Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be due to meticillin-resistant Staphylococcus aureus
Abstract number: O80
Itani K., Weigelt J., Stevens D., Dryden M., Bhattacharyya H., Kunkel M., Baruch A.
Objectives: Linezolid (LZD) is an oxazolidinone antibiotic used to treat infections caused by Gram-positive pathogens, including MRSA. A randomised, open-label, controlled, multicentre phase 4 study was conducted comparing LZD to vancomycin (VAN) in the treatment of complicated skin and soft-tissue infections (cSSTI) proven due to MRSA.
Methods: Subjects 18 years with defined, proven MRSA cSSTI were randomised to receive either LZD (600 mg IV/PO q12h) or VAN (15 mg/kg IV q12h, adjusted for CLCR) for 714 d. Aztreonam and metronidazole coverage were permitted. The primary efficacy endpoint was clinical outcome at end of study (EOS; 710 d after the last dose) in subjects with MRSA who met inclusion/exclusion criteria (per protocol [PP] population). Secondary endpoints included clinical outcome at end of therapy (EOT) and microbiological outcome at EOS and EOT as well as analyses based on the modified intent-to-treat (mITT) population. Noninferiority was assessed by a 2-sided 95% confidence interval (CI) for the difference in the success rate at EOS (delta = 10%).
Results: Subjects included 537 randomised to LZD and 515 to VAN, for a total of 1052. There were 481 with abscess (243 LZD, 238 VAN), 234 with surgical wound infection (111 LZD, 123 VAN), 106 with diabetic ulcer (61 LZD, 45 VAN), and 231 with other cSSTI (122 LZD, 109 VAN). 452 subjects were in the PP population (235 LZD, 217 VAN) and 654 in the mITT group (329 LZD, 325 VAN). Success at EOS was comparable between the 2 groups (193 LZD [83.2%] 171 VAN [79.5%]; P = 0.321; 95% CI [-0.036, 0.109]) demonstrating that LZD was noninferior to VAN (Table). For microbiological success, treatment groups were comparable at EOS. At EOT, there was a statistically significant difference between LZD and VAN (211 LZD [85.8%]; 158 VAN [69.3%]; P = 0.000; 95% CI [0.091, 0.239]). Overall, in the ITT population, the mean treatment durations were comparable for the groups, with 8.8 d for LZD subjects and 7.6 d for VAN subjects. PP mean IV treatment lasted 5.4 d (LZD) and 10.3 d (VAN). The 3 most common drug-related adverse events were gastrointestinal (65 LZD [12.1%], 23 VAN [4.5%]), infection/infestation (26 LZD [4.8%], 10 VAN [1.9%]), and skin/subcutaneous tissue disorder (10 LZD [1.9], 35 VAN [6.8%]). There were 18 deaths: 11 LZD (2.0%), 7 VAN (1.4%), and 1 VAN considered study drug-related.
Conclusion: LZD was at least as effective as VAN for the treatment of proven MRSA cSSTI, and was well-tolerated.
Table. Clinical and microbiological response in the per protocol (PP) population
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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