Successful Treatment of Persistent Vancomycin‐Resistant Enterococcus faecium Bacteremia with Linezolid and Gentamicin

eral) grew gram-positive cocci; consequently, vancomycin therapy Successful Treatment of Persistent Vancomycin-Resistant was added.Both sets of cultures contained Staphylococcus aureus Enterococcus faecium Bacteremia with Linezolid and and vancomycin-resistant E. faecium.Due to her profound neutro- Gentamicinpenia (absolute neutrophil count, õ100/mL), the patient was enrolled in a linezolid compassionate-use study.Vancomycin-resistant enterococci (VRE) have emerged as im-Her antimicrobial regimen was changed to that with ceftazidime portant nosocomial pathogens in medical centers throughout the 2 g every 8 hours, linezolid 600 mg intravenously every 12 hours, United States.Recently, Enterococcus faecium isolates that are plus gentamicin 1 mg/kg every 8 hours.Before the initiation of resistant to all currently available antimicrobial agents have been linezolid, blood cultures had yielded VRE for four consecutive days; reported 1.Therefore, therapy for patients infected with these however, no additional cultures yielded staphylococci.Due to this multidrug-resistant organisms is particularly difficult, as many of persistent bacteremia, all central venous catheters were removed and the infections are virtually untreatable.In addition, serious enteroechocardiography was performed.No endovascular source of infeccoccal infections, such as persistent bacteremia and endocarditis, tion was identified.Therapy with linezolid and gentamicin was continmay be associated with a high mortality 2, 3.ued for 14 days, whereas the ceftazidime was discontinued following Linezolid (PNU-100766) is a member of a new class of antibacthe resolution of her neutropenia on the ninth day of linezolid therapy.terial agents called oxazolidinones, which are chemically unrelated Blood cultures obtained after the first day of therapy with linezolid to currently available agents.This agent selectively binds to the and gentamicin revealed VRE.All subsequent cultures of blood ob-50S ribosomal subunit, thereby inhibiting protein synthesis.It is tained while the patient was receiving antimicrobial therapy and at highly active against gram-positive organisms and it is difficult to 14 and 30 days after completion of therapy were negative.select for resistance in vitro 4.To our knowledge, we report the Antimicrobial susceptibility testing was performed according to first case of a neutropenic patient with persistent VRE bacteremia National Committee for Clinical Laboratory Standards (NCCLS) who responded clinically and microbiologically to therapy with guidelines 5.Enterococcus faecalis ATCC 29212 was used as a linezolid and gentamicin.control isolate and included each time a test run was performed.A 23-year-old woman, who was 18 weeks pregnant, was admittedThe antimicrobial agents were obtained from their manufacturers, to Northwestern Memorial Hospital (Chicago) and found to have a and linezolid was generously provided by Pharmacia and Upjohn high-grade B-cell immunoblastic lymphoma with multiorgan involve-(Kalamazoo, MI).The provisional susceptibility breakpoints for ment.Following the administration of chemotherapy, she had a sponlinezolid are £8 mg/mL, susceptible; 16 mg/mL, intermediate; and taneous abortion and then developed acute renal failure resulting from §32 mg/mL, resistant.For each isolate tested, the inoculum was tumor lysis syndrome.Prolonged neutropenia ensued complicated by prepared from 18-24-hour-old colonies inoculated into 5 mL of fever.Initially she received empiric therapy with ceftazidime and trypticase soy broth.Just before testing, the broth was adjusted to amikacin for 5 days; however, due to the persistence of fever, intravea 0.5 McFarland turbidity standard to yield Ç1 1 10 8 cfu/mL.nous vancomycin was added.Two sets of cultures of blood obtained Then 0.1 mL of the prepared inoculum was added to macrobroth during a febrile episode revealed Candida krusei; therefore, amphoterdilution tubes.icin B cholesteryl sulfate complex was administered.She remained A time-kill experiment was performed, according to methods fungemic, despite removal of all central venous access devices.Ultipreviously described 6, to determine if the addition of gentamicin mately, her fungemia cleared, then her neutropenia and acute renal would provide in vitro synergy with linezolid.All testing was failure resolved.performed in duplicate.As the next part of her treatment regimen she received a second course of cytotoxic chemotherapy, which again resulted in pro-The bacteremic isolates from this patient possessed high-level longed neutropenia.It is noteworthy that before the initiation of resistance to vancomycin (MIC, §256 mg/mL) and ampicillin chemotherapy, cultures of a rectal swab revealed vancomycin-(MIC, §128 mg/mL) and were resistant to all currently available resistant E. faecium.Twelve days after the initiation of this second antimicrobial agents except chloramphenicol (table 1).The linezocourse of chemotherapy, she developed a fever (temperature, to lid MIC was 2 mg/mL.Time-kill studies with the combination of 38.9ЊC) and was started empirically on therapy with ceftazidime linezolid and gentamicin failed to demonstrate any in vitro synergy.and amikacin.The following day, two sets of cultures of blood Enterococci possess intrinsic resistance to many antimicrobial obtained from different sites (central venous catheter and periphagents including the b-lactams and aminoglycosides.Therefore, for the treatment of serious enterococcal infections, a cell-wall active agent in combination with an aminoglycoside is required for synergistic, bactericidal activity 7.However, for patients infected