Clinical efficacy of oral linezolid compared with intravenous vancomycin for the treatment of methicillin-resistant Staphylococcus aureus-complicated skin and soft tissue infections: a retrospective, propensity score-matched, case-control analysis.
ABSTRACT Linezolid is 100% bioavailable in oral and intravenous formulations. In a recent prospective, randomized, open-label, comparator-controlled, multicenter, phase 4 clinical trial in adults with complicated skin and soft tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA), linezolid achieved clinical and microbiologic success comparable to appropriately dosed intravenous vancomycin. Although patients were randomly assigned to receive linezolid or vancomycin, the protocol allowed patients to start therapy using oral or intravenous linezolid on the basis of investigator discretion and patient ability to tolerate oral medication.
The objective of this study was to assess the efficacy and tolerability of linezolid when administered orally in adults with cSSTI caused by MRSA. In this retrospective analysis, we examined data collected from the aforementioned trial to compare outcomes in patients who received either oral linezolid or intravenous vancomycin therapy.
This study analyzed outcomes in patients who received treatment for 7 to 14 days with either oral linezolid (600 mg q12h; n = 95) or intravenous vancomycin (15 mg/kg q12h, adjusted for creatinine clearance and trough concentration; n = 210). By design, these groups were not randomized. Propensity score matching on baseline variables was used to balance these groups by identifying a comparable group of patients who received vancomycin therapy and comparing them with patients who received oral linezolid therapy. Clinical and microbiologic success rates at the end of treatment and the end of the study (EOS) were then directly compared between the groups using matched-pair logistic regression. The tolerability of the 2 treatments (within this matched group) was also described.
Ninety-two patients with well-matched baseline characteristics were included in each treatment group. At EOS, the odds ratio for clinical success of oral linezolid therapy vs intravenous vancomycin therapy was 4.0 (95% CI, 1.3-12.0; P = 0.01), and the odds ratio for microbiologic success at EOS was 2.7 (95% CI, 1.2-5.7; P = 0.01). Overall rates of adverse events in each group were consistent with reported safety profiles for each drug.
A favorable clinical cure rate was achieved with oral linezolid therapy when compared with intravenous vancomycin therapy in propensity score-matched patients with cSSTI proved to be caused by MRSA. ClinicalTrials.gov Identifier: NCT00087490.
- SourceAvailable from: Norio OhmagariJournal of Infection and Chemotherapy 05/2013; · 1.55 Impact Factor
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ABSTRACT: Complicated skin and soft tissue infections (cSSTIs) are a diverse group of infections, with a range of presentations and microbiological causes. Hospitalization is common for patients with a cSSTI, which is treated by drainage of the affected area and with antibiotics. Host factors such as co-morbidities, and microbial factors, in particular drug resistance, complicate the management of these infections. Methicillin-resistant Staphylococcus aureus (MRSA) is an important cSSTI pathogen in Europe, and its involvement can be associated with poor patient outcomes. European guidelines recommend vancomycin, teicoplanin, linezolid, daptomycin, tigecycline or ceftaroline for treatment of MRSA cSSTIs. Of primary importance when treating cSSTIs is the agent's clinical efficacy against the causative pathogens, as well as its bioavailability in the skin and associated structures. Linezolid is well-suited for the treatment of MRSA cSSTIs; it achieves high penetration into skin and soft tissues with 100% oral bioavailability, and therefore enables an intravenous to oral switch and outpatient treatment. When eligible patients are offered oral therapy the associated length of hospital stay and overall costs can be reduced. Linezolid has demonstrated clinical efficacy and favourable outcomes in patients for the treatment of MRSA cSSTIs including the treatment of lower extremity infections. Furthermore, efficacy has been documented in key defined populations, such as individuals with renal impairment and the obese. The safety profile of linezolid is well-documented, making this antibacterial a viable choice for the treatment of MRSA cSSTIs.Clinical Microbiology and Infection 04/2014; 20 Suppl 4:3-18. · 4.58 Impact Factor
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ABSTRACT: Acute bacterial skin and skin structure infection (ABSSSI) is a common and significant indication for antibiotic treatment. The microbial aetiology is becoming more resistant to available antibiotics and the treatment of patients is additionally challenged by extremes of age, obesity, diabetes and other co-morbidities. This review examines recent antimicrobial developments. In many parts of the world, multidrug-resistant (MDR) staphylococci are the predominant cause of ABSSSI in both the community and in hospital. Increasing resistance in Gram-negative organisms presents problems in the management of surgical-site infections. Most new antibiotics have been developed to treat MDR Gram-positive bacteria and there are few agents to treat infections caused by MDR Gram-negative pathogens. A number of novel agents are available clinically, with other agents of related chemical structure under development. There are no entirely new classes of antibiotics. Maintaining the efficacy of antimicrobial treatment require effective antibiotic stewardship, good infection prevention and the development of further new antibiotics.Current Opinion in Infectious Diseases 02/2014; · 4.87 Impact Factor