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J Appl Microbiol. 2008 Sep;105(3):822-8. doi: 10.1111/j.1365-2672.2008.03820.x. Epub 2008 Apr 29.

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

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1
Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, West Bengal, India.

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.

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