(My thanks to David Armstrong, DPM, PhD for bringing this press release to my attention)
According to its manufacturer TaiGen, nemonoxacin, a novel, non-fluorinated quinolone has shown promising results in a single armed, multinational, proof of concept Phase II clinical trial against diabetic foot infections (DFI). What is unique about this drug is that, unlike other currently available quinolones, nemonoxacin has activity against MRSA and vancomycin resistant gram positive organisms. Those who have heard me lecture know that I have not been a huge fan of quinolones in the treatment of gram positive infections since, especially earlier generation drugs such as ciprofloxacin could, and often did, cause rapid development of resistance in these organisms. In fact, a number of quinolones have been implicated in potentiating MRSA development. Seeing a new agent in this class with this broadened gram positive coverage is really interesting and has potential to be an important therapeutic advance.
The use of quinolones in the treatment of DFI has an interesting history. The first antibiotic ever officially labeled by the FDA for the treatment of “complicated skin and skin structure infections including diabetic foot infections” was a quinolone…trovafloxacin (Trovan®, Pfizer). Unfortunately, the drug, having been granted the most indications of any new antibiotic at the time of release, 14, was heavily marketed and possibly over utilized. A number of deaths resulted, although there has been question about the agent’s role in those deaths, and the drug was essentially pulled from the market (although it was technically still available it had extreme restrictions placed on its use by the FDA). Trovan was unique in that it was extremely broad spectrum including activity against many common gram-positives, gram-negatives, and even anaerobes. So, its spectrum of activity was extremely promising for use in DFI. Few other quinolones that have been developed share the broad spectrum that Trovan possessed. A number of other broad spectrum, anti-anaerobic quinolones looked to show promise in the treatment of DFI but were never pursued. Gemifloxacin received indications only for respiratory infections. Gatifloxacin was marketed for skin and skin structure infections but was pulled from the market when it was found to cause problems with glucose homeostasis. Moxifloxacin has a spectrum of activity very similar to Trovan and should be useful in DFI. It does have an indication for complicated skin and skin structure infections, is given orally and once daily. However, it has not received a DFI indication. A number of years ago a DFI trial was started but, from what I understand, was stopped mid stream. I am not privy to the reasons the trial was halted and development for this indication stalled. The drug has recently been acquired my Merck in its merger with Schering Plough. Merck has a long history of DFI drug development so it will be interesting to see if anything comes of this.
Quinolone have been perhaps the most abused class of antibiotic. They have been massively overused because of their perceived broad spectrum and safety. However, a significant number of these drugs have been pulled from the market for toxicities. I mentioned 2 above, trovafloxacin and gatifloxacin. There have been others. Be aware of problems ranging from liver and renal toxicity to neurotoxicity and photosensitivity. Last but not least, in the past few years they have received the dreaded FDA “Black Box” warning for the role they can play in tendon ruptures, particularly of the Achilles tendon. Please use these antibiotics prudently when indicated.
