Overuse of antibiotics has contributed towards drug-resistant bacteria emerging and spreading. Antibiotics have frequently been accused for so-called “superbugs” spreading. In the United States, virulent strains of MRSA (methicillin-resistant Staphylococcus aureus), a leading cause of community-acquired soft tissue and skin infections, are of paramount public health concern, due to the accelerated expansion of the highly drug-resistant strains, such as MRSA-USA300.
At present, large health organization’s as well as government bodies recognize the urgent need for novel generations of antimicrobial agents. For these novel drugs to be effective they must be fast-acting, effective against drug-resistant bacteria, and minimize the probability of bacteria resistance.
According to an investigation published in Emerging Infectious Diseases, researchers from Japan revealed data indicating a role for over-the-counter (OTC) topical antibiotic ointments, which are prevalently used in the United States in helping MRSA-USA300 spread. Often, bacitracin and neomycin (active drugs) are contained in triple-antibiotic ointments, such as Neosporin. The investigation, which examined over 250 clinical isolates of MRSA from Korea and Japan, discovered that although the drug combination was effective against several MRSA strains, it was primarily ineffective against the virulent MRSA-USA300 strains.
Based on the association between the use of OTC medications and the prevalence of MRSA-USA300 in Korea and Japan (of which both are generally low in comparison to the U.S.), the researchers concluded that the selective pressure applied by indiscriminate use of OTC antibiotics may be partially accountable for the fast expansion of MRSA-USA300.
AgaDerm (NVC-422 Gel), designed by NovaBay Pharmaceuticals, Inc., represents a novel class of topical anti-infectives known as Aganocides®. The gel is designed to mirror the human body’s natural defense system against fighting infection. Via a differentiated mechanism of action, Aganocides have been demonstrated to be widely effective against both Gram-negative and Gram -positive pathogens. In human clinical trials Aganocides were proven well tolerated and safe.
At present, AgaDerm is in Phase II clinical development for treating individuals with impetigo. Impetigo is an extremely contagious skin infection caused by Staphylococcus aureus, including MRSA, Streptococcus pyogenes, or both. The condition affects children throughout the world.
According to results from a clinical investigation published recently in the International Journal of Clinical and Experimental Pathology, AgaDerm showed a 100% response rate for treating individuals with impetigo caused by MRSA, whether MRSA was in a mixed infection or was the only organism. Furthermore, the investigation examined NVC-422 against 55 recent clinical isolates of MRSA obtained from a database of European and U.S. patients, where the prevalence of MRSA-USA300 is greater. The researchers discovered that again, NVC-422 demonstrated to be rapidly bactericidal against all bacterial isolates, regardless of resistance phenotype. Even though the size of the investigation did not exactly distinguish MRSA sub-types, it is possible that the USA300 clone was presented in participants.
According to the researchers, the primary evidence is extremely encouraging and indicates that AgaDerm might be effective against clinically relevant strains of MRSA that are not well managed by present treatments.
AgaDerm makes it very hard for bacteria to become naturally resistant as it uses a unique mechanism of action that is not specific to one, or a small group of molecular targets. A poster presented earlier in 2011 by NovaBay at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), NVC-422 was demonstrated to maintain its antimicrobial activity against several vital human pathogens, including MRSA, in a serial passage investigation. Researchers of the investigation analyzed NVC-422 activity under laboratory conditions that assist the bacterial resistance to evolve. The team discovered that the minimum inhibitory concentration (MIC) of NVC-422 did not change after 50 passages, suggesting that over time bacteria do not seem to develop resistance.
According to the investigators, this basis may reside in the mechanism of action of Aganocides connected with medications like neomycin and bacitracin. Neomycin is part of a class of antibiotics called aminoglycosides, which have rather poor activity against Gram-positive bacteria such as MRSA. Among strains of MRSA resistance to neomycin is common. The study in Japan was consistent with these prior discoveries.
Bacitracin is an extremely strong drug that interferes with the construction of the bacterial cell wall by inhibiting a single pathway. Although, bacteria that develop the ability to push bacitracin outside of the cell or restore the pathway by using different cellular machinery rapidly become resistance to the drug.
AgaDerm could become a much-needed logical alternative to conventional topical antibiotics like bacitracin and neomycin, which are prevalently used in the United States to treat individuals suffering with soft tissues infections. As the investigation demonstrated, overuse of these drugs might unintentionally encourage expansion of highly drug-resistant MRSA as they cannot kill the most dangerous strains. In addition to being efficient in destroying virulent strains of MRSA, AgaDerm showed to considerably reduce risk of promoting resistance to drugs, in comparison to other antibiotics.
Written by Grace Rattue