A Guide To Emerging Antibiotics For Diabetic Foot Infections
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).
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