Linezolid-Resistant Enterococcus faecalis Isolated from a Cord Blood Transplant Recipient

Abstract

We report a linezolid-resistant Enterococcus faecalis infection in a cord blood stem cell transplant recipient previously treated with linezolid for bloodstream infections by vancomycin-resistant enterococci. Sequencing showed a G2576U mutation in the 23S rRNA gene. Because of the important niche of linezolid in cancer treatment, linezolid-resistant E. faecalis is noteworthy. CASE REPORTA 37-year-old woman underwent allogeneic cord blood stem cell transplantation as therapy for acute myeloid leukemia in second remission at Roswell Park Cancer Institute (Buffalo, N.Y.). The pretransplant course was complicated by invasive pulmonary filamentous fungal infection morphologically consistent with an Aspergillus species. The patient had a complete response to voriconazole. The posttransplant course was complicated by prolonged neutropenia and acute graft-versus-host disease (GVHD) involving skin and bowel, necessitating a prolonged course of high-dose corticosteroid therapy. Multiple courses of antibiotics were administered for persistent neutropenic fever and polymicrobial bacteremia with Klebsiella pneumoniae and a viridans group streptococcus. Six weeks after transplant, vancomycin-resistant Enterococcus gallinarum bacteremia developed and was treated initially with quinupristindalfopristin and then with linezolid due to hepatic toxicity associated with quinupristin-dalfopristin. Three months after transplant, the patient developed sternal chest pain and a computed tomography scan showed a lytic lesion in the sternum. A culture of a needle aspirate grew vancomycin-resistant Enterococcus faecium. The patient was treated with a 7-week course of linezolid for sternal osteomyelitis. A transthoracic echocardiogram did not show evidence of vegetations; a transesophageal echocardiogram was not performed because of mucositis associated with persistent neutropenia.Two weeks after linezolid therapy was stopped, bilateral pulmonary infiltrates developed, and the patient required mechanical ventilation. Bronchoalveolar lavage fluid grew linezolid-resistant Enterococcus faecalis and cytomegalovirus. Treatment with foscarnet and intravenous immunoglobulin was initiated for presumed cytomegalovirus pneumonitis. The E. faecalis isolate was considered to be a respiratory colonizer unrelated to the respiratory failure.Further complications developed, including pancolitis associated with GVHD, colonic pseudo-obstruction, progressive liver failure (probably related to GVHD and medication-related toxicity), azotemia, and Candida glabrata cholecystitis requiring percutaneous drainage. In the setting of refractory multiorgan disease, aggressive therapy was withdrawn and the patient died.

Novel Mechanism of Resistance to Oxazolidinones, Macrolides, and Chloramphenicol in Ribosomal Protein L4 of the Pneumococcus

“…Mutations in 23S rRNA and riboproteins L4 and L22 have more recently been found to confer macrolide resistance (6,29,30). Nonsusceptibility to linezolid in laboratory-generated resistant Escherichia coli isolates (35) and enterococci (21) as well as in clinical isolates of methicillin-resistant Staphylococcus aureus (17,32) and enterococci (4,15) has been found to be conferred by mutations in domain V of 23S rRNA. To date, linezolid-nonsusceptible pneumococcal strains are extremely rare.…”

Comparison of Testing Methods for Detection of Decreased Linezolid Susceptibility Due to G2576T Mutation of the 23S rRNA Gene in Enterococcus faecium and Enterococcus faecalis

“…However, the emergence of resistance during linezolid treatment has been reported for clinical strains of Enterococcus (1,2,7,9,12,13). Clinical resistance to linezolid is associated with a G2576T mutation in domain V of 23S rRNA genes of Enterococcus, and the level of linezolid resistance is directly related to the number of 23S rRNA genes containing this mutation (11,15).…”

Novel biaryl oxazolidinones: in vitro and in vivo activities with pharmacokinetics in an animal model

“…MRSA and VRE infections in the hospital set up and in the community have resulted in increased mortality and economic loss [10,13,14]. Although recent years have seen the release of several new antibacterials such as quinupristin/dalfopristin, LNZ and daptomycin, there is still an unmet need for agents to treat multidrug-resistant (MDR) Gram-positive pathogens.…”