Khalil, Sarwat

Background: Aortic endograft infection (AEGI) is a rare complication of abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). Surgical explantation with reconstruction is recommended, but data on medical management remain limited. We present our institutional experience with AEGI. Objective: To describe the clinical presentation, microbiology, management strategies, and outcomes of patients with AEGI, with the aim of addressing current gaps in the literature and informing future research to improve patient outcomes. Design: Retrospective descriptive study. Methods: Adult patients admitted with AEGI at our institution between January 2017 and August 2024 were identified using ICD-10 codes and confirmed using the Management of Aortic Graft Infection Collaboration (MAGIC) diagnostic criteria. Clinical, microbiological, radiographic, treatment, and outcome data were collected and analyzed. Results: We screened 517 patients, and 46 met AEGI criteria (EVAR 54%, TEVAR 46%). Most (63%) presented with late-onset infections (⩾3 months). Fever (54%) and sepsis (48%) were common presenting symptoms. Computed tomography (CT) (85%) was the primary imaging modality. Blood cultures were positive in 54% of the cases, with Staphylococcus aureus being the most common monomicrobial pathogen (24%), and 24% of cases were polymicrobial. The majority (67%) received combined medical and surgical therapy. Chronic antibiotic suppressive therapy was used in 34 (74%), most often tetracyclines (33%). Overall, treatment success rates were similar between surgical and medical groups (58% vs 60%, p = 0.250) with comparable mortality. However, relapses were more frequent in the medical-only group (33% vs 16%, p = 0.185). Conclusion: Most patients presented with late-onset AEGI. Fever was absent in nearly half of cases, and blood cultures were positive in only 54%. Overall, surgical and medical therapy had similar success, though relapses were more frequent in those treated medically alone.

AbstractBackgroundOptimal timing of cardiovascular implantable electronic device (CIED) re‐implantation following device removal due to infection is undefined. Multinational guidelines reflect this and include no specific recommendation for this timing, while others have recommended waiting at least 14 days in cases of CIED related infective endocarditis (CIED‐IE). The current work seeks to clarify this issue.MethodsWe retrospectively reviewed institutional data at Mayo Clinic, Minnesota of patients aged ≥ 18 years who developed CIED‐IE from January 1, 1991 to February 1, 2016. CIED‐IE was defined as echocardiogram reported device lead or valvular vegetation. Regression analyses were used to relate the risk of clinical outcomes to the interval between CIED removal and re‐implantation and the location of vegetations.ResultsA total of 109 patients met study inclusion criteria. A majority (68.8%) of patients were men and the median age was 68.0 years. Transoesophageal echocardiogram (TEE) was performed in 95.4% of patients, with valve vegetations detected in 33.9% (n = 37). Survival analysis comparing patients in whom device re‐implantation was < 14 days vs. ≥14 days, and further categorized by those with and without valve vegetation, showed a significant difference (P = 0.028); patients with valve vegetation and reimplantation interval < 14 days had the lowest (58.7%) 12‐month survival. When adjusted for valve vegetation, longer time interval for reimplantation trended toward increased hospital length of stay (P = 0.079).ConclusionOur findings suggest that the recommended 14‐day delay between CIED extraction and re‐implantation in CIED‐IE patients is associated with a survival benefit, but longer length of hospital stay following re‐implantation.

Introduction: Cardiovascular implantable electronic devices (CIED) infections are frequently complicated with bloodstream infection (BSI). Complete device removal and prolonged antimicrobial therapy is essential for cure. The frequency of persistent BSI after source control (device extraction) is not well described. This study aims to assess the utility of repeat blood cultures (BC) after device extraction as recommended by the American Heart Association (AHA) guidelines. Methods: We selected patients who presented with BSI in the setting of CIED infection and underwent device removal at Mayo Clinic Rochester between 2012 and 2017. Cases where BC were not drawn prior to extraction, or repeated within 72 hours of device extraction, or met criteria for contamination were excluded. Results: Of 656 patients who underwent CIED extraction for device infection, 190 with post-extraction BC met study criteria. Among the final study cohort (Table 1), 159 patients had negative BC, while 31 had positive BC following CIED extraction. Pre-extraction, the most common causative organism was Staphylococcus aureus (91/190, 48%) (Figure 1a). Post-extraction, 22 of the 31 (71%) cases of persistent BSI were due to S. aureus (Fig 1b). The median duration of BSI was not significantly different between negative and positive BC groups (3 versus 4 days, p=0.92). Conclusions: Majority of patients had resolution of BSI after CIED extraction. S. aureus was the most common cause of persistent BSI post-extraction. Our findings support the AHA guidelines of repeating BC after device extraction, especially for S aureus .

Abstract Background Conventional blood cultures were compared to plasma cell-free DNA–based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR)/next-generation sequencing (NGS) for detection and identification of potential pathogens in patients with sepsis. Methods Plasma was prospectively collected from 60 adult patients with sepsis presenting to the Mayo Clinic (Minnesota) Emergency Department from March through August 2019. Results of routine clinical blood cultures were compared to those of 16S rRNA gene NGS. Results Nineteen (32%) subjects had positive blood cultures, of which 13 yielded gram-negative bacilli, 5 gram-positive cocci, and 1 both gram-negative bacilli and gram-positive cocci. 16S rRNA gene NGS findings were concordant in 11. For the remaining 8, 16S rRNA gene NGS results yielded discordant detections (n = 5) or were negative (n = 3). Interestingly, Clostridium species were additionally detected by 16S rRNA gene NGS in 3 of the 6 subjects with gastrointestinal sources of gram-negative bacteremia and none of the 3 subjects with urinary sources of gram-negative bacteremia. In the 41 remaining subjects, 16S rRNA gene NGS detected at least 1 potentially pathogenic organism in 17. In 15, the detected microorganism clinically correlated with the patient’s syndrome. In 17 subjects with a clinically defined infectious syndrome, neither test was positive; in the remaining 7 subjects, a noninfectious cause of clinical presentation was identified. Conclusions 16S rRNA gene NGS may be useful for detecting bacteria in plasma of septic patients. In some cases of gram-negative sepsis, it may be possible to pinpoint a gastrointestinal or urinary source of sepsis based on the profile of bacteria detected in plasma.

Abstract Background Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. Methods We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. Results A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2–31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P &lt; .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. Conclusion 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections.

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 &lt; 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 Q fever is a zoonotic disease caused by Coxiella burnetii. Primary infection can progress to persistent infection irrespective of initial symptomatology. Our aim is to describe the clinical features, treatment, risk of progression, use of prophylaxis, and outcomes of Coxiella burnetii infection at our institution. Methods We did a retrospective review of all adult patients with positive Coxiella burnetii serology at Mayo Clinic, Rochester from 1st January 2012 to 31st December 2018. Centers for Disease Control and Prevention (CDC) case definition and classification were used to group the patients into confirmed and probable acute Q fever, and confirmed and probable chronic/persistent Q fever. Data on demographics, clinical presentation, comorbid conditions, exposure history, risk factors associated with progression, serology, treatment and outcomes were collected. Results We found 266 patients with positive titres of Coxiella IgG or IgM greater than 1:16, of which 49 patients met the CDC case definition for Q fever. Median age at presentation was 62 years. 45/49 (91. 8%) were men, while 4/49 (8%) were women. 20/49 (40. 8%) patients presented with acute Q fever of which 5 (25%) patients progressed to persistent infection. 29/49 (59%) patients presented with persistent Q fever of which 4 patients could recall symptoms suggestive of acute Q fever. The most common presentation of acute Q fever was acute febrile illness (65%). Endocarditis (11/29) was the most common presentation of chronic/persistent Q fever. Of the 5 patients with acute Q fever that progressed to persistent infection, 3/5(60%) progressed despite being on doxycycline and hydroxychloroquine. 8/29 patients with persistent Q fever had serological resolution at last follow-up. 2/4(50%) deaths were attributable to Q fever. Conclusion Minority of the patients tested met the case definition. 25% of patients with acute disease progressed to chronic Q fever out of which 60%(3/5) progressed despite prophylaxis. Endocarditis and vascular infections were the most common chronic cases. Interestingly we found 4 cases of MPGN in association with Q fever. Prosthetic valves are the most important risk factors for progression (P = 0.02). Serological cure often lags behind clinical cure (27% vs. 68% in persistent infection)(Table 4). Disclosures All authors: No reported disclosures.

Abstract Background Ocular syphilis is an infrequent presentation of Treponema pallidum infection. It is often seen in association with neurosyphilis but can occur in isolation as well. Here we describe a case series of 10 patients with ocular syphilis seen at our institution. Methods Patients with a diagnosis of ocular syphilis at the three sites of Mayo Clinic were identified from June 2006 to February 2019. Patient’s baseline characteristics, clinical presentation, diagnostic testing, and treatment were abstracted from Electronic Medical Records. Results We identified 10 patients (17 eyes) during the study period, half being diagnosed in the last 5 years. The median age was 51 years (IQR 21–66), and the majority were males (7/10). Characteristics of the patients are outlined in Table 1. Common presenting symptoms included vision loss (8/10), photophobia (4/10), and irritation (5/10). Seven of 10 patients had bilateral involvement. Of the 17 eyes, 59% had pan-uveitis and 82% had disc edema (Table 2). Rapid Plasma Reagin (RPR) was positive in 9 patients and median serum RPR was 1:128 (IQR 1:2-1:1024). One patient was diagnosed with a positive TP-PA, and characteristic ocular findings. One patients had positive 16S Ribosomal RNA Gene PCR/Sanger Sequencing on vitreous humor specimen for Treponema species. The majority of patients had isolated ocular symptoms at presentation; two patients also had an associated skin rash. All patients underwent a lumbar puncture (LP). Half had pleocytosis (TNC > 5) and elevated protein elevated (mean 63.6 mg/dL), although not significantly high. 3/10 patients had VDRL positive in the CSF. Protein levels were much higher in those with positive VDRL. Each patient was treated with intravenous (IV) penicillin for at least 2 weeks. Nine patients received ocular steroids as well. At last available follow-up, 8 had complete and 1 had partial resolution. One had worsened eye findings with eventual scarring. Conclusion Our findings are congruent with increasing incidence of ocular syphilis nationwide. Bilateral eye involvement and pan-uveitis were the most common ocular findings. Although only 3 patients had a positive VDRL in the CSF, pleocytosis and elevated protein were found in a large number of patients. Majority of the patients had clinical resolution with appropriate treatment. Disclosures All authors: No reported disclosures.

Abstract Background Polymerase chain reaction (PCR)/sequencing targeting the 16S ribosomal RNA (rRNA) gene to detect bacteria in normally sterile tissues and fluids has become increasingly popular in clinical medicine. This culture-independent technique can detect bacteria that are nonviable or difficult to cultivate using conventional methods. The clinical value of this type of testing is not well defined. We aimed to assess the diagnostic value of 16S rRNA PCR/Sanger sequencing as a clinical diagnostic assay at Mayo Clinic. Methods This is an interim analysis of the first 173 of 478 patients who had 16S rRNA PCR/Sanger sequencing done on sterile tissues or fluids at our institution from April, 2017 to November, 2018 as part of routine clinical practice. Medical records are being retrospectively reviewed, with results compared with those of culture. Results We reviewed 207 specimens from 173 patients (musculoskeletal 79%, cardiovascular 7%, central nervous system 4%, other 9%) that underwent 16S rRNA PCR/Sanger sequencing by clinical request (Table 1). In 90% of these specimens, the test was pre-planned rather than added-on. Nine specimens were excluded from analysis, as cultures were not performed. Overall concordance of culture with PCR/sequencing was 81% (160/197; P < 0.0001). Of 44 culture-positive specimens, PCR detected the same bacterium in 21 (48%) (Table 2). 45% (20/44) of those with positive cultures and 46% of those with positive PCR/sequencing results had received prior antimicrobial therapy (Table 3). PCR was negative in 139/144 specimens that were culture-negative (97%). PCR/sequencing was helpful in detecting a putative bacterial pathogen in 4 patients with negative cultures (Table 4). Conclusion Overall, 16S rRNA PCR/Sanger sequencing improved diagnostic yield compared with culture in a minority of cases. The described assay is limited by its inability to detect polymicrobial infections, a technical limitation that could possibly be addressed using massive parallel sequencing. Careful selection of cases and a save and add-on approach may be more cost-effective than upfront testing, although this was requested in a minority of cases. 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.

Abstract Background Brevibacterium species are non-motile, catalase-positive, obligate aerobic gram-positive bacilli. Colonies are yellow to gray-white, non-hemolytic, smooth, 6.5% sodium chloride tolerant. B. fermentans post neurosurgical meningitis was first described in 1969 in an infant. B. casei remains the most commonly isolated species (Table 4). The most commonly reported syndromes are bloodstream infections (BSIs) and endocarditis. Despite these reports, this organism continues to be listed on CDC’s NHSN commensal database. Methods Isolates of Brevibacterium from clinical samples at Mayo Clinic, Rochester from January 1, 2014 to December 31, 2018 were identified. Charts were reviewed to determine patient demographics, immune status, source of culture, comorbidities, antibiotic susceptibility test (AST), length of stay (LOS) in hospital and intensive care unit (ICU), and mortality. Likelihood ratio (L-R) and Pearson correlation coefficient (PCC) of nominal data were calculated using the Chi-square test and Fischer exact test (FET). We defined statistical significance as P ≤ 0.05. Results We identified 48 isolates from 45 unique patients, 46% were females. Distribution of age, hospital and ICU LOS, and time to culture growth, and AST data are shown in Table 1. 15.5% patients received allogeneic or autologous stem cell (SCT), or solid-organ transplant (SOT) recipients. 89% cultures were from sterile sources and 68.75% were blood cultures. Of these, 63.64% were monomicrobial. 62% of isolates identified to species level were B. casei. 5 patients were treated; an additional 10 received active antibiotics for other indications. Statistically significant variables are reported in Tables 2 and 3. Thirty-day mortality was 13%. This was higher in patients with bacteremia (L-R: 5.3 [P = 0.02]) but FET was not statistically significance (P = 0.15). Conclusion Accurate diagnosis of Brevibacterium may require molecular techniques. At our center, SCT or SOT recipient status and recent chemotherapy were associated with bacteremia. In these patients, this organism could represent an opportunistic cause of BSI. AST data suggest that Vancomycin offers a reasonable empiric treatment option. Additional data are needed to further define host populations in whom this organism presents pathogenicity. Disclosures All authors: No reported disclosures.