It’s an exciting time to be involved with antibiotics! The antibiotic research pipeline and new approvals had all but dried up through the first decade of this new century. In the 1980s, over 40 new antibiotics were FDA approved, whereas between 2000 and 2010 only six or seven. Now, thanks to a number of governmental incentive programs that provide for lengthened patent protection and expedited review for new antibiotics, especially those effective against multi-drug resistant organisms (MDROs), there has been a bit of a renaissance in new antibiotic development. The past two years alone have seen the approval of at least five new drugs.

Most of the new antibiotics are fairly specific for methicillin resistant gram positive bacteria, with more recent development concentrating on the MDRO gram negative pathogens including those that produce Extended Spectrum Beta-Lactamase (ESBL) and Carbapenem Resistant Enterobacteriacea (CRE). Unfortunately, although a number have been approved for the treatment of skin and skin structure infections, NONE are specifically approved for diabetic foot infections. In 2013, the FDA released an updated “Guidance for Industry” to direct new antibiotic research in the field of “acute bacterial skin and skin structure infection” (aBSSSI). Unlike the previous Guidance, which allowed for research into diabetic foot infections, the aBSSSI document specifically excludes it without a drug company petitioning the FDA to discuss study design. Given the somewhat limited potential market perceived by the companies, few are willing to go through the extra time and expense.

Just because they are not formally approved does not mean that they cannot be useful in the treatment of, not only diabetic foot infections, but any lower extremity infection. Some of the more recently approved antibiotics with direct application to lower extremity infections include:

Tedizolid – This oral/IV oxazolidinone class antibiotic is active against most gram positive organisms including MRSA and vancomycin resistant enterococcus (VRE). Although of the same class as linezolid, it has a number of advantages. As opposed to being dosed 600 mg twice daily for 10 days, tedizolid is dosed 200 mg once daily for only six days. Because of the lower overall dose, there appears to be a lower risk for thrombocytopenia and a drug-drug interaction leading to serotonin syndrome when used at the same time as a select serotonin reuptake inhibitor (SSRI).

Oritavancin – This lipoglycopeptide antibiotic is similar in structure and antimicrobial coverage to vancomycin, but has a unique dosing regimen. For aBSSSI the drug is given as a single 1200 mg IV infusion.

Dalbavancin – Another lipoglycopeptide agent, this drug also has an unusual dosing regimen. It is given as a 1000 mg infusion followed seven days later by a 500 mg dose.

The final antibiotic that is important to discuss has not yet been FDA approved.

Pexiganan - A topical antimicrobial peptide derived from the skin of the African Clawed Frog, it has a broad spectrum of activity including those MDROs discussed above. As of the time of this writing, the drug is currently in Phase III clinical trials for the topical treatment of IDSA mild diabetic foot infections. This trial is the first “vehicle controlled” study for a new antibiotic against DFI. If successful, it will also be the only topical approved for DFI and the only antibiotic approved for mild infections.