Elsevier

Clinical Therapeutics

Volume 34, Issue 7, July 2012, Pages 1521-1527
Clinical Therapeutics

Pharmacotherapy
Brief report
Daptomycin Compared to Vancomycin for the Treatment of Osteomyelitis: A Single-Center, Retrospective Cohort Study

https://doi.org/10.1016/j.clinthera.2012.06.013Get rights and content

Abstract

Background

Osteomyelitis (OM) is a serious infection with high rates of recurrence. Vancomycin has been used for decades in the treatment of OM, but, despite adequate dosing, 30% to 50% of patients experience infection recurrence within 12 months. Daptomycin, a novel lipopetide antibiotic, is also active against resistant gram-positive organisms, but there is little published about its efficacy and tolerability in the treatment of OM.

Objective

Our aim was to compare the recurrence rates of OM in patients treated with daptomycin or vancomycin.

Methods

A retrospective cohort study of all patients at a VA Medical Center between January 1, 2003, and July 31, 2009, who received daptomycin for the treatment of OM was undertaken. Patients with a diagnosis of OM who received at least 2 weeks of daptomycin and had at least 1 follow-up visit within 6 months after completion of therapy were included. Each patient was matched with 2 controls treated with at least 2 weeks of vancomycin for OM. Matching criteria included previous OM, diabetes, peripheral vascular disease, hardware involvement, and surgical therapy. Patients were excluded from the evaluation if they received <14 days of therapy, had no follow-up in the 6 months after therapy was discontinued, had an absolute neutrophil count <500 cells/mm3, or were receiving vancomycin and daptomycin concurrently. The primary outcome was recurrence of infection within 6 months after the discontinuation of therapy. Secondary outcomes included mean change in creatine phosphokinase (CPK), incident thrombocytopenia, and mean doses of antibiotics. The χ2 test was used to compare rates of recurrence between groups.

Results

Seventeen patients received at least 2 weeks of daptomycin for the treatment of OM and were matched to 34 vancomycin controls. Twenty-nine percent of patients receiving daptomycin had a recurrence of infection compared with 61.7% in the vancomycin group (P = 0.029). The mean change in CPK for the daptomycin group was +28.8 U/L. No thrombocytopenia developed in any patients receiving daptomycin compared with 2 (5.9%) patients in the vancomycin group.

Conclusions

In a limited number of cases, significantly fewer patients treated with daptomycin for OM had a recurrence of their infection. Daptomycin may be a tolerable and effective alternative to vancomycin for the treatment of OM.

Introduction

Osteomyelitis (OM) is a serious infection associated with significant morbidity and high rates of recurrence. Early and aggressive management of the disease seems to be associated with the best outcomes. Currently, the Infectious Diseases Society of America recommends most bone infectious be treated with 4 to 6 weeks of intravenous antibiotics with or without surgical intervention.1 Gram-positive organisms remain the predominant pathogens in cases of OM, with Staphylococcus aureus being identified most often.2

Given the prevalence of methicillin-resistant S. aureus (MRSA) in today's health-care setting and in the community, empiric therapy with vancomycin, along with other broad-spectrum antibiotics, has become the standard of care for the treatment of OM. However, even when a broad-spectrum regimen including vancomycin is initiated, rates of recurrence of OM have been found to be as high as 30% to 50% within 12 months of completing therapy.2, 3 Vancomycin also requires close monitoring of serum trough concentrations and renal function to ensure efficacy and avoid adverse effects, which can be challenging when patients are outside of a controlled health-care setting. In addition to high rates of failure with vancomycin-based regimens and logistical problems associated with monitoring concentrations, practitioners must now contend with MRSA isolates that are expressing increased minimum inhibitory concentrations (MICs) to vancomycin.2, 3, 4, 5 With the potential decrease in efficacy, high rates of recurrence, and monitoring burden with vancomycin, there is a great need to investigate the efficacy and safety of other gram-positive active agents for the treatment of OM.

Daptomycin is a cyclic lipopeptide antibiotic with activity against many commonly encountered gram-positive pathogens, including MRSA and vancomycin-resistant Enterococcus (VRE).2, 6 Daptomycin is rapidly bactericidal and associated with relatively few side effects; increases in patients' creatine phosphokinase (CPK) and some associated muscle damage have been the most serious observed.2, 6, 7 Daptomycin is approved by the US Food and Drug Administration (FDA) for the treatment of complicated skin and skin-structure infections at a dose of 4 mg/kg IV daily, and bacteremias and right-sided infective endocarditis caused by S. aureus (including MRSA) at a dose of 6 mg/kg IV daily. Although not FDA approved, doses of 8 to 10 mg/kg IV daily have been used to treat various infections and have been fairly well tolerated.8 Daptomycin's broad spectrum of activity against many resistant gram-positive pathogens, rapid bactericidal action, and favorable safety profile make it an attractive option for the treatment of OM, but when PubMed is searched for comparative studies of daptomycin and vancomycin, few data are available. This investigation set out to compare rates of recurrence of infection between daptomycin and vancomycin for the treatment of OM.

Section snippets

Methods

A retrospective cohort study of patients treated with daptomycin for OM was undertaken. All patients at the St. Louis VA Medical Center who had received at least 14 days daptomycin for the treatment of OM between January 1, 2003, and July 31, 2009, were identified. Patients were first identified by searching pharmacy records for all individuals who had received daptomycin between January 2003 and July 2009. Each record was then searched to determine whether the patient received daptomycin for

Patients

From January 1, 2003, to July 31, 2009, 17 patients treated with daptomycin for OM at the St. Louis VA Medical Center met inclusion criteria. These patients were matched with 34 others who received vancomycin for the treatment of OM; all patients identified were male. Table I outlines the pertinent characteristics of all patients included. Fifty-three percent of patients previously had OM, 58% had diabetes, 18% had received a diagnosis of PVD, and 64.7% also had surgery as part of their

Discussion

In this retrospective analysis of 17 patients treated with daptomycin for OM compared with matched control subjects treated with vancomycin, significantly fewer patients treated with daptomycin had a recurrence of infection within 6 months of stopping therapy (29% vs 61.7%, P = 0.029). When results were evaluated by specific patient characteristics (patients receiving surgical management in addition to antibiotics, patients with a first occurrence of OM, and those with previous occurrences of

Conclusions

Overall, in this small, retrospective analysis comparing daptomycin and vancomycin for the treatment of OM, daptomycin-treated patients tolerated therapy well and had an overall lower rate of recurrence of infection than vancomycin-treated patients. Based on what was observed in this study, the development of larger, prospective investigations of the role of daptomycin as a treatment for OM is prudent. Future investigations should evaluate the potential importance and effect of dosing of

Conflicts of Interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

Acknowledgments

This paper was presented in poster format at the 2010 Infectious Diseases Society of America Annual Meeting in Vancouver, BC, Canada, October 23, 2010. All authors contributed equally to the literature search, data interpretation, figure creation, and writing of the manuscript.

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