1185. Report of Linezolid Activity from the Linezolid Experience and Accurate Determination of Resistance (LEADER) Program for 2014: Monitoring Resistance Trends and Mechanisms
Session: Poster Abstract Session: Resistance Mechanisms
Friday, October 9, 2015
Room: Poster Hall
  • IDWeek15 LEADER 1185.pdf (173.6 kB)
  • Background: Linezolid (LZD) was the first oxazolidinone approved (2000) in the USA and is indicated for the treatment of complicated skin and skin structure infection and nosocomial pneumonia. It is active against Gram-positive (GP) organisms such as MRSA, drug-R S. pneumoniae and vancomycin-R enterococci that are resistant (R) to conventional drugs. The LEADER Program has monitored LZD activity, spectrum and R rates since 2004.

    Methods: A total of 6,865 GP pathogens from 60 medical centers from 36 states were submitted.  The organism groups (no.overall) were: S. aureus (SA; 3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (ENT; 855), S. pneumoniae (SPN; 874), viridans group (VGS; 359), and β-hemolytic streptococci (BHS; 874). All susceptibility (S) testing was performed by reference broth microdilution methods. LZD-R isolates were confirmed by Etest (bioMerieux, Hazelwood, MO) and by repeated reference S testing. PCR and sequencing was performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins, and an acquired gene (cfr).


    LZD activity against GP organisms remains high (99.78% S). The MIC50/90 for SA was at 1/1 μg/ml. MRSA rates were at 47.2% (47.9% in 2013; declining since 2007 [58.2%]).  Among the LZD-non-S (NS) MRSA, one strain harbored cfr only (MIC, 4 µg/ml), one harbored G2576T (MIC, 8 µg/ml) and one contained cfr and G2576T with L3 changes (MIC, ≥8 µg/ml).  Among CoNS, six isolates, 0.75% of all strains (0.52% in 2013, 0.92% in 2012) demonstrated LZD MIC results of ≥4 μg/ml. Five of these were identified as S. epidermidis; 4 of which contained cfr in addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six ENT (0.7%) were LZD-NS (≥4 μg/ml; G2576T mutations and one with an additional cfr). LZD was active against all SPN and BHS with a MIC50/90 of 1/1, μg/ml and VGS with an MIC50/90of 0.5/1 μg/ml. SPN penicillin NS (MIC, ≥0.12 μg/ml) occurred at a rate of 41.5% and NS ceftriaxone at 7.2%.

    Conclusion: LZD demonstrates excellent activity and a sustained susceptibility rate of 99.78% overall (99.62-99.83% during 2008-2013 LEADER Program). LZD MIC population distributions remained unchanged without evidence of “MIC creep” among monitored, indicated species.

    Jennifer M. Streit, BS1, Robert K. Flamm, PhD1, James E. Ross, MBA1, Rodrigo E. Mendes, PhD1, Ronald N. Jones, MD1 and Patricia a. Hogan, MBA2, (1)JMI Laboratories, Inc., North Liberty, IA, (2)Pfizer Inc., Collegeville, PA


    J. M. Streit, Pfizer: Research Contractor , Research support

    R. K. Flamm, Pfizer: Research Contractor , Research support

    J. E. Ross, Pfizer: Research Contractor , Research support

    R. E. Mendes, Pfizer: Research Contractor , Research support

    R. N. Jones, Pfizer: Research Contractor , Research support

    P. A. Hogan, Pfizer: Employee , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.