Resistance emerges in severely ill patients

A recent report of linezolid resistance in five patients infected with vancomycin-resistant enterococci (VRE), included the following case descriptions:

Patient 1 — a 79-year-old man who underwent repair of an aortic aneurysm. He developed an abscess around the graft with bacteremia secondary to VRE. He was started on linezolid, but his blood cultures were persistently positive throughout therapy. The isolate tested on day 21 of therapy was intermediately resistant to linezolid. He was switched to quinupristin-dalfopristin and doxycycline. He died of uncertain causes nine weeks later.

Patient 2 — a 62-year-old kidney transplant patient who developed an empyema due to VRE. He required decortication and was treated with quinupristin-dalfopristin for 14 days, then was switched to linezolid. His initial VRE isolate was sensitive to both drugs. After finishing 40 days of linezolid, he developed a fistula and the pleural fluid grew linezolid-resistant VRE. He was changed back to quinupristin-dalfopristin and is currently in the intensive care unit for acute graft rejection.

Patient 3 — a 56-year-old man who developed a liver abscess complicating liver transplantation. Cultures from the abscess grew VRE. He received two three-week courses of linezolid until blood cultures grew linezolid-resistant VRE. He was then switched to quinupristin-dalfopristin. He developed multiorgan failure and died; no necropsy was done.

Patient 4 — a 24-year-old man with acute lymphoblastic leukemia, who became neutropenic and febrile after bone-marrow transplantation. Empirical broad-spectrum antibiotics were given for four weeks. All cultures were negative except a rectal swab that grew VRE. He received linezolid for four weeks and repeat cultures showed linezolid-resistant VRE.

Patient 5 — a 28-year-old man who had several liver abscesses after liver transplantation. Both wound and blood cultures grew VRE susceptible to quinupristin-dalfopristin and linezolid. He received four weeks of linezolid with a good clinical response. However, peritoneal washings before closure of his abdominal wound showed VRE resistant to linezolid.¹

Reference

1. Gonzales RD, Schreckenberger PC, Graham MB, et al. Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid. Lancet 2001; 357:1,179.