Endovascular Infection Research Articles

Mural Endocarditis: The GAMES Registry Series and Review of the Literature.

IntroductionMural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis.MethodsPatients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series.ResultsTwenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device-associated IE (DIE), patients with MIE were younger (median age 59 years, p < 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p < 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p < 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p < 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non-MIE, p = 0.006). Mortality was similar.MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p < 0.001), the Charlson Index was lower (1.3 vs. 4.3, p = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p = 0.035). Systemic complications were more common but mortality was similar.ConclusionMIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00490-y.

Complete Genome Sequence of Streptococcus oralis SF100, Isolated from Blood Cultures from a Patient with Infective Endocarditis.

ABSTRACTStreptococcus oralis is a commensal viridans group streptococcus of the human oral cavity and a frequent cause of endovascular infection. Here, we report the complete whole-genome sequence of S. oralis strain SF100, which was originally isolated from the blood of a patient with infective endocarditis. This strain contains the lysogenic bacteriophage SM1, which enhances the virulence of SF100 in animal models of endocardial infection.

A clinical and in vitro assessment of outpatient parenteral benzylpenicillin and ceftriaxone combination therapy for enterococcal endovascular infections.

BackgroundAmoxicillin plus ceftriaxone combination therapy is now standard of care for enterococcal endocarditis. Due to amoxicillin instability in infusion devices, benzylpenicillin plus ceftriaxone may be substituted to facilitate outpatient parenteral antimicrobial therapy (OPAT) delivery, despite lack of guideline endorsement.ObjectivesTo assess the clinical efficacy of benzylpenicillin plus ceftriaxone for the management of enterococcal endovascular infections, in addition to assessing this combination’s in vitro synergy.Patients and methodsRetrospective cohort study assessing unplanned readmissions, relapses and mortality for 20 patients with endovascular Enterococcus faecalis infections treated with benzylpenicillin plus ceftriaxone delivered via OPAT. For a subset of isolates, synergism for both amoxicillin and benzylpenicillin in combination with ceftriaxone was calculated using a chequerboard method.ResultsPatients had endovascular infections of native cardiac valves (n = 11), mechanical or bioprosthetic cardiac valves (n = 7), pacemaker leads (n = 1) or left ventricular assistant devices (n = 1). The median duration of OPAT was 22 days, and the most frequent antimicrobial regimen was benzylpenicillin 14 g/day via continuous infusion and ceftriaxone 4 g once daily via short infusion. Rates of unplanned readmissions were high (30%), although rates of relapsed bacteraemia (5%) and 1 year mortality (15%) were comparable to the published literature. Benzylpenicillin less frequently displayed a synergistic interaction with ceftriaxone when compared with amoxicillin (3 versus 4 out of 6 isolates).ConclusionsLower rates of synergistic antimicrobial interaction and a significant proportion of unplanned readmissions suggest clinicians should exercise caution when treating enterococcal endovascular infection utilizing a combination of benzylpenicillin and ceftriaxone via OPAT.

Distinct contribution of hyperbaric oxygen therapy to human neutrophil function and antibiotic efficacy against Staphylococcus aureus.

Staphylococcus aureus (SA) causes superficial and severe endovascular infections. The present in vitro study investigates the anti-SA mechanisms of hyperbaric oxygen therapy (HBOT) on direct bacterial killing, antibiotic potentiation, and polymorphonuclear leukocyte (PMN) enhancement. SA was exposed to isolated human PMNs, tobramycin, ciprofloxacin, or benzylpenicillin. HBOT was used as one 90-min session. Bacterial survival was evaluated after 4h by quantitative bacteriology. PMN functionality as reactive oxygen species (ROS) production was measured by means of dihydrorhodamine 123 analysis. We showed that HBOT exhibits significant direct anti-SA effects. HBOT increased the anti-SA effects of PMNs by 18% after PMA stimulation (p=0.0004) and by 15% in response to SA (p=0.36). HBOT showed an additive effect as growth reductions of 26% to sub-MICs of tobramycin (p=0.0057), 44% to sub-MICs of ciprofloxacin (p=0.0001), and 26% to sub-MICs of penicillin (p=0.038). The present in vitro study provides evidence that HBOT has differential mechanisms mediating its anti-SA effects. Our observation supports the clinical possibility for adjunctive HBOT to augment the host immune response and optimize the efficacy of antibiotic treatments.

Methicillin-Resistant Staphylococcus Aureus Bacteremia: Epidemiology, Clinical Characteristics, Risk Factors, and Outcomes in a Tertiary Care Center in Riyadh, Saudi Arabia.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has become increasingly common in hospitals worldwide. In an era of pandemics, it is important to understand all types of infectious diseases in order to control its outcome and reduce mortality rates related to it. This study aims to identify the epidemiology of MRSA bloodstream infection, risk factors, and mortality in King Abdulaziz Medical City in Riyadh.MethodsThis is a retrospective chart review study from January 2013 to June 2017. All patients with positive blood culture for MRSA at King Abdulaziz Medical City (KAMC), which is a tertiary care center in Riyadh, Saudi Arabia, were included. Data were extracted from electronic and paper medical records for patients who had a positive blood culture for MRSA. Data collected included demographics, microbiological details, risk factors, and 30-day mortality.ResultsFrom 2013 through June 2017, 633 Staphylococcus aureus bacteremia were reported in KAMC, of which 184 (29.1%) were MRSA with a mean age of 60±19 years. Almost all of our isolates were susceptible to vancomycin, linezolid, and tigecycline. The most common infectious syndrome these patients presented with was an endovascular infection which accounts for 30.4% while 19.9% presented as a case of pneumonia. The mortality within 30 days of collection of the positive blood culture was 20.65%. Male gender (OR = 2.33; 95% CI = 1.34-4.05; P-value = 0.003) and patients with history of recent hospital (OR = 2.34; 95% CI = 1.27-4.34; P-value = 0.007) or ICU (OR = 1.66; 95% CI = 1.09-2.52; P-value = 0.018) admissions were more likely to acquire MRSA.ConclusionsThe incidence of MRSA bacteremia at King Abdulaziz Medical City is high and increasing in conjunction with incidence rate posing a significantly high rate of mortality. Recent history of hospital admission, ICU admission and males were found to be significantly associated with higher rates of MRSA infection. Some modifiable risk factors that could be used to facilitate the reduction of MRSA acquisition rates is to avoid unnecessary hospital and ICU admissions.

Ticagrelor Increases Platelet-Mediated Staphylococcus aureus Killing, Resulting in Clearance of Bacteremia.

Platelets are a critical immune defense against Staphylococcus aureus bloodstream infections. Staphylococcus aureus α-toxin is a virulence factor that decreases platelet viability and accelerates platelet clearance. It has been shown that ticagrelor blocks α-toxin-mediated platelet injury and resulting thrombocytopenia, protecting mice in a lethal S. aureus sepsis model. We now present the use of ticagrelor as adjunctive therapy in a patient with a S. aureus endovascular infection and thrombocytopenia, associated with restoration of platelet count and bacteremia clearance. Ticagrelor enhanced platelet killing of the S. aureus bloodstream isolate from the treated patient in vitro.

A Review of Salmonella Species Bacterial Endocarditis Pathogenic Mechanisms and Populations at Risk

Bacterial endocarditis refers to an infection of the endocardial surface of the heart, and is associated with high morbidity and mortality. The true incidence of bacterial endocarditis is difficult to define but has been estimated to be between 2.6 - 7 cases per 100,000 in developed countries, with an even higher incidence in developing countries. The most common causative organisms of bacterial endocarditis are Streptococcus and Staphylococcus. Salmonella is a rare cause of infective endocarditis, accounting for only 1.3 - 4.8% of total cases, however it is associated with an even greater morbidity and mortality due to the aggressive nature of this pathogen. Given the importance of prompt diagnosis and treatment of Salmonella endocarditis, it is crucial to recognize who is at risk for developing endocarditis due to Salmonella species. In order to understand which populations are at risk, a review of the pathophysiology of Salmonella endocarditis is necessary. This article describes a clinical case of Salmonella endovascular infection, as well as a literature review of the pathophysiology of Salmonella endocarditis. The literature review included case reports, review articles and microbiology textbooks. Findings of the literature review suggest that individuals with gastroenteritis and inflammatory bowel disease are at risk for the development of Salmonella endocarditis due to mechanisms of bacterial translocation and the susceptibility of the intravascular intima to Salmonella species.

Heterogeneidad del tratamiento para cándida parapsilosis en endocarditis micótica de válvula nativa

Las infecciones por cándida en el ámbito intrahospitalario han ido en ascenso en las últimas décadas en especial en las unidades de cuidado intensivo (UCI), dado el uso cada vez más frecuente de antibióticos de amplio espectro y de procedimientos invasivos tanto diagnósticos como terapéuticos. Hoy se consideran las especies de cándida como la cuarta causa de infección del torrente sanguíneo en los Estados Unidos de Norteamérica, con alto riesgo de complicaciones que incluyen endocarditis, trombosis y embolismo séptico al sistema nervioso central (SNC) entre otros. En relación con la endocarditis por especies de cándida, se han considerado de mal pronóstico por el alto riesgo de afectación al SNC, por lo que se ha recomendado el manejo quirúrgico como piedra angular de su tratamiento. A continuación, se describe el caso clínico de un paciente con endocarditis y con candidemia por cándida parapsilosis a quien se le realizó manejo médico.

Systematic Review of the Management of Ureteroarterial Fistulas After Ileal Conduit Urinary Diversion.

OBJECTIVE. No studies or guidelines exist to direct management of ureteroarterial fistula (UAF) after ileal conduit urinary diversion in which the possible risks and complications associated with stent-graft infection from the conduit flora must be reconciled with those of open surgical repair. This study seeks to characterize the clinical presentation, pathogenesis, and optimal diagnostic and therapeutic management of this entity through a systematic review of the literature. MATERIALS AND METHODS. A systematic search of the English-language literature using the PubMed, Scopus, and ScienceDirect databases was performed: 264 abstracts were identified. From those abstracts, 32 studies comprising 40 patients with 43 UAFs were selected for analysis. Data points including demographics, clinical presentation, UAF specifications, procedural details, postprocedural complications, and clinical outcomes were reviewed. RESULTS. Predisposing factors included female sex, chronic ureteral stent placement, and past surgical intervention and irradiation for pelvic malignancy. Fistulization was overwhelmingly unilateral (95.0% of patients) and included the common iliac artery (90.7% of UAFs). Combined endovascular and endoureteral modalities presented similar outcomes compared with surgical approaches in terms of UAF-related mortality (7.1% vs 13.3%, respectively) and complication rates (28.6% vs 26.7%) during a similar median follow-up period (9.5 vs 14.0 months). Endovascular stent-graft infections were present in 14.3% of cases and represented a leading indication for reintervention after endovascular management (50.0%). CONCLUSION. Short- and intermediate-term outcomes of combined endovascular and endoureteral techniques compare favorably with those of surgical approaches in the treatment of UAF after ileal conduit urinary diversion. Although there is a relatively low stent-graft infection rate, close follow-up within the first year after the procedure is required given the propensity of complications to develop during this window. The use of postprocedural antibiotics is uncertain but is likely prudent.

Internación prolongada en un servicio de clínica Médica

In orcler to idenhify detcrmining factors and complicatioris ¡ti illness, we evaluatccl patients under long period hospitalization, in a Clinical Service. Methocls: retrospective and descriptive stud les. Figures were evaluated by Chi, Fisher T and Test T, thrue variables. Wc cal[ long penad hospitalizatíon to a staying of 10 days or longer. Results: 322 patients were evaluated. 50(15,5%) presented (LS) and 272 &lt; 10 days staying. Age average vas 63,8 for &lt; 10 days and 66 for (LS). Mostly of diagnosis at adniission for &lt; 10 days were respiratory dysfunction (25 %) including pneumonia (10 %), urinary infection and heart failure, and for LS pneumonia 20 %, acute neut- ological disease 18 %. The 46 % of LS requireci surgery va. 20,6 % (p &lt; 1,01). The LS neecled parenteral nutrition 26 % vs. 2,5 % (p &lt; 0,02). The average of inaxinuin aniount of drugs/day in staying was: 5.8 for &lt; 10 days and 8.76 for LS (p &lt; 0.01). Hospital coinplications in LS were 28 % VS. 11 % (p &lt; 0.01). mainly nosocoinial pneumonia (p &lt; 0,01) and endovascular infections (p &lt;0.01). Staying in ICU was 54 % for LS va. 19 % (p &lt; 0.01), and average of days in intensive care unit (ICU) vas 8 in LS vs. 3 (p &lt;0,01). There wasn't any difference ¡ti inortality. Conclusion: the admlssi on's diagnosis and the ICU's staying were the main causes of LS, but not so age and co-morbilities studied. The LS patients require more compiex and expensive staying. They present more hospital complications

Intravenous to Oral Switch in Complicated Staphylococcus aureus Bacteremia Without Endovascular Infection: A Retrospective Single-Center Cohort Study.

In this retrospective cohort study, selected patients with disseminated Staphylococcus aureus bacteremia, but without endovascular infection on echocardiography and 18F-FDG-PET/CT, were free of relapse after IV-oral switch. Mortality was low and similar to patients who received prolonged intravenous treatment. IV-oral switch was associated with a shorter length of hospital stay.

Infections Due to Salmonella

Salmonella, which is acquired via ingestion, is classified as nontyphoidal or typhoidal disease. Typhoidal disease is caused by S typhi or S paratyphi, and nontyphoidal disease is caused by all other serovars. Salmonella causes a range of infectious syndromes that include gastroenteritis, bacteremia, endovascular infections, and enteric fever. For immunocompromised hosts or patients with extraintestinal disease, antibiotic therapy should be provided. Effective agents often include third-generation cephalosporins and fluoroquinolones, although rates of resistance of Salmonella isolates to many antibiotics are increasing. A carrier state exists whereby patients may shed bacteria despite being asymptomatic. To eradicate the carrier state, longer courses of antibiotics and, in rare instances, surgical removal of the reservoir, which is most commonly the gallbladder, may be required. This review contains 2 figures, 4 tables, and 24 references. Key Words: Salmonella, typhoidal, non-typhoidal, enteric fever, endovascular infection, gastroenteritis, carrier, food-borne, antibiotic resistance

Susceptibility of Clinical Isolates of Staphylococcus aureus to Ceftaroline

Introduction: Methicillin-Resistant Staphylococcus aureus(MRSA) infection is a major global healthcare problem, the prevalence of which varies from 25-50% in India. It is known to cause Skin and Soft tissue Infections (SSI), endovascular infections, endocarditis, pneumonia, septic arthritis, osteomyelitis, and sepsis. Vancomycin is the drug of choice for treating severe MRSA infections. Ceftaroline, a fifth-generation cephalosporin has been approved by the United States Food and Drug Administration (US FDA) for treating acute bacterial SSI caused by susceptible micro-organisms including MRSA, Community acquired respiratory tract infection, MRSA bacteremia and endocarditis. Aim: To assess the susceptibility of clinical isolates of S. aureusto ceftaroline, in a Tertiary Care Hospital. Materials and Methods: This prospective study was conducted in the Department of Microbiology of a Tertiary Care Hospital over a period of two months from June 2019 to July 2019. S.aureus isolates from various clinical samples were screened for methicillin resistance by disc diffusion method using cefoxitin disc and ceftaroline susceptibility of these isolates was assessed by E-strip method. The isolates were classified as ceftaroline susceptible, Susceptibility Dose Dependent (SDD) and ceftaroline resistant respectively as per CLSI guidelines. A descriptive analysis of the data was done and the results were presented as frequencies and percentages. Results: All the S.aureus isolates were found to be susceptible to ceftaroline. Methicillin Sensitive Staphylococcus aureus(MSSA) isolates had lower Minimum Inhibitory Concentration (MIC) when compared to MRSA. The highest MIC among MRSA was 0.5 μg/mL. Conclusion: Ceftaroline can be considered as an effective alternative for treatment of infections caused by MRSA.

255. Ticagrelor Aids Platelet-Mediated Clearance in a Refractory Staphylococcus aureus Endovascular Infection with Septic Emboli

BackgroundThe pore-forming alpha-toxin produced by Staphylococcus aureus (SA) decreases the viability and increases the clearance of platelets, a critical element of innate immune defense in endovascular infection. Our group recently identified that ticagrelor (TICA) blocks alpha-toxin-induced platelet clearance, protecting mice in a lethal systemic SA infection model. Here, we describe a case report in which TICA, added to antimicrobial therapy of a persistent methicillin-susceptible SA (MSSA) bacteremia associated with a septic aortic thrombus, resulted in immediate bacteremia clearance. We further explore TICA synergy with antibiotics and human platelets in vitro.MethodsAntibiotic susceptibility of an MSSA strain from a patient treated with TICA for refractory bacteremia was tested by MIC and checkerboard assays in MHB or RPMI at standard (105 CFU/mL) or high (107 CFU/mL) inocula using TICA, ertapenem (ETP), cefazolin (CZ), or nafcillin (NAF) alone vs. ETP+CZ ± TICA. Killing assays with human platelets ± TICA against SA were also performed.ResultsSA bacteremia secondary to a septic aortic thrombus (>4 mm) with multiple secondary pyogenic foci refractory to standard CZ and subsequent salvage CZ+ETP for 5 days rapidly cleared within 24 h after the addition of TICA. Thrombocytopenia resolved concurrently. Discontinuation of TICA on day 12 led to rebound thrombocytopenia, and TICA was restarted, once again resulting in resolution of thrombocytopenia. TICA alone lacked in vitro activity against SA, nor was TICA synergistic with ETP+CZ. In contrast, addition of a physiological achievable concentration of TICA dramatically sensitized SA to human platelet killing (p< 0.001) in vitro.Figure 1 Figure 2 Figure 3 ConclusionIn a complex case of aortic plaque rupture with septic thrombus, multiple septic emboli, and refractory MSSA bacteremia, addition of TICA to antimicrobial therapy yielded unanticipated immediate clinical and microbiological success. The profound therapeutic effect of TICA in vivo was corroborated by the enhanced staphylocidal activity of human platelets in vitro in the presence of physiological concentrations of the antiplatelet agent. TICA warrants further study as adjunctive treatment of refractory SA bacteremia due to a primary endovascular focus when thrombocytopenia is present.Disclosures Victor Nizet, MD, Centauri Therapeutics (Advisor or Review Panel member)Cidara Therapeutics (Advisor or Review Panel member)InhibRx (Advisor or Review Panel member)Roche Pharmaceutical (Advisor or Review Panel member)

1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections

BackgroundMSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections.MethodsSixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts.ResultsTwenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578)ConclusionPrevious studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon.Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)

622. Risk Factors for 30-Day Unplanned Readmissions in Patients Discharged with Outpatient Parenteral Antimicrobial Therapy

BackgroundOutpatient parenteral antimicrobial therapy (OPAT) programs have shown to reduce hospital readmissions; however, 20-25% of OPAT patients are readmitted. As 30-day readmissions is a healthcare quality measure, it is important to recognize predictors for readmissions in OPAT patients in an effort to minimize risk factors and optimize patient outcomes. The aim of this study was to identify modifiable and non-modifiable risk factors for 30-day unplanned readmission in patients discharged with OPAT.MethodsThis was a retrospective cohort study of patients admitted to University of Virginia (UVA) Health System between March 2019 and December 2019 who were discharged home with intravenous antimicrobials followed by the UVA OPAT program. Data collected included patient demographics, comorbidities, infection diagnosis, source control, and antimicrobial class. Variables were compared between patients with a 30-day unplanned readmission and those without a readmission. Mann-Whitney U, Pearson chi-squared, and Fisher’s exact tests were utilized, as appropriate. A multiple logistic regression analysis was performed to determine predictors of 30-day unplanned readmission.ResultsThere were 334 OPAT patients who met inclusion criteria. Median age was 58 years, 58% were male, and the most common infection diagnoses were bone/joint (49%), bloodstream (22%), and endovascular (13%). There were 64 (19%) patients who had an unplanned 30-day readmission. The most common reasons for readmission included non-infection related (45%), worsening infection (28%), and antimicrobial-related complication (17%). Readmitted patients were more likely to have a higher Charlson Comorbidity Index (CCI); prior admissions; bloodstream, endovascular, or pulmonary infection; no source control; and an infection caused by a multi-drug resistant organism. CCI was found to be an independent predictor of readmission (OR 1.096, 95% CI 1.001-1.200).ConclusionUnplanned readmissions were common in patients discharged with OPAT. There should be an emphasis on interventions to prevent readmissions in OPAT patients, particularly those with high-risk clinical characteristics.Disclosures All Authors: No reported disclosures

850. External Validation of the Methicillin-Resistant Staphylococcus aureus Bacteremia Score

BackgroundPredictive scoring systems, such as the Pitt Bacteremia Score (PBS) and Acute Physiology and Chronic Health Evaluation II (APACHE-II), can optimize clinical decisions and provide adjustment for confounding among patients with Methicillin-Resistant Staphylococcus aureus bacteremia (MRSAB). The recently introduced MRSAB score demonstrated superior discriminatory ability in mortality prediction compared to APACHE-II and PBS, however external validation is lacking.MethodsSingle center, retrospective cohort study of adult patients admitted to University of Colorado Hospital from 2013–2020 with initial episode of MRSAB were included. Patients transferred from an outside hospital, left against medical advice, or died/pursued comfort care within 24 hours of index culture were excluded. The primary outcome was discrimination of 30-day all-cause mortality. The discriminatory abilities of APACHE-II, PBS and MRSAB were compared using receiver operating characteristic (ROC) analysis. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were analyzed, and optimal MRSAB score was identified by Youden Index.ResultsOverall, 170 patients met study inclusion. The median (IQR) age was 57 (47-66) years, 69% were male, and 19% were in an ICU during blood culture collection. The most common infection sites were skin and soft tissue (41%), musculoskeletal (23%), and line-related (19%), whereas endovascular (14%) infections were less common. The median (IQR) PBS, APACHE-II and MRSAB scores were 2 (0-4),17 (12-23), and 6.5 (3-11), respectively. Thirty-day all-cause mortality was 12.9%. ROC curve analysis revealed an area (95% CI) for the APACHE-II, PBS, and MRSAB scores of 0.84 (0.77-0.92), 0.71 (0.57-0.85), 0.79 (0.68-0.90), respectively. A threshold MRSAB score of ≥10 was identified, whereby mortality was 3.6% with MRSAB < 10, and 30% with MRSAB ≥10. A MRSAB ≥10 had a sensitivity, specificity, PPV and NPV with corresponding 95% CIs of 0.82 (0.63-0.94), 0.72 (0.68-0.79), 0.30(0.19-0.42) and 0.96(0.92-0.99), respectively.Receiver operator characteristic (ROC) curves for the prediction of 30-day mortality ConclusionThe MRSAB score is a useful predictive scoring model, with discriminatory ability comparable to APACHE-II, and excellent NPV at ≥10. Our findings support routine clinical and research application.Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

Abstract 17411: De Novo Protein Synthesis of Alpha-Toxin Activated Platelets

Introduction: Endovascular infections with bacteria are often devastating with subsequent high morbidity and mortality. Exo- and or endotoxins of bacteria can activate endothelial cells, leukocytes and platelets. Platelets are first line defence they accumulate at sites of vascular injury or infection. Platelet activation is a necessary step in thrombus formation. Nevertheless, stimulation of platelets will result in de novo protein synthesis despite missing nucleus since platelets armed with translational equipment. Methods: In the present study we determined the effect of staphylococcus aureus α-toxin on platelet activation and de novo protein synthesis analysed with 2-D gels, proteomics and phosphorylation analysis. Results: α-toxin induced platelet activation resulted in modulation of de novo protein synthesis of DJ-1 Protein, ras suppressor protein1, PLEK protein, fumaryl aceto acetase sowie das coronin actin binding protein. This synthesis was time- and concentration-dependent and was markedly increased when platelets adhered to collagen or fibrinogen and required ligation of α IIb β 3 . Accumulation of protein synthesis in platelets was blocked by global translational inhibitors and attenuated by inhibitors that regulate signalling through the mammalian Target of Rapamycin (mTOR). In addition with phosphorylation analysis we were able demonstrate modulation of threonine phosphorylation of fumaryl aceto acetase, phosphor threonin signal of coronin actin binding protein, phosphorylation of peroxiredoxin-6, phosphorylation of tropomyosin-2, phosphothreonin signal of H + transporting two sector ATPase upon α-toxin stimulation. Conclusion: Interactions with staphylococcus aureus α-toxin and platelets might lead to their activation and de novo protein synthesis. These results suggest that platelets have an important role in inflammation besides their aggregating duties in inflammatory disease.

Limited Clinical Utility of Follow-up Blood Cultures in Patients With Streptococcal Bacteremia: An Opportunity for Blood Culture Stewardship.

BackgroundThe value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia.MethodsAdults ≥18 years of age, admitted with at least 1 positive blood culture for Streptococcus spp between 2013 and 2018 followed by at least 1 FUBC, were potentially eligible. Positive FUBCs were defined as cultures positive for the same streptococcal species drawn >24 hours after the index culture. We excluded patients with polymicrobial bacteremia. We compared the characteristics of patients with and without a positive FUBC.ResultsIn our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Streptococcus spp (3.2%), 4 (1.3%) had a contaminant identified, and 3 (1.0%) had a new pathogen isolated. Endocarditis (5 of 10 [50.0%] vs 35 of 304 [11.5%]), epidural abscess (2 of 10 [20%] vs 4 of 304 [1.3%]), and discitis or vertebral osteomyelitis (3 of 10 [30.0%] vs 14 of 304 [4.6%]) were associated with positive FUBC. Patients with positive FUBC had a longer median length of stay (12.9 vs 7.1 days, P = .004) and longer duration of antibiotic treatment (14.9 vs 43.2 days, P = .03).ConclusionsFollow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection.

Aortic Prosthesis-Associated MDR Pseudomonas Infections as a Diagnostic and Therapeutic Challenge

Endovascular prostheses are used to treat life-threatening conditions such as ruptured aortic aneurysms. Prosthetic infection cause significant morbidity and mortality, posing important diagnostic and therapeutic challenges. It is particularly difficult to diagnose and, in the era of multidrug resistance (MDR), these type of infections may become even more difficult to treat. Herein, we reported a case of a secondary prosthetic endovascular infection following repeated bacteremia episodes from a urinary source. This case illustrates an MDR Pseudomonas aeruginosa aortic infection that was difficult to diagnose with no oral antibiotic treatment options.