379. Rapid emergence of daptomycin resistance in Enterococcus faecium during daptomycin therapy
Session: Poster Abstract Session: MRSA, MSSA, Enterococci
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
Background: Daptomycin non-susceptible Enterococcus (DNSE) are an emerging issue, but little is known about how quickly a daptomycin non susceptible (NS) phenotype may emerge following daptomycin therapy in vivo.

Methods: We retrospectively reviewed 30 cases of DNSE (defined as daptomycin MIC >4 µg/ml) identified at a tertiary center from January 2007-January 2013. Cases were evaluated for rapid (within one week) acquisition of DNSE phenotype after exposure to daptomycin.

Results: Two of 30 (6.7%) DNSE isolates developed the NS phenotype within 7 days of exposure to daptomycin. Patient 1 was a 42 year old female who developed sepsis with neutropenia and persistent gastrointestinal bleeding after chemotherapy for relapsed leukemia. She remained on imipenem for 4 weeks for ongoing neutropenic fevers and developed high grade bacteremia with vancomycin resistant Enterococcus faecium (VRE) (daptomycin MIC, 2ug/mL). She was treated with daptomycin 12 mg/kg IV daily but had persistent VRE bacteremia so amikacin and quinupristin/dalfopristin were also added. DNSE was re-isolated from blood cultures on day 7 of daptomycin therapy. Patient 2 was a 28 year old female who underwent Whipple resection for pancreatic tumor that was complicated by intraabdominal abscess from which VRE was isolated (daptomycin MIC, 2µg/ml). She was started on daptomycin 6 mg/kg IV every 48 hrs, cefepime and metronidazole. After 7 days of daptomycin therapy, DNSE was isolated from urine and intraabdominal fluid. The patient was switched to IV tigecycline, and defervesced. Analysis of the isolates from the two patients by rep-PCR determined they were not clonally related. Whole genome sequencing of the three isolates in the second case was performed. Only 4 single nucleotide variants (SNVs) were identified between the daptomycin susceptible and NS isolates. Both DNSE isolates harbored a single SNV in the cardiolipin gene, although at discrete loci.

Conclusion: Clinicians should be vigilant that rapid emergence of DNSE may be associated with limited mutations in the bacterial genome and may occur in the setting of immunosuppression, malignancy and gastrointestinal disease. Further studies need to confirm these observations.

Theodoros Kelesidis, MD, David Geffen School of Medicine at UCLA, Los Angeles, CA and Romney M. Humphries, Ph.D., Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA

Disclosures:

T. Kelesidis, None

R. M. Humphries, None

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