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Abstract Background We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10–15 hours) from the initial and 21 hours (17–29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)–infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3–5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases.

Abstract Background The role of sequential blood culture time to positivity (TTP) as a surrogate marker for bacterial load and as a prognostic indicator in S. aureus bacteremia (SAB) is not well established in the literature. Methods We performed a single healthcare system, multi-site, retrospective review of adult patients with positive blood culture for S. aureus between January 2019 and December 2019. Sequential TTP was defined as the TTP of the first subsequent blood cultures obtained from patients with SAB for at least 24 hours. We adapted the previously described TTP ratio of < 1.5 as the cut-off for study groups. Infective endocarditis (IE) was defined according to modified Duke’s criteria. High-grade bacteremia was defined as the growth of the organism in two or more sets of blood cultures or growth in >50% of all bottles collected. Descriptive, comparative statistics and survival analysis were performed using Python 3 and IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp. Results A total of 602 patients with SAB were identified, and 186 patients who met the study criteria were included. Sixty-nine patients (37%) were female, and the mean age was 63.6 years. Patients with initial TTP < 12 hours had higher 30-day and 90-day mortality than those with initial TTP ≥ 12 hours. Patients with TTP ratio of > 1.5 had higher rates of cardiac prosthetic device (30 [26.1%] vs. 9 [12.7%], p = .03) and high-grade bacteremia (106 [92.2%] vs. 56 [78.9%], p = .01). In univariate analysis, history of myocardial infarction, cardiac prosthetic device, and findings of high-grade bacteremia and native valve vegetation in echocardiogram were significant predictors for a TTP ratio of < 1.5. In multivariate analysis, native valve vegetation (OR 2.4; 95% CI 1.2-4.84), and high-grade bacteremia (OR, 0.3; 95% CI, 0.13- 0.77) were independent predictors (Table 1 and 2). No differences in 30- day or 90-day survival based on the TTP ratio were seen (Figure 1). Figure 1.Kaplan-Meier (KM) curves and log rank test results based on time to positivity (TTP) of initial blood cultures and TTP ratio of sequential to initial blood culture The X-axis represents the days elapsed from the initial blood culture collection. Number of patients at risk and events are given below the x-axis for each group. 30-day and 90-day survival rates were significantly lower in patients with initial TTP of < 12 hours compared with those with ≥ 12 hours. There were no statistically significant differences in survival based on TTP ratio. Conclusion In patients with SAB, a second TTP to first TPP ratio of > 1.5 was associated with higher rates of presence of the cardiac prosthetic device and high-grade bacteremia. Initial TTP < 12 hours was associated with lower survival; however sequential TTP ratio didn’t predict mortality. Disclosures All Authors: No reported disclosures.

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia requires weeks of IV antimicrobial therapy for treatment with antistaphylococcal penicillins (ASP) and first-generation cephalosporins being mainstays of therapy. While effective, use of these agents in the outpatient setting requires frequent dosing along with close toxicity monitoring through the duration of therapy. Ceftriaxone is an appealing alternative given daily dosing and tolerability, but efficacy in this setting remains uncertain. We sought to review outcomes of patients who received ceftriaxone versus an ASP and first-generation cephalosporins for definitive therapy of MSSA bacteremia. Methods Following IRB approval, we reviewed medical records of a retrospective adult cohort diagnosed with MSSA bacteremia treated with ceftriaxone, cefazolin, or an ASP between January 2018 and December 2019 at Mayo Clinic campuses. Treatment was defined as the antibiotic used in the outpatient setting. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic relapse. Secondary outcomes were 30-day treatment failure and individual components of treatment failure. Multivariable Cox regression analysis was performed to analyze for an association between ceftriaxone use and the primary outcome after adjusting for factors that may also impact outcomes. Kaplan-Meier curves were compared utilizing a log-rank test for survival between groups. Results A total of 223 patients with the accompanying characteristics met study criteria (Table 1). Thirty-seven received ceftriaxone (16.5%) and 186 (83.4%) were treated with cefazolin or an ASP. Ninety and 30-day treatment failure were higher in those treated with ceftriaxone (27%, 8.1%) compared to cefazolin or an ASP (8.6%, 3.8%). Multivariable analysis for risk of 90-day treatment failure revealed a hazard ratio of 2.91 for ceftriaxone (Table 2) and a significant difference in event-free survival for those treated with ceftriaxone compared to cefazolin or an ASP (Figure 1). Conclusion Patients receiving definitive therapy with ceftriaxone for MSSA bacteremia experienced a higher rate of 90 and 30-day treatment failure and a lower rate of event-free survival as compared to those treated with cefazolin or an ASP. Disclosures All Authors: No reported disclosures.

AbstractBackgroundThere is insufficient evidence regarding postoperative systemic antibiotic prophylaxis use for more than 24 h following cardiovascular implantable electronic devices (CIED) implantation and its impact on infection prevention. However, this strategy remains a common practice in many institutions.MethodsWe conducted a systematic review and meta‐analysis including studies that compared the outcomes of patients: (1) who received preoperative plus 24 h or more of postoperative antibiotic prophylaxis (intervention group); and (2) who received either preoperative only or preoperative plus less than 24 h of antibiotic prophylaxis (control group). Risk of bias was assessed with ROBINS‐I and ROB‐2 tools. Risk ratio (RR) was pooled using random‐effect meta‐analyses with inverse variance method.ResultsEight studies that included two randomized controlled trials (RCTs) and six cohort studies with a total of 26,187 patients were included in the analysis. Overall, there were no differences in outcomes between the two groups, which included rates of CIED infection (RR 0.77, 95% CI 0.42, 1.42), mortality (RR 1.19, 95% CI 0.69, 2.06), pocket hematoma (RR 1.15, 95% CI 0.44, 3.00) or reintervention (RR 0.87, 95% CI 0.22, 3.46). Of note, the results were primarily impacted by the larger RCT.ConclusionsThere was no benefit of postoperative antibiotic prophylaxis for more than 24 h following CIED implantation in the current systematic review and meta‐analysis. This supports the practice advocated by current guidelines which foster antibiotic stewardship and may result in reductions of adverse drug events, selection for antibiotic resistance, and financial costs of prolonged postoperative antibiotic prophylaxis.

Abstract Background Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4–78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0–36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0–51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1–27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

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 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