A Guide To Emerging Antibiotics For Diabetic Foot Infections

By Mark Kosinski, DPM, and Warren Joseph, DPM

   Many exciting antibiotics have either recently been approved, received a new FDA indication or will soon become available. Some are well known and have already been incorporated into clinical practice. Many are the first in their respective classes and have novel mechanisms of action. What place, if any, do these drugs have in the treatment of diabetic foot infections (DFIs)?    That said, let us take a look at a number of newer as well as time-tested antibiotics and assess their efficacy for DFIs.    • Linezolid (Zyvox, Pfizer) and quinupristin/dalfopristin (Synercid®, Monarch Pharmaceuticals). While quinupristin/dalfopristin is active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), the drug has limited clinical use due to its administration via a slow infusion of a large volume or through a central line.    Linezolid, the first-in-class oxazolidinone, has 100 percent bioavailability after oral administration, is active against MRSA and VRE, and has proven efficacy in treating DFIs. Although treatment failures and resistant strains of S. aureus have been reported, linezolid remains a valuable new antibiotic and has received an FDA indication for diabetic foot infections. Both linezolid and quinupristin/dalfopristin are active against Enterococcus faecium but only linezolid is active against E. faecalis. Vancomycin-resistant Enterococcus are almost always E. faecium.

What The Research Reveals About Ertapenem

   • Ertapenem (Invanz, Merck). Ertapenem is a broad-spectrum carbapenem approved for the treatment of complicated skin and skin structure infections (cSSSIs), including diabetic foot infections without osteomyelitis.    Ertapenem has a narrow spectrum of activity compared to imipenem/cilastatin (Primaxin, Merck). It has good activity against methicillin susceptible S. aureus (MSSA), gram negatives and anaerobes. However, it has unreliable activity against Pseudomonas aeruginosa and enterococci. Researchers have shown that ertapenem has excellent in vitro activity against the most common aerobic pathogens and almost all anaerobes recovered from patients with infections of the skin and skin structures.1 It is not active against MRSA.    Perhaps ertapenem’s strongest benefit is its long half life, lending itself to once a day dosing and making it particularly attractive for IV outpatient therapy.    In a prospective, randomized, double-blind trial comparing ertapenem (1 g once daily) to piperacillin-tazobactam (3.375 g every 6 h) as parenteral treatment for 540 adults with complicated skin and skin-structure infections, 82.4 percent of those who received ertapenem and 84.4 percent of those who received piperacillin-tazobactam were cured. The most common infections in the study were deep soft tissue abscess (18.9 percent) and diabetic lower extremity infection (18.1 percent). With the exception of MRSA, almost all of the predominant aerobic pathogens were susceptible to both drugs in the study. Out of the 141 anaerobes tested for susceptibility, 97.2 percent were susceptible to ertapenem and 97.9 percent were susceptible to piperacillin-tazobactam.2    In another study known as SIDESTEP (the Study of Infections in Diabetic Feet Comparing Efficacy, Safety and Tolerability of Ertapenem vs Piperacillin/Tazobactam) Lipsky, et. al., recruited 576 patients to a randomized, double-blinded, multicenter trial. In the trial, 289 patients received 1 g of ertapenem daily and 287 patients received 3.375 g of piperacillin/tazobactam four times daily. All patients had moderate to severe diabetic foot infections. By the end of intravenous therapy, the clinical success rates were 94.2 percent for the ertapenem group and 92.2 percent for the piperacillin/tazobactam group, with no difference in the incidence of drug-related adverse events. The findings support the use of ertapenem as an important treatment option for DFIs.3

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