Sohail, M. Rizwan

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 We describe and compare the clinical, diagnostic evaluation and outcomes of patients who underwent therapeutic management for pyogenic brain abscess. Methods We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009 through June 30, 2020. Results 231 patients were identified during the study period. Sixty-one (26.4%) patients received antibiotic therapy alone, and 170 (73.6%) had a combination of antibiotic therapy and surgical intervention. The median age for the medical and combined therapy group was 59 years and 58 years, respectively. Patients who received medical treatment had a higher prevalence of infective endocarditis than those who received combined therapy (6.6% vs. 0.6%; P=0.005). The medical therapy group was more likely to have brain MRI and cranial CT than the patients with combined therapy (75.4% vs. 63.5%; P=0.041). Midline shift (11.5% vs. 31.2%; P=0.002), a single (21% vs. 83%; P=0.001) and greater size (1.4 cm vs. 2.5 cm; P=0.007) brain abscess was significant when comparing medical vs. surgically managed abscess. Stereotactic surgical technique was the preferred diagnostic approach for the medical group (65.6% vs. 46.5%; P=0.010), and excision/craniotomy for the combined group (31.1% vs. 53.5%; P=0.002). Streptococcus viridans group was the predominant organism (32.8% and 25.9%; P=0.30). Compared to those who received combined therapy, patients with medical therapy alone were most likely to receive cephalosporin (72.1% vs. 41.2%; P=< 0.0001), vancomycin (23% vs. 12.4%; P=0.047) and metronidazole (27.9% vs. 14.7%; P=0.022). In both groups, median duration of antimicrobial therapy was 42 days (P=0.12). Patients with medical therapy alone had a higher mortality rate (18% vs. 7.1%; p=0.014) but less neurologic sequelae (21.3% vs. 30.6%; P=0.16) compared with combined therapy. Medical Management. Organism isolated in the medical management group Combined Management. Organism isolated in the combined management group Demographic and Clinical Characteristics of Patients with Brain Abscess who Underwent Therapeutic Management Conclusion Most patients with pyogenic brain abscess had no identified risk factors, and brain MRI and cranial CT were the diagnostic imaging modalities of choice. Compared to those who received medical therapy alone, patients with combined treatment had a single and greater size fluid collection with the presence of midline shift. A prompt combined surgical and medical approach with prolonged antimicrobial therapy can cure the infection. Outcomes of Patients with Bacterial Brain Abscess Radiologic and Surgical Diagnosis of Patient with Brain Abscess who Underwent Therapeutic Management Disclosures John C. O’Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant) M. Rizwan Sohail, MD, Medtronic Inc., Philips, and Aziyo Biologics, Inc (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Individual(s) Involved: Self): Consultant; Philips (Individual(s) Involved: Self): Consultant

Abstract Background Based on expert opinion, solid organ transplant recipients from donors with bacteremia are treated with 7-14 days of pre-emptive antibiotic therapy (PAT). However, studies addressing necessity, optimal duration of therapy, and outcomes in kidney transplant recipients (KTR) are lacking. Methods We retrospectively reviewed all kidney transplants performed at our institution from 01/01/2015-01/01/2021 to identify those cases where matched deceased donors had positive blood cultures. Bacteremia was defined per CDC criteria. We analyzed rate of infection in the KTR with the same organism identified in the donor blood culture within 30 days of transplantation. Results A total of 56 KTRs with donor positive blood cultures were identified. Demographic data are summarized in Table 1. Twenty of 56 cases (35.8%) had bacteremia and 36 (64.2%) had organisms classified as common commensals. The most common organisms in the bacteremia group were Gram-negative bacteria (12/20) and Staphylococcus aureus (6/20). Most common commensals were coagulase-negative staphylococci (26/36) (Table 2). All KTR received preoperative antibiotics at the time of transplantation, primarily cefazolin (15/20), and vast majority received TMP/SMX prophylaxis, for Pneumocystis jirovecii, post-transplant (19/20). PAT was administered in 70% (14/20) cases of bacteremia for a median of 8.5 days (IQR 7-14), while six cases were left untreated (Table 2). In contrast, majority of cases with common commensals were not treated (75%, 27/36). Of the cases treated (9/36), median duration of therapy was 7 days (IQR 5-14). No cases of infection with the same organism identified in the donor blood culture were reported in KTR within 30 days of transplantation. Conclusion KTR donors with bacteremia who were treated received a median of 8.5 days of PAT with no instances of breakthrough infection. In contrast, majority of donor blood cultures with organisms classified as common commensals were not treated and did well. Future studies are needed to assess whether perioperative antibiotics coupled with TMP/SMX prophylaxis post-transplantation are sufficient in select cases of transplantation from donors with bacteremia. Disclosures All Authors: No reported disclosures

Abstract Background Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past two decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED and determination of device infection among patients without clinical findings of pocket site infection is often difficult. Our study examines the characteristics, management, and outcomes of SAB in patients living with CIED using 2019 international criteria to define CIED infection. Methods We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from January 1, 2012 to December 31, 2019. Patients who met CIED infection criteria following SAB based on the 2019 European Heart Rhythm Association International Concensus Document were identified. A time-to-event analysis was used to determine the impact, if any, of complete device extraction on outcomes. Results Overall, 110 patients with CIED developed SAB and 92 (83.6%) of them underwent transesophageal echocardiogram (TEE). Eighty-eight (80%) had CIED infection with 57 (51.8%) and 31 (28.2%) patients meeeting criteria for definite and possible CIED infections, respectively. Forty-three (75.4%) patients with definite CIED infection underwent complete device extraction. For possible and rejected CIED infection, the rates of complete device extraction were 35.5% and 27.3%, respectively (p< .001 for each). The primary endpoint of a composite of one-year mortality and SAB relapse had a rate that was significantly lower in patients with CIED infection who underwent complete device extraction as compared to that of patients who did not undergo device extraction (25.9% vs. 76.5%, p< .001). No significant difference in outcomes was seen in the rejected CIED infection group (33.3% vs. 62.5%, p =.27). Conclusion The rate of CIED infections following SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria were likely operative, in part, in accounting for the the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with either definite or possible CIED infection as defined by the 2019 consensus document to improve one-year mortality and SAB relapse rates. Disclosures 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 Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)

Abstract Background Serial blood cultures are integral in managing Staphylococcus aureus bacteremia (SAB) as clinicians rely on the results to determine infectious complication risks and antibiotic duration. Current IDSA guidelines suggest a single set of negative blood cultures is adequate evidence of SAB clearance. Several studies, however, have identified the skip phenomenon (SP), which is the occurrence of intermittent negative blood cultures, and have recommended obtaining additional blood cultures to document bacterial clearance (Table 1). We therefore examined patients who manifested the SP to determine its clinical significance and to study this, associations were tested for SP in relation to various baseline factors as well as clinical outcomes. Methods We performed a retrospective, multicenter study of all patients with a positive blood culture for S. aureus from January 2019 to December 2019 using data collected from electronic health records and the clinical microbiology laboratory. Results A total of 602 patients with SAB were identified and 495 patients were included in the investigation (Figure 1). Overall, 25 (5.1%) patients had the SP. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use, automatic implantable cardioverter defibrillator, and community onset of infection in the SP cohort (Table 2). Moreover, the median duration of SAB was longer (3.2 [2.3-5.4] vs 1.90 [1.2-2.9] days, p=0.002), and high-grade SAB, (88.0% vs 58.7%, p=0.004), complicated bacteremia (92.0% vs 67.9%, p=0.011) and IE diagnosis (28.0% vs 11.3%, p=0.013) were all more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached statistical significance (p=0.055). Analysis of 435 hospital survivors revealed no significant differences in rates of 1-year mortality or 90-day relapse between the two groups (Table 3). Conclusion Findings of the current investigation demonstrates an increased risk of SAB complications in patients with the SP and support the notion that serial negative blood cultures are needed to document clearance of SAB. Disclosures 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 Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)

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

Aim To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. Methods A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. Results Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. Conclusion Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. Trial registeration number CRD42020191196.

Abstract Background The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. Methods A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. Results Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. Conclusions The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Objectives: Clinicians need to identify which patients presenting with S. aureus bacteremia (SAB) have underlying cardiovascular implantable electronic device (CIED) infection and therefore need device extraction. The goal of this study was to identify clinical predictors of CIED infection in patients presenting with SAB. Methods: We retrospectively reviewed all cases of SAB in CIED recipients at Mayo Clinic from Jan 2001 to Dec 2011. CIED infection was defined using clinical, microbiologic and echocardiographic criteria. Patients who presented with clinical signs of CIED pocket infection were excluded. A multivariable model was developed to identify independent predictors of CIED infection. Model discrimination was summarized using the area under a receiver operating characteristics curve (AUC). Results: Among the 131 patients with SAB and CIED, 45 (34%) had underlying CIED infection. Permanent pacemaker (PPM) devices (OR 3.90, 95% CI 1.65-9.23, p=0.002), >1 device-related procedure (OR 3.30, 95% CI 1.23-8.86, p=0.018), and duration of SAB ≥4 days (OR 5.54, 95% CI 3.32-13.23, p <0.001) were independently associated with an increased risk of CIED infection. The AUC for this multivariable model was 0.79 indicating good discriminatory capacity to separate SAB patients with and without CIED infection. Various combinations of these three features and the corresponding predicted probabilities of CIED infection are summarized in Table. Conclusions: An individual patient’s risk of underlying CIED infection can be calculated based on the type of device, number of device-related procedures, and duration of SAB. Patients without any of these high-risk features have very low risk of underlying CIED infection and may be monitored closely without immediate device extraction.

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.