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Rapid emergence of resistance to linezolid during linezolid therapy of an Enterococcus faecium infection

Abstract number: p1602

Seedat  J., Zick  G., Klare  I., Konstabel  C., Weiler  N., Sahly  H.

Objectives: 

Linezolid (LZD) is an important antibiotic for the treatment of enterococcal infections, especially when the corresponding strain possesses multiresistance including resistance to vancomycin (VAN). We report the emergence LZD resistance in clonally related VAN-susceptible and VAN-resistant Enterococcus faecium isolates originated from an ICU patient only 12 days after initiation of linezolid therapy.

Patient and Methods: 

VAN-resistant E. faecium was repeatedly isolated from intraabdominal cultures of a 76-year-old female ICU-patient with infected necrotizing pancreatitis after pancreaticoduodenectomy (Whipple´s procedure). Antibiotic susceptibility testing of the bacteria was performed by E-tests; vanA gene were detected by PCR. The possible LZD resistance mechanism (mutation in the 23S rDNA of one or more of the six 23S rRNA alleles of E. faecium) was examined by a PCR-based method. Molecular typing of the strains was performed by SmaI macrorestiction analysis.

Results: 

VAN-resistant but LZD-sensitive E. faecium (VRLSE) were initially detected in intraabdominal cultures, however, already twelve days after initation of LZD therapy, VAN- and LZD-resistant E. faecium (VRLRE) strains were detected. Resistance to LZD was confirmed: MICs ranged from 16 to 32 mg/l. All E. faecium isolates showed identical or closely related PFGE patterns. Throughout the ICU period, VAN- and LZD-susceptible E. faecium (VSLSE) strains were repeatedly detected in the same specimens from which the VRLSE and VRLRE were isolated. Additionally, VAN-susceptible E. faecium isolates with resistance to LZD (VSLRE) were detected. Mutations in the 23S rDNA of three out of six alleles led to LZD resistance in the E. faecium isolates examined. Two weeks after termination of the LZD therapy, no LZD-resistant strain could be detected in follow-up swabs.

Conclusions: 

Resistance to LZD in E. faecium can occur already shortly after the initiation of LZD therapy. Assessment of antibiotic susceptibilities of all isolates at the start of therapy and regularly during the therapy is advisable, especially during therapy of severe infections. The epidemiological and clinical repercussions of resistance to LZD among enterococci cannot be predicted at this time. Attention to proper dosing and prompt removal of infected devices, when feasible, could limit occurrence and spread of LZD-resistant E. faecium.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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