Mahmood, Maryam

Abstract Patients with blood culture-negative endocarditis due to Bartonella infection frequently presented with fever, cytopenias, kidney failure, and positive PR3-ANCA. Bartonella IgG titers were variable. Patients commonly underwent surgery with overall low mortality.

Objective: Our study aimed to assess the impact of pharmacogenomic panel testing in people with HIV (PWH). Design: Prospective, observational intervention assessment Methods: One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants’ current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes. Results: Ninety-six participants (median age 53 years, 74% white, 84% men, 89% viral load <50 copies/ml) completed panel testing, yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild–moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in one participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants. Conclusion: Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.

Abstract Background Deep brain stimulator (DBS)–related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9–6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Abstract Background Eculizumab, an inhibitor of terminal complement activation, has been utilized in pre-transplant desensitization, treatment of antibody-mediated rejection and thrombotic microangiopathy in solid organ transplant recipients (SOTR). Eculizumab is associated with meningococcal disease, leading to guidelines for vaccination against serogroups ACWY (menACWY) and B (menB) at least 2 weeks prior to eculizumab therapy. In persons requiring emergent use of eculizumab, prophylaxis for at least 2 weeks is recommended. SOTRs respond suboptimally to vaccination, raising consideration for pre-transplant vaccination and prolonged prophylaxis in those undergoing eculizumab therapy. We sought to describe meningococcal vaccination and prophylaxis practices among SOTRs receiving eculizumab. Methods We performed a retrospective chart review of meningococcal vaccination, including number and timing pre- or post-transplant, along with prophylaxis prescribing and duration in SOTRs receiving eculizumab across 3 distinct Mayo Clinic Enterprise sites (Rochester, Arizona, and Florida). Results 200 SOTRs receiving at least one dose of eculizumab between 1/1/2008 and 9/16/2021 were reviewed. Eculizumab indications included antibody mediated rejection (38%), desensitization (26%), and thrombotic microangiopathy (19%). 83% (166/200) of SOTRs received eculizumab for an unanticipated post-transplant complication. Vaccination rates were 82% (164/200) and 35.5% (71/200) for menACWY dose 1 and 2, respectively, and 54% (108/200) and 28.5% (57/200) for menB dose 1 and 2, respectively. The majority received their first vaccination post-transplant: menACWY 66.5% (133/200) and menB 2.5% (185/200). Among those without vaccination pre-eculizumab, 22.3% (41/184) were not prescribed prophylaxis. The median duration of prophylaxis was 62 (range 4-2651) days. Conclusion Most SOTRs underwent meningococcal vaccinations near the time of eculizumab administration post-transplant for an unanticipated complication. One-fifth of those meeting criteria were not provided meningococcal prophylaxis. These findings may support pre-transplant administration of meningococcal vaccinations and heightened awareness for meningococcal prophylaxis in SOTRs receiving eculizumab. Disclosures All Authors: No reported disclosures.

Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.

Abstract We provide an elaborate review of cases published between January 2005 and April 2021 on hemophagocytic lymphohistiocytosis (HLH) in HIV patients. Seventy articles describing 81 adult patients (age ≥19 years) were included. The median age was 40 years, and 78% were males. Only 65% were known to have HIV before presentation. CD4 count was ≥200 cells/mm3 in 23%, and HIV viral load was &lt;200 copies/mL in 41%. The lack of meticulous reporting of ≥5 of 8 criteria for HLH diagnosis was evident in a third of cases. At least 1 infectious agent—other than HIV—was believed to trigger HLH in 78% of patients. The most common were Epstein-Barr virus (26%), human herpesvirus 8 (21%), and Histoplasma capsulatum (17%). Sixty percent survived. Among those, 93% received treatment for identified secondary trigger(s), while 51% received HLH-directed therapy. There was significant heterogeneity in the treatment regimens used for HLH.

Abstract Background Increasing use of deep brain stimulation (DBS) over the past 20 years is paralleled by a rise in DBS infections. There is a paucity of data on the diagnosis, management, and outcomes in such infections. We describe our center’s experience with DBS infections. Methods Adults ( &gt;18 years) diagnosed with DBS associated infection between January 1, 2000 and May 1, 2020 were retrospectively reviewed. Data on patient demographics, clinical presentation, microbiology, and management was collected. Results Seventy cases were identified (table 1). The mean age at diagnosis was 58.9 ± 16.5 years. The bulk were free of comorbidities. Parkinson’s disease and essential tremors were the most common indications for DBS placement. The median time from implantation to infection was 4 months [IQR 1,24]. The neurotransmitter and extension wires were the most frequently infected parts. A microbiological diagnosis was made in 89% of cases, 47% of which were polymicrobial. The most commonly identified organisms were Staphylococcus aureus, Cutibacterium acnes, and coagulase-negative staphylococci. For patients with deep infection, 71% had complete device extraction, 20% partial extraction, and 9% device retention; clinical cure at 3 months occurred in 97%, 64% and 100%, respectively (figure 1). On the other hand, 93% of patients with superficial infection had device retention; cure at 3 months was seen in 64% (figure 2). Suppressive oral antibiotics were rarely used, 45% of patients with partial extraction and 26% with device retention. DBS was reimplanted in 71% of patients after complete extraction and led to reinfection in 30% at 1 year follow up. Median time to reimplantation was 2.7 months. All patients who failed at 3 months in the partial extraction and device retention cohorts subsequently underwent complete device removal leading to clinical cure sustained at 1 year follow up. Conclusion All patients who had complete extraction achieved clinical cure at 3-months follow-up, while high failure rates occurred in those with device retention. Most infections were polymicrobial and predominantly caused by gram-positive pathogens. Thirty percent of patients with re-implantation after complete device extraction developed re-infection within 1 year. Disclosures All Authors: No reported disclosures

Endogenous endophthalmitis caused by Enterococcus gallinarum, an organism with intrinsic resistance to vancomycin, has rarely been reported. We present a case of persistent E. gallinarum bacteremia in a female recipient of hematopoietic stem cell transplant (HSCT) complicated by endophthalmitis and meningoventriculitis, resulting in a fatal outcome despite treatment with intravenous ampicillin and daptomycin. Treatment of endophthalmitis often presents a challenge due to the lack of options for antimicrobials with reliable ocular penetration. Therapeutic decisions can become particularly complex with the involvement of drug-resistant pathogens and host characteristics that limit the choice of antimicrobials due to drug toxicity. This case illustrates a rare manifestation of an opportunistic pathogen.

Abstract Background Human Immunodeficiency Virus (HIV) outcomes have significantly improved at the expense of other age-related diseases including chronic kidney disease. Early reports of people living with HIV (PLWH) undergoing deceased-donor kidney transplantation (DDKT) showed poor outcomes, but these have notably improved after introduction of antiretrovirals. Despite years of experience, the optimal induction immunosuppression (IIS) in PLWH remains subject of debate. Large-scale studies describing the current ISS practices in PLWH undergoing DDKT are lacking. Here, we describe the U.S. national trends of IIS used in PLWH undergoing DDKT from 2000 to 2018 using the United Network of Organ Sharing (UNOS) database. Methods We analyzed the UNOS database to determine the selection of IIS in PLWH undergoing first-time DDKT between 1/1/2000 and 12/31/2018. Cases with unknown HIV status at the time of transplant were excluded. Age, sex and demographics were analyzed. The regimen used for IIS was compared based on HIV serostatus and the change in induction regimen was trended over time. Results A total of 139,650 cases underwent DDKT during the study period. Among these, 1,384 were identified as HIV-positive. PLWH were significantly younger than HIV-negative (49±10 years vs. 51.6 ± 15.3 years; p&lt; 0.001) (Table 1). A greater proportion of men was seen in the PLWH group compared to HIV-negative persons (76.2% vs. 60.4%; p&lt; 0.0001). In the HIV-negative group, 12.1% undergoing DDKT did not receive IIS compared to 16.4% in PLWH (p&lt; 0.0001). Medications that have significantly increased in use with years in PLWH included rabbit anti-thymocyte globulin (rATG), steroids, and basiliximab (3.54, 3.25, 2.28, respectively; p&lt; 0.001). On our trend analysis (Figure 1), the percentage of PLWH receiving any IIS is increasing by 4.04% each year (p&lt; 0.001). Table 1 Figure 1 Conclusion Our study suggests that IIS is an increasing practice in PLWH undergoing DDKT, predominantly using rATG, steroids, and basiliximab. Understanding the current practices might lead to further studies to determine the long-term outcomes after different induction regimens in PLWH. Disclosures All Authors: No reported disclosures