The Pre-brief
An excellent review of LVAD specific infections was recently published by Qu and colleagues. Here are the highlights.
Case:
A 54 year-old male with a history of insulin dependent diabetes, nonischemic cardiomyopathy status post LVAD implantation 6 months ago presents to the emergency department with subjective fever and chills. He states that he has not noticed any low flow alarms, nor recent changes in the power on his LVAD controller. There have been no recent medication changes to his heart failure regimen and he is compliant with his warfarin anticoagulation. He denies any headache, neck pain, cough, nausea/vomiting, abdominal pain, dysuria/urinary frequency or new rash.
On physical exam, the patient is febrile to 100.6, and mildly tachycardic to 103. Blood pressure is 89/68. Lungs are clear, and the LVAD hum is auscultated just left and inferior to the midline of the chest. The LVAD controller confirms the patients’ baseline pump speed, flow, power and pulsatility index. On inspection of the exit-site of the driveline, you appreciate 5 cm of erythema and can express purulent discharge. You are concerned for a VAD associated infection.
VAD associated infections are classified into three categories:
The rest of this review will focus on VAD-specific infections, the most common presentation being a driveline infection.
Driveline infections occur at an incidence of ~10-20% per patient-year, with most presenting between 2 and 6 months following implantation. Risk factors include longer duration of support, injury to the driveline exit-site, and comorbidities (such as obesity and diabetes).
The nature of the VAD infection does have an impact on patient outcomes. VAD-specific infections have not been shown to decrease the chances of successful heart transplantation. Unfortunately, untreated driveline infection can lead to bloodstream infections (VAD-related) and are associated with a decrease in survival to transplantation. As such, early identification and treatment of driveline infections are paramount to optimizing the outcomes of VAD patients.
Diagnosis of driveline infections can be made on clinical grounds. Erythema or induration of tissue surrounding the exit site and purulent drainage are common. Microbiological diagnosis can be gleaned from swabbing the exit site. Of note, driveline infections often track from the exit-site into deeper tissues such as the tunnel, the pocket or even the pump. Invasive exploration and sampling guided by ultrasound or computed tomography is possible but not recommended given the chance to damage VAD components or introducing microorganisms into sterile sites. Nuclear medicine assisted CT imaging, 18 F-FDG PET/CT can increase the sensitivity and specificity for diagnosing deeper infections compared to traditional imaging. A reasonable initial workup would include local wound culture, blood cultures and a CT chest abdomen pelvis with contrast to look for driveline tract and pump pocket infections.
Epidemiologically, the most common pathogens causing driveline infections are Gram positive bacteria that colonize the skin such as Staphylococcus aureus and Staphylococcus epidermidis. They then form biofilms and migrate up the driveline. These bugs cause half of all driveline infections.These organisms are readily acquired during the implant hospitalization. Later onset driveline infections can be caused by Gram negative bacteria such as Pseudomonas aeruginosa.
Case Continued:
Wound culture of the exit site grows pseudomonas. CT scan of the chest and abdomen shows ascending infection along the driveline. More concerningly, peripheral blood cultures are positive for pseudomonas as well.
Treatment of driveline infections depends on identification of the causative pathogen, location of the infection, systemic manifestations, and the transplant candidacy of the patient. Superficial driveline infections require oral or intravenous antibiotics for at least 2 weeks, with antibiotic selection ideally reflective of bacterial speciation and susceptibility. Unfortunately, up to 50% of driveline infections may relapse following a two week course and this treatment failure is associated with increased mortality. Patients with concern for driveline infection are likely to be admitted to the hospital, with the appropriate device team consulted (cardiothoracic surgery or advanced heart failure cardiology).
Deep VAD-specific infection requires prolonged antibiotic therapy (6-8 weeks), followed by long-term antibiotic suppression therapy to prevent relapse. Rifampin is commonly used as part of deep VAD infection therapy given its activity against biofilms. Caution is required with rifampin as it induces the metabolism of warfarin, requiring uptitration of the warfarin dose to maintain anticoagulation and avoid pump thrombosis or stroke.
Infections of the driveline tunnel, pump pocket or the VAD site itself requires surgical intervention. These interventions range from incision and drainage followed by vacuum assisted closure, to omental wrapping, to placement of antibiotic impregnated beads, and in some cases VAD exchange or transplantation.
VAD exchange is considered in those with relapsing infections or fungal driveline infections. This is a last resort given the complexity of the surgical procedure and the concern for reinfection of the new device. The ideal treatment for deep VAD infection is to proceed to heart transplant. If this is not the clinical scenario, VAD exchange is pursued. Unfortunately, over 50% of patients experience recurrence of infections within one year after device exchange.
Case Conclusion:
Despite 8 weeks of intravenous antibiotics and local incision and drainage with vacuum assisted closure, the patient continues to experience intermittent bacteremia. As the patient had the LVAD implanted as destination therapy, he undergoes LVAD exchange.
Given the complexity and morbidity of treatment for driveline infection, prevention is paramount to avoid this complication. Helpfully, several efforts can decrease the incidence of infection. Advances in VAD design: Transition from early generation paracorporeal pulsatile flow VADs to implantable centrifugal flow devices has reduced the occurrence of VAD associated infections. Further, smaller outer diameter and lower stiffness of drivelines are associated with less driveline infections
Standard precautions and protocols can prevent many DLIs:
Driveline care: Hand and skin disinfection, exit-site preparation, using maximal sterile barrier precautions, and limiting the number of driveline manipulations are all critical. A standard of care protocol for prevention of driveline infections has recently been published
Antibiotic Prophylaxis: Immediate post-implantation intravenous antibiotic prophylaxis with a cephalosporin (cefazolin or cefuroxime) for 24-48 hours is pursued by most VAD centers.
In the future transcutaneous energy transfer systems may eliminate the need for a driveline, and hence, driveline infections. These are not yet reliable enough for clinical use. Until then, continued focus on prevention and improved designs to repel biofilm formation are needed to limit this morbid complication of LVADs.
The Debrief
- LVAD driveline infections are common (10-20% incidence per year) and are diagnosed clinically
- Treatment ranges from antibiotic therapy to LVAD exchange
- An ounce of prevention is worth a pound of cure: Driveline care in-hospital and at home is paramount to preventing this morbid complication
References
- Qu, Y., Peleg, A. Y., & McGiffin, D. (2021). Ventricular Assist Device-Specific Infections. Journal of Clinical Medicine, 10(3), 453.
- Hannan, M. M., Husain, S., Mattner, F., Danziger-Isakov, L., Drew, R. J., Corey, G. R., … & Mooney, M. L. (2011). Working formulation for the standardization of definitions of infections in patients using ventricular assist devices. The Journal of Heart and Lung Transplantation, 30(4), 375-384.
- Kirklin, J. K., Naftel, D. C., Pagani, F. D., Kormos, R. L., Stevenson, L. W., Blume, E. D., … & Young, J. B. (2015). Seventh INTERMACS annual report: 15,000 patients and counting. The Journal of Heart and Lung Transplantation, 34(12), 1495-1504.
- Blanco-Guzman, M. O., Wang, X., Vader, J. M., Olsen, M. A., & Dubberke, E. R. (2021). Epidemiology of Left Ventricular Assist Device Infections: Findings From a Large Nonregistry Cohort. Clinical Infectious Diseases, 72(2), 190-197.
- Martin, B. J., Luc, J. G., Maruyama, M., MacArthur, R., Bates, A. R., Buchholz, H., … & Conway, J. (2018). Driveline site is not a predictor of infection after ventricular assist device implantation. Asaio Journal, 64(5), 616-622.
- Qu, Y., McGiffin, D., Hayward, C., McLean, J., Duncan, C., Robson, D., … & Peleg, A. Y. (2020). Characterization of infected, explanted ventricular assist device drivelines: The role of biofilms and microgaps in the driveline tunnel. The Journal of Heart and Lung Transplantation, 39(11), 1289-1299.
- Ten Hove, D., Treglia, G., Slart, R. H. J. A., Damman, K., Wouthuyzen-Bakker, M., Postma, D. F., … & Glaudemans, A. W. J. M. (2020). The value of 18 F-FDG PET/CT for the diagnosis of device-related infections in patients with a left ventricular assist device: a systematic review and meta-analysis. European Journal of Nuclear Medicine and Molecular Imaging, 1-13.
- Kusne, S., Mooney, M., Danziger-Isakov, L., Kaan, A., Lund, L. H., Lyster, H., … & Huprikar, S. (2017). An ISHLT consensus document for prevention and management strategies for mechanical circulatory support infection. The Journal of Heart and Lung Transplantation, 36(10), 1137-1153.
- Joost, I., Bothe, W., Pausch, C., Kaasch, A., Lange, B., Peyerl-Hoffmann, G., … & Rieg, S. (2018). Staphylococcus aureus bloodstream infection in patients with ventricular assist devices–Management and outcome in a prospective bicenter cohort. Journal of Infection, 77(1), 30-37.
- Sezai, A., Unosawa, S., Taoka, M., Osaka, S., Kitazumi, Y., Suzuki, K., … & Tanaka, M. (2020, March). New Treatment for Driveline Infection Following Implantation of a Ventricular Assist Device. In The heart surgery forum (Vol. 23, No. 2, pp. E132-E134).
- Ustunsoy, H., Gokaslan, G., Hafiz, E., Koc, M., Asam, M., Kalbisade, E. O., & Delibas, L. (2015, June). An old friend in the treatment of drive line infection after left ventricular assist device implantation: omentoplasty–a case report. In Transplantation proceedings (Vol. 47, No. 5, pp. 1540-1541). Elsevier.
- Kretlow, J. D., Brown, R. H., Wolfswinkel, E. M., Xue, A. S., Hollier Jr, L. H., Ho, J. K., … & Izaddoost, S. A. (2014). Salvage of infected left ventricular assist device with antibiotic beads. Plastic and reconstructive surgery, 133(1), 28e-38e.
- Zinoviev, R., Lippincott, C. K., Keller, S. C., & Gilotra, N. A. (2020, May). In full flow: left ventricular assist device infections in the modern era. In Open forum infectious diseases (Vol. 7, No. 5, p. ofaa124). US: Oxford University Press.
- Yost, G., Coyle, L., Gallagher, C., Cotts, W., Pappas, P., & Tatooles, A. (2020). Outcomes Following Left Ventricular Assist Device Exchange: Focus on the Impacts of Device Infection. ASAIO Journal (American Society for Artificial Internal Organs: 1992).
- Schaffer, J. M., Allen, J. G., Weiss, E. S., Arnaoutakis, G. J., Patel, N. D., Russell, S. D., … & Conte, J. V. (2011). Infectious complications after pulsatile-flow and continuous-flow left ventricular assist device implantation. The Journal of heart and lung transplantation, 30(2), 164-174.
- Imamura, T., Murasawa, T., Kawasaki, H., Kashiwa, K., Kinoshita, O., Nawata, K., & Ono, M. (2017). Correlation between driveline features and driveline infection in left ventricular assist device selection. Journal of Artificial Organs, 20(1), 34-41.
- Bernhardt, Alexander M., et al. “Prevention and early treatment of driveline infections in ventricular assist device patients–The DESTINE staging proposal and the first standard of care protocol.” Journal of critical care 56 (2020): 106-112.
- Walker, Paul C., et al. “Surgical infection prophylaxis for left ventricular assist device implantation.” Journal of cardiac surgery 26.4 (2011): 440-443.
- Lucke, L., & Bluvshtein, V. (2014, August). Safety considerations for wireless delivery of continuous power to implanted medical devices. In 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (pp. 286-289). IEEE.
