Combination approaches to combat multidrug-resistant bacteria
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The increasing prevalence of infections caused by multidrug-resistant bacteria is a global health problem that has been exacerbated by the dearth of novel classes of antibiotics entering the clinic over the past 40 years. Herein, we describe recent developments toward combination therapies for the treatment of multidrug-resistant bacterial infections. These efforts include antibiotic-antibiotic combinations, and the development of adjuvants that either directly target resistance mechanisms such as the inhibition of β-lactamase enzymes, or indirectly target resistance by interfering with bacterial signaling pathways such as two-component systems (TCSs). We also discuss screening of libraries of previously approved drugs to identify nonobvious antimicrobial adjuvants.
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Drug combinations have been utilized efficiently to treat various bacterial and viral infections and cancer.
“Historically, drug combinations have been utilized efficiently to treat various bacterial and viral infections and to fight cancer [18–21].”
From Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of<i>Candida auris</i>and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [18]
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- Authors
- Worthington, R. J., & Melander, C.
- Affiliations
- North Carolina State University (US)
- Corresponding author
- Melander, Christian
- ORCID
- Melander, Christian
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 31
- Issue
- 3
- Pages
- 177-184
- ISSN
- 0167-7799 (ISSN-L)
- PMC
- PMC3594660
- OpenAlex
- W1982551127
- Cited by
- 625
- References
- 64
- Citations by year
- 2026: 24 · 2025: 47 · 2024: 51 · 2023: 74 · 2022: 64 · 2021: 60 · 2020: 64 · 2019: 73 · 2018: 40 · 2017: 42 · 2016: 47 · 2015: 16 · 2014: 18 · 2013: 4
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Trends in biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM055769)
- National Institute of Allergy and Infectious Diseases (R21AI096015)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- multidrug-resistant bacteria, combination therapy, antibiotic adjuvants, beta-lactamase inhibition, two-component systems, bacterial signaling pathways, antibiotic resistance mechanisms, antibiotic resistance
- MeSH terms
- Adjuvants, Pharmaceutic, Anti-Bacterial Agents, Bacterial Infections, Drug Therapy, Combination, Humans, Drug Resistance, Multiple, Bacterial
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