Garrigos, Zerelda Esquer

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)

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.

In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.

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 Approximately one-third of cases of cardiovascular implantable electronic device (CIED) infection present as CIED lead infection. The precise transesophageal echocardiographic (TEE) definition and characterization of “vegetation” associated with CIED lead infection remain unclear. Methods We identified a sample of 25 consecutive cases of CIED lead infection managed at our institution between January 2010 and December 2017. Cases of CIED lead infection were classified using standardized definitions. Similarly, a sample of 25 noninfected patients who underwent TEE that showed a defined lead echodensity during the study period was included as a control group. TEEs were reviewed by 2 independent echocardiologists who were blinded to all linked patient demographic, clinical, and microbiological information. Reported echocardiographic variables of the infected vs noninfected cases were compared, and the overall diagnostic performance was analyzed. Results Descriptions of lead echodensities were variable and there were no significant differences in median echodensity diameter or mobility between infected vs noninfected groups. Among infected cases, blinded echocardiogram reports by either reviewer correctly made a prediction of infection in 6 of 25 (24%). Interechocardiologist agreement was 68%. Sensitivity of blinded TEEs ranged from 31.5% to 37.5%. Conclusions Infectious vs noninfectious lead echodensities could not be reliably distinguished on the basis of size, mobility, and general shape descriptors obtained from a retrospective blinded TEE examination without knowledge of clinical and microbiological parameters. Therefore, a reanalysis of criteria used to support a diagnosis of CIED lead infection may be warranted.

Abstract Background Using synthetic antibiotic‐eluting envelope (ABE) is an effective intervention for prevention of cardiovascular implantable electronic device (CIED) infection. The biologic extracellular‐matrix envelope (ECME), may offer potential advantages over the synthetic ABE. To further minimize the risk of infection, the ECME can be hydrated in gentamicin prior to CIED implantation. We aimed to evaluate the efficacy and pharmacokinetics (PK) of gentamicin containing ECME in an animal model. Methods For all experiments, the ECME was hydrated in gentamicin (40 mg/Ml) (treatment) for 2 min. In vitro antimicrobial efficacy against six different bacterial species was assessed. In vivo experiments were conducted using a rabbit model of CIED pocket infection. Serum and ECM gentamicin concentrations were measured. Five different organisms were inoculated into the device pocket of control (ECME hydrated in 0.9% saline) and treatment groups. Macroscopic appearance and colony forming units from CIED, ECME, and tissue were determined. Results No bacteria were recovered from any culture after 12 h of exposure to the gentamicin containing ECME. Serum gentamicin levels dropped below the limit of quantification at 15 h after implant. Gentamicin concentration in the ECME remained relatively stable for up to 7 days. Signs of clinical infection were observed in the control but not in the treatment group. In the presence of gentamicin, statistically significant reduction was demonstrated across all tested bacterial species. Conclusions In this preclinical animal infection model, gentamicin containing ECME was highly effective in reducing bacterial burden in the implant pocket, while systemic exposure after implantation remained low.

Abstract Background Demographic and epidemiologic characteristics of Hepatitis E virus (HEV) infected patients in the United States are not well-described. HEV infection may result in severe complications and lead to chronic infection and cirrhosis, especially in immunocompromised patients. There are no widely accepted guidelines for HEV screening and testing in the United States. Identifying traits of known seropositive patients and comorbidities may inform better screening and prevention strategies. In this study, we describe rates of liver disease, transplant status, chronic kidney diseases, and diabetes mellitus among patients serologically tested for HEV at our institution. Methods We retrospectively reviewed all patients for whom HEV IgM or IgG serologic testing was performed across the Mayo Clinic enterprise using the Advanced Cohort Explorer tool. For patients with any documented HEV serologic test, we abstracted baseline patient characteristics and underlying comorbidities at the time of testing. We then grouped subjects according to serologic testing results by antibody type. Survival at one year from date of testing was also assessed. Results A total of 979 unique subjects were identified. The preponderance of subjects was Caucasian (781, 79.8%). Of subjects tested for HEV with serology, 123 (12.6%) had any positive serology. Breakdown of baseline characteristics and selected comorbidities are summarized in Table 1. The largest proportion of subjects, 458 (46.8%), were both IgG and IgM negative and 432 subjects received only IgM or IgG testing. Liver disease was more prevalent in patients with positive vs. negative testing (5.8% vs. 2.1%) as was higher age (average 55.1 years vs. 52.2). One-year survival was similar in all groups. Conclusion HEV serology is not commonly tested. Among those tested, seropositivity is uncommon. Our data show higher HEV seropositivity in older adults, which may represent increase risk of exposure over time. Higher percentage of positive testing was also observed in subjects with liver disease, which may indicate a possible etiologic association. Further population-based studies are needed to estimate prevalence of HEV infection and associated liver disease, outcomes in infected patients, and indications for testing in at-risk populations. Disclosures All authors: No reported disclosures.

Abstract Background We recently demonstrated that 16S rRNA PCR/sequencing performed on biofilms dislodged from extracted CIEDs into a salt solution—referred to as “sonicate fluid’ (SF)—may be used to detect pathogens in culture-negative CIED infection (Clinical Infectious Diseases, ciz266, doi:10.1093/cid/ciz266). The method we described included a DNA extraction/purification step, which can be time consuming and costly. Here, we evaluated an extraction-free approach to 16S rRNA gene PCR/sequencing. Methods 28 SF samples derived from explanted clinically-infected CIEDs were tested. Cases were categorized as “culture-positive” (C-P) if ≥20 cfu/10 mL were recovered, and as “culture-negative” (C-N), if <20 cfu/10 mL were detected in SF culture. The extraction-free method consisted of a single step of lysis at 1,000 rpm, 95°C for 5 minutes using an Eppendorf ThermoMixer®. DNA extraction (the comparator method) was performed using the ZymoBIOMICSTM Kit with modifications. Samples were processed using both methods, followed by amplification of the 16S rRNA gene and bidirectional Sanger sequencing. Crossing points (CPs) generated by the two approaches were compared. Organisms detected by the two PCR methods were compared with those detected with culture. Results Of the 28 samples tested, 13 were C-N and 15 C-P. The extraction-free method generated an amplicon in 13/15 C-P cases, with CPs ranging from 26 to 36 cycles vs. 100% (15/15) detected with the DNA extraction method and Cps of 19 to 32. Usable sequence length for the extraction-free method was of 359 (interquartile range, 307–390) vs. 390 (interquartile range, 308–396) base pairs with DNA extraction. Genus-level concordance between bacteria detected by culture in C-P samples and those found using the extraction-free and extraction methods was 92% (12/13) and 93% (14/15), respectively. Bacteria were detected by the extraction method in 2/13 C-N specimens, with none detected with an extraction-free method. Conclusion The described extraction-free method may be suitable for testing SF derived from CIEDs using 16S rRNA gene PCR/sequencing, saving time and cost. More studies are needed to establish clear cutoffs for interpretation of results and to assess for PCR inhibitors in the studied specimen-type. Disclosures Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursement, editor’s stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents.