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

   Although there have been no human trials involving osteomyelitis, animal studies suggest tigecycline may have a role in treating bone infection. After a 28-day course of treatment of experimentally induced osteomyelitis, rabbits receiving tigecycline/oral rifampicin showed a 100 percent infection clearance. Subjects treated with vancomycin/oral rifampicin showed a 90 percent clearance. For the tigecycline group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. Tigecycline, at least in preliminary studies, shows promise as an effective alternative to vancomycin in the treatment of MRSA osteomyelitis. It remains to be seen if these results will carry over to human subjects.6

Assessing The Potential Of Daptomycin And Dalbavancin

   • Daptomycin (Cubicin®, Cubist Pharmaceuticals). Daptomycin is a novel, parenteral lipopeptide and the first drug in its class in clinical use. It is the only once-daily agent approved for treating MRSA in cSSSIs.

   Daptomycin is bactericidal and has activity against resistant gram-positive pathogens including methicillin resistant and vancomycin resistant (VRSA) strains of S. aureus.7

   Lipsky and Stoutenburgh conducted a study comparing the effectiveness of daptomycin against semi-synthetic penicillins or vancomycin. The authors concluded that among 103 clinically evaluable patients, the clinical and microbiological efficacy and safety of daptomycin was not statistically different from comparator antibiotics (66 percent versus 70 percent respectively) for treating infected diabetic foot ulcers caused by gram-positive pathogens.8

   Although one should consider daptomycin for treating diabetic foot infections, its lack of gram-negative and anaerobic activity may necessitate combination therapy for moderate and severe diabetic foot infections when these organisms are a concern.

   • Dalbavancin (Vicuron Pharmaceuticals/Pfizer). Dalbavancin is a novel, parenteral liopoglycopeptide antibiotic with strong activity against gram-positive organisms including resistant staphylococci (MRSA). Its long half-life allows for once-a-week dosing. Still awaiting FDA new drug approval for the treatment of cSSSIs, dalbavancin should become available in early 2006. As with daptomycin, combination therapy with an agent active against gram-negatives and anaerobes may be necessary in moderate to severe diabetic foot infections.

   Telavancin, another antibiotic of the same class, has a similar spectrum of activity but with once daily rather than once weekly dosing.

In Conclusion

   Many other new agents are in the pipeline and will be available in the coming years. Although currently available cephalosporins have no activity against MRSA, one agent under study is ceftobiprole. It is the first of a new class of broad-spectrum cephalosporins with bactericidal activity against gram-positive resistant bacteria including MRSA. Its gram-negative coverage is similar to that of third-generation cephalosporins. Trials are currently ongoing in patients with cSSSIs as well as nosocomial pneumonia.9

Dr. Kosinski is a Professor in the Department of Medicine at the New York College of Podiatric Medicine. He is a member of the Infectious Diseases Society of America.

Dr. Joseph is a Consultant in lower extremity infectious diseases and is a Fellow of the Infectious Diseases Society of America. He is an Attending Podiatrist at the Coatesville Veterans Affairs Medical Center in Coatesville, Pa.

Dr. Steinberg (pictured) is an Assistant Professor in the Department of Surgery at the Georgetown University School of Medicine in Washington, D.C. He is a Fellow of the American College of Foot and Ankle Surgeons.


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