Ann Thorac Surg 2003;76:1719-1720
© 2003 The Society of Thoracic Surgeons
Case report
Successful treatment of vancomycin resistant Enterococcus faecium mediastinitis associated with left ventricular assist devices
Preeti N. Malani, MDa,
David B. S. Dyke, MDb,
Francis D. Pagani, MD, PhDa,c,
Wendy S. Armstrong, MDa,
Carol E. Chenoweth, MDa,d*
a department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA
b department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA
c department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
d department of Infection Control and Epidemiology, University of Michigan Health System, Ann Arbor, Michigan, USA
Accepted for publication March 17, 2003.
* Address reprint requests to Dr Chenoweth, Division of Infectious Diseases, University of Michigan Health System, 1500 E Medical Center Dr, Room 3116, Ann Arbor, MI, USA 48109-0378
e-mail: cchenow{at}umich.edu
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Abstract
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We present 2 cases of vancomycin-resistant Enterococcus faecium mediastinitis associated with left ventricular assist devices in the setting of heart transplantation. Despite complicated operative courses and deep infection secondary to antimicrobial resistant organisms, both patients were successfully treated and have remained infection free in the long term.
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Introduction
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Left ventricular assist devices (LVAD) have revolutionized the field of heart transplantation. Infection remains a major complication of this emerging technology. Several investigators have reported infectious complications, noting that treating an established infection is both expensive and difficult [1–4]. Risk factors associated with infection include extended duration of LVAD support, prolonged intensive care unit stay, need for hemodialysis, and delayed sternal closure [1].
Among infectious complications, mediastinitis poses a particular challenge because treatment generally requires an organ to be placed into an infected field. This in combination with the need for immunosuppressive therapy compounds the difficulty of treating a serious infection related to an antimicrobial resistant organism. We report 2 cases of vancomycin-resistant Enterococcus faecium (VREF) mediastinitis associated with LVADs. Expedited device removal and heart transplantation along with surgical debridement (and flap closure in 1 patient) followed by extended courses of antimicrobial therapy resulted in successful treatment of both patients.
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Case reports
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Case 1
In a 61-year old man with long-standing ischemic cardiomyopathy, intractable ventricular fibrillation developed during an electrophysiology study. After unsuccessful percutaneous transluminal coronary angioplasty he was placed on venoarterial extracorporeal membrane oxygenation. Three days later he was listed for transplantation and underwent implantation with a Heartmate IP-1000 LVAD (Thoratec, Pleasanton, CA) and Abiomed right ventricular assist device ([RVAD] Abiomed, Danvers, MA) for biventricular failure. Surgical antimicrobial prophylaxis included vancomycin, cefuroxime, fluconazole, and ciprofloxacin. Delayed sternal closure was completed on postoperative day 4.
The patient stabilized, permitting RVAD removal on postoperative day 23. The following months were spent uneventfully in hospital awaiting transplant. On postoperative day 186, development of a drive-line air leak prompted urgent HeartMate replacement. During the following days, fevers developed in the patient and incisional drainage appeared from the abdominal wound. Despite 37 days of empiric treatment with vancomycin, ceftazidime, and intermittent ciprofloxacin, his clinical condition worsened. His temperature rose to 102.1°F and an abdominal ultrasonogram revealed a fluid collection above the drive-line entry. Surgical drainage and washout of the HeartMate pocket was done on device day 220. Upon entering the pocket a large amount of cloudy, straw-colored fluid was noted. Inflammation and fibrinous exudate were observed along the entire wall of the pocket. Fluid cultures revealed VREF. Two days later the patient underwent heart transplantation after 222 days of support. Perioperative antimicrobial prophylaxis included ceftazidime, vancomycin, ciprofloxacin, and fluconazole. Operative cultures taken from the HeartMate graft to the aorta demonstrated VREF.
Postoperatively the patient continued to have fevers and VREF was repeatedly demonstrated from multiple mediastinal drains. On posttransplant day 10, quinupristin/dalfopristin (obtained through compassionate release) was initiated at 7.5 mg/kg every 8 hours for treatment. Therapy was complicated by the development of severe myalgias that required frequent dosing of intravenous pain medications. The patient demonstrated clinical improvement and resolution of fever without further surgical intervention. After 24 days of full-dose quinupristin/dalfopristin the drug was discontinued because of the severity of the myalgias. Other unrelated complications during this period included acute renal failure requiring intermittent hemodialysis and pericardial tamponade secondary to endocardial biopsy. The patient regained full renal function and remains free of recurrent VREF infection more than 4 years after transplant.
Case 2
A previously healthy 23-year-old woman presented with multiorgan failure secondary to presumed viral cardio-myopathy. After extended ventilatory and hemodynamic support the patient was listed for transplantation and on hospital day 10 underwent HeartMate implantation. Vancomyin, fluconazole, rifampin, ciprofloxacin, and cefuroxime were administered for 5 days perioperatively. She was extubated and slowly stabilized hemodynamically. Despite a complicated course the patient was transferred to the stepdown unit on postoperative day 22. On postoperative day 24 fevers and drainage from the HeartMate abdominal wound site developed. Vancomycin, cefuroxime, and fluconazole were restarted for empiric antimicrobial coverage. On postoperative day 37 a bedside incision and drainage of the abdominal wound obtained purulent fluid. Cultures demonstrated Candida krusei, C. albicans, and VREF. The patient’s antimicrobial regimen was changed to amphotericin B lipid complex (4 mg/kg) and doxycycline (100 mg intravenously twice daily).
The wound failed to improve, progressing to a point at which the hardware was exposed. A barium swallow study demonstrated a gastrocutaneous fistula secondary to erosion from the hardware. The patient’s clinical condition worsened; there was copious drainage from the wound and she remained febrile. Her United Network for Organ Sharing (UNOS) status was upgraded and a donor organ was identified.
The patient underwent transplantation after 68 days of LVAD support. An intraaortic balloon pump was placed owing to inability to wean the patient from the cardiopulmonary bypass circuit. The sternal wound was left open for delayed closure. Standard perioperative prophylaxis consisting of vancomycin and cefuroxime was given. On posttransplant day 3, a transesophageal echocardiogram revealed an ejection fraction of 10% to 20%. An endocardial biopsy demonstrated vascular rejection prompting treatment with cytoxan, plasmapheresis, and antithymocyte globulin.
By posttransplant day 4, operative cultures from the HeartMate device and graft to the heart demonstrated VREF. The patient was febrile and required inotropic support. Intravenous doxycycline was started at 100 mg every 12 hours. Blood cultures done the same day subsequently demonstrated high-grade VREF bacteremia. On day 6 after heart transplant the patient returned to the operating room for mediastinal exploration, additional sternal debridement, and right rectus flap closure. Cultures taken from the deep sternal wound during this procedure grew VREF. Follow-up blood cultures on postoperative day 8 demonstrated clearance of the bacteremia. On posttransplant day 12, doxycycline was discontinued and intravenous linezolid 600 mg every 12 hours was initiated after being obtained thorough a compassionate use protocol. During the following days the patient’s cardiac function improved. She received a total of 6 weeks of intravenous linezolid therapy, completing the course just before being discharged to home after an extended inpatient and rehabilitation stay. Linezolid was well tolerated except for thrombocytopenia. Her flap healed without complication. The patient remains free of VREF infection with no further sternal or abdominal wound issues 4 years after transplant.
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Comment
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This report describes the successful treatment of HeartMate-associated mediastinitis. Both cases add to the growing body of literature that supports expedient device removal and transplant in the setting of LVAD infection [3, 4]. In our experience even severe infection associated with highly resistant pathogens did not preclude successful transplantation.
Vancomycin-resistant E faecium infections pose a significant challenge as therapeutic options are limited [5]. The antimicrobials that are available are often poorly tolerated or ineffective, making treatment of a serious infection difficult. Quinupristin/dalfopristin is a streptogramin with bacteriostatic activity against VREF. The drug’s adverse effects include phlebitis, severe arthralgias, and myalgias. Linezolid is an oxazolidinone that also demonstrates bacteriostatic activity against VREF. This agent is generally well tolerated but frequently causes thrombocytopenia especially with prolonged use. Given the limitations of antimicrobial therapy, removal of infected foci such as device and intravenous catheters and drainage of infected fluid collections are essential adjunctive measures. The risk of serious VREF infection is increased among certain patient groups including patients with hematologic malignancies, stem cell or solid organ transplant recipients, and intensive care unit patients [6].
Vancomycin-resistant E faecium has demonstrated resistance to these and newer agents, sometimes developing resistance during the course of treatment. Clinical trials with daptomycin, LY333328, and tigicycline are ongoing. Although these drugs may eventually prove clinically useful, infection control measures and prudent antimicrobial use are essential to the prevention of VREF infections.
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References
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- Malani P.N., Dyke B.D.S., Pagani F.D., Chenoweth C.E. Nosocomial infections associated with left ventricular assist devices. Clin Infect Dis 2002;34:1295-1300.[Medline]
- McCarthy P., Schmitt S., Vargo R., et al. Implantable LVAD infections: implications for permanent use of the device. Ann Thorac Surg 1996;61:359-365.[Abstract/Free Full Text]
- Fischer S., Trenholme G., Costanzo M., et al. Infectious complications in left ventricular assist device recipients. Clin Infect Dis 1997;24:18-23.[Medline]
- Argenziano M., Catanese K., Moazami N., et al. The influence of infection on survival and successful transplantation in patients with left ventricular assist devices. J Heart Lung Transplant 1997;16:822-831.[Medline]
- Murray B.E. Vancomycin-resistant enterococcal infections. N Engl J Med 2000;342:710-721.[Free Full Text]
- Hayden M.K. Insights into the epidemiology and control of infection with vancomycin-resistant enterococci. Clin Infect Dis 2000;31:1058-1065.[Medline]
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Abstract
Introduction
