Study finds daptomycin outperforms vancomycin

Better overall resource use and more rapid resolution

Research conducted at the Detroit Medical Center found that Cubist Pharmaceuticals' daptomycin for injection (Cubicin®) outperformed vancomycin in resolving the signs and symptoms of complicated skin and skin structure infections.

Lead researcher Michael Rybak, PharmD, MPH, professor of pharmacy, adjunct professor of medicine, and director of the anti-infective research laboratory at Wayne State University, tells Drug Formulary Review in a news briefing on his group's research that while daptomycin is significantly more expensive than vancomycin, total treatment costs were comparable between the two drugs because daptomycin works faster than vancomycin.

"Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin," Rybak says of his results, which were published in the December 2007 issue of Pharmacotherapy.

Hospitals have to be concerned about skin and skin structure infections, given that Centers for Disease Control and Prevention data for 2004 showed that such infections were the primary diagnosis in some 562,000 hospital discharges, with an average length of stay of 4.7 days. Bacterial skin diseases cover a wide spectrum of clinical conditions, ranging from local superficial infections to life-threatening aggressive infections. In any event, prompt treatment with an appropriate antibiotic is a key to limiting subsequent complications.

Skin and skin structure infections are most commonly caused by gram-positive organisms, including Staphylococcus aureus and Streptococcus species. "The increasing prevalence of methicillin-resistant S. aureus [MRSA] in the hospital and community complicates treating skin and skin structure infections," Rybak says. "An important concern is that MRSA is associated with a significant increase in cost of care."

For Rybak's study, eligible patients included adults between ages 18 and 85 who were admitted to the hospital with complicated skin and skin structure infections. Patients in the study's treatment arm were required to meet institutional criteria for receiving vancomycin, including established risk factors for MRSA. Matched controls (4:1 match) were selected from all patients with complicated skin and skin structure infections treated with vancomycin identified at a concurrent period of time in which data were available in medical records for all necessary clinical evaluations.

Treatment population

Of the 56 patients who were enrolled to receive daptomycin in the treatment arm, three were ultimately found to be not evaluable. So the research evaluated 53 patients who received daptomycin and 212 patients treated with vancomycin. "There were no significant differences noted in age, sex, severity of illness, comorbidities, or type of infection between the two groups," Rybak says. However, a significantly higher proportion of patients who received vancomycin was admitted to a surgical service and had a history of antibiotic use or hospitalization.

While all patients in both groups achieved clinical success by the end of therapy, a significantly higher proportion of patients who were treated with daptomycin achieved clinical success by days 3 and 5. Thus, according to Rybak, 90% of daptomycin patients showed clinical success at day 3 and 98% at day 5, compared with 75% of vancomycin patients at day 3 and 81% at day 5. And a significantly greater proportion of patients receiving daptomycin achieved clinical cure at the end of inpatient antimicrobial therapy (77% of daptomycin patients vs. 42% of vancomycin patients).

While the cost of antistaphylococcal therapy was greater by itself in patients treated with daptomycin than in those treated with vancomycin, because the cost to hospitals of branded daptomycin is much higher than the cost of generic vancomycin, the total cost of hospitalization still was reduced in the daptomycin group.

Overall resource use better with daptomycin

"Although no benefit in end-of-therapy mortality was seen," Rybak says, "overall resource utilization was reduced approximately $2,500 in patients treated with daptomycin, likely because of the shorter duration of intravenous antibacterial agents required for treatment. Despite the higher costs of daptomycin when comparing intravenous antistaphylococcal therapy alone, the cost between groups was similar when other inpatient antimicrobial agents were included in the analysis."

One explanation was the high cost of oral agents, often linezolid (Pfizer's Zyvox®), in patients who were initially treated with vancomycin and then transitioned to linezolid. "When considering total cost of hospitalization, treatment with daptomycin appears to be a cost-effective alternative," Rybak says. "One important limitation of this analysis was our inability to control for a higher prevalence of S. aureus and MRSA in patients receiving vancomycin, and it has been reported that patients with MRSA tend to have a longer length of stay than patients with methicillin-susceptible S. aureus."

Rybak says that while he would not say to hospitals that daptomycin should be considered the primary drug to be used in such cases, he believes hospitals should always consider it as an option.

Asked about the issue of antibiotic resistance, Rybak tells Drug Formulary Review it "can be a particular concern when one agent such as vancomycin has been relied upon for a long time. Vancomycin has been clinically available for close to 50 years and susceptibility to it has been significantly changing in the last 10-20 years. There have been some reports of resistance to daptomycin, and other alternative agents to vancomycin, but so far these cases have been infrequent. Resistance to daptomycin could increase in the future, but we now have several drugs for treating MRSA and don't have to rely on just one. This should ease the burden in relying only on vancomycin as our primary treatment for MRSA."

Rybak says physicians need to look at each patient individually in determining which drug to use, including each drug's safety profile, implications for possible drug interactions, and overall compatibility with each patient. "We need to use serious drugs to treat serious infections especially with a pathogen as problematic as MRSA," he concludes.

[Editor's note: Contact Dr. Rybak at m.rybak@wayne.edu.]