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Director/Pharmacology, The JONES Group/JMI Laboratories, North Liberty, IA; Adjunct Associate Professor, College of Pharmacy, University of Iowa, Iowa City, IA
Postdoctoral Research Assistant, University of Bristol, Bristol, England
Director/CEO, The JONES Group/JMI Laboratories; Adjunct Professor of Medicine, School of Medicine, Tufts University, Boston, MA
Reprints: Alan H Mutnick PharmD, The JONES Group/JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317-9258, FAX 319/665-3371, E-mail alan-mutnick{at}jmilabs.com
BACKGROUND: The oxazolidinone class of antimicrobials has demonstrated remarkable activity against gram-positive cocci. Linezolid has proven to be a first-line therapeutic option for vancomycin-resistant strains. Linezolid clinical trial results and subsequent published case reports cite rare resistance emerging in patients receiving prolonged therapy.
OBJECTIVE: To report the initial linezolid-resistant organisms from cases obtained through the SENTRY Antimicrobial Surveillance Program, after screening >40 000 gram-positive cocci without resistance between 1998 and 2000.
METHODS: During 2001–2002, 8 resistant strains (from 8 different patients) located in 6 states from 7 different participating SENTRY institutions in the US were identified among bloodstream, respiratory, skin and soft tissue, and urinary tract infection isolates of Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidermidis, and Streptococcus oralis. Resistance was detected by reference broth microdilution methods and confirmed by identical results using Etest (AB BIODISK, Solna, Sweden) and the standardized disk diffusion method.
RESULTS: Minimum inhibitory concentration (MIC) and disk
diffusion tests showed elevated MICs (
8 µg/mL) and small inhibitory
zone diameters (
15 mm) for all strains to both linezolid and the
investigational oxazolidinone AZD2563. Vancomycin resistance was detected in 2
of the 8 linezolid-resistant strains. All enterococci and the viridans-group
streptococcus (S. oralis) strain showed resistance to erythromycin.
E. faecium strains were resistant to penicillins, but susceptible to
quinupristin/dalfopristin. Only 3 of the patients had previously received the
drug.
CONCLUSIONS: Linezolid resistance remains rare, with only 8 isolates among 9833 (0.08%) monitored isolates identified between January 1, 2001, and June 30, 2002. Resistance, however, was no longer limited to enterococci. Clinical laboratories should test linezolid more widely to detect emerging resistance, especially for patients receiving oxazolidinone therapy. Longitudinal surveillance programs are warranted to detect a trend in the development of resistance, determine the molecular mechanism of resistance, and recommend alternative therapies or epidemiologic interventions.
Key Words: linezolid, resistance, surveillance
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