Enhancement of the efficacy of erythromycin in multiple antibiotic-resistant gram-negative bacterial pathogens.

Abstract

AIMS:

To improve the efficacy of erythromycin, a hydrophobic antibiotic, against multiple antibiotic-resistant gram-negative bacterial pathogens by enhancing their outer membrane permeability.

METHODS AND RESULTS:

Fifty-one nonrepeat gram-negative bacterial pathogens of various genera, resistant to multiple antibiotics, including erythromycin, were selected by disc agar diffusion tests. The amphiphilic cationic steroid antibiotic, Ceragenin CSA-13, a potent permeabilizer of bacterial outer membranes, reduced the minimum inhibitory concentration of erythromycin in 92% of the bacterial pathogens selected for the test, when supplemented with erythromycin. A synergistic effect of Ceragenin CSA-13 and erythromycin in combination was also observed. Spectrofluorimetric study confirmed that Ceragenin CSA-13 acts by depolarizing the bacterial outer membrane. The toxicity of Ceragenin CSA-13 was evaluated to be insignificant by measuring 'median lethal dose' (LD(50)) on mouse model.

CONCLUSIONS:

Ceragenin CSA-13 may be useful as an agent to make erythromycin effective against infections caused by multiple antibiotic resistant gram-negative bacteria.

SIGNIFICANCE AND IMPACT OF THE STUDY:

The outcome of the study suggests erythromycin-Ceragenin combination as a new approach to overcome the problem associated with the rapid emergence of multi-drug-resistant pathogens. The insignificant toxicity of Ceragenin CSA-13, as found, supports the possibility of the application of this compound for human therapeutics.

• Authors: S Saha, P B Savage, M Bal
• Journal: Journal of applied microbiology (J Appl Microbiol) Vol. 105 Issue 3 Pg. 822-8 (Sep 2008) ISSN: 1365-2672 [Electronic] England
• PMID: 18452533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Steroids
• ceragenin CSA-13
• Erythromycin

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Disk Diffusion Antimicrobial Tests (methods)
• Drug Resistance, Multiple, Bacterial (drug effects)
• Drug Therapy, Combination
• Erythromycin (therapeutic use)
• Gram-Negative Bacterial Infections (drug therapy)
• Humans
• Mice
• Mice, Inbred Strains
• Microbial Sensitivity Tests
• Steroids (therapeutic use)
• Toxicity Tests, Acute