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

• Published in: Clinical therapeutics 2012-08, Vol.34 (8), p.1667-1673.e1
• Main Authors: Itani, Kamal M.F., MD, Biswas, Pinaki, PhD, Reisman, Arlene, MPH, Bhattacharyya, Helen, PhD, Baruch, Alice M., MD, PhD
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - adverse effects; Administration, Oral; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Biological and medical sciences; Clinical Trials, Phase IV as Topic; complicated skin and soft tissue infections; Drug therapy; Female; Humans; Hypotheses; Infusions, Intravenous; Internal Medicine; Linezolid; Logistic Models; Male; Medical Education; Medical sciences; methicillin-resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Middle Aged; Multicenter Studies as Topic; Odds Ratio; Oxazolidinones - administration & dosage; Oxazolidinones - adverse effects; Pharmacology. Drug treatments; Propensity Score; Randomized Controlled Trials as Topic; Retrospective Studies; Soft Tissue Infections - drug therapy; Soft Tissue Infections - microbiology; Staphylococcal Skin Infections - drug therapy; Staphylococcal Skin Infections - microbiology; Staphylococcus infections; Statistical methods; Studies; Success; Treatment Outcome; vancomycin; Vancomycin - administration & dosage; Vancomycin - adverse effects
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2012.06.018

Abstract Background 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. Objective 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. Methods 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. Results 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. Conclusion 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