Duration Of Bacteremia Research Articles

2441. Outcomes of Patients With Vancomycin-Resistant Enterococcus Blood Stream Infections (BSI) Treated With Daptomycin

BackgroundReports of poor outcomes in patients (patients) infected with VRE strains with daptomycin (DAP) minimum inhibitory concentrations (MIC) near the susceptible breakpoint (<=4 μg/ml) are noted in the literature. We assessed the relationship of clinical outcomes for patients treated with DAP to the initial MIC.MethodsRetrospective study of consecutive adult patients with VRE BSI treated with DAP for at least 48 hours (November 2011–January 2015) in a tertiary hospital in Cleveland, OH. Patients were grouped based on the initial DAP MIC (MIC ≤ 2 μg/mL and MIC = 4 μg/mL) determined by a commercial broth microdilution method (Sensititre). Demographic and clinical data were extracted via EMR. Outcomes for all-cause mortality at 30 days (30-D mortality) and 90 days (90-D mortality), 30-day mortality attributed directly to VRE BSI (30-D mortality VRE) and microbiological failure (MF) were measured. MF was defined as duration of bacteremia ≥4 days after at least 48 hours of DAP use and achievement of source control when possible. We also assessed the impact of concomitant β-lactam use on MF.ResultsA total of 192 patients were identified. Baseline characteristics are shown in Table 1. Outcomes for MF, 30-D mortality VRE, 30-D mortality and 90-D mortality are shown in Table 2. Impact of concomitant β-lactam use on MF is shown in Figure 1.ConclusionIn this retrospective study, MF and mortality were not significantly higher for BSI caused by VRE with DAP MICs of 4 μg/ml, regardless of concomitant β-lactam use. Disclosures S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant.

2322. Reduced Vancomycin Susceptibility Among Pediatric Staphylococcus aureus Bloodstream Infections

BackgroundReduced vancomycin susceptibility (RVS) is considered to be present when the minimum inhibitory concentration (MIC) is equal to 2 µg/mL. RVS Staphylococcus aureus (SA) bloodstream infections (BSI) have been associated with worse outcomes than non-RVS BSI in adults but not been well studied in children.MethodsWe reviewed the electronic medical records of infants and children admitted to Penn State Children’s Hospital with ≥1 blood culture positive for SA from 2005 to 2015. We abstracted demographic information, potential risk factors, laboratory results and clinical outcomes. We defined RVS as a vancomycin MIC = 2 µg/mL as determined by the clinical microbiology laboratory at the time of the infection. We used Chi square and Wilcoxon rank-sum tests to compare patient factors for RVS and non-RVS infections. Using a logistic regression adjusted for year and the presence of an infection-related complication, we calculated the odds of treatment failure for children with RVS and non-RVS BSI. For children with a central line in place at the time of the first positive culture, we also calculated the odds of treatment failure adjusted for year, presence of a complication and line removal. We defined treatment failure as death within 30 days of the first positive culture, recurrence of SA BSI within 30 days or a duration of bacteremia > 3 days.ResultsOf the 216 identified pediatric SA BSI, 139 (64%) had RVS: RVS was present in 63% of MSSA BSI and 65% of MRSA BSI, P = 0.835. There was no difference in age, sex, and racial distributions among children with RVS vs. non-RVS BSI. Similarly, hospitalization in the prior year, surgery within the prior 30 days, the presence of an underlying comorbidity or use of immunosuppressing medications were not more common for RVS vs. non-RVS BSI. RVS was not associated with an increased risk of treatment failure overall, odds ratio (OR)=1.34 (95% confidence interval: 0.71, 2.55), but did increase the odds of treatment failure if an indwelling central venous catheter was present and not removed, OR=3.14 (1.16, 8.54).ConclusionRVS is common among pediatric SA BSI. For central line associated SA BSI, RVS was associated with increased odds of treatment failure compared with non-RVS infections if the line was retained.Disclosures All authors: No reported disclosures.

637. Β-Lactam (BL) Antibiotics Promote an IL-1β Response in Patients with Staphylococcus aureus Bacteremia (SaB)

BackgroundBL therapy has been associated with reduced SaB duration compared with non-BL therapy. It has been shown that patients with SaB who fail to generate increased serum IL-1β are at risk for prolonged SaB (> 4 days duration), a predictor of mortality. This suggests a major role for the IL-1β host response in prompt clearance of SaB. Furthermore, BL result in reduced peptidoglycan cross-linking, reduced peptidoglycan O-acetylation, and increased alpha-toxin expression, all of which have independently been shown to enhance IL-1β release. This study aims to show that BL therapy results in a more robust IL-1β host response compared with non-BL therapy to explain, in part, more rapid SaB clearance.MethodsFifty-nine patients (47 MRSA and 12 MSSA) with diverse SaB sources, including endovascular, extravascular (e.g., pneumonia), and catheter-related infections were included. In the first 48 hours, patients were treated with either BL, including oxacillin, ceftaroline, or cefazolin (n = 24), vs. non-BL vancomycin or daptomycin (n = 35). IL-1β concentrations were determined by ELISA on serum samples obtained on Days 1, 3 and Day 7 after bacteremia onset and compared between groups by Mann–Whitney U test.ResultsPatients in BL and non-BL groups had similar IL-1β concentrations on Day 1 of bacteremia (median BL 6.1 pg/mL vs. non-BL 2.8 pg/mL, P = 0.090). BL-treated patients had significantly higher IL-1β serum concentrations on Day 3 (median 7.54 mg/mL vs. 1.9 pg/mL; P = 0.007) and Day 7 (12.52 pg/mL vs. 1.56 pg/mL, P = 0.016) when compared with non-BL-treated patients. BL therapy resulted in 23% and 105% increase in IL-1β at Days 3 and 7, respectively, while non-BL treatment resulted in 32% and 44% reduction in IL-1β. The median duration of SaB was similar between BL and non-BL-treated patients (2.5 vs. 2.0 days, respectively, P = 0.590).ConclusionGiven that a lack of inflammasome-mediated IL-1β production is associated with prolonged SaB, the significant increases in IL-1β levels in patients treated with BL has important therapeutic implications. Previously observed reduced duration of MRSA bacteremia with the addition of BL to vancomycin may have its basis on enhancing IL-1β release. A therapeutic regimen of vancomycin or daptomycin in combination with BL to treat MRSA bacteremia and use of BL therapy in MSSA bacteremia is strongly advised to improve outcomes based on these results.Disclosures G. Sakoulas, Allergan: Consultant and Speaker, Consulting fee and Speaker honorarium. Sunovion: Speaker, Speaker honorarium. The Medicines Company: Speaker, Consulting fee. Paratek Pharmaceuticals: Consultant, Consulting fee. Cidara Therapeutics: Scientific Advisor, None. Arsanis Pharmaceuticals: Scientific Advisor, None. W. Rose, Merck: Grant Investigator, Research grant.

2429. The Epidemiology and Outcomes of Enterobacter cloacae Bloodstream Infections in Children

BackgroundBloodstream infections cause significant morbidity and mortality in children admitted to intensive care units (ICUs). Enterobacter cloacae bloodstream infections can be particularly challenging to treat given increasing antibiotic resistance and presence of inducible β-lactamases on some strains. The objective of this study was to describe the epidemiology and clinical outcomes for critically ill children with E. cloacae bloodstream infections.MethodsWe performed a retrospective cohort study of children ≤19 years hospitalized in the critical care unit at the Children National Medical Center in Washington, DC with E. cloacae bloodstream infections between 2007 and 2016. We excluded polymicrobial infections. We performed chart review to collect baseline characteristics, treatment regimens, and outcomes. Recurrence of infection was defined as new E. cloacae bacteremia within 30 days of discontinuing antibiotics for initial infection.ResultsTwenty-six episodes of E. cloacae bacteremia met inclusion criteria. Median age was 7 months (IQR 2–16 months), and 6/26 (23%) patients were African-American. All patients had at least one underlying chronic medical condition, the most common being neuromuscular (35%), end-stage renal disease (27%), oncologic (12%), and short bowel syndrome (15%). Central venous catheter was present in 18 (75%) patients and 10 (38%) had hemodynamic instability requiring vasopressor support at time of bacteremia. Seven isolates (27%) were not susceptible to third-generation cephalosporins. Antibiotic treatment varied, with 7 (27%) receiving carbapenems empirically within 72 hours. Mean duration of bacteremia was 2.9 days. Infection recurred within 30 days in 2 patients (8%) and 2 patients (8%) died within 30 days of the initial positive blood culture.ConclusionAll episodes of E. cloacae bacteremia occurring in children admitted to the ICU occurred in patients with underlying comorbid conditions, and more than half of affected children were infants <1 year. More than one-third of these infections were associated with severe sepsis and nearly one in ten infected patients died within one monthDisclosures All authors: No reported disclosures.

Impact of Empiric Treatment for Vancomycin-Resistant Enterococcus in Colonized Patients Early after Allogeneic Hematopoietic Stem Cell Transplantation

In recent years, vancomycin-resistant Enterococcus (VRE) colonization is being increasingly encountered in transplant recipients, and VRE has become one of the leading causes of bacteremia early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data are sparse on the effect of empiric VRE therapy for febrile, neutropenic allo-HSCT recipients colonized with VRE. All allo-HSCT recipients aged ≥18years who developed VRE bacteremia (VREB) between 2005 and 2014 were identified and categorized as to whether they received empiric or directed VRE therapy. There were 434 (33%) VRE-colonized and 872 (67%) non-VRE-colonized patients during the study period, and 172 of the 434 (40%) VRE-colonized patients received empiric therapy. There was no significant difference in incidence of VREB among colonized patients who did or did not receive empiric therapy (28 of 172 [16%] vs 55 of 262 [21%]; P = .22). There were 95 patients with VREB, of which the majority (83 of 95; 87%) was known to be VRE-colonized. Of the 95 VREB episodes, 29 (31%) were treated with empiric VRE therapy, whereas 66 (69%) were treated with directed therapy. No significant differences in clinical outcomes, including median duration of bacteremia (2 days vs 2 days; P = .39), recurrent VREB (3 of 29 [10%] vs 5 of 66 [8%]; P = .65), 30-day all-cause mortality (1 of 29 [3%] vs 4 of 66 [6%]; P = .62), or VRE-attributable mortality (1 of 29 [3%] vs 1 of 66 [2%]; P = .55), were observed between the empiric therapy and directed therapy groups. Kaplan-Meier curve analysis showed no significant difference in survival at 30days in allo-HSCT recipients with VREB who received empiric therapy and those who received directed therapy (97% vs 94%; P = .62). Based on our data, we recommend against empiric use of VRE-active agents for fever and neutropenia in VRE-colonized patients undergoing allo-HSCT.

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. UK NHS trust hospitals. Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.

Duration and Persistence of Staphylococcus Aureus Bacteremia: A Prospective Cohort Study

Background: The purpose of the study was to describe and compare duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and primary foci of infection. We also aimed to redefine persistent SAB considering those results. Methods: We analyzed non-duplicated episodes of SAB in adult patients from three prospective SAB cohorts encompassing 14 hospitals in Korea. The duration of SAB was defined as the number of days from the administration of a susceptible antibiotic after the onset of SAB to the last day of positive blood culture for S. aureus. SAB durations were described and compared based on methicillin resistance and the primary foci of infection. The Cox proportional hazards regression was performed to explore independent risk factors for prolonged bacteremia. Cases in the top quartile for the duration of bacteremia were designated as newly-defined persistent SAB. Findings: A total of 2050 cases were analyzed. The duration of SAB was longer in methicillin-resistant SAB (MRSAB) than in methicillin-susceptible SAB (MSSAB) (median [IQR], 1 [1-3] in MSSAB vs. 1 [0-7] in MRSAB, p < 0.001). While the duration of bacteremia was shortest in the skin and soft tissue infections, they were longer in endocarditis, bone and joint, and endovascular infections, and were independently associated with those foci of infection. Newly-defined persistent SAB showed independent association with in-hospital mortality (aOR, 1.99; 95% CI, 1.54-2.58; p < 0.001). Interpretation: Durations of SAB were dependent on methicillin resistance and the primary foci of infection. The newly-defined persistent SAB is independently associated with in-hospital mortality. Funding: Seoul National University Bundang Hospital Research Fund. Declaration of Interest: None to declare. Ethical Approval: The analyses of cases from April 2015 to February 2018 were approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-1801-442-102).

Daptomycin versus placebo as an adjunct to beta-lactam therapy in the treatment of Staphylococcus aureus bacteremia: study protocol for a randomized controlled trial

BackgroundStaphylococcus aureus bacteremia is associated with significant morbidity and mortality. To treat this infection, the current standard of care includes intravenous anti-staphylococcal beta-lactam antibiotics and obtaining adequate source control. Combination therapy with an aminoglycoside or rifampin, despite early promise, can no longer be routinely recommended due to an absence of proven benefit and risk of harm. Daptomycin is a rapidly acting bactericidal antibiotic that is approved for the treatment of Staphylococcus aureus bacteremia as monotherapy but has not been shown to be superior to the current standard of care. As demonstrated in vitro, the addition of daptomycin to beta-lactam therapy may result in enhanced anti-staphylococcal activity. Our objective is to assess the efficacy and safety of prescribing the combination of daptomycin with cefazolin or cloxacillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in adults. We hypothesize that adjunctive therapy with daptomycin will reduce the duration of bacteremia in this population.MethodsThe DASH-RCT trial is a randomized, double blind, placebo-controlled trial designed per the Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) guidelines. We recruit adults with confirmed MSSA bacteremia, at the McGill University Health Center. Patients are eligible if they are 18 years or older, can receive cefazolin or cloxacillin monotherapy, and are enrolled within 72 h of the first blood culture being drawn. Exclusion criteria include anaphylaxis to study drugs, having polymicrobial bacteremia, anticipated hospital admission for < 5 days, and healthcare team refusal. While receiving standard of care, study patients are randomized to a 5-day course of adjunctive daptomycin or placebo. The trial began in December 2016 and is expected to end in December 2018, after recruiting an estimated 102 patients.DiscussionThe DASH-RCT will compare the use of daptomycin as an adjunct to an anti-staphylococcal beta-lactam versus placebo in the treatment of MSSA bacteremia. We believe that a short course of dual therapy will result in earlier eradication of bacteremia and that subsequent research could evaluate effects on metastatic infection, relapse, and/or mortality. Ongoing issues in the trial include a delay between presentation of infection, enrollment in the trial, and the potential for unrecognized deep foci of infection at diagnosis.Trial registrationClinicalTrials.gov, NCT02972983. Registered on 25 November 2016.Trial protocol: http://individual.utoronto.ca/leet/dash/dashprotocol.pdf

Impact of Vancomycin MIC on Clinical Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin at an Institution with Suppressed MIC Reporting.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of bacteremia and is associated with significant morbidity and mortality. Prior studies evaluating the association of vancomycin MICs with clinical outcomes in patients with MRSA bacteremia have been inconsistent. This study evaluated the association between vancomycin MICs and 30-day in-hospital mortality rates for patients with MRSA bacteremia. This was a retrospective cohort study of patients with MRSA bacteremia treated with vancomycin for ≥72 h from January 2013 to August 2016. Vancomycin MICs were determined by broth microdilution via automated susceptibility testing methods. Study groups consisted of patients with MRSA isolates that had vancomycin MICs of <2 μg/ml and those with vancomycin MICs of 2 μg/ml. Covariates included demographics, severity of illness, comorbidities, intensive-care unit (ICU) admission, infectious disease consultation, infectious sources, and hospital onset of bacteremia. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included the duration of bacteremia, persistent bacteremia for ≥7 days, recurrence within 30 days, change to alternative antibiotic therapy, and length of hospital stay. Multivariate logistic regression models were analyzed to control for potential confounding variables. A total of 166 patients were included for analysis: 91 patients with vancomycin MICs of <2 μg/ml and 75 patients with vancomycin MICs of 2 μg/ml. In the multivariate logistic regression model, a vancomycin MIC of 2 μg/ml, compared to a MIC of <2 μg/ml, was not significantly associated with 30-day in-hospital mortality after adjustment for confounders. Additionally, all secondary outcomes were not statistically significantly different between study groups. In patients with MRSA bacteremia treated with vancomycin, the vancomycin MIC was not associated with differences in clinical outcomes.

Early use of peripherally inserted central catheters is safe in Staphylococcus aureus bacteraemia.

Management of Staphylococcus aureus bacteraemia (SAB) includes prolonged intravenous antibiotics often administered through a peripherally inserted central catheter (PICC). Optimal timing of PICC insertion for SAB treatment is unknown. There are concerns that early insertion may increase the risk of subsequent line infection. This retrospective audit aims to determine if early PICC insertion is safe. The outcomes considered included crude mortality, attributable mortality, PICC line infections, duration of bacteraemia and relapsed SAB. Patients with SAB at our institution between March 2013 and September 2016 were identified. Early PICC line insertion was defined as occurring within 48 h of index positive blood culture. This retrospective audit identified 357 patients with SAB who subsequently received a PICC. This study did not show any significant differences between the early and late PICC insertion groups for attributable mortality (6.3% and 4.8%, P = 0.27), duration of bacteraemia (median 2 days for both groups, P = 0.48) and relapsed SAB (4.7% and 4.1%, P = 0.74). Importantly, no confirmed PICC infections were identified in either group. Early PICC insertion in SAB appears safe in this retrospective audit. If validated in prospective studies, this should allow for the early establishment of safe, reliable intraveous access in SAB patients.

Infective endocarditis today

Endocarditis is an infectious disease caused by numerous microorganisms, many of which habitually colonize the oral cavity and skin. Various bacteria and bacterial factors influence the duration of bacteremia and the possible colonization of cardiac valves. If not recognized and treated early, the disease may have serious consequences until death: despite the possibility of setting up targeted antibiotic therapy, it may occur in 30% of cases. This event is related to sepsis that develops in these patients and can result in cellular functional alterations in many districts, resulting in multi-organ failure (MOF) status. This paper is aimed to present an overview of this condition, based on the author’s own clinical experience and literature review.

Telavancin for refractory MRSA bacteraemia in intermittent haemodialysis recipients.

Patients with end-stage renal disease (ESRD) requiring intermittent haemodialysis (IHD) are at high risk of MRSA bacteraemia (MRSA-B) and often fail first-line therapy. The safety, effectiveness and optimal dosing of telavancin for MRSA-B in this patient population are unclear. We aimed to describe clinical outcomes of telavancin in the treatment of refractory MRSA-B in patients with ESRD requiring IHD. This was a retrospective study of hospitalized patients at two tertiary care academic medical centres with recurrent or persistent (≥3 days) MRSA-B treated with telavancin monotherapy. Outcomes included duration of MRSA-B (pre-telavancin versus post-telavancin) and microbiological failure (duration of MRSA-B ≥3 days after initiation of telavancin). Telavancin dosed 10 mg/kg three times weekly post-IHD or 10 mg/kg every 48 h resulted in microbiological cure in 7/8 (87.5%) refractory MRSA-B cases. Telavancin monotherapy was associated with a significant reduction in median duration of bacteraemia [16 days pre-telavancin (IQR 8-19 days) versus 1 day post-telavancin (IQR 0-2 days); P = 0.018]. Telavancin was well tolerated by all patients and no adverse events were reported. Telavancin was very safe and highly effective in the treatment of refractory MRSA-B in a cohort of patients with ESRD requiring IHD. These data support the utility of telavancin in the armamentarium against refractory MRSA-B, particularly in the high-risk IHD-dependent population.

Early Administration of Adjuvant β-Lactam Therapy in Combination with Vancomycin among Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis.

To determine whether early administration of adjuvant β-lactam in combination with vancomycin (COMBO) affects clinical outcomes compared to standard vancomycin therapy alone (STAN) among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection. Retrospective, multicenter cohort study. Five academic or community hospitals throughout the United States. Adults with MRSA bloodstream infections treated with vancomycin (≥72hrs)with or withoutan intravenous β-lactam (≥48hrs) initiated within 24hours of initiating vancomycin. The primary outcome was clinical failure, a composite endpoint including 30-day mortality, persistent bacteremia (≥7days), bacteremia relapse, or change in antibiotic therapy during treatment due to clinical worsening. A multivariable logistic regression examined the impact of patient-, treatment-, and pathogen-level characteristics on clinical failure. A total of 201 patients were evaluated of whom 97 (48.3%) met the criteria for study inclusion; 40 (41.2%) in STAN and 57 (58.8%) in COMBO groups. Among patients in the STAN and COMBO groups, 30% and 24.6% experienced clinical failure, respectively (p=0.552). The median (interquartile range) duration of bacteremia in the STAN and COMBO groups was 4days (2.5-6.5) and 3days (2-5), respectively (p=0.048). In a multivariable analysis, receipt of COMBO therapy was inversely associated with clinical failure (adjusted odds ratio [aOR] 0.237, 95% confidence interval [CI] [0.057-0.982]; p=0.047). Other independent predictors of clinical failure included complicated bacteremia (aOR 6.856, 95% CI [1.641-28.649]; p=0.008) and antibiotic therapy not continued at discharge (aOR 45.404, 95% CI [9.383-219.714]; p<0.001). Receipt of COMBO therapy did not decrease the rate of clinical failure but was associated with expedited bacteremia clearance. Early adjuvant β-lactam therapy deserves continued evaluation and clinical consideration.

Impact of Vancomycin Serum Trough Concentrations and Vancomycin AUC/MIC on Vancomycin Response, In-Hospital Outcomes and Acute Kidney Injury in Pediatric Staphylococcus aureus Pneumonia

BackgroundVancomycin AUC/MIC > 400 was initially shown to be beneficial in adults with staphylococcal pneumonia. Current practice guidelines recommend targeting serum vancomycin trough concentrations (VTC) of 15–20 µg/ml in adults with severe MRSA infection to approximate these AUC/MIC goals. Small studies have shown no benefit to VTC > 15 µg/ml in children with osteomyelitis or bacteremia. We describe the impact of VTC and AUC/MIC on outcomes of pediatric S. aureuspneumonia.MethodsCases of S. aureuspneumonia from January 1, 2011 to December 31, 2016 were reviewed. Patients treated with vancomycin <48 hours were excluded. Suboptimal vancomycin response (SVR) was considered any combination of duration of fever, bacteremia or ICU stay > 75%-tile, need for re-operation, or mortality. The highest VTC and AUC obtained in the first 96 hours of therapy was used in analyses. Vancomycin MIC was determined with the E-test. Acute kidney injury (AKI) was defined as a doubling of the baseline serum creatinine.ResultsThirty-six patients were identified meeting inclusion criteria with a median age of 0.74 years. 75% of isolates were MRSA and 70.4% were USA300. 80.6% of patients were admitted to the ICU and 52.8% were intubated. No benefit was observed in terms of duration of fever, bacteremia, ICU stay, ventilator or hospital days or rates of SVR between patients with VTC > or <15 µg/ml. There were substantial increases in rates of AKI with higher VTC (66.7 vs. 24.2%, P < 0.001). Among 23 patients for whom AUC/MIC determinations were possible, none achieved an AUC/MIC >400; the median AUC/MIC = 42 (IQR: 32–51). Eighty-eight% of isolates had an MIC ≥1.5 µg/ml. There was no correlation between values of AUC/MIC and length of ICU or hospital stay or SVR (AUROC 0.45).ConclusionWhile the sample size is limiting, VTC >15 µg/ml did not provide clinical benefit to children with S. aureus pneumonia compared with lower VTC levels while at the same time predisposing to nephrotoxicity. AUC/MIC > 400 is rarely achieved in children with S. aureus pneumonia and may not be a realistic goal in this infection given the rarity with which this occurs, the frequency of high MICs and the very young age of the typical patient. Large multicenter studies are required to understand optimal vancomycin dosing and monitoring in children with invasive MRSA infections.Disclosures J. McNeil, NIAID, NIH: Grant Investigator, Grant recipient; S. L. Kaplan, Allergan: Grant Investigator, Grant recipient and This grant pertains to unrelated research

The Utility of Repeat Blood Cultures for Bacteremic Urinary Tract Infections and Associated Durations of Therapy

BackgroundUrinary tract infections (UTIs) are common among hospitalized patients with 10–40% of cases complicated by bacteremia. Recent literature suggests limited utility in repeating blood cultures for non-Staphylococcus aureus bacteremia; however, clinicians often repeat blood cultures to document clearance prior to selecting definitive therapy for bacteremias. Additionally, comparative data evaluating treatment duration for bacteremic UTIs are lacking and clinical practice guidelines do not address optimal duration for bacteremic UTIs. We aimed to evaluate local practice patterns and utility of repeat blood cultures and their influence on treatment durations for bacteremic UTIs.MethodsWe identified patients with bacteremia from a urinary source at the Salt Lake City Veterans Affairs (VA) hospital from a previously compiled cohort of inpatients with bacteremia from any source between November 2013 and October 2015. Demographic and clinical information including presence of comorbidities, source of infection, number of repeat blood cultures collected, repeat blood culture positivity, planned duration of antibiotic therapy and recurrent bacteremia with the same organism within 30 days of discharge were collected by manual chart review.ResultsFifty-three bacteremic UTIs were included during the study period. Ninety-four percent of patients were male with a median age of 77. Repeat blood cultures were drawn in 77% (41/53) of cases; however, only 7% (3/41) of repeats were positive, all with Enterococcus faecalis. Median duration of therapy was 14 days (IQR 14, 15), with a longer mean duration in patients with repeat blood cultures as compared with not (15 vs.. 12 days, P = 0.03). Two patients had recurrent bacteremia with the same organism within 30 days; both with negative repeat blood cultures at the time of initial bacteremia and undetected metastatic complications.ConclusionPatients with bacteremic UTIs are at low risk of persistent bacteremia. Repeat blood cultures are of low utility, specifically with Gram-negative organisms, and may lead to prolonged durations of therapy. The impact of reducing repeat blood culture collection on outcomes, length of stay, and antibiotic durations warrants further evaluation.Disclosures All authors: No reported disclosures.

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.

Association Between Vancomycin Trough Concentrations and Duration of Methicillin-Resistant Staphylococcus aureus Bacteremia in Children.

In a multicenter retrospective study, we sought to determine the optimal vancomycin trough concentration that would impact the duration of methicillin-resistant Staphylococcus aureus bacteremia in children. We found that a median vancomycin trough concentration of <10 µg/mL within the first 72 hours may be associated with a longer duration of bacteremia compared to a median trough concentration of ≥10 µg/mL.

The Influence of the Route of Antibiotic Administration, Methicillin Susceptibility, Vancomycin Duration and Serum Trough Concentration on Outcomes of Pediatric Staphylococcus aureus Bacteremic Osteoarticular Infection.

Bacteremia is often one factor used in deciding the need for prolonged intravenous antimicrobial therapy in osteoarticular infections (OAIs). We examined treatment practices and outcomes of Staphylococcus aureus bacteremic osteoarticular infections (BOAIs) evaluated at Texas Children's Hospital. Cases of acute hematogenous OAI in children with positive blood cultures for S. aureus at Texas Children's Hospital between 2011 and 2014 were reviewed. Orthopedic complications included chronic osteomyelitis, growth arrest, pathologic fracture, avascular necrosis and chronic dislocation. Acute kidney injury was defined as a doubling of the baseline creatinine. One hundred and ninety-two cases of S. aureus OAI were identified with 102 cases of BOAI included [35 methicillin-resistant S. aureus (MRSA)]. Twenty-five patients were discharged home on oral antibiotics. Patients discharged on oral antibiotics had a shorter duration of fever, had a more rapid decline in C-reactive protein and were less likely to have MRSA. The frequency of orthopedic complications did not increase in patients who received early transition to oral antibiotics. For patients with MRSA bacteremia, the rates of complications between those who received ≥7 days versus <7 days of vancomycin did not differ. Vancomycin serum troughs >15 µg/mL were not associated with a decreased duration of fever, bacteremia or hospitalization, need for repeat operation or orthopedic complications but were associated with acute kidney injury. S. aureus BOAIs are associated with substantial morbidity. Early transition to oral therapy may be a safe option for select patients with S. aureus BOAI, including those due to MRSA. Prolonged courses of vancomycin and vancomycin troughs >15 μg/mL were not associated with improved outcomes for MRSA OAI.

Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni.

Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

Comparison of Daptomycin and Linezolid in the Treatment of Vancomycin-Resistant Enterococcus faecium in the Absence of Endocarditis

Background Although linezolid and daptomycin are frequently used for the management of vancomycin-resistant Enterococcus (VRE) bloodstream infection, optimal treatment is undefined. Methods We conducted a retrospective cohort study from January 2010 to December 2013 of patients with VRE faecium (VREF) bloodstream infection in the absence of endocarditis treated with daptomycin or linezolid at a single 802-bed teaching hospital in Detroit, Mich. Ninety-day all-cause mortality, length of stay, bacteremia duration, antibiotic duration, and recurrence at 30 days were evaluated. Multivariable analysis was performed to determine the effect of treatment selection on mortality. Results One hundred eighteen patients were included. Seventy-four patients received daptomycin and 44 linezolid. There was no significant difference in baseline characteristics between the 2 groups with the exception of nursing home residence (P = 0.007), intensive care unit admission (P = 0.049), receipt of chemotherapy (P = 0.013), and neutropenia (P = 0.007). Ninety-day all-cause mortality was 46% and 27% (odds ratio = 2.27; 95% confidence interval, 1.1–5.07; P = 0.044) and mean bacteremia duration was 3.6 and 2.6 days (odds ratio = 2.52; 95% confidence interval, 1.17–5.42; P = 0.037) for daptomycin and linezolid, respectively. There was no significant difference in mean length of stay, mean antibiotic duration, and recurrence between the 2 groups. Moreover, there were no significant differences in mortality between the 2 groups after controlling for variables such as chemotherapy, neutropenia, and renal replacement therapy that were associated with increased mortality. Conclusions Our study showed that there was no significant difference in mortality between linezolid and daptomycin for therapy of VRE bacteremia in the absence of endocarditis after controlling for other variables that were associated with increased mortality.