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Study assesses clinical impact of linezolid-resistant S. epidermidis in leukemia patients
Patients with leukemia who have linezolid-resistant Staphylococcus epidermidis and are treated with linezolid are significantly more likely to have persistent bacteremia compared with patients who have linezolid-sensitive isolates, according to findings published in Open Forum Infectious Disease.
“In leukemia patients, vancomycin has been relegated to a second- or third-line agent for gram-positive coverage at our institution because of concerns for nephrotoxicity,” Samuel L. Aitken, PharmD, clinical pharmacy specialist in infectious diseases at The University of Texas MD Anderson Cancer Center in Houston, told Infectious Disease News. “Much of the empiric vancomycin use that would usually occur with at other institutions is replaced with linezolid and so what we have seen in our previous report is that this has led to a clonal spread of linezolid-resistant S. epidermidis among our leukemia patients.”
In a previous study, Aitken, along with lead author Xiqi Li, research assistant at MD Anderson, and colleagues investigated the increase in linezolid-resistant S. epidermidis isolates in patients with leukemia at MD Anderson. Using whole-genome sequencing, the researchers identified a clonal spread of the linezolid-resistant S. epidermidis driven by linezolid use. In the current study, Aitken and colleagues assessed the clinical implications the spread of linezolid-resistant S. epidermidis may have in patients with leukemia who have S. epidermidis bloodstream infections.
All adult patients with leukemia with S. epidermidis bacteremia treated with empiric linezolid at MD Anderson between 2012 and 2015 were included in the retrospective, single-center, cohort study. Adverse clinical outcomes on day 3 — defined as a combination of persistent bacteremia, fever, ICU admission or death — were set as the primary outcome. Aitken and colleagues also evaluated 14- and 30-day mortality.
They identified 82 unique patients with leukemia with S. epidermidis, and linezolid resistance was observed in 40% (n = 33). Aitken said that although global surveillance studies have shown low rates of linezolid-resistant S. epidermidis isolates in the United States, “it’s a common problem in leukemia patients at MD Anderson and increasingly common in Europe.”
The researchers reported persistent bacteremia in 41% of patients with linezolid-resistant S. epidermidis but only in 7% of patients with linezolid-sensitive strains of S. epidermidis (adjusted RR = 5.15; 95% CI, 1.63-16.30, P =.005). Overall, short-term adverse clinical outcomes were not shown to be more common in patients with linezolid-resistant S. epidermidis (61% vs. 33%; aRR = 1.46; 95% CI, 0.92-2.32, P =.108). Furthermore, no observable differences were reported for 14- and 30-day mortality.
Aitken and colleagues recommend the use of antimicrobial stewardship to limit the clinical impact of linezolid-resistant S. epidermidis.
“Through excessive empiric use of linezolid, we have created a situation where linezolid resistance occurs in our clinical isolates and then that resistance affects patients downstream,” Aitken said. “It highlights the adverse consequences of excessive antimicrobial use.” – by Marley Ghizzone
Disclosures: Aitken reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.