Early use of Daptomycin Compared to Vancomycin for MRSA Bacteremia

By Richard R. Watkins, MD, MS, FACP, Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH. Dr. Watkins reports no financial relationships in this field of study.

This article originally appeared in the July 2013 issue of Infectious Disease Alert. It was edited by Stan Deresinski, MD, FACP, FIDSA, and peer reviewed by Timothy Jenkins, MD. Dr. Deresinki is Clinical Professor of Medicine, Stanford University, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, and Dr. Jenkins is Assistant Professor of Medicine, University of Colorado, Denver Health Medical Center. Dr. Deresinski does research for the National Institutes of Health, and is an advisory board member and consultant for Merck, and Dr. Jenkins reports no financial relationships relevant to this field of study.

SYNOPSIS: In a matched, retrospective cohort study, early use of daptomycin compared to vancomycin in MRSA bacteremia with vancomycin MICs > 1 µg/mL resulted in improved clinical outcomes, including less clinical failure at 30 days, lower mortality and less persistent bacteremia.

SOURCE: Murray KP, et al. Early Use of Daptomycin Versus Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia with Vancomycin Minimum Inhibitory Concentration > 1 mg/L: A Matched Cohort Study. Clin Infect Dis 2013; 56:1562-1569

Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) is a frequently-encountered infection that can lead to a number of serious complications, such as infective endocarditis, septic arthritis, and vertebral osteomyelitis. This has led to the increased use of vancomycin, followed by a corresponding increase in MRSA strains with vancomycin minimum inhibitory concentrations (MICs) > 1 µg/mL. Data suggest MRSA isolates with higher vancomycin MICs are associated with worse clinical outcomes, although current clinical guidelines from the Infectious Diseases Society of America do not recommend the early use of alternative therapy.1 A recent case-control study showed a mortality benefit in patients switched to daptomycin after failing vancomycin.2 Murray and colleagues sought to compare clinical outcomes in patients with MRSAB and vancomycin MICs > 1 µg/mL who were switched to daptomycin within 72 hours after starting vancomycin therapy.

The investigators conducted a retrospective, matched cohort study on patients with MRSAB treated with vancomycin or daptomycin at four hospitals within the Detroit Medical Center between January 2005 and March 2012. Starting in February 2008, one of the centers implemented a treatment guideline that required the use of daptomycin if the vancomycin MIC was between 1/µg/mL and 2 µg/mL. Included patients were adults with an MRSA bloodstream isolate with an initial vancomycin MIC > 1 µg/mL who received vancomycin or daptomycin for at least 72 hours. Exclusion criteria were if pneumonia or an intravenous catheter was the source of bacteremia, dialysis for acute or chronic renal failure, or if an alternative MRSA therapy was used for ≥ 72 hours prior to starting daptomycin or vancomycin.

Among 1863 consecutive cases of MRSAB with a vancomycin MIC > 1µg/mL, 85 daptomycin-treated patients were matched to 85 vancomycin-treated patients. There was no significant difference in median length of ICU stay (7 days in the daptomycin group vs. 5 days in the vancomycin group; P = .824). The median duration of vancomycin therapy prior to daptomycin was 1.7 days and the median daptomycin dose was 8.4 mg/kg. In the crude analysis, treatment with daptomycin was associated with significantly less clinical failure at 30 days than vancomycin (20.0% vs. 48.2%; P < .001). In multivariate logistic regression analysis, vancomycin was associated with significantly higher risk of clinical failure at 30 days (adjusted odds ratio, 4.5). Furthermore, patients in the daptomycin group had lower mortality compared to those who received vancomycin (3.5% vs 12.9%; P = .047), less persistent bacteremia (18.8% vs. 42.4%; P = .001), and shorter duration of bacteremia (3 days vs. 5 days; P = .003). Length of stay and duration of therapy was not significantly different between the two groups. Average hospital charges were higher in the daptomycin group ($95,244 vs. $86,504; P = .643). In the vancomycin group, 25.9% of patients experienced nephrotoxicity, with the median vancomycin trough 18.1 µg/mL. However, many of them were also receiving an aminoglycoside. One patient in the daptomycin group had a significant elevation in serum CPK concentration but it was not associated with any symptoms and promptly returned to normal after the daptomycin was switched to vancomycin.

Commentary

The results of this study strongly suggest a benefit from using daptomycin instead of vancomycin early in the course of MRSAB when the vancomycin MIC is > 1µg/mL. However, a few words of caution are necessary. First, the average dosage of daptomycin (8.4 mg/kg per day) was higher than is often used in clinical practice, although this did not result in increased toxicities. One interpretation of this finding is perhaps the FDA-approved dose of 6 mg/kg per day is too low for some MRSABs. Second, this was a retrospective study and the results may have been influenced by missed cases, selection bias and/or other unknown variables. Third, patients with intravenous catheter-associated MRSABs (one of the most common clinical etiologies for the condition) were excluded from the study. As noted in an accompanying editorial, patients with renal failure were excluded and there is some evidence that daptomycin is less effective in this population.3 Another concern about the early switch to daptomycin is cost. Changing from vancomycin to daptomycin increased medication charges by an average of $11,000 per patient. Likewise, hospital charges were also higher in the daptomycin group (approximately $9,000 more per patient) despite the improved clinical parameters.

How do the results of this study affect clinical practice? Ideally a multicenter, prospective study that includes a broad range of patients and conditions (i.e., central-line related bacteremias, dialysis patients) should be conducted to give clinicians better insight into which patients would most benefit from an early switch to daptomycin. However, until such a study is performed it is unlikely that current practice guidelines will be modified. Nonetheless, there seems to be little downside (except cost) and increasing data based on this study and others that early daptomycin is beneficial for many patients with MRSAB. Additional pharmacoeconomic analyses that take into account the impact of daptomycin vs. other agents on length of stay and readmission rates would also be welcome.

References

  1. Liu C, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52:285-292.
  2. Moore CL, et al. Daptomycin versus vancomycin for bloodstream infections due to methicillin-resistant Staphylococcus aureus with a high vancomycin minimum inhibitory concentration: a case-control study. Clin Infect Dis 2012; 54:51-58.
  3. Weston A, et al. Early high-dose daptomycin for methicillin-resistant Staphylococcus aureus bloodstream infections with elevated vancomycin minimum inhibitory concentrations: ready for prime time? Clin Infect Dis 2013; 56:1570-1572