A Guide To Emerging Antibiotics For Diabetic Foot Infections

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As you can see, this diabetic patient has an infected neuropathic ulcer and a gangrenous digit. (Photo courtesy of Lawrence Karlock, DPM)
Here is a view of a medial space diabetic foot infection secondary to a retained foreign body. (Photo courtesy of David G. Armstrong, DPM, PhD)
A Guide To Emerging Antibiotics For Diabetic Foot Infections
By Mark Kosinski, DPM, and Warren Joseph, DPM

   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

What You Should Know About Moxifloxacin

   • Moxifloxacin (Avelox®, Schering-Plough). Like ertapenem, moxifloxacin is not new but it did receive a new indication for complicated skin and skin structure infections (cSSSIs) in July. Although it does not have a formal FDA indication for diabetic foot infections, its spectrum of activity lends itself to single agent therapy of mixed infections.

   Moxifloxacin shows good activity against methicillin susceptible strains of Staph aureus, gram negatives and anaerobes. As with all quinolones, it has high bioavailability after oral administration.

   Researchers used NCCLS testing methods to determine the in vitro activities of moxifloxacin, ciprofloxacin, levofloxacin, gatifloxacin, imipenem, piperacillin-tazobactam, clindamycin and metronidazole against 900 surgical isolates. Moxifloxacin exhibited good to excellent antimicrobial activity against most aerobic (90.8 percent) and anaerobic (97.1 percent) microorganisms. Moxifloxacin not only showed good activity against methicillin susceptible strains of Staph aureus (MIC90 = 0.25 mg/liter) but also exhibited excellent activity against B. fragilis, equaling that of metronidazole (MIC90 = 1.0 mg/liter). Moxifloxacin showed poor activity against MRSA.4

   Moxifloxacin also does not require dose adjustment for patients with renal impairment. This is an important feature since so many patients with diabetes present with varying degrees of kidney disease. The dose, regardless of renal function, is 400 mg once daily.

Key Considerations With Tigecycline

   • Tigecycline (Tygacyl, Wyeth Pharmaceuticals). Tigecycline, a parenteral minocycline derivative, received FDA approval in June for the treatment of cSSSIs and intraabdominal infections. It is a first-in-class glycylcycline antibiotic. Although it does not have a formal indication for DFIs, tigecycline is of interest because it is a broad spectrum drug with activity against MRSA, gram negatives and anaerobes.

   In clinical trials, empiric monotherapy with tigecycline provided comparable clinical cure rates in cSSSIs to combination therapy with vancomycin/aztreonam. Empiric monotherapy with tigecycline also provided clinical cure rates comparable with those of imipenem/cilastatin.5

   Unfortunately, tigecycline’s potential use as single agent therapy for diabetic foot infections may be offset by its adverse event profile. The most common treatment-emergent adverse events listed in the Manufacturers Prescribing Information were nausea (29.5 percent) and vomiting (19.7 percent).

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