Therapeutic potential of cationic steroid antibacterials

Antibiotics were one of the great health successes of the 20th century. Antibiotics, both naturally derived and synthetic, have resulted in huge decreases in both morbidity and mortality from bacterial infections. As a consequence, the 'antibiotic age' has changed public expectations about the results of infectious disease. However, this has led to high levels of inappropriate prescribing, where antibiotics may be administered to fulfil patient expectations rather than for clinical benefit. Along with unwise uses in agriculture and elsewhere, this has contributed to recent rises in numbers of antibiotic-resistant bacteria. As a result, many commentators have described this as the end of the antibiotic age and the term 'superbug' has entered the common vocabulary for multi-drug-resistant bacteria such as vancomycin-resistant Enterococcus, multi-drug-resistant Staphylococcus aureus and multi-drug-resistant Pseudomonas aeruginosa. In this context, an attractive approach for the development of antibacterial agents is the use of a new class of cationic steroidal compounds mimicking polymyxin activities. The permeabilization properties of these agents of the outer membranes of Gram-negative bacteria are reported in this review, as well as a discussion of literature results.