Antibiotic Booster Adjuvants: Allies in Fight Against Resistant Bacteria

As drug-resistant bacteria continue to challenge the existing armamentarium of antibiotics and scant new options emerge from the pipeline, scientists and clinicians are exploring a new strategy that may make existing drugs more effective and prevent new resistant strains from emerging.

They are seeking so-called antibiotic adjuvants. Just like adjuvants used for improving the immunogenicity of vaccines, these compounds enhance the action of antibiotics. They may do so through a variety of mechanisms, including by weakening the bacteria themselves, making them more vulnerable to antibiotics, or by interfering with bacterial mechanisms of antibiotic resistance. Teams working in this area have recently published or presented work highlighting promising antibiotic adjuvants—some found among drugs currently used for other applications, others derived from compounds in ocean environments. _JAMA

Anti-Diarrheal Drug Loperamide Boosts Minocycline Potency

Combining common antibiotics with additional compounds could make previously resistant bacteria more susceptible to the same antibiotics. ‘Resuscitation’ of existing antibiotics has the potential to make infections caused by multidrug-resistant bacteria easier to control, reducing antibiotic usage and levels of antimicrobial resistance, say scientists presenting their work at the Society for General Microbiology’s Spring Conference in Dublin this week.

Researchers from University College Dublin (UCD) studied a variety of bacteria that are frequently associated with hospital-acquired infections, including Pseudomonas, Klebsiella, Enterobacter and Staphylococcus. Bacterial samples were collected from hospital patients and from these, strains that showed resistance to a commonly prescribed antibiotic – ciprofloxacin - were selected for study.

The team tested ciprofloxacin in combination with one of five different ‘adjuvant’ compounds against these bacteria, to determine which combinations, if any, were more effective than treatment with ciprofloxacin alone. Results showed that all five adjuvant compounds increased the efficacy of ciprofloxacin; making it more active against the bacteria by up to six-fold. .

...The team believes that adjuvant therapy could revolutionize the way that antibiotics are used nowadays. “Hopefully this work will allow antibiotics to be incorporated into treatment regimes and administered in more effective ways,” said Dr Martins. “As well as extending the lifespan of current antibiotics, this approach could ultimately reduce levels of antimicrobial resistance in hospitals as well as in the community, allowing hard-to-treat bacterial infections to be successfully controlled,” she said. _SGMNews_via_SD

From the abstract of a Feb 2011 paper:

The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising. One approach to combat this growing problem is the use of combination drug antibiotic adjuvant therapy, which potentiates the activity of antibiotics....Adjuvant therapies include antibiotic combinations, synergy between antibiotics and nonantibiotics, inhibition of resistance and molecules that alter the physiology of antibiotic-insensitive cells, such as those in biofilms.... _NIHPubmed

The combination drug Augmentin can be consider as a forerunner of this new class of combination, anti-resistance antibiotics. The clavulinic acid in augmentin blocks a penicillinase enzyme that would otherwise inactivate the amoxicillin antibiotic.

As stated previously on Al Fin, bacteria are shifty, but humans have brains. Perhaps the global increase in antibiotic multi-resistance will spur more humans to use the brains they have to find solutions to the problem.