Source: Radiology  |  Posted 4 years ago

By Chris Berrie

MUNICH, GERMANY -- April 2, 2007 -- Linezolid shows excellent potency and spectrum against a range of rarely-isolated, non-indicated Gram-positive species, according to a study presented here at the 17[^]th[] European Congress of Clinical Microbiology and Infectious Diseases and 25[^]th[] International Congress of Chemotherapy (ECCMID-ICC).

Ronald M. Jones, MD, principal investigator, and president and chief executive officer, JMI Laboratories, North Liberty, Iowa, United States, presented the results of an analysis of linezolid's activity against species of Gram-positive cocci that are rarely isolated (<1%) and are non-indicated Gram-positive species.

Linezolid is the first of the new class of the oxazolidinones. It was introduced in 1997 and was initially released in the United States in spring of the year 2000, Dr. Jones said in a presentation on March 31[^]st[].

The drug has specific indications for Staphylococcus aureus (including methicillin resistance), Enterococcus faecium (including vancomycin-resistant enterococci), S. pyrogenes, S. agalactiae and S. pneumonium. Despite some reports of linezolid resistance, it is thought to have a wide spectrum of Gram-positive coverage, he said.

In their study, Dr. Jones and colleagues evaluated data from the SENTRY Antimicrobial Surveillance Programme database, which provided a spectrum of quality-assured isolates obtained over 7 years from over 100 participating medical centres worldwide. Data were available for a total of 3,251 strains from validated results using Clinical and Laboratory Standards Institute-approved broth microdilution methods, which used only species that had more than 10 isolates.

These strains were distributed among 9 major bacterial groups: Aerococcus spp. (n = 22), Bacillus spp. (n = 202), Corynebacteria (n = 342), various uncommon enterococci (n = 378; 6 species), Listeria monocytogenes (n = 137), Micrococcus luteus (n = 29), Rotha mucilaginosus (n = 18), beta-haemolytic streptococci (n = 865; three serotypes) and S. viridans group (n = 1,258; 12 species). The linezolid-resistant strains at greater than or equal to 8 mcg/mL were processed by polymerase chain reaction for target-site mutations.

The corynebacteria were the most susceptible to linezolid, with a 50% minimum inhibitory concentration (MIC50) of 0.25 mcg/mL. These were followed by M. luteus and R. mucilaginosus, with a MIC50 of 0.5 mcg/mL. With 1 of the 12 species of the viridans group streptococci also with a MIC50 of 0.5 mcg/mL (Streptococcus parasanguis), the remaining viridans streptococci and Aerococcus spp., Bacillus spp., Enterococcus avium and the 2 serotypes of beta-haemolytic streptococci, all showed a MIC50 of 1 mcg/mL. The remaining uncommon enterococci had a MIC50 of 2 mcg/mL, as did L. monocytogenes.

Dr. Jones noted that this generally put these species into 3 major groups: very susceptible (MIC50, 0.25-0.5 mcg/mL; Corynebacteria, Micrococcus, Rothia), moderately susceptible (MIC50, 1 mcg/mL; Aerococcus, Bacillus, streptococci) and less susceptible (MIC50 2 mcg/mL; enterococci, Listeria).

At the strain level, only 4 (0.12%) had a MIC greater than or equal to 4 mcg/mL: E. avium (1), E. casseliflavus (2) and E. gallinarum (1). Finally, the 1 strain (0.03%) that was resistant (MIC >8 mcg/mL; S. oralis) had a proven 23S target mutation of G2576T. Dr. Jones said, "This S. oralis isolate was described approximately 5 years ago in a report from our laboratories and to date within the worldwide surveillance programme it is still the only strain to be reported to have a mutational target problem."

Therefore, as well as showing good activity against the more frequently cultured and indicated species, linezolid shows excellent activity against these rare Gram-positive species, although Dr. Jones said that linezolid should still be monitored, even with respect to these rarer species as it is becoming more widely used.

Publication of this study is due out in Antimicrobial Agents and Chemotherapy on Monday (April 2007). The study was sponsored by Pfizer.

[Presentation title: Activity of Linezolid Against a Worldwide Collection of Uncommonly Isolated Gram-Positive Organisms (3,251 Strains). Abstract O33]