New developments in tetracycline antibiotics: Glycylcyclines and tetracycline efflux pump inhibitors

Chopra, Ian

doi:10.1016/s1368-7646(02)00051-1

Cited by 143Antibiotic Resistance in BacteriaAntimicrobial Resistance in StaphylococcusAntibiotics Pharmacokinetics and Efficacy

New developments in tetracycline antibiotics: Glycylcyclines and tetracycline efflux pump inhibitors

Chopra, Ian·2002·Drug Resistance Updates

DOI 10.1016/s1368-7646(02)00051-1

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Abstract

The tetracyclines, discovered in the 1940s, are a well-established class of antibiotics that still have a role in treating microbial infections in man. However, the widespread emergence of bacterial resistance due to efflux and ribosomal protection mechanisms has severely limited their effectiveness. A new generation of tetracyclines, the glycylcyclines, has been developed to overcome resistance to earlier tetracyclines. One of the new glycylcyclines, 9-t-butylglyclamido-minocycline (GAR-936, tigecycline) is currently undergoing clinical trials. This review considers the current status of glycylcyclines and the possibility that resistance to these agents might arise in the future. Other approaches are also being taken to address the emergence of resistance to tetracyclines. Recently, a number of tetracycline efflux pump inhibitors have been discovered that might be used in combination with earlier tetracyclines to restore their activity against resistant organisms. However, the development of tetracycline efflux pump inhibitors is complicated by the occurrence of several efflux pump sub-families and by the presence of both efflux and ribosomal protection mechanisms in the same organism, especially in naturally occurring, Gram-positive clinical isolates.

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Third-generation tetracycline derivatives such as tigecycline display enhanced antimicrobial activity, overcoming efflux and ribosome protection mechanisms.
“The third generation of tetracycline derivatives, such as tigecycline (Tgc), display enhanced antimicrobial activity, overcoming efflux and ribosome protection mechanisms (6)(7)(8).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [6]

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Authors: Chopra, I.
Affiliations: University of Leeds (GB)
Corresponding author: Chopra, Ian
Venue: Drug Resistance Updates
Publisher: Elsevier BV
Published: 2002-06
Volume: 5
Issue: 3-4
Pages: 119-125
ISSN: 1368-7646 (ISSN-L)
DOI: 10.1016/s1368-7646(02)00051-1
OpenAlex: W1970691146
Cited by: 143
References: 42
Citations by year: 2026: 4 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 8 · 2012: 9
FWCI: 3.50
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Drug Resistance Updates (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords: tetracycline, glycylcyclines, tigecycline, antibiotic resistance, efflux pumps, multidrug resistance, Gram-positive bacteria, combination therapy
MeSH terms: Tigecycline, Humans, Microbial Sensitivity Tests, Minocycline, Structure-Activity Relationship, Tetracycline Resistance, Tetracyclines

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New developments in tetracycline antibiotics: Glycylcyclines and tetracycline efflux pump inhibitors

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