737. Linezolid Experience and Accurate Determination of Resistance (LEADER) Program for 2012: Regional Activity of Linezolid and Comparator Compounds
Session: Poster Abstract Session: Antimicrobials: Resistance Mechanisms
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
  • IDWEEK 2013 LEADER 737.pdf (115.9 kB)
  • Background: Linezolid (LZD) remains the only marketed oxazolidinone antimicrobial available in the USA since its approval in 2000. It is active against Gram-positive (GP) organisms that are resistant (R) to conventional drugs, such as MRSA, drug-R S. pneumoniae (DRSP) and vancomycin-R enterococci (VRE). The LEADER Program has monitored LZD-R rates in the USA through the collection of nearly 55,000 isolates since 2004.

    Methods: A total of 7,429, GP pathogens were submitted from 60 medical centers in 37 states (representing all 9 Census Regions).  The organism groups (no.overall) were: S. aureus (SA; 2,980), coagulase-negative staphylococci (CoNS; 753), enterococci (ENT; 937), S. pneumoniae (SPN; 1273), viridans group (VGS; 526), and β-haemolytic streptococci (BHS; 960). CLSI broth microdilution susceptibility (S) testing was performed. LZD-R isolates were confirmed by Etest (bioMerieux, Hazelwood, MO) and CLSI disk diffusion methods. PCR and sequencing was performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins, and an acquired gene (cfr).

    Results: LZD activity against GP organisms remains high (99.83% S). The MIC50/90 for SA was at 1/2 μg/ml. MRSA rates varied by region from 35.1 to 58.7%.  Only one SA isolate was LZD-R (MSSA; LZD MIC, 32 µg/ml; G2576T and L3 alteration) and two MRSA (LZD MIC, 4 µg/ml) contained the cfr gene (Indiana and Illinois). Among CoNS, seven isolates (0.92% of all strains [1.18% in 2011 and 1.48% in 2010]) demonstrated linezolid MIC results of ≥8 μg/ml. Four E. faecium (≥8 μg/ml; G2576T mutations; 0.4% of ENT) were LZD non-S. LZD was active against all SPN with a MIC50/90 of 1/1 μg/ml. Penicillin-R rates for SPN ranged from 12.4 to 32.3% and ceftriaxone–non-S varied by region from 2.7 to 13.8%. For VGS and BHS, compromised S was noted for erythromycin, clindamycin and tetracycline, while LZD MIC values were dominantly 1 μg/ml (MIC50/90, 1 μg/mL,).

     Conclusion: LZD demonstrated excellent activity with a S rate of 99.83% with no evidence of MIC creep when compared to previous years (2004-2011) of the LEADER Program. While rates of MRSA and DRSP vary moderately between USA Census regions, LZD-R in the USA remains below 1.0% in all regions. Surveillance networks should be maintained to detect emerging R types to LZD and geographic variances.

    Jennifer Streit1, James Ross1, Rodrigo Mendes1, Robert Flamm1, Ronald Jones, MD2 and Patricia Hogan3, (1)Jmi Laboratories Inc, North Liberty, IA, (2)JMI Laboratories Inc, North Liberty, IA, (3)Pfizer Inc, New York, NY


    J. Streit, Pfizer Inc: Grant Investigator, Grant recipient

    J. Ross, Pfizer Inc: Grant Investigator, Grant recipient

    R. Mendes, Pfizer Inc: Grant Investigator, Grant recipient

    R. Flamm, Pfizer Inc: Grant Investigator, Grant recipient

    R. Jones, Pfizer Inc: Grant Investigator, Grant recipient

    P. Hogan, Pfizer Inc: Employee and Shareholder, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.