Brumble, Lisa

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures

Abstract Background. Renal transplant recipients are at increased risk for developing complications of vaccine-preventable diseases. They benefit from a comprehensive pre-transplant evaluation when they might safely receive live vaccines. The primary aim of our study was to investigate the number of renal transplant recipients who were evaluated for serologic status against measles, mumps, rubella (MMR), and varicella. Secondarily, we investigated if pre-transplant Infectious Diseases consultation (IDC) improved vaccination rates. Methods. We retrospectively analyzed 282 kidney-alone and kidney-plus adult transplant recipients who were born in or after 1957. Patients were evaluated at Mayo Clinic, Florida Transplant Center between January 2015 and December 2017. Serologic status evaluation and vaccination rates were compared in two groups created based on IDC and no ID consultation (NIDC). Results. 235 (83%) of a total 282 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 235 IDC candidates. Among the IDC patients, mumps, measles and rubella IgG serologies were performed in 7 (3%), 143 (61%) and 144 (61%), respectively. Among 44 patients seronegative for any of MMR, 24 (55%) were vaccinated. Ten (66%) of 15 varicella seronegative patients were vaccinated. Zostavax was not given to 18% of IDC patients. Zostavax and MMR were administered more frequently in the IDC group compared to NIDC (p < .001 and p = 0.0016, respectively). Conclusion. Although the majority of patients had IDC, the screening rate for MMR serologies was lower than varicella. A protocol-driven serologic screening similar to the one for VZV is required for MMR. Pre-transplant IDC increases vaccination rates.

AbstractOptimizing immunity against vaccine‐preventable diseases improves outcomes in kidney transplant (KT) patients (Arora et al,World J Transplant, 2019, 9:1; Sester et al,Transplant Rev, 2008, 22:274; Fishman,N Engl J Med, 2007, 357:2601). The American Society for Transplantation (AST) Clinical Practice Guidelines advises that serologic screening for measles, mumps, and rubella (MMR) be conducted for all KT candidates, since live‐attenuated vaccines are contraindicated post‐transplantation (Malinis et al,Clin Transplant, 2019, 33:e13548). Our team at Mayo Clinic Florida (MCF) conducted a quality improvement (QI) initiative to establish a best MMR screening and immunizations clinical practice in KT candidates using a Plan‐Do‐Study‐Act (PDSA) model. By retrospective chart review of all KT candidates evaluated at our institution from January 1, 2016 to December 31, 2017, baseline data determining the rate of MMR serologic screening was established. PDSA cycles were implemented to adopt protocol‐driven testing for MMR serologies, immunization documentation, and vaccination in cases of seronegativity to any of the three MMR viruses in all pre‐KT candidates. Two PDSA cycles were completed in 4 months. The study population totaled 447 patients (baseline n = 283, PDSA 1 n = 61, PDSA 2 n = 103). Baseline data showed that 83% (n = 235) of pre‐KT candidates received infectious disease consultation (IDC). Complete MMR (all three viruses) serological screening in KT candidates improved from baseline 3.9%‐87.4% post‐PDSA cycle 2 (P < .001). Necessary immunizations per AST guidelines were ordered in only 41.1% (n = 23) of the control cohort vs 100% (n = 12) and 96.9% (n = 31) of PDSA cycles 1 and 2, respectively (P < .001). The data reflect significant practice improvements in MMR screening and immunization rates among KT candidates by using protocol‐driven orders combined with our pre‐existing IDCs.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory B-cell lymphoid malignancies. Axicabtagene ciloleucel (axi-cel), an anti-CD19 CAR-T not only targets the malignant B-cell, but can potentially also target and eliminate normal B-cells. This can interfere with the normal B-cell repertoire, compromising host humoral immunity such as decreased titers of common vaccines (DTaP, MMR). To assess if this was a clinically significant problem, we evaluated all recipients of axi-cel at our center between 6/2018 through 7/2019. Patients and methods: For patients who received commercial axi-cel, humoral immunity was evaluated both quantitatively [absolute lymphocyte count (ALC)] as well as qualitatively by serology titers [IgG antibodies (Abs)] for diphtheria, tetanus, pertussis, measles, mumps, and rubella, and total Immunoglobulin G (IgG) levels. Data was collected within 30 days prior to CAR-T infusion, then at day +30 and between days +60 and +100 after CAR-T infusion. Results: We identified 10 patients (males = 5, 50%), with a median age of 49.9 years (range 30-65) who received commercial axi-cel during the study period. Patient characteristics and indications for CAR-T therapy are shown in Table 1; the cohort represented a heavily pre-treated aggressive B-cell lymphoma patient population. Baseline information on antibody (Ab) titers was available in 8 patients. At baseline, all patients had positive tetanus IgG Abs (≥0.01 IU/mL), 7 had positive diphtheria IgG Abs (≥0.01 IU/mL), 6 had positive measles IgG Abs (≥ 1.1 AI), 5 had positive rubella IgG Abs (≥ 1.0 AI), 3 had positive mumps IgG Abs (≥ 1.1 AI). None of the patients had a positive pertussis IgG Abs (≥100 IU/mL). At follow-up, all patients with positive Ab at baseline maintained titers in the positive range at day +30 and between days +60 and +100 (Figure 1). None of the patients demonstrated a clinically meaningful decrease in Abs titers, despite a drop in ALC and IgG levels (table 2). Conclusions: Albeit a small sample size, IgG Ab titers for diphtheria, tetanus, measles, mumps, and rubella did not appear to be affected by axi-cel at a short interval follow-up after infusion (up to day +100). We plan to extend this analysis in a larger cohort with a longer-term prospective follow-up to validate our findings, especially in light of dropping absolute lymphocyte counts and IgG levels. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding. Foran:Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Mundi-pharma: Research Funding; DTRM Biopharma: Research Funding; BMS: Research Funding. Chanan-Khan:Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; AbbVie: Research Funding; Xencor: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

AbstractBackgroundSolid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre‐transplant infectious disease consultation (IDC) improves vaccination rates.MethodsThis study was an institution‐based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC).ResultsOne hundred and eighty‐seven (77%) of a total 242 patients received an IDC pre‐transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients, vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre‐transplant IDC patients and only in 9 (16.7%) NIDC patients (P < .001).ConclusionsDespite the relatively high IDC rate, patients’ screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol‐driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.

AbstractBackgroundInvasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited.MethodThe present analysis describes data from 15 US centers that prospectively identified IC from nearly 17 000 OTRs. Analyses were undertaken to determine predictors of infection and mortality.ResultsA total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra‐abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All‐cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non‐white race and female gender were more commonly associated with non‐albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species.ConclusionThese data highlight the common and distinct features of IC in OTRs.

SummaryAs invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti‐fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk‐groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995–2003) and E2, (2004–2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while ‘other’ dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin‐echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90‐day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti‐fungal therapy has not improved survival.

ABSTRACT Here we describe the first reported case of Nocardia beijingensis infection in the United States, made rarer by its presence in an immunocompetent patient.

Background necrotizing fasciitis (NF) represents a life-threatening bacterial infection characterized by a rapid necrosis of deep subcutaneous tissue and facia underlying the skin. Despite its lethal nature, NF occurs infrequently, leaving many physicians unfamiliar with the disease process, common pathogens, and treatment strategies. Here we present a case of NF caused by an unlikely organism,Vibrio parahaemolyticus. We highlight the innocuous nature of initial presentation and the potentially devastating sequela.