Challener, Douglas W.

Abstract Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Abstract Background Staphylococcus aureus bacteremia (SAB) is common and is characterized by high rates of morbidity and mortality. The clinical importance of a single positive blood culture bottle (SPBCB), however, is poorly defined despite it being a frequent laboratory finding. We therefore examined patients with SPBCB to determine its clinical significance and to understand the rationale of current practice. Methods We performed a retrospective, multicenter study of patients with a SPBCB for S. aureus in initial cultures from January 2019 to December 2019 using data collected from both electronic health records and the clinical microbiology laboratory. Results Overall, 534 patients with SAB were identified, and 118 (22.1%) had a SPBCB. Among SPBCB cases, 106 (89.3%) were classified as clinically significant while 12 were considered contaminated or of unclear clinical significance. Baseline characteristics were similar between the groups (Table 1). A majority (92.4%) received antibiotic therapy, but patients with clinically significant bacteremia were treated with a longer antibiotic course (25.9 vs 5.7 days, p< 0.001). Outcomes between those with SPBCB (contaminant vs clinically significant) were similar (Table 2). Of note, while there was no difference in use of echocardiography based on PREDICT criteria between the clinically significant SPBCB vs. the multiple positive blood culture bottles (MPBC) cohorts (Table 3), significant differences were seen in both frequency of echocardiography (65.1% vs. 84.6%, P< 0.001) and IE diagnosis (3.8% vs. 14.2%, P=0.002) for patients in the SPBCB vs. MPBC groups, respectively. In addition, those with MPBC had higher 90-day, 6-month and 1-year mortality rates. Conclusion SPBCB was documented in almost one-quarter of SAB cases and should trigger a thorough investigation as its associated mortality was high and complications, including IE, occurred. Although some SPBCB cases may represent contamination, antibiotic treatment of SPBCB was commonplace. Patients with clinically significant SPBCB were less likely to undergo echocardiography and had a reduced prevalence of an IE diagnosis as compared to those with MPBC. Patients with SPBCB may have a more favorable long-term prognosis as compared to that in patients with MPBC. Disclosures Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant) Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant

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 Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess. Methods Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020. Results Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica, followed by Nocardia wallacei and Nocardia cyriacigeorgica. Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection. Conclusions Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control.

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 < .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 Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.

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

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID pos ; n = 2,317) versus COVID-19-negative (COVID neg ; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID pos over COVID neg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID pos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

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.