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)
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.
References (27)
- et al.
Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). SENTRY Study Group (North America)
Diagn Microbiol Infect Dis
(1999) - et al.
Hospital resource use and cost of treatment with linezolid versus teicoplanin for treatment of serious gram-positive bacterial infections among hospitalized patients from South America and Mexico: results from a multicenter trial
Clin Ther
(2003) - et al.
Economic impact of oral ciprofloxacin following standard intravenous therapy
Diagn Microbiol Infect Dis
(1990) - et al.
Clinical and economic evaluation of oral ciprofloxacin after an abbreviated course of intravenous antibiotics
Am J Med
(1991) - et al.
Cost analysis of switching from i.v. vancomycin to p.o. linezolid for the management of methicillin-resistant Staphylococcus species
Clin Ther
(2003) Clinical trial results with linezolid, an oxazolidinone, in the treatment of soft tissue and postoperative gram-positive infections
Surg Infect (Larchmt)
(2001)Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: emerging problems and new prospects for management
Ann Acad Med Singapore
(2001)Staphylococcus aureus: a well-armed pathogen
Clin Infect Dis
(1998)- et al.
Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999
Clin Infect Dis
(2001) Costs of treating infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci
J Antimicrob Chemother
(1999)
Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection
Clin Infect Dis
Comparison of length of hospital stay for patients with known or suspected methicillin-resistant Staphylococcus species infections treated with linezolid or vancomycin: a randomized, multicenter trial
Pharmacotherapy
The economic impact of Staphylococcus aureus infection in New York City hospitals
Emerg Infect Dis
Cited by (112)
Staphylococcal Skin and Soft Tissue Infections
2021, Infectious Disease Clinics of North AmericaLinezolid versus vancomycin cost in the treatment of staphylococcal pneumonia
2020, Medecine et Maladies InfectieusesBacteriological relevance of linezolid vs. vancomycin in postoperative empirical treatment of osteoarticular infections: a retrospective single-center study
2018, International Journal of Antimicrobial AgentsManaging skin and soft-tissue infection and nosocomial pneumonia caused by MRSA: A 2014 follow-up survey
2015, International Journal of Antimicrobial Agents