1318. A Comparative Evaluation of Serotonin Toxicity among Veterans’ Affairs Patients Receiving Linezolid and Vancomycin
Session: Oral Abstract Session: Clinical Management of Infectious Disease
Saturday, October 20, 2012: 10:30 AM
Room: SDCC 26 AB
Background: Because linezolid (L) is a weak, reversible, nonselective monoamine oxidase inhibitor, it has the potential to cause serotonin toxicity (ST), especially when used in combination with another serotonergic agent (SA). To date, published, real-world clinical evaluations of the risk of ST in pts receiving L have been limited to case reports and non-comparator, retrospective studies. The objective of this study was to evaluate risk of ST among pts who received L or vancomycin (V) at the Upstate New York Veterans’ Affairs (VA) Healthcare Network (VISN-2). 

Methods: An observational, matched (1:1) cohort study was conducted among hospitalized pts at VISN-2 who received L and V between 2005- 2008. Matching criteria: hospital in VISN-2; hospital ward (ICU vs. non-ICU), hospital LOS prior to start of L or V (± 7 d); age (<50, 51-75, >75 yrs); and (4) baseline platelets (>100,000 or <100,000 cell/mm3) Electronic medical records of pts were evaluated for symptoms consistent with ST and the Hunter Serotonin Toxicity Criteria (HSTC) using an intensive, natural word search algorithm.  Exact and surrogate terms consistent with ST and the HSTC were included in the natural word search algorithm. 

Results: The study included 502 pts (251 matched pairs). Baseline demographics and comorbidities were similar between L and V. Of the 502 pts, 60% (L: 53% vs. V: 66%) received a concomitant SA and 19% (L: 19% vs. V: 19%) concurrently received a SSRI.  No pts in either group were reported to have an adverse event (AE) identified as ST.  A comparable number of L and V patients met the HSTC by the exact term search overall and when stratified by receipt of a concurrent SA. For the HSTC surrogate term word search, a greater proportion of pts in the V group met the HSTC relative to pts in the L group. 

Overall

Patients receiving concurrent SA

Linezolid

Vancomycin

Linezolid

Vancomycin

n= 251

n=251

n =132

n= 167

Serotonin toxicity (exact terms)

0

0

0

0

Serotonin toxicity (surrogate terms)

0

0

0

0

Hunter ST Criteria (exact terms)

2 (0.8)

  4 (1.6)

2 (1.5)

3 (1.8)

Hunter ST Criteria (surrogate term)

10 (4.0) 

35 (13.9)

7 (5.3)

       29 (17.4)

Conclusion: While there is a theoretical potential for ST to occur with L, especially in combinations with SA, our study of hospitalized VA pts revealed comparably low frequencies of adverse events related to serotonin toxicity among pts that received L or V.

Thomas Lodise, Pharm D1, Nimish Patel, PharmD1, Antonio Rivera, Pharm.D2, Linda Tristani, PharmD2, Hillary Vandewall1, R Smith, MD2,3 and Louise-Anne McNutt, PhD4, (1)Albany College of Pharmacy and Health Sciences, Albany, NY, (2)Stratton Veterans' Affairs Medical Center, Albany, NY, (3)Albany Med. Coll., Albany, NY, (4)State University of New York at Albany School of Public Health, albany, NY

Disclosures:

T. Lodise, Pfizer: Consultant, Grant Investigator and Speaker's Bureau, Consulting fee, Grant recipient, Research support and Speaker honorarium

N. Patel, None

A. Rivera, None

L. Tristani, None

H. Vandewall, None

R. Smith, None

L. A. McNutt, PhD, None

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