Can Daptomycin Have An Impact With Skin And Skin Structure Infections?
Podiatrists commonly encounter and treat skin and skin-structure infections (SSSIs), ranging from cellulitis to more complicated surgical site infections and infected diabetic foot ulcers. Aerobic gram-positive cocci, such as Staphylococcus aureus and streptococci, are the most common causative agents of skin infections.1
While the treatment of simple and superficial infections is relatively straightforward with brief courses of oral antibiotics, many skin infections of the foot are complicated by diabetes.1,2 Foot ulceration, usually secondary to peripheral neuropathy or peripheral vascular disease, often leads to infection in the diabetic foot.2 Gram-positive aerobic bacteria are the most commonly isolated pathogens as S. aureus constitute almost half of all isolates, according to one study.3 However, chronic wounds and more severe infections are usually polymicrobial and may also involve anaerobes and gram-negative bacilli (see “An Overview Of Common Organisms In Chronic Foot Wounds”).1,2
The increasing prevalence of methicillin-resistant S. aureus (MRSA) infections in both the hospital and community setting is well documented. Bear in mind that MRSA is now involved in almost 60 percent of intensive care unit (ICU) infections in hospitals in the United States.4 Authors of a British study found that MRSA was isolated from 30 percent of outpatients with diabetic foot ulcers during 2001. This was twice the rate of MRSA found in patients three years earlier.3
Vancomycin And MRSA: Why Treatment Alternatives Are Needed
Since the emergence of MRSA in U.S. hospitals during the 1980s, vancomycin has been the standard of care for the majority of infections caused by MRSA. Vancomycin helped fill the clinical need for an agent that could consistently cure the growing number of MRSA infections. However, when it comes to patients receiving vancomycin, one must monitor drug serum peaks and troughs in order to achieve the drug levels required to eradicate MRSA.5 One study of 95 patients, most of whom had MRSA pneumonia or bacteremia, found that those who had reached target serum trough levels were significantly more likely to have positive clinical responses to vancomycin than patients who had serum troughs below target levels.6 However, the study also found significantly more nephrotoxicity (12 percent) in the group of patients who achieved the target trough levels in comparison with the low level group.6
In the last several years, clinicians have detected MRSA isolates with reduced susceptibility and outright resistance to vancomycin after decades of successful clinical application. Although still very rare, the first documented case of vancomycin-resistant S. aureus (VRSA) in the U.S. involved a patient who had a polymicrobial diabetic foot infection in which vancomycin-resistant enterococci (VRE), containing the vancomycin resistance gene vanA, transferred resistance to MRSA.7 In addition, S. aureus strains with reduced susceptibility to vancomycin — so-called vancomycin-intermediate S. aureus (VISA) — also exist and may be linked to clinical failures.8,9
Perhaps of even greater concern are reports that strains of MRSA that appear to be susceptible to vancomycin (based on susceptibility testing (minimum inhibitory concentration [MIC] ≤ 2 µg/mL)) may not actually respond to vancomycin therapy. For example, one study showed that among patients with MRSA bacteremia, those patients who had MIC levels 8
Given that vancomycin can no longer be considered a universally effective drug against MRSA, safe and effective anti-MRSA drugs are needed. However, there are only a few alternatives for patients who cannot tolerate vancomycin or fail vancomycin therapy.
Podiatrists commonly use linezolid (Zyvox, Pfizer) as it is effective against MRSA in complicated SSSIs. However, one may need to limit the duration of therapy due to hematologic adverse events (suppression of blood cell counts).1 Newer options approved for use against MRSA in complicated SSSIs include tigecycline (Tygacil, Wyeth) and daptomycin (Cubicin, Cubist Pharmaceuticals). With this in mind, let us take a closer look at daptomycin.