Median Duration Of Bacteremia Research Articles

Clinical Impact of Vancomycin MIC on Outcomes in Patients With Coagulase-negative Staphylococcal Bacteremia

Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.

95. What To Do With Prolonged Bacteremia in Staphylococcus aureus Osteoarticular Infection? A Retrospective Analysis at Two Children's Hospitals

Abstract Background Staphylococcus aureus is the most frequent cause of osteoarticular infection (OAI, including hematogenous osteomyelitis and septic arthritis) in children and is commonly associated with bacteremia. Current guidelines suggest that persistent bacteremia may warrant more aggressive treatment, however, data supporting this are limited. We retrospectively evaluated the management and outcomes of children with S. aureus OAI with respect to bacteremia duration. Methods Cases were identified through prospective S. aureus surveillance studies at Texas Children’s and St. Louis Children’s Hospitals. Children &amp;lt; 18 years old with OAI secondary to S. aureus from 2011-2021 were eligible. Prolonged bacteremia was defined a priori as the upper quartile of duration. Orthopedic complications included pathologic fractures, avascular necrosis, angular deformity and chronic osteomyelitis. Results Overall, 532 cases were identified of which 343 (64.5%) had ≥1 positive blood culture; 61 developed orthopedic complications (11.4%, Figure 1). The median duration of bacteremia in the cohort was 1 day (IQR: 1-3 days). Patients with prolonged (≥ 3 days) and non-prolonged bacteremia were similar in terms of demographics. Children with prolonged bacteremia had a longer duration of fever in hospital (median 6 vs. 3 days, p&amp;lt; 0.001), more often had MRSA, pyomyositis and venous thromboses and were less often transitioned to oral therapy (Figure 2). Duration of bacteremia also influenced discharge antibiotic choice (Figure 3). Within the subset of patients with prolonged bacteremia, those who were transitioned to oral therapy had similar outcomes to those treated with prolonged intravenous antibiotics; such patients received a median of 11.5 days (IQR: 6-23) of IV therapy prior to discharge (median 7 days [IQR: 4-20] after last positive blood culture). Conclusion Prolonged bacteremia in the setting of S. aureus OAI greatly impacts management and should prompt evaluation for other foci of infection. However, our data show that a subset of children with S. aureus OAI and prolonged bacteremia can be safely transitioned to oral antibiotics after a period of IV therapy. Additional work is needed to delineate optimal management of OAI with prolonged bacteremia. Disclosures Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support Kristina G. Hulten, PhD, Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria

970. The Time for Action is Now: The Impact of Timing with Infectious Diseases Consultation for Staphylococcus aureus Bacteremia

Abstract Background Staphylococcus aureus bacteremia (SAB) is one of the leading causes of bloodstream infections complicated by metastatic diseases leading to extended lengths of stay (LOS). Infectious disease (ID) consultation is associated with greater adherence to standards of care and improved clinical outcomes. There are sparse data evaluating the impact of the timing for ID consult on SAB management. The purpose of this study was to compare the difference in clinical outcomes in patients with SAB who received an early (&amp;lt; 5 days) versus late (≥ 5 days) ID consult. Methods This was an IRB-approved, retrospective, cohort study in hospitalized adult patients with SAB who received an ID consultation between 2015 and 2020. The timing of the ID consult was defined from the order of the index positive blood culture to the placement of the consult. The composite primary endpoint included: identifying the source of SAB, follow-up cultures, obtaining an echo, use of parenteral therapy, and treatment duration. Secondary endpoints included mortality, recurrence, LOS, duration of bacteremia, and readmission rates (30, 60, and 90-day). A machine learning algorithm (MLA) was utilized to determine an alternative to the 5 days threshold for early vs late. Results A total of 321 patients with SAB were included with baseline characteristics (Table 1). The early group was more likely to meet the primary endpoint (62.5% vs. 28.3%, p &amp;lt; 0.001). The median duration of bacteremia and length of stay was shorter in the early group (p &amp;lt; 0.001) (Table 2). MLA determined an alternative threshold of ≤ 3.5 days for early ID consult. Multivariable analyses reported early ID consult in ≥ 5 days (adjusted OR: 6.42, 95% CI [3.20, 12.89]; p &amp;lt; 0.001) and ≤ 3.5 days (adjusted OR: 3.47, 95% CI [2.08, 5.81]; p &amp;lt; 0.001) as independent predictors for achieving the five quality care indicators (Table 3). Comparing the predefined definition of early infectious diseases consultation as &amp;lt; 5 days and late infectious diseases consultation as &amp;gt;= 5 days in univariate analyses to baseline and clinical characteristics. A comparison of an alternative threshold of 3.5 days was also performed in univariate analyses. PWID: persons who inject drugs; ESRD: end-stage renal disease; SD: standard deviation; IQR: interquartile range; MRSA: methicillin-resistant Staphylococcus aureus; ICU: intensive car unit. Comparing the predefined definition of early infectious diseases consultation as &amp;lt; 5 days and late infectious diseases consultation as &amp;gt;= 5 days in univariate analyses to primary and secondary endpoints. A comparison of an alternative threshold of 3.5 days was also performed in univariate analyses. Bivariate analyses were performed with covariates of interest that may be associated with five quality indicators of Staphylococcus aureus bacteremia management (composite primary endpoint). Multivariable analysis was performed to control for covariates statistically significant in the bivariate analyses. Early infectious diseases consultation &amp;lt; 5 days was an independent predictor for meeting the five quality indicators of SAB management. Another multivariable analysis confirmed early ID consultation &amp;lt;= 3.5 days as an independent predictor for meeting the five quality indicators of SAB management. Conclusion Patients with SAB who received an early ID consultation were more likely to achieve the quality care indicators and have a shorter duration of bacteremia and LOS. These data suggest that patients with SAB should have an ID consultation &amp;lt; 5 days from index culture acquisition. Future studies should evaluate if an earlier time frame of 3.5 days for ID consultation improves clinical outcomes. Disclosures All Authors: No reported disclosures.

1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs

Abstract Background Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID. Methods We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria. Results Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone. Conclusion Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen. Disclosures All Authors: No reported disclosures.

1239. Ceftaroline versus Vancomycin as First-Line Therapy for MRSA Bacteremia

BackgroundBeta-lactams have demonstrated superior outcomes over vancomycin in MSSA bacteremia. Despite this, studies of the anti-MRSA beta-lactam ceftaroline in MRSA bacteremia (MRSAB) are largely limited in size or focus on combination or salvage regimens. This study sought to further examine ceftaroline as first-line therapy for MRSAB.MethodsThis was a retrospective matched cohort study at the San Diego VA Medical Center between November 2010 and June 2020. Patients had to have received at least 72 hours of ceftaroline or vancomycin for MRSAB and less than 72 hours of prior MRSA therapy. Adjunct MRSA therapy was allowed only if routinely indicated for the infection (e.g. rifampin for prosthesis). Patients in the vancomycin group were matched 1:1 to patients in the ceftaroline group by age (+/- 10 years) and Pitt bacteremia score (+/- 1 point). The primary outcome was duration of bacteremia after initiation of MRSA therapy, including time on prior MRSA therapy.ResultsFifteen patients were included in each group, with a median age of 65 years and Pitt bacteremia score of 0. Patients in the ceftaroline group were more likely to have CKD; to have been on a different MRSA agent prior to initiation of the study drug, with a median of 1 day of prior treatment; and to have been on adjunctive rifampin or clindamycin. Though not significant, more patients in the ceftaroline group also had endovascular sources, uncontrolled sources, and longer durations of therapy. The median duration of bacteremia after initiation of MRSA therapy did not significantly differ between ceftaroline and vancomycin (4 vs. 3 days, p = 0.806). In addition, 30-day all-cause mortality, in-hospital mortality, 90-day readmission or treatment failure, inpatient length of stay, total duration of bacteremia, and rate of adverse events did not significantly differ between groups.ConclusionThis study suggests ceftaroline may be an appropriate first-line agent for the treatment of MRSA bacteremia with similar outcomes between groups despite the ceftaroline group likely experiencing more difficult-to-treat infections. However, it was not powered to detect differences between groups, and its retrospective nature has the potential to introduce bias. Prospective comparative studies are needed to corroborate these findings.Disclosures All Authors: No reported disclosures

204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. MethodsA retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. ResultsThirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. ConclusionThis study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

#81: Care Process Measures and Outcomes of Percutaneous Pulmonary Valve Implantation-associated Infective Endocarditis

Abstract Background Percutaneous pulmonary valve implantation (PPVI) is being increasingly used as a minimally invasive corrective procedure for right ventricular outflow tract (RVOT) dysfunction. Ten-year survival following PPVI is estimated at over 90% due to the durability of the various bioprosthetic valves. However, infective endocarditis (IE) remains a potential complication of such valves with significant morbidity and mortality. We evaluated the presenting symptoms, clinical features, pathogens, and outcomes of patients with IE following PPVI to identify opportunities to improve early diagnosis and management. Methods A convenience sample of patients at a large Pediatric Cardiology practice in Northern Virginia was queried for PPVI and IE from January 1, 2016, to June 30, 2019. Manual chart review was done to extract clinical points of interest and descriptive analyses were performed. Patients were classified as having IE per modified Duke’s criteria. Results We identified 14 patients who underwent PPVI. Five of these patients (36%) developed IE. All IE patients had underlying Tetralogy of Fallot and none had previous episodes of IE. 60% of patients with IE were male with a median age of 26 years old (IQR 20–30). Four IE patients had a Melody valve and 1 had a SAPIEN valve. The median elapsed time between PPVI and IE diagnosis was 128 days (IQR 32–391) with a median duration of illness prior to the diagnosis of IE of 6 days (IQR 5–9). All IE patients had to present fever. 40% of IE patients had to present chest pain and 20% had presenting musculoskeletal pain. All IE patients had an elevated initial C-reactive protein (CRP) with a median value of 13.1 mg/dL (IQR 12.5–15.2). The median initial white blood cell count was 9.3 × 103/μL (IQR 8.1–10.3). The median duration of bacteremia was 1 day (IQR 1–2). A pathogen was recovered in all five IE patients with different organisms amongst the patients: coagulase-negative Staphylococcus species were recovered in patients who developed IE within 60 days from PPVI (Staphylococcus lugdunensis and Staphylococcus epidermidis) whereas coagulase-negative Staphylococcus species and oral commensal organisms were found in IE patients beyond 60 days from PPVI (Staphylococcus sanguinis, Gamella haemolysans, and Neisseria elongata). The initial echocardiogram did not show vegetations in any of the patients and 40% went on to have sternotomy with valve replacement. There were no deaths. Conclusions With an increase in PPVI, clinicians should have a high index of suspicion for IE in patients with underlying Tetralogy of Fallot who present with fever and elevated CRP, regardless of elapsed time from PPVI or valve type. Empiric antimicrobial therapy for suspected IE following PPVI should remain broad with other possible pathogens beyond coagulase-negative Staphylococcus species.

269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia

Background Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.MethodsWe reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.ResultsOf the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia Fig 1. Duration of Staphylococcus aureus bacteremia ConclusionIn persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.Disclosures All Authors: No reported disclosures

1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality.MethodsThis was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.ResultsSixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04).ConclusionThere were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy.Disclosures All Authors: No reported disclosures

Follow-up Blood Cultures in Children With Staphylococcus aureus Bacteremia.

Staphylococcus aureus is a common pathogen seen in pediatric bloodstream infections. Currently, no evidence-based recommendations are used to guide decisions on the number of follow-up blood cultures (FUBCs) needed to demonstrate infection clearance. Unnecessary cultures increase the risk of false-positives, add to health care costs, and create additional trauma to children and their families. In this study, we examined risk factors for persistent S aureus bacteremia (SAB) and intermittent positive blood cultures (positive cultures obtained after a documented negative FUBC result) to determine the number of FUBCs needed to demonstrate infection clearance in children. Patients ≤18 years who were hospitalized with SAB at Texas Children's Hospital in 2018 were reviewed. We assessed the impact of an infectious disease diagnosis (central line-associated bloodstream infection, osteomyelitis, soft tissue infection, endocarditis, etc) and medical comorbidities on bacteremia duration. Patients with intermittent positive blood cultures were studied to determine the characteristics of this group and overall frequency of reversion to positive cultures. A total of 122 subjects met the inclusion criteria. The median duration of bacteremia was 1 day (interquartile range: 1-2 days). Only 19 patients (16%) had bacteremia lasting ≥3 days, all of whom had a diagnosis of central line-associated bloodstream infection, osteomyelitis, or endocarditis. Intermittent positive cultures occurred in 5% of patients, with positive cultures after 2 negative FUBC results seen in <1% of patients. Intermittent positive cultures were strongly associated with osteomyelitis and endocarditis. On the basis of our sample of children with SAB, additional blood cultures to document sterility are not necessary after 2 FUBC results are negative in well-appearing patients.

209. What’s So Complicated About Complicated Staphylococcus aureus Bacteremia: Does Day 5 Matter?

BackgroundProlonged Staphylococcus aureus bacteremia (SAB) poses challenges in clinical practice, particularly when a source is not readily identified. While SAB greater than 3 days has been identified as a risk factor for complications, little is known about risk for specific complications with each successive day of bacteremia. We sought to determine the risk for specific complications with the duration of bacteremia.MethodsWe retrospectively reviewed all cases of SAB between 1 January 2017 and 31 December 2017 at a 500-bed academic hospital. Adult patients (≥18 years) with at least one blood culture positive for S. aureus were identified. Patients were excluded if withdrawal of care or death occurred within 48 hours of blood culture results or if the infection was associated with a ventricular assist device. Medical records were reviewed for the duration of bacteremia, complications, treatment decisions and clinical outcomes. This study was approved by the Institutional Review Board.ResultsOne hundred forty-two discrete episodes of SAB were identified with a median age of 54 years (IQR 40–63). Most cases were community-acquired (83.8%) and 33.8% were MRSA. Active injection drug use was present in 22.5% (33.3% MRSA, 17% MSSA). The median duration of bacteremia was 2.6 days (IQR 1.8–4.6) and 3.9 days (IQR 2.2–7.5) for MSSA and MRSA, respectively. The median time to first source control procedure was twice as long with bacteremia over 5 days than with a shorter duration of bacteremia (2.6 vs. 1.3 days). Complication rates increased with bacteremia duration and bacteremia longer than 5 days was associated with significantly higher rates of endocarditis (46.2%, P < 0.001), epidural abscesses (35.9%, P = 0.001), intracranial infections (12.8%, P = 0.02), and presence of at least one endovascular nidus (76.9%, P < 0.001) compared with bacteremia less than 5 days (28.4%), but 30 day mortality rates were similar (7.7% and 9.8%, respectively).ConclusionComplication rates increase significantly with SAB greater than 5 days duration. Early source control and investigation to identify metastatic and especially endovascular foci of infection are paramount in patients with prolonged bacteremia even if complications are not discovered on initial evaluation. Disclosures All authors: No reported disclosures.

The Yield of Echocardiography in the Diagnosis of Infective Endocarditis in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia

INTRODUCTION:The pathogenesis of infective endocarditis (IE) , a typical biofilm-associated infectious disease frequently caused by commensal or pathogenic bacteria, is mainly attributed to the formation of septic vegetations, which are fibrin-platelet complexes embedded with bacteria on heart valves detected by echocardiography. Patients with acute myeloid leukemia (AML) are prone to neutropenia, immunosuppression and central venous catheters leading to high rates of bacteremia. It has been postulated that despite high rates of bacteremia, patients with AML undergoing intensive chemotherapy are only rarely able to form vegetations due the frequent thrombocytopenia associated with such treatment (McCormick 2002). Here, we sought to determine the rate of echocardiographic detection of IE in patients with AML and chemotherapy induced thrombocytopenia .METHODS:To assess the yield of echocardiography, we conducted a retrospective, single center, analysis of patients with AML who underwent treatment using anthracycline or fludarabine induction and intermediate/high dose cytarabine based consolidation. At all time points, patients with febrile neutropenia were empirically treated with piperacillin/tazobactam ± aminoglycosides and underwent appropriate investigations including blood cultures. Cultures were drawn every 24 to 48 hours with fevers and daily, if positive, till culture clearance. Patients with positive blood cultures for organisms associated with IE underwent an echocardiogram as standard of care.RESULTS:From January 2010 to January 2018, 296 patients underwent curative intent chemotherapy for treatment of acute myeloid leukemia (AML) at the University of Alberta Hospital, Edmonton, Canada. The median age of all patients was 56.7 years (IQR: 44-64) and 40.2% were females. During the induction or consolidation chemotherapy , 53 echocardiogram were done to investigate 53 episodes of bacteremia in 50 patients (16.9%) who had organisms associated with IE (Table 1). Two echocardiograms were done to investigate possible culture negative IE based upon clinical suspicion. Transesophageal echocardiogram were utilized in 19 patients (36%) while transthoracic echocardiogram were done in 34 patients (64%). The median platelets count on the day of the echocardiogram was 23 x109/L (IQR: 14-38). Viridans Group Streptococci and Staphylococcus aureus were the most frequent isolates cultured in the blood in 36% and 16% of cases, respectively. The median duration of bacteremia was 1 day (IQR 1-2). Three (5.6%) patients had echocardiographic findings suggestive of IE based on a positive transesophageal study (n=2) or transthoracic study (n=1). Among these, two were secondary to Enterococcus bacteria and involved the mitral valve and the third was secondary to a non-HACEK gram-negative bacteria leading to tricuspid valve involvement .CONCLUSION:This study is the first to suggest that despite the high prevalence of Viridans Group Streptococci and Staphylococcusaureus in patients with AML undergoing chemotherapy, echocardiographic findings of IE in these patients are rare, with the notable exception of Enterococcal and Non-HACEK gram negative organisms. In contrast, in the general population, Viridans Group Streptococci and Staphylococcus aureus and bacteremia are associated with IE in 20% and 63% %, respectively (Westling 2009, Rasmussen 2011). The low incidence in our cohort may be attributed to impaired fibrin-platelet deposition in these patients with inability to mount a vegetation response, or the early initiation of broad spectrum antibiotics. Given these findings, the value of routine echocardiography should be questioned in patients with AML without other clinical features of IE. DisclosuresSandhu:Bioverativ: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Brandwein:Pfizer: Consultancy; Celgene: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Novartis: Consultancy; Lundbeck: Consultancy.

Central line associated bloodstream infections in the NICU: Does vancomycin-intermediate heteroresistance of coagulase-negative Staphylococcus matter?

Objective: To determine whether the duration of bacteremia among patients in the NICU, as well as risk of thrombocytopenia, differed between those with a central line associated bloodstream infection (CLABSI) due to a hetero-resistant vancomycin-intermediate Staphylococcus epidermidis (hVISE) and those whose CLABSI was due to vancomycin-susceptible S. epidermidis (VSSE). Methods: This retrospective cohort study covering the period from November 2009 through April 2014 examined records for 114 patients with coagulase-negative staphylococci (CoNS) CLABSI from two tertiary-care NICUs in Québec. Results: Of 111 patients included in the final analysis, 98 had an hVISE infection. The median duration of bacteremia was 4 days (range 0–33 days) for patients with hVISE and 4 days (range 2–8 days) for patients without hVISE. The duration of bacteremia was not significantly different between those with and without hVISE infection (B=−0.56, 95% CI −2.76 to 1.65). Further, the risk of thrombocytopenia for patients with and without hVISE was not significantly different (OR 0.42, 95% CI 0.076 to 2.72). Conclusions: hVISE was not shown to be associated with a longer duration of bacteremia or a greater risk of thrombocytopenia. This suggests that hVISE may not have a greater clinical impact than VSSE in infants with CLABSI. However, due to the small number of patients with VSSE in our cohort, firm conclusions cannot be drawn. Larger, multi-centre studies are needed to assess the true clinical relevance of vancomycin-intermediate hetero-resistant coagulase-negative staphylococci (hVICoNS) and before concluding on the need for hV identification in a clinical laboratory.

Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model.

To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection. Two groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.5-1 × 103 CFU). Participants were monitored in an outpatient setting with daily clinical review and collection of blood and stool cultures. Antibiotic treatment was started when prespecified diagnostic criteria were met (temperature ≥38°C for ≥12 hours and/or bacteremia) or at day 14 postchallenge. The primary study objective was achieved following challenge with 1-5 × 103 CFU (group 1), which resulted in an attack rate of 12 of 20 (60%). Compared with typhoid challenge, paratyphoid was notable for high rates of subclinical bacteremia (at this dose, 11/20 [55%]). Despite limited symptoms, bacteremia persisted for up to 96 hours after antibiotic treatment (median duration of bacteremia, 53 hours [interquartile range, 24-85 hours]). Shedding of S. Paratyphi A in stool typically preceded onset of bacteremia. Challenge with S. Paratyphi A at a dose of 1-5 × 103 CFU was well tolerated and associated with an acceptable safety profile. The frequency and persistence of bacteremia in the absence of clinical symptoms was notable, and markedly different from that seen in previous typhoid challenge studies. We conclude that the paratyphoid challenge model is suitable for the assessment of vaccine efficacy using endpoints that include bacteremia and/or symptomatology. NCT02100397.

Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L

PurposeCase reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. MethodsWe performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. FindingsForty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). ImplicationsDuration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.

No survival benefit with empirical vancomycin therapy for coagulase-negative staphylococcal bloodstream infections in infants.

Coagulase-negative Staphylococcus (CoNS) is the most common cause of bloodstream infections (BSI) in hospitalized infants. CoNS BSI is most reliably treated with vancomycin; however, concerns about side effects and promoting resistance often delay empirical vancomycin therapy until culture results become available. All infants with CoNS BSI discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2012 were identified. Empirical vancomycin therapy was defined as vancomycin exposure on the day of the first positive blood culture. Delayed vancomycin therapy was defined as vancomycin exposure 1-3 days after the first positive blood culture. We used multivariable logistic regression with random effects for site to evaluate the association between the use of empirical vancomycin therapy versus delayed vancomycin therapy and 30-day mortality, controlling for gestational age, small-for-gestational age status, postnatal age on the day of the first positive culture, oxygen requirement, ventilator support and inotropic support on the day the first positive culture was obtained. A total of 4364 infants with CoNS BSI were identified; 2848 (65%) were treated with empirical vancomycin. The median postnatal age at first positive culture was 14 days (interquartile range: 9, 21). Unadjusted 30-day mortality was similar for infants treated with empirical vancomycin and infants treated with delayed vancomycin therapy [166/2848 (6%) vs. 69/1516 (4%); P = 0.08]. There was no significant difference in 30-day mortality on multivariable analysis [odds ratio: 1.14 (0.84, 1.56)]. The median duration of bacteremia was 1 day longer for infants with delayed vancomycin therapy [4 days (interquartile range: 2, 6) vs. 3 days (2, 5); P < 0.0001]. The median duration of bacteremia was 1 day longer in infants with CoNS BSI who received delayed vancomycin therapy. Despite this finding, empirical vancomycin therapy for CoNS BSI was not associated with improved mortality.

Treatment of Vancomycin-Resistant Enterococcal Bacteremia in an Observational Cohort of Neutropenic Oncology Patients

Background Vancomycin-resistant Enterococcus (VRE) is an increasingly common nosocomial pathogen causing significant morbidity and mortality in patients with neutropenic cancer. We evaluated outcomes in an observed cohort of subjects with VRE bacteremia and compare the effectiveness of 2 antibiotics commonly used to treat VRE infections: daptomycin and linezolid. Methods Patients with neutropenic cancer with VRE blood stream infections treated with daptomycin or linezolid were identified through electronic medical record, and a retrospective chart review was conducted. Results Eighty-one patients were included. There were 49 men (60%) and 32 women; the mean age was 59.3 years. Mean white blood cell count at the time of blood stream infection was 0.3, and the median duration of bacteremia was 2 days (range, 1–25 days). Leukemia was the underlying diagnosis in 82.7%. Only 4 patients received anti-VRE therapy within 4 hours, 14 patients received VRE-specific therapy within 24 hours of first positive culture. The overall treatment failure rate was 35.8%; daptomycin, 41.4%; and linezolid, 21.7% (P = 0.13). Primary causes of treatment failure were persistent bacteremia and death. The 30-day mortality rate was 38.3%. Of these 31 deaths, 22.6% were directly attributable to VRE, with VRE being contributory in an additional 22.6%. Overall mortality in patients treated with daptomycin (39.7%) or linezolid (34.8%) did not differ (P = 0.80). Resistance to both agents was observed. Conclusions We found a 38.3% 30-day mortality rate, emphasizing the need for prevention and perhaps early inclusion of VRE-specific therapy for those with known colonization. Outcomes of culture-directed therapy with linezolid or daptomycin did not differ by antibiotic choice.

Single center experience of a vancomycin resistant enterococcal endocarditis cohort

Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is an increasing nosocomial problem. We describe the clinical management and outcomes of a cohort of patients with VRE IE at a tertiary endocarditis referral center. Retrospective review of all proven cases of VRE IE, from July 2000 through January 2008 was performed. Demographics, comorbidities and therapeutic details were collected and analyzed to assess for risk factors and clinical outcomes. Fifty cases of VRE IE were identified: 26 (52%) were Enterococcus faecium and 24 were Enterococcus faecalis. Vancomycin resistant E. faecalis IE was associated with the presence of a central venous line, liver transplantation, and mitral valve infection while VR E. faecium IE was significantly associated with tricuspid valve infection (p=0.03). The median duration of bacteremia was 14 days for E. faecium and 4 days for E. faecalis, respectively (p=0.002). Factors associated with mortality on bivariate analysis were hemodialysis via a catheter with VR E. faecium (OR=11.7. CI 1.1-122, p=0.02) and liver transplantation with both species. Combination antimicrobial therapy (OR=0.5 CI=0.06-3.2, p=0.1) and valve surgery (OR 1.3 CI 0.8-20, p=0.02) trended toward improved survival with E. faecalis on bivariate analysis. On multivariate analysis, none of the associations were significant. Hemodialysis and liver transplantation were factors associated with acquisition of VRE IE. There was a higher mortality and prolonged bacteremia with VR E. faecium IE than VR E. faecalis IE. Although not significant, combination antimicrobial therapy and surgical intervention trended toward improved survival.

Clinical Features of Heteroresistant Vancomycin-IntermediateStaphylococcus aureusBacteremia versus Those of Methicillin-ResistantS. aureusBacteremia

Heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infections are emerging, but their clinical significance remains unclear. Our objective was to compare patients who had hVISA bacteremia with patients who had methicillin-resistant S. aureus (MRSA) bacteremia. A total of 27 case patients with hVISA bacteremia were compared with 223 control patients with MRSA bacteremia. Medical records of all patients were reviewed, and factors independently associated with infection-related mortality were assessed by logistic regression. Patients with hVISA bacteremia were not significantly different from those with MRSA bacteremia with respect to age, comorbidities, duration of hospital stay, and infection-attributable mortality. However, the median duration of bacteremia among patients with hVISA was significantly longer than that among patients with MRSA (12 vs. 2 days; P = .005), and patients with hVISA had a greater prevalence of complications, such as endocarditis (18.5% vs. 3.6%; P = .007) and osteomyelitis (25.9% vs. 7.2%, respectively; P = .006). Rifampin resistance emerged more frequently among hVISA isolates than among MRSA isolates (44% vs. 5.9%; P < .001). Factors independently associated with infection-related mortality in all patients were age, Charlson comorbidity index, female sex, and being bedridden. hVISA bacteremia was significantly associated with prolonged bacteremia duration, greater rates of complications, and emergence of rifampin resistance, compared with MRSA bacteremia. However, no significant difference in mortality existed between patients with hVISA bacteremia and those with MRSA bacteremia.

Impact of Vancomycin Resistance on Mortality among Patients with Neutropenia and Enterococcal Bloodstream Infection

We performed a retrospective cohort study to measure the impact of vancomycin resistance on clinical outcome for 83 episodes of enterococcal bloodstream infection (BSI; 22 with vancomycin-resistant enterococci [VRE] and 61 with vancomycin-susceptible enterococci [VSE]) in 77 patients with neutropenia. Cox proportional hazards models showed that vancomycin resistance was an independent predictor of mortality, after controlling for severity of illness, enterococcal species, gram-negative copathogens, sex, race, duration of neutropenia before bacteremia, and early administration of active antibiotics. This effect was evident only > or =10 days after the onset of bacteremia (P=.0263; hazard ratio [HR], 4.969) but not after adjustment for duration of bacteremia. The median duration of bacteremia was 4.5 days for VRE BSI and <1 day for VSE BSI (P=.0001). The only independent predictor of bacteremia duration was vancomycin resistance (P=.0284; HR, 3.863). Vancomycin resistance is associated with increased mortality in patients with neutropenia, possibly because of prolonged duration of bacteremia.