Cevallos, Edison Cano

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.

Initial microbiologic diagnosis of infective endocarditis (IE) relies on blood cultures and Bartonella and Coxiella burnetii serology. Small case series and one prospective study have preliminarily reported application of metagenomic sequencing on blood or plasma for IE diagnosis.

Abstract Background Central-line associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters can prevent extraluminal infections, intraluminal infections remain a source of CLABSIs with limited prevention options. Methods In this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally on the surface of platinum electrodes polarized at a constant potential of 1.5 VAg/AgCl was developed. After 24h of pre-polarization at 1.5 VAg/AgCl, their activity was tested by inoculating four clinical isolates derived from catheter-related infections, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium and Escherichia coli. Figure 1. In vitro catheter and e-catheter models. Results E-catheters generated a mean HOCl concentration of 15.86±4.03 μM and had a mean pH of 6.14±0.79. e-catheters prevented infections with all four species, with an average reduction of 8.41±0.61 log10 CFU/mL at 48h compared to controls. Figure 3. Measurement of pH and HOCl at 48 hours in polarized e-catheters. Each dot represents a replicate; bars represent means. Figure 4. Prevention of infection after 48 hours of polarization (24 hours of infections) using e-catheters (polarized and non-polarized) compared to blank catheters. * indicates statistically significant reduction of cell counts in polarized e-catheter compared to blank catheter (p <0.05). Conclusion Polarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection. Disclosures Haluk Beyenal, Ph.D, patent (Other Financial or Material Support, HB holds a patent: Beyenal H CD, Fransson BA, Sultana ST. . 2018. Electrochemical reduction or prevention of infections. U.S. patent 20180207301A1, international patent WO/2017/011635.) Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor's Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor's stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant

Catheter-related infections constitute an economic and mortality burden in health care. Several options are available to reduce the risk of infection, but only a few focus on preventing intraluminal infection, which occurs in long-term catheters, most often used for dialysis, prolonged treatment, or chemotherapy.

Abstract Coccidioidomycosis is an endemic fungal infection that is typically asymptomatic or associated with pulmonary disease. Extrapulmonary disease may involve the skin, bones, or central nervous system, yet endovascular infections are exceedingly rare. We report the first case, to our knowledge, of coccidioidomycosis of the native aorta in an immunocompromised host.

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold, or e-scaffold, that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations toxic to humans as a prototype of a device being developed to treat wound infections in humans.

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< 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< 0.0001). In the HIV-negative group, 12.1% undergoing DDKT did not receive IIS compared to 16.4% in PLWH (p< 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< 0.001). On our trend analysis (Figure 1), the percentage of PLWH receiving any IIS is increasing by 4.04% each year (p< 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

Abstract Background More than 90% of reported penicillin allergies are found inaccurate when formally assessed. These allergy labels lead to decreased utilization of first-line beta-lactam antibiotics, and adverse clinical outcomes. The objective of this study was to develop a multi-disciplinary approach to decrease inaccurate labeling among hospitalized patients with documented penicillin allergy. Methods A team of clinicians, pharmacists, and nurses utilized the DMAIC quality strategy to improve accuracy of penicillin allergy labeling. Allergic reactions were stratified to develop a penicillin allergy de-labeling algorithm (Figure 1). Admission to the intensive care unit (ICU) for anaphylaxis was defined as a balancing measure. We reviewed baseline data from patients with a documented penicillin allergy admitted to a single inpatient floor at Mayo Clinic, Rochester between June and October 2019. A cause and effect diagram was used to conduct a root cause analysis. The intervention was then applied to patients who reported penicillin allergy admitted to the same floor from November 2019 to January 2020. Study data were collected and basic descriptive statistics generated. Figure 1: Penicillin allergy delabeling algorithm Results 96 patients were included in the control group with mean age of 71 years (range 65–84 years) and 55% females. Breakdown of documented allergic reactions are represented in Figure 2. 58 (60%) received an antibiotic for a median duration of 1.5 days (IQR: 0 – 6). Of these, 7(12%) received penicillin-class antibiotics, and 41 (70.6%) received non-beta-lactam antibiotics. 2 (2%) of these patients were de-labeled without any penicillin skin tests. Detailed metrics of each PDSA cycle are shown in Table 1. During PDSA cycle 2, inaccurate penicillin documentation was removed in 9/19 (47.4%) of hospitalized patients. There were no ICU admissions for anaphylaxis. Figure 2: Graphic representation of proportion of type of documented allergic reactions to penicillin Table 1: Metrics and outcomes at baseline and during successive PDSA cycles Conclusion Various factors contribute to penicillin allergy mislabeling. Our comprehensive algorithm addresses nuances of penicillin allergic reactions and increased accurate penicillin allergy labeling in 47.4% of the cases. Beta-lactam use also increased to 37% through our pilot project while maintaining patient safety. A multi-disciplinary and patient-centered approach aligned with institutional workflows is necessary to improve patient outcomes. Disclosures All Authors: No reported disclosures

Abstract Background Cryptococcus spp is a major cause of opportunistic infections in immunocompromised patients, primarily due to Cryptococcus neoformans and Cryptococcus gattii. There are occasional reports of other Cryptococcus species causing invasive human disease. However, their epidemiology and clinical significance are not fully defined. We sought to describe cases with cultures positive for Cryptococcus species other than C neoformans and C gattii. Methods A retrospective descriptive analysis of clinical and laboratory data of patients with cultures growing Cryptococcus species other than C neoformans and C gattii from November 2011 to February 2019 was performed. Three Mayo Clinic sites in Arizona, Florida, and Minnesota were included. Results From 176 cases with a culture growing Cryptococcus spp, 54 patients (30%) had a culture for Cryptococcus other than C neoformans and C gattii in the study time frame. The most common species were Cryptococcus magnus, Cryptococcus laurentii, and Cryptococcus ater. The organisms were isolated and identified in culture of bronchoalveolar lavage (11), skin (11), urine (7), oral (4), sinus (3), intraoperative soft tissue (3), sputum (2), synovial fluid (2), cerebrospinal fluid (2), and intravenous catheter (2), among others (7). Only 8 (15%) cases were considered to be potentially pathogenic, with 1 case of invasive disease. Antifungal treatment was fluconazole, itraconazole, and griseofulvin, for a mean systemic antifungal duration of 42 days. Conclusions This large series of patients with Cryptococcus spp other than C neoformans and C gattii suggests that these species rarely cause clinically significant infection in humans. Only 1 case of invasive disease was found.

Abstract Background Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention. Methods The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient’s isolate and determined by safranin staining. Results Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.