Abstract Candida infective endocarditis (CIE) is a rare but serious complication of candidemia. Incidence and risk factors associated with CIE among candidemic patients are poorly defined from small cohorts. Identification of clinical predictors associated with this entity may guide more judicious use of cardiac imaging. We conducted a retrospective analysis of all inpatients aged ≥18 years diagnosed with candidemia at our institution. CIE was diagnosed by fulfilling two of the major Duke criteria: specifically a vegetation(s) on echocardiogram and positive blood cultures for Candida spp. We used univariable and multivariable regression analyses to identify risk factors associated with CIE. Of 1,873 patients with candidemia, 47 (2.5%) were identified to have CIE. In our multivariable logistic model, existing valvular heart disease was associated with a higher risk for CIE (adjusted odds ratio [aOR], 7.66; 95% confidence interval [CI], 2.95–19.84). Predictors that demonstrated a decreased risk of CIE included infection with C. glabrata (aOR, 0.17; 95% CI, 0.04–0.69), hematologic malignancy (aOR, 0.09; 95% CI, 0.01–0.68), and receipt of total parenteral nutrition (aOR, 0.38; 95% CI, 0.16–0.91). The 90-day crude mortality for CIE was 48.9%, similar to the overall non-CIE mortality of 41.9% (P = .338). We identified a set of clinical factors that can predict the presence of CIE among patient with candidemia. These findings may reduce the need for unnecessary expensive and invasive imaging studies in a subset of patients with a lower risk profile for endocarditis and alternative infection source.

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients’ 2nd test samples underwent SARS-CoV-2 antigen testing, and culture with Vero-hACE2-TMPRSS2 cells. Viral RNA and cultivable virus were recovered from the cultured cells after qRT-PCR and plaque assays. Of 20 patients, 10 (50%) had a solid organ transplant and 5 (25%) had a hematologic malignancy. For most patients, RT-PCR Ct values increased over time. There were 2 patients with positive viral cell cultures; one patient had chronic lymphocytic leukemia treated with venetoclax and obinutuzumab who had a low viral titer of 27 PFU/mL. The second patient had marginal zone lymphoma treated with bendamustine and rituximab who had a high viral titer of 2 x 106 PFU/mL. Most samples collected ≥7 days after an initial positive SARS-CoV-2 RT-PCR had negative viral cell cultures. The 2 patients with positive viral cell cultures had hematologic malignancies treated with chemotherapy and B cell depleting therapy. One patient had a high concentration titer of cultivable virus. Further data are needed to determine risk factors for persistent viral shedding and methods to prevent SARS-CoV-2 transmission from immunocompromised hosts.

BackgroundDetermining the extent of cryptococcal disease (CD) is key to therapeutic management. Treatment with fluconazole is only recommended for localised pulmonary disease. Induction therapy with amphotericin B (AmB) and flucytosine is recommended for disease at other sites, irrespective of central nervous system (CNS) involvement, but this is not often followed in patients without meningitis. In this study, we compared treatment and mortality between patients with CD of the CNS and other extrapulmonary (OE) sites.MethodsThis is a retrospective, single‐centre study of all hospitalised patients with nonpulmonary cryptococcal infection from 2002 to 2015 who underwent lumbar puncture. Demographics, predisposing factors, comorbidities, clinical presentation, laboratory values, antifungal treatment and mortality data were collected to evaluate 90‐day mortality and treatment differences between patients with OE and CNS CD. Survival analysis was performed using multivariable Cox regression analysis.ResultsOf 193 patients analysed, 143 (74%) had CNS CD and 50 (26%) had OE CD. Ninety‐day mortality was 23% and similar between the OE and CNS CD groups (22% vs 23%, p = .9). In the comorbidity‐adjusted multivariable Cox regression model, mortality risk was similar in the OE and CNS groups. Fewer patients with OE CD received induction therapy with AmB and flucytosine compared to those with CNS disease (28% vs 71.3%, p < .001).ConclusionPatients with OE CD had similar 90‐day mortality compared to those with CNS disease. Despite current guideline recommendations, patients with OE disease were less likely to receive appropriate induction therapy with AmB and flucytosine compared to patients with CNS disease.

Background Immunocompromised (IC) patients (pts) can have prolonged SARS-CoV-2 PCR positivity, even after resolution of COVID-19 symptoms. This study aimed to determine if viable virus could be detected in samples collected &gt; 21 days after an initial positive (pos) SARS-CoV-2 PCR in IC pts. Methods We obtained 20 remnant SARS-CoV-2 PCR pos nasopharyngeal swabs from IC pts (bone marrow or solid organ transplant, high dose steroids, immunosuppressive medications) with a pos repeat PCR within the previous 30 days. The repeat specimens were cultured on Vero-hACE2-TMPRSS2 cells and incubated for 96 hours to assess viral viability. Viable RNA and infectious virus in the cultured cells were measured by qPCR and infectious plaque assays. RNA sequencing was performed on a HiSeq platform (Illumina). Samples also underwent SARS-CoV-2 antigen (Ag) testing (BD Veritor). Clinical data were extracted from the electronic health record by chart review. Results Pt characteristics are in Table 1. Viral cultures from the repeat specimen were negative (neg) for 18 pts and pos for 2 (Table 2). Pt 1 is a 60M treated with obinatuzumab 19 days prior to his first pos PCR test, with repeat specimen collected 21 days later (cycle threshold (Ct) not available). Pt 1 had a low viral titer (27 PFU/mL) & a D614G mutation on sequencing. Pt 2 is a 75M treated with rituximab 10 days prior to his first pos PCR test, with repeat specimen collected 23 days later (Ct 27.56/27.74). Pt 2 had a high viral titer (2e6 PFU/mL) and D614G, S98F, and S813I mutations. Demographics of Study Population (N=20) Characteristics of patients with a positive SARS-CoV-2 viral culture Conclusion 90% of specimens collected &gt; 21 days after an initial pos SARS-CoV-2 PCR did not have viable virus detected on their repeat specimen. The 2 pts with pos viral cultures had active hematologic malignancies treated with an anti-CD20 mAb at the time of COVID-19 diagnosis. One pt had a high concentration of active, viable virus. No known variants of concern were noted in this cohort, collected in Q2 2020, though prolonged replication is a risk for variant development. Further data are needed about risk factors for persistent viable viral shedding & methods to prevent transmission of viable virus from IC hosts. Disclosures Victoria J. Fraser, MD, CDC Epicenters (Grant/Research Support)Cigna/Express Scripts (Other Financial or Material Support, Spouse is Chief Clinical Officer)Doris Duke Fund to Retain Clinical Scientists (Grant/Research Support, Research Grant or Support)Foundation for Barnes-Jewish Hospital (Grant/Research Support, Research Grant or Support)NIH (Grant/Research Support, Research Grant or Support) Victoria J. Fraser, MD, Centers for Disease Control and Prevention (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; Cigna/Express Scripts (Individual(s) Involved: Spouse/Partner): Employee; Doris Duke Charitable Foundation (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; The Foundation for Barnes-Jewish Hospital (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Michael S. Diamond, MD, PhD, Carnival Corporation (Consultant)Emergent BioSolutions (Grant/Research Support)Fortress Biotech (Consultant)Immunome (Advisor or Review Panel member)Inbios (Consultant)Moderna (Grant/Research Support, Advisor or Review Panel member)Vir Biotechnology (Consultant, Grant/Research Support) Carey-Ann Burnham, PhD, BioFire (Grant/Research Support, Other Financial or Material Support)bioMerieux (Grant/Research Support)Cepheid (Consultant, Grant/Research Support)Luminex (Grant/Research Support)Roche (Other Financial or Material Support) Carey-Ann Burnham, PhD, BioFire (Individual(s) Involved: Self): Grant/Research Support; bioMerieux (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator, Speakers’ bureau; Cepheid (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator; Luminex (Individual(s) Involved: Self): Scientific Research Study Investigator Hilary Babcock, MD, MPH, FIDSA, FSHEA, Nothing to disclose