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


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.


CONCLUSIONS
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.
Saha
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Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, West Bengal, India.
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D052978:Disk Diffusion Antimicrobial Tests / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004917:Erythromycin / Q000627:therapeutic use*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D013256:Steroids / Q000627:therapeutic use*; D023382:Toxicity Tests, Acute
D000900:Anti-Bacterial Agents; D013256:Steroids; C521528:ceragenin CSA-13; D004917:Erythromycin