Cardiac transplantation from infected donors: is it safe?

BACKGROUND: Transplantation of a cardiac allograft from an infected donor risks transmission of disease to the immunocompromised recipient. Such organs are often not utilized despite little supporting evidence. We sought to evaluate outcomes following cardiac transplant with the use of an infected allograft. METHODS: The UNOS/OPTN database was used to identify first time, adult heart transplant recipients from 1995 to 2009. Patients receiving allografts from blood culture positive donor (CPD) were compared to those who did not (NCPD). RESULTS: A total of 26,813 recipients were included. Nine hundred ninety-five (3.7%) received a heart from a CPD. Recipients of hearts from CPDs were more likely to be diabetic (24% vs. 20%, p = 0.01), hypertensive (42% vs. 38%, p = 0.02), status 1 (80% vs. 76%, p = 0.0021), have a BMI > 30 (19% vs. 16%, p = 0.001), on intra-aortic balloon pump (IABP) support (7% vs. 5%, p = 0.017), and worse functional status. Recipients with a CPD were more likely to be treated for a post-transplant infection (28% vs. 23%, p = 0.003) but not for an episode of rejection in the first year after transplantation (39% vs. 40%, p = 0.73). Receipt of a CPD allograft was not a multivariate predictor for mortality. CPD and NCPD survival was similar at one year (86% vs. 87%, p = 0.2585) and 15 years (34% vs. 36%, p = 0.0929). CONCLUSION: Use of allografts from CPD has no influence on survival despite the fact that these recipients tend to have a higher acuity and more comorbidities at the time of transplantation. Utilization of a heart from a donor with a confirmed blood stream infection should be carefully considered.

Antimicrobial agents, drug adverse reactions and interactions, and cancer.

The intent of this chapter is to review the types of adverse drug reactions and interactions associated with antimicrobial agents, specifically in the setting of patients with malignancies. The initial sections will discuss categorizing and describing the mechanisms of adverse reactions and interactions. The later sections include a detailed discussion about adverse reactions and drug interactions associated with commonly used antibacterial, antiviral, and antifungal agents in this subpopulation. Where relevant, the clinical use and indication for the drugs will be reviewed. The antibacterial section will specifically address the emergence of antimicrobial resistance and drugs of last resort (newer agents, such as linezolid and daptomycin and novel uses of older previously retired agents, such as polymyxin B). The antifungal section will address the ramification of pharmacokinetic interactions and the need to measure drug levels. The chapter is not meant to be exhaustive and as such will not extensively address all antimicrobials or all interactions for each of these agents.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to resolve complex clinical cases of patients with recurrent bacteremias.

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms. Throughout Europe, it is already in routine use but has not yet been widely implemented in the United States, pending FDA approval. Here, we describe two medically complex patients at a large tertiary-care academic medical center with recurring bacteremias caused by distinct but related species. Bacterial identifications were initially obtained using the Vitek-2 system with the GPI card for Enterococcus and the API system for staphylococci. Initial results misled clinicians as to the source and proper management of these patients. Retrospective investigation with MALDI-TOF MS clarified the diagnosis by identifying a single microorganism as the pathogen in each case. To our knowledge, this is one of the first reports in the United States demonstrating the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with recurrent bacteremias of unclear source.

Multicenter, prospective clinical evaluation of respiratory samples from subjects at risk for Pneumocystis jirovecii infection by use of a commercial real-time PCR assay.

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection. Microscopic diagnosis, including diagnosis using the Merifluor-Pneumocystis direct fluorescent antigen (MP-DFA) test, has limitations. Real-time PCR may assist in diagnosis, but no commercially validated real-time PCR assay has been available to date. MycAssay Pneumocystis is a commercial assay that targets the P. jirovecii mitochondrial large subunit (analytical detection limit, ≤ 3.5 copies/µl of sample). A multicenter trial recruited 110 subjects: 54 with transplants (40 with lung transplants), 32 with nonmalignant conditions, 13 with leukemia, and 11 with solid tumors; 9 were HIV positive. A total of 110 respiratory samples (92% of which were bronchoalveolar lavage [BAL] specimens) were analyzed by PCR. Performance was characterized relative to investigator-determined clinical diagnosis of PCP (including local diagnostic tests), and PCR results were compared with MP-DFA test results for 83 subjects. Thirteen of 14 subjects with PCP and 9/96 without PCP (including 5 undergoing BAL surveillance after lung transplantation) had positive PCR results; sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were 93%, 91%, 59%, and 99%, respectively. Fourteen of 83 subjects for whom PCR and MP-DFA test results were available had PCP; PCR sensitivity, specificity, PPV, and NPV were 93%, 90%, 65%, and 98%, respectively, and MP-DFA test sensitivity, specificity, PPV, and NPV were 93%, 100%, 100%, and 98%. Of the 9 PCR-positive subjects without PCP, 1 later developed PCP. The PCR diagnostic assay compares well with clinical diagnosis using nonmolecular methods. Additional positive results compared with the MP-DFA test may reflect low-level infection or colonization.

Gallium-67 Single-Photon Emission Computed Tomography Affects Management of Infections of Left Ventricular Assist Devices.

Our institution employs gallium-67 single-photon emission computed tomography low-dose CT (Ga-SPECT-CT) to determine the presence and extent of left ventricular assist device (LVAD) infections. We present a retrospective single-center study of 41 LVAD recipients who underwent Ga-SPECT-CT from January 2011 to June 2018 to determine whether Ga-SPECT-CT led to changes in antimicrobial therapy, LVAD revision or exchange, or application for 1A exception. The average age was 56.6 years, predominantly male (80.5%) and diabetic (68.3%), divided between ischemic (48.8%) and nonischemic (51.2%) cardiomyopathy. The majority had HeartMate II devices (82.9%). Device-related infections were classified as possible (12.2%), probable (36.6%), proven (36.6%), or rejected (14.6%). Sensitivity was 68.6% and specificity was 100%. Most VAD-specific infections were percutaneous deep driveline infections (DRIs) (34.1%), and VAD-related infections were primarily bloodstream infections (31.7%). Staphylococcus aureus was the major pathogen isolated. Gallium-67 single-photon emission computed tomography low-dose CT resulted in changes in management in more than half (53.7%) of patients: starting (24.4%) or stopping (17.1%) antimicrobial therapy, LVAD revision (22.0%) or exchange (12.2%), and the application for 1A exception for transplant listing (17.1%). We conclude that Ga-SPECT-CT is an effective modality for determining the presence and extent of LVAD DRIs, and contributed to a change in management in more than half of cases.

Continuous-Flow Left Ventricular Assist Device Survival Improves With Multidisciplinary Approach.

BACKGROUND: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy. METHODS: Between January 2012 and December 2016, 124 consecutive patients underwent primary HeartMate II implantation at our institution. In January 2015, we instituted a HTMCS approach consisting of (1) daily simultaneous cardiology/cardiac surgery/critical care/pharmacy/coordinator rounds, (2) pharmacist-directed anticoagulation, (3) speed optimization echocardiogram before discharge, (4) comprehensive device thrombosis screening and early intervention, (5) blood pressure clinic with pulsatility-adjusted goals, (6) early follow-up after discharge and individual long-term coordinator/cardiologist assignment, and (7) systematic basic/advanced/expert training and credentialing of ancillary in-hospital providers. All patients completed 1-year of follow-up. RESULTS: Demographic characteristics for pre-HTMCS (n = 71) and HTMCS (n = 53) groups, including age (55.8 ± 12.1 versus 52.5 ± 14.1 years, p = not significant), percentage of men (77.5% versus 71.7%, p = not significant), and Interagency Registry for Mechanically Assisted Circulatory Support class 3 (84.5% versus 83.0%, p = not significant), were comparable. One-year survival was 74.6% versus 100% for the pre-HTMCS and HTMCS groups, respectively (p = 0.0002). One-year survival free of serious adverse events (reoperation to replace device or disabling stroke) was 70.4% versus 84.9% for the pre-HTMCS and HTMCS groups, respectively (p = 0.059). Event per patient-year rates for disabling stroke (0.15 versus 0, p = 0.019), gastrointestinal bleeding (0.87 versus 0.51, p = 0.11), and driveline infection (0.24 versus 0.10, p = 0.18) were lower for the HTMCS group, whereas pump thrombosis requiring device exchange was higher (0.09 versus 0.18, p = 0.14). CONCLUSIONS: Implementing a comprehensive multidisciplinary approach substantially improved outcomes for recipients of continuous-flow left ventricular assist devices.

False positive hepatitis C antibody test results in left ventricular assist device recipients: increased risk with age and transfusions.

Left ventricular assist devices (LVADs) have been successfully used in patients with heart failure. However, LVADs may trigger immune activation, leading to higher frequencies of autoantibodies. We describe the clinical, epidemiological, and laboratory characteristics of LVAD recipients with false positive hepatitis C (FPHC) serology among 39 consecutive adult LVAD recipients who bridged to heart transplantation from January 2007 to January 2013 at Montefiore Medical Center. FPHC patients were identified as those with post-LVAD positive hepatitis C ELISA antibody tests and negative confirmatory testing with hepatitis C RNA PCR and/or radioimmunoblot assay. Ten (26%) patients previously seronegative for hepatitis C were found to have FPHC after device placement. Of the 39 patients, 32 had HeartMate II devices. The mean age at LVAD placement was 55 years. FPHC correlated with older age at the time of LVAD implantation and with receipt of packed red blood cell transfusions, but not with gender, fresh frozen plasma transfusions, panel reactive antibodies, globulin fraction, rheumatoid factor, or anticardiolipin antibodies. Clinicians should be aware of this increased risk of FPHC in older LVAD patients and those more heavily transfused in order to avoid unnecessary apprehension and possible delay in transplantation. Further studies should be done to evaluate the possible relationship between transfused blood products and immunomodulation.

Role of gallium SPECT-CT in the diagnosis of left ventricular assist device infections.

Infection remains a well-established complication after the placement of left ventricular assist devices (LVADs). Defining the extent of infection is a challenging task as there are few effective imaging modalities and no standardized guidelines regarding imaging in the diagnosis of device-related infections (DRIs). The use of gallium with single photon emission tomography-computed tomography (Ga-SPECT-CT) has not been previously reported in localizing DRIs. We reviewed the charts and images of five patients with LVADs who underwent Ga-SPECT-CT for the diagnosis of various types of DRIs. Gallium SPECT-CT further clarified the extent of infections among LVAD patients, allowing for patient-specific tailored treatments including surgical debridement. Gallium SPECT-CT is a useful tool when diagnosing LVAD infections and could potentially be the imaging modality of choice in the near future. With improved imaging studies, such as Ga-SPECT-CT, allowing for earlier and more accurate diagnoses of DRIs, the outcome of such infections is likely to improve.