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More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S. aureus developed resistance to methicillin (MRSA), invalidating almost all antibiotics, including the most potent beta-lactams. Vancomycin, a glycopeptide antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan horses to deliver vancomycin into bacterial cells. These nanoparticles are biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles enhance the transport of vancomycin across epithelial surfaces and show its efficient drug action, which has been understood from studies of the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show that vancomycin loaded into nanoconjugate is very effective and has a strong bactericidal effect on VRSA.

We confirm the presence of MRSA carrying the mecC gene in Spain, the ability of this livestock-associated MRSA to cause severe infections in humans and the need to perform culture-based susceptibility testing methods in order to detect these emerging strains.

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’ (LD50) 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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