Citations

Abstract Background Transcatheter aortic valve replacement (TAVR) was initially approved as an alternative to surgery for patients at high surgical risk. However, it is now being considered for patients with intermediate and low surgical risk. This will result in the expansion of patient pool for TAVR; hence it is of interest to ascertain risk of blood stream infection (BSI) and infective endocarditis (IE) following TAVR. We aim to study the incidence, epidemiology and risk factors associated with IE in patients who underwent TAVR and subsequently developed a BSI. Methods A population-based study was conducted in 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (E-REP) for all adult (≥18 years) patients who underwent TAVR from January 1st, 2010 to December 31st, 2018. Transcatheter procedures that included replacement of either the aortic or mitral valve were included. Medical records were screened for development of BSI from time of TAVR until May 15th, 2020. Patients were classified as having BSI only, BSI with IE at outset, or BSI with subsequent development of new IE. ‘Early’ IE was defined as that occurring < 12 months following TAVR, with subsequent cases defined as ‘late’ IE. Results A total of 247 patients underwent TAVR during the study period. There were 24 patients with of BSI and 10 (42%) developed IE with an annual incidence of 5 per 1000 persons-years. Median age for patients who developed IE was 85.4 years. Male gender was affected predominantly (70%). Six developed IE at outset of BSI, while four developed IE subsequent to IE. The median time to development of IE was 791 days following TAVR. There was an equal number of early and late IE cases (n=5). The most common pathogen causing IE was viridians group streptococci (n=4) followed by enterococci and coagulase-negative staphylococci with 2 patients each. Mean Charlson comorbidity index was 6.6. Two patients with IE died before resolution of infection (20%). Conclusion The incidence of BSI and subsequent IE in patients with TAVR was low in our population. Due to the small number of BSI and IE cases, statistical analysis was not feasible. An analysis of all cases seen at Mayo Clinic is planned since the number of cases would be much higher to investigate potential risk factors associated with BSI and IE. Disclosures Larry M. Baddour, MD, Boston Scientific (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)

Abstract Background The etiology of febrile neutropenia in patients with hematological malignancy is identified in only 20–30% of cases. Sinus computed tomography (CT) is often used, regardless of symptoms, to rule out rhinocerebral source of infection. There are no clear guidelines on when to perform sinus CT in this population. In this study, we evaluated the role of sinus CT in febrile neutropenic patients. Methods We retrospectively reviewed medical records of all adults (age ≥18 years) with febrile neutropenia (T≥ 38.3ºC, ANC < 0.5 x 109/L) and hematological malignancies who underwent sinus CT from January 2014 to May 2020. We present the preliminary analysis of the impact of sinus CT findings on the management of febrile neutropenia. Results 47 patients with a total of 56 episodes of febrile neutropenia met the inclusion criteria. The median age at presentation was 57 years (IQR: 42 - 68 years). The most common underlying malignancy was acute myeloid leukemia (51%), followed by myelodysplastic syndrome (19%). At presentation, 47% had refractory disease, 21% were newly diagnosed, 15% had relapsed, 15% were in complete remission, and 2% were in partial remission. Of the total 56 episodes, 29 (52%) had symptoms of rhinorrhea (20%), facial pain (14%), and sinus congestion (14%). The remaining 27 of 56 episodes (48%) had no sinus symptoms. Sinus CT was abnormal in 48 of 56 episodes (86%); the most common finding was mucosal thickening (47/48; 98%), followed by air-fluid levels (7/48; 14.5%), partial opacification (6/48; 12.5%), complete opacification (2/48; 4%), and bony invasion (2/48; 4%). The source of febrile neutropenia was attributed to the CT sinus findings in 9 cases (9/48; 29%), leading to a change in therapeutic management. All 9 patients were symptomatic, with evidence of necrosis in 22% (2/9) and purulence in 22% (2/9) on nasal endoscopy. Table 1 Conclusion Mucosal thickening is a frequent and non-specific imaging finding, particularly in patients without sinus symptoms. Sinus CT findings in patients with febrile neutropenia without sinus symptoms had no impact on clinical management. Consequently, sinus CT may be reserved for patients presenting with sinus symptoms. Disclosures M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)

Abstract Background The survival benefit of combination antifungal therapy for invasive mucormycosis (IM) in patients with hematologic malignancy (HM) and hematopoietic cell transplant (HCT) is not well defined. Methods This multicenter, retrospective study included HM and HCT recipients with proven or probable IM between January 1, 2007 and December 31, 2017 from 10 transplant centers across North America. Results Sixty-four patients with proven (n = 47) or probable (n = 17) IM defined by 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) consensus definitions were included. Thirty-nine (61%) were HCT recipients (95% allogeneic). Sites of infection included rhino-orbital-cerebral (33), pulmonary (30%), disseminated (19%), gastrointestinal (3%), and cutaneous (3%). Surgical debridement was performed in 66%. Initial antifungal treatment consisted of the following: lipid formulation of amphotericin B (AmB) alone (44%), AmB + posaconazole (25%), AmB + echinocandin (13%), AmB + isavuconazole (8%), posaconazole alone (5%), and isavuconazole alone (3%). All-cause mortality at 30 days and 1 year were 38% and 66%, respectively. Initial treatment with AmB plus posaconazole or isavuconazole (n = 28) was associated with a trend toward lower treatment failure compared with AmB (n = 21) (42% vs 64%, P = .136). Conclusions Long-term survival with IM among HM and HCT populations remains poor. However, initial use of AmB + azole in conjunction with surgery may result in less treatment failure. More evidence from prospective controlled studies is needed to confirm this observation.

AbstractBackgroundAscertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources.MethodsWe retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.ResultsA total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.ConclusionsPatients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.

Abstract Objectives Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. Methods We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. Results Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96–1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00–1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. Conclusions Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.

Abstract Background Post-operative management of patients undergoing cardiac transplantation with an infected left ventricular assist device (LVAD) is unclear. Methods We retrospectively screened all adults with an LVAD who underwent cardiac transplantation at our institution from 2010 through 2018. We selected all cases of LVAD-specific and LVAD-related infections who were receiving antimicrobial therapy as initial treatment course or chronic suppression at the time of cardiac transplantation. Non-LVAD infections, superficial driveline-infection, or concurrent use of right ventricular assist device or extracorporeal membrane oxygenation device were excluded. Results A total of 54 cases met study criteria with 18/54 (33.6%) classified as LVAD- specific or related infections and 36/54 (66.6%) as non-infected. Cases of LVAD-infection had a higher median Charlson Comorbidity Index score at the time of transplantation compared to non-infected cases (P=.005). Of the 18 cases of infection, 13/18 (72.2%) were classified as LVAD-specific and 5/18 (27.8%) as LVAD-related. A total of 9/13 (69.2%) cases had proven LVAD-specific infections. Antimicrobial therapy was extended post-transplant to treat preceding LVAD-specific infection in all nine cases (9/13, 69.2%) with a median duration of 14 days (IQR 14-28). Following LVAD removal, antimicrobial treatment was not continued for preceding LVAD-related infections. Conclusions Patients with an LVAD-specific infection were treated with two weeks of pathogen-directed therapy post heart transplant without any relapses. For those without LVAD-specific infection or uncomplicated LVAD-related bacteremia who had completed antimicrobial therapy pre-transplant, antibiotics were discontinued after standard peri-operative prophylaxis and no relapses were observed.

Abstract Background We aim to investigate the incidence, clinical presentation, management, and outcome of infections due to Actinotignum species observed at Mayo Clinic Rochester over the last 5 years. Methods We searched the clinical microbiology laboratory database to identify isolates of Actinotignum spp. from all body sites between January 1, 2014 and December 31, 2018. Results Fifty-four patients with positive culture with Actinotignum were identified. Mean age was 67 years and 27 (50%) had an underlying urogenital condition. Actinotignum was isolated in 26 urine cultures, 6 blood cultures, 12 abscess fluid cultures, and 10 bone/joint tissue cultures (Table 1). Fifteen (28%) specimens were monomicrobial while 39 (72%) were polymicrobial. Recovery from urine cultures was interpreted as colonization in 11 (20%) cases. Of the 54 patients with positive cultures, 43 patients had Actinotignum-associated clinical infection; 15 (35%) with urinary tract infections (11 with cystitis and 4 with pyelonephritis), 12 (28%) with abscesses (skin, intraabdominal, and surgical site infections), 10 (23%) with bone/joint infection, and 6 (14%) with bacteremia (Table 2). Most frequently isolated species was A. schaalii (n = 40); followed by 2 cases of A. sanguinis. Susceptibility testing (n = 40) showed that all stains were susceptible to penicillin (MIC< = 0.5), 36% were susceptible to clindamycin (MIC < = 2) and 10% susceptible to metronidazole (MIC < = 8). There was no recurrence of Actinotignum-related infections in any of the treated cases. Two patients with bone/joint infection underwent repeat surgical intervention due to worsening infection while on antibiotic treatment prior to resolution of infection. There was 1 death in a patient with bacteremia (polymicrobial) who had presented with a massive stroke (Table 3). Conclusion A. schaalii was most commonly associated with urinary tract infections followed by abscesses and bone/joint infections in elderly population. Majority of the infections were polymicrobial. All tested isolated were susceptible to penicillin; however, resistance was frequent for clindamycin and metronidazole. All appropriately treated patients had resolution of infection without recurrence from Actinotignum, except for one patient with bacteremia who died from massive stroke Disclosures All authors: No reported disclosures.

Abstract Background Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, “PREDICT,” that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. Methods We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. Results Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke’s criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. Conclusions We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.

Abstract Importance:SARS-CoV-2 virus gains access and infects target cells via angiotensin converting enzyme 2 (ACE2) receptor. Because angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) could increase the expression of ACE2, there are growing concerns that their use could increase the risk of SARS-CoV-2 infection. Cardiac societies have called for epidemiological research about this emerging controversy. Objective:We sought to systematically review the literature and perform a meta-analysis about prior use of ACEI/ARBs and risk of SARS-CoV-2 infection.Data source:We searched multiple data sources including PubMed , ClinicalTrial.org , and medrxiv.org from November 2019 through May 16, 2020. Study selection:Any study that reported on the adjusted association of prior use of ACEIs / ARBs and risk of acquiring SARS-CoV-2 infection was eligible. Two authors independently reviewed eligible studies and extracted data into a prespecified data collection form. Data synthesis:An inverse variance meta-analytic approach was used to pool adjusted odds ratios using a random effect model meta-analysis. I2 test was used to assess in-between studies heterogeneity. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies. Main outcome and Measures:The association between the prior use of ACEIs or ARBs and risk of SARS-CoV-2 infection was assessed using pooled OR and 95% confidence interval. Results:Six case control studies that enrolled a total of 5657 patients (2536 patients in ACEIs arm and 3121 patients in ARBs arm ) and 721,859 controls were included in our meta-analysis. Two of the included studies were from the USA, one from Italy, one from China, one from Spain, and one from South Korea. All included studies scored high based on NOS scale. Prior use of ACEIs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.93, CI (0.85,1.02), I2=20%. Similarly, prior use of ARBs was not significantly associated with an increased risk of SARS-CoV-2 infection, OR 0.86, CI (0.67,1.10), I2=93%. Sensitivity analysis was performed by removing a study that could have been affected by residual confounding; OR for ARB 1.04, CI (0.96,1.12), I2=32%.Conclusion:Findings from this systematic review and meta-analysis suggest that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19. Our results are in support of the recent recommendations of cardiac societies and provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs due to fear of COVID-19.