Reverse Thinking

Post date:2018.07.24

Fluoroquinolone (FQ) Antibiotics are synthetic antibiotics offering a broad-spectrum of bactericides and having sterilizing activity. Therefore, they have been most important for human and veterinary medicine. The Food Safety Commission evaluated FQ antibiotics which effect human health through food, as critically important. In veterinary medicine, FQ antibiotics are recommended for use as second-line drugs only if first-line drugs are of no effect. However, recently, various bacteria tend to show resistance to FQ antibiotics on the back of improper uses by doctors and veterinarians. We would like to ensure the proper use of FQ antibiotics which are “drug of the last resort” for veterinarians.

By the way, bacteria acquiring resistance to FQ antibiotics is caused by their low affinity to mutations in the quinolone-resistance determining region (QRDR). Much stronger antibiotics are needed for infectious diseases caused by such FQ-resistant bacteria. However, bacteria will acquire resistance immediately even if new antibiotics are used, therefore, we require new stronger ones, such as spiral of antimicrobial resistant bacteria and antibiotics.

Recently, an antibiotic which may solve such a problem has been discovered. A team led by Professor Hiramatsu of Juntendo University reported that Nybomycin is active against Staphylococcus aureus (MRSA) with mutation sites of QRDR, but not against wild strains which are susceptible to FQ antibiotics. Surprisingly, nybomycin-resistant MRSA has re-acquired susceptibility to FQ antibiotics. Therefore, Prof. Hiramatsu announced a new concept of “reverse antibiotics”. Interestingly, nybomycin had been already discovered before FQ antibiotics were developed. Reversal thinking, in which existing antibiotics are re-examined for antimicrobial resistant bacteria as a target, can be made to regulate those bacteria. It was also reported that many bacteria in nature have mutation of QRDR, thus, the mutated strain may be a wild strain. In either case, we hope that pharmaceutical companies develop new antibiotics with novel ideas to meet antimicrobial resistance.