Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA)

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Abstract

We compared the health outcomes in patients treated with linezolid or vancomycin for complicated skin and soft tissue infections (cSSTIs). This analysis is part of a randomised, open-label, multinational trial involving 1200 adult patients hospitalised with cSSTIs due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Subjects received linezolid 600 mg intravenous (i.v.) or oral, or vancomycin 1 g i.v. every 12 h. A test-of-cure was assessed at 7 days post therapy. Compared with vancomycin, linezolid treatment was associated with significantly shorter length of stay (all P < 0.01), decreased i.v. antibiotic treatment duration (all P < 0.0001) and higher discharge rates (all P < 0.05). Thus, linezolid has the potential to reduce medical resource use for the treatment of cSSTIs.

Introduction

Skin and soft tissue infections (SSTIs), which include cellulitis, abscesses, and diabetic foot and surgical site infections, are frequently caused by Staphylococcus aureus [1]. Whilst superficial infections can be treated with local care with or without antibiotics, complicated SSTIs (cSSTIs) require hospitalisation, treatment with intravenous (i.v.) antibiotics and surgical intervention [2]. Routine treatment of cSSTIs due to Gram-positive pathogens is complicated by a rising prevalence of methicillin-resistant S. aureus (MRSA). There is also a concern regarding the emergence of strains of enterococci resistant to vancomycin [3], the traditional first-line therapy against MRSA [4], [5].

Antibiotic resistance increases the length of stay (LOS) in hospital, costs of treatment and mortality [3], [6], [7], [8], [9]. In a recent US study, patients with surgical sites infected with MRSA were hospitalised for 5 days longer and had a three times greater 90-day mortality rate than patients infected with methicillin-sensitive S. aureus (MSSA). Hospital charges for these MRSA patients were 1.19-fold greater than for patients with MSSA [7].

Linezolid is the first member of a new synthetic class of antibiotics, the oxazolidinones. This antibiotic class offers a wide spectrum of activity against most clinically significant Gram-positive bacteria without displaying cross-resistance with other classes of antimicrobial agents. Linezolid is approved for treatment of MRSA [8], [10], [11], [12]. An important characteristic of linezolid is its 100% oral bioavailability, which distinguishes it from vancomycin. Thus, patients treated with linezolid for cSSTIs can take a full course of oral therapy or can be switched from i.v. to oral dosing, potentially allowing earlier hospital discharge without the need for i.v. administration. Our earlier preliminary data suggested that linezolid therapy offers favourable health economic outcomes compared with conventional treatments in patients hospitalised due to infections caused by MRSA [8], [13], [14]. However, there is a lack of trials studying a large sample of patients with culture-confirmed MRSA cSSTIs in order to draw more definitive conclusions.

The present study was part of the largest multinational trial comparing the clinical efficacy, safety and health outcomes of linezolid with vancomycin for the treatment of cSSTI. The efficacy and safety data were published elsewhere [12]. The present analysis compared the health outcomes of patients hospitalised for cSSTIs due to suspected or proven MRSA treated with linezolid or vancomycin. In addition, two other outcomes research endpoints, namely weekly discharges and duration of i.v. antibiotic treatment, were compared between the two treatment arms. Re-admission during the 35-day study period and its influence on LOS were also assessed.

Section snippets

Study design

This was a multinational, multicentre, randomised, open-label, comparator-controlled clinical study conducted between October 2003 and March 2003. A detailed description of the trial has been published elsewhere [12]. A total of 1200 hospitalised patients with cSSTIs due to suspected or proven MRSA were enrolled. Entry criteria included suspected or proven MRSA infection that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers or burns (<10%

Results

Baseline patient demographic and clinical characteristics were comparable between the linezolid and the vancomycin groups. Treatment groups were similar with regard to age, race, gender, geographic region, type of cSSTI and pathogen frequency. In no case were the differences between the two treatment groups statistically significant (all P > 0.05; Table 1).

Kaplan–Meier analyses of the initial LOS showed that patients receiving linezolid had a shorter LOS than those receiving vancomycin (all P < 

Discussion

The prevalence of antibiotic resistance is increasing in many countries [16]. Particularly alarming is the emergence of Gram-positive organisms resistant to glycopeptides, traditionally the last line of defence against infections with these organisms. Vancomycin and teicoplanin are traditionally considered the drugs of choice for MRSA infections. However, the narrow therapeutic index for vancomycin limits its use as an option to boost plasma concentrations by increasing dosage without incurring

Acknowledgments

This study was supported financially by Pfizer Inc. J. Weigelt is a member of the Linezolid Global Advisory Board. J. Weigelt and K.M.F. Itani have conducted research on behalf of Pfizer and have been on the Pfizer speakers bureau. J.Z. Li and S. Duttagupta are employees of Pfizer Inc.

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