Maitra, R., Bormon, R., Czekanska, M., Meiers, J., Titz, A., Verma, S., & Chopra, S. (2023) · npj Antimicrobials and Resistance · doi:10.1038/s44259-023-00016-1 · Cited by 217
Metadata
- Authors
- Domalaon, R., Idowu, T., Zhanel, G. G., & Schweizer, F.
- Venue
- Clinical Microbiology Reviews
- Publisher
- American Society for Microbiology
- Published
- 2018-04
- Volume
- 31
- Issue
- 2
- ISSN
- 0893-8512 (ISSN-L)
- 1098-6618
- OpenAlex
- W2792453421
- Cited by
- 285
- References
- 266
- FWCI
- 10.44
- Type
- journal article
- Language
- en
- Open access
- green
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