Related Experiment Video

Updated: Jun 8, 2026

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
12:03

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method

Published on: April 18, 2019

Resistance to polymyxins: Mechanisms, frequency and treatment options

Matthew E Falagas1, Petros I Rafailidis, Dimitrios K Matthaiou

  • 1Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece. m.falagas@aibs.gr

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|September 17, 2010
PubMed

Insights

Polymyxin resistance in gram-negative bacteria is primarily due to lipopolysaccharide modifications. Understanding these mechanisms is crucial for combating infections, especially in specific regions with higher resistance rates.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Polymyxins target bacterial lipopolysaccharide (LPS) to disrupt membranes.
  • Resistance mechanisms involve modifications to the LPS structure, often regulated by two-component systems like PmrA/PmrB and PhoP/PhoQ.
  • Gram-negative bacterial resistance to polymyxins is generally low (<10%) but varies geographically.

Purpose of the Study:

  • To elucidate the mechanisms of polymyxin resistance in gram-negative bacteria.
  • To investigate factors contributing to increased resistance rates in specific regions.
  • To identify potential therapeutic strategies for polymyxin-resistant infections.

Main Methods:

  • Review of existing literature on polymyxin-bacterial interactions and resistance.
  • Analysis of geographical variations in polymyxin resistance prevalence.
  • Examination of the role of LPS modification and regulatory systems in resistance.
  • Evaluation of alternative treatment options for resistant infections.

Main Results:

  • Lipopolysaccharide modification, mediated by PmrA/PmrB and PhoP/PhoQ systems, is a key resistance mechanism.
  • Higher polymyxin resistance rates are observed in regions like the Mediterranean basin, Korea, and Singapore.
  • Heteroresistance is linked to polymyxin exposure and suboptimal dosing.
  • Polymyxin combination therapies, tigecycline, and fosfomycin show promise against resistant strains.

Conclusions:

  • Bacterial outer membrane modifications, particularly LPS alterations, are central to polymyxin resistance.
  • Geographical variations and clinical factors like exposure and dosing influence resistance prevalence.
  • Combination therapies and alternative agents are vital for managing polymyxin-resistant gram-negative infections.

More Related Videos

Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing08:19

Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing

Published on: July 7, 2020

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations11:15

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations

Published on: July 24, 2021

Related Concept Videos

Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Antibiotic Selection00:57

Antibiotic Selection

Overview