Duration Of Bacteremia Research Articles

Reduced Vancomycin Susceptibility, MRSA and Treatment Failure in Pediatric Staphylococcus aureus Bloodstream Infections.

Clinical implications of reduced vancomycin susceptibility (RVS) among pediatric Staphylococcus aureus bloodstream infections are unknown. We identified all children at 2 children's hospitals with ≥1 blood culture positive for S. aureus. We compared patient and clinical factors for RVS and non-RVS infections using Wilcoxon rank-sum and chi-squared tests. Treatment failure and the duration of bacteremia for RVS versus non-RVS and for methicillin-resistant Staphylococcus aureus (MRSA) versus methicillin-susceptible Staphylococcus aureus (MSSA) infections were compared using multivariable logistic and Poisson regressions, respectively. For MRSA infections, the association of empiric vancomycin monotherapy with treatment failure was assessed using multivariable logistic regression. RVS was present in 72% (309/426) of cases. No patient or infection characteristics, including methicillin resistance, were associated with RVS. RVS was associated with an increased duration of bacteremia compared with non-RVS infections, aIRR = 1.15 (95% confidence interval: 1.02-1.30). The odds of treatment failure was similar for RVS and non-RVS infections, aOR = 1.04 (0.62-1.74). In contrast, MRSA infections were more likely to have treatment failure than MSSA infections, aOR = 3.03 (95% confidence interval: 1.84-5.00). For MRSA infections, empiric vancomycin monotherapy was associated with an increased odds of treatment failure compared with non-vancomycin or combination anti-MRSA antibiotics, aOR = 3.23 (1.12-9.26). RVS was common and was associated with a longer duration of bacteremia but not with treatment failure. Treatment failure was more common for MRSA than for MSSA bloodstream infections. Empiric vancomycin monotherapy increased the odds of treatment failure for MRSA infections.

Updates on Combination Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with a large clinical burden and high rates of treatment failure with first-line treatment options. Literature for combination antimicrobial therapies for initial treatment or salvage therapy in the setting of persistent bacteremia is developing. Various combination strategies have emerged for the treatment of MRSA bacteremia, including vancomycin or daptomycin in combination with either anti-staphylococcal penicillins, early- and late-generation cephalosporins, ceftaroline, trimethoprim-sulfamethoxazole, or fosfomycin. When used as second-line or salvage therapy, evidence suggests use of these combinations shorten the duration of bacteremia. More recently, data have emerged evaluating this strategy for initial therapy, although results are conflicting. Use of combination therapy for MRSA bacteremia may shorten bacteremia duration, but the optimal combination, doses, timing of use, and exact impact on clinical outcomes are still evolving.

Outcomes of Outpatient Parenteral Antimicrobial Therapy With Ceftriaxone for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections—A Single-Center Observational Study

Background Staphylococcus aureus bloodstream infections (BSIs) are associated with significant morbidity and mortality. Ceftriaxone is convenient for outpatient parenteral antimicrobial therapy (OPAT), but data for this indication are limited.MethodsAdult patients with methicillin-susceptible Staphylococcus aureus (MSSA) BSI discharged on OPAT with cefazolin, oxacillin, or ceftriaxone for at least 7 days were included. We compared outcomes of ceftriaxone vs either oxacillin or cefazolin. Ninety-day all-cause mortality, readmission due to MSSA infection, and microbiological failure were examined as a composite outcome and compared among groups. Rates of antibiotic switches due to intolerance were assessed.ResultsOf 243 patients included, 148 (61%) were discharged on ceftriaxone and 95 (39%) were discharged on either oxacillin or cefazolin. The ceftriaxone group had lower rates of intensive care unit care, endocarditis, and shorter duration of bacteremia, but higher rates of cancer diagnoses. There was no significant difference in the composite adverse outcome in the oxacillin or cefazolin group vs the ceftriaxone group (18 [19%] vs 31 [21%]; P = .70), comprising microbiological failure (6 [6.3%] vs 9 [6.1%]; P = .94), 90-day all-cause mortality (7 [7.4%] vs 15 [10.1%]; P = .46), and readmission due to MSSA infection (10 [10.5%] vs 13 [8.8%]; P = .65). Antibiotic intolerance necessitating a change was similar between the 2 groups (4 [4.2%] vs 6 [4.1%]; P = .95).ConclusionsFor patients with MSSA BSI discharged on OPAT, within the limitations of the small numbers and retrospective design we did not find a significant difference in outcomes for ceftriaxone therapy when compared with oxacillin or cefazolin therapy.

Impact of antimicrobial stewardship and rapid diagnostics in children with Staphylococcus aureus bacteremia

AbstractIntroductionRapid diagnostic testing (RDT) in combination with antimicrobial stewardship programs (ASPs) has been associated with improved outcomes in adults with Staphylococcus aureus bacteremia (SAB); however, pediatric data are limited.ObjectivesThe primary objective of this study was to assess the clinical impact of concomitant implementation of an ASP and RDT in children with SAB.MethodsThis pre‐post quasi‐experimental study compared time to optimal antibiotic in children with SAB in 2015/2016 (pre‐intervention [PRE]) and 2017/2018 (post‐intervention [POST]). During the PRE period there was no RDT or ASP available. However, in the POST period, RDT was performed on all positive blood cultures, followed by feedback from an ASP. Secondary outcomes included time to effective antibiotic, antibiotic exposure, duration of bacteremia, hospital length of stay (LOS), transfer to the intensive care unit (ICU), SAB recurrence, and inpatient mortality.ResultsSixty‐eight patients were included in the study (PRE: n = 32, POST: n = 36). Median time to optimal antibiotic therapy decreased by 23 hours (PRE: 44.3 hours vs POST: 21.3 hours; P = .008). Duration of bacteremia (PRE: 65 hours vs POST: 40.9 hours; P = .03) and inpatient mortality (PRE: 12.5% vs POST: 0%; P = .04) were also reduced. However, further review revealed that only one death was related to SAB. Differences in time to effective therapy, antibiotic exposure, and hospital LOS were not significantly different between the groups. There were similar rates of infectious disease (ID) consultation (PRE: 78% vs POST: 89%, P = .23), but a shorter time to central line removal in the POST group (PRE: 68.2 hours vs POST: 19.8 hours; P = .04). Throughout the study period, recurrence of SAB only occurred in one patient (PRE).ConclusionASP interventions, facilitated by RDT, resulted in a shorter time to optimal antibiotic therapy in children with SAB. Although these interventions may have led to improved overall SAB management, further studies are needed to confirm clinical benefits.

Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study

Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. None.

Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial.

Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI. A randomized, double-blind, placebo-controlled trial was performed at 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard-of-care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days. Of 318 participants screened, 115 were enrolled and 104 were included in the intention-to-treat analysis (median age, 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P = 1.0). Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered. NCT02972983.

Paradoxical Antibiotic Effect of Ampicillin: Use of a Population Pharmacokinetic Model to Evaluate a Clinical Correlate of the Eagle Effect in Infants With Bacteremia.

High doses of ampicillin are often used to achieve therapeutic drug concentrations in infants. A paradoxical antibiotic effect, often called the Eagle effect, occurs when increasing concentrations of antibiotic above a threshold results in decreased efficacy. It is unknown if infants treated with ampicillin are at risk for this paradoxical effect. We identified infants <28 days of age with Escherichia coli, Enterococcus or Streptococcus agalactiae (group B streptococcus) bloodstream infections from 1997 to 2012 and previously included in an ampicillin pharmacokinetic (PK) modeling study. We compared the odds of death for ampicillin dose, estimated time above the minimum inhibitory concentration (T > MIC) and PK parameters using separate logistic regression models. Adjusted logistic regression and Poisson models were used to calculate the odds of prolonged bacteremia ≥3 days and the duration of bacteremia, respectively, for dose, T > MIC and multiple PK parameters. Among 1272 infants meeting inclusion criteria, odds of death 7 or 30 days after the positive blood culture were not consistent with a paradoxical effect across any of the dosing regimens or PK parameters evaluated. The odds of prolonged bacteremia was lowest at the lowest dose category and the lowest daily dose category but not associated with the area-under-the-concentration time curve from 0 to 24 hours, or the maximum or minimum concentrations at steady state. T > MIC of ≥50% of the dosing interval was associated with decreased duration of bacteremia and odds of prolonged bacteremia. It is unlikely that a paradoxical antibiotic effect will have a clinical correlate when ampicillin is used for neonatal bacteremia. A T > MIC ≥50% decreased both duration of bacteremia and odds of prolonged bacteremia.

Prevalence of bacteraemia following dental extraction – efficacy of the prophylactic use of amoxicillin and clindamycin

Objectives To evaluate the efficacy of single-dose antibiotic prophylaxis (AP) in the prevention of bacteraemia following tooth extractions at our clinic. Material and methods Fifty patients undergoing tooth extractions were enrolled. The need of AP was determined according to the health status and possible allergies of the patients. Blood culture samples were collected at baseline, 5 min after the first tooth extraction and 20 min after the last extraction. Results The majority (76%) received prophylactic oral amoxicillin or intravenous ampicillin (AMX/AMP) (2 g), 12% received clindamycin (CLI) (600 mg) and 12% received no prophylaxis (NO AP). All baseline blood cultures were reported negative. The prevalence of bacteraemia was significantly higher in the CLI and NO AP groups compared to the AMX/AMP group 5 min after the first tooth extraction (p < .0001 and p = .015, respectively). Twenty minutes after the last extraction positive blood cultures were reported only for CLI (p = .0015) and NO AP groups. There was no significant difference in the prevalence of positive blood cultures between CLI and NO AP groups. Conclusions Appropriately administered AMX/AMP proved its efficacy in reducing both the prevalence and duration of bacteraemia following tooth extractions whereas CLI was not effective in preventing bacteraemia following tooth extractions.

Longitudinal Study of Bacterial Infectious Agents in a Community of Small Mammals in New Mexico.

Background and Objectives: Vector-borne bacterial diseases represent a substantial public health burden and rodents have been recognized as important reservoir hosts for many zoonotic pathogens. This study investigates bacterial pathogens in a small mammal community of the southwestern United States of America. Methods: A total of 473 samples from 13 wild rodent and 1 lagomorph species were tested for pathogens of public health significance: Bartonella, Brucella, Yersinia, Borrelia, Rickettsia spp., and Anaplasma phagocytophilum. Results: Three animals were positive for Yersinia pestis, and one Sylvilagus audubonii had a novel Borrelia sp. of the relapsing fever group. No Brucella, Rickettsia, or A. phagocytophilum infections were detected. Bartonella prevalence ranged between 0% and 87.5% by animal species, with 74.3% in the predominant Neotoma micropus and 78% in the second most abundant N. albigula. The mean duration of Bartonella bacteremia in mark-recaptured N. micropus and N. albigula was 4.4 months, ranging from <1 to 18 months, and differed among Bartonella genogroups. Phylogenetic analysis of the Bartonella citrate synthase gene (gltA) revealed 9 genogroups and 13 subgroups. Seven genogroups clustered with known or previously reported Bartonella species and strains while two were distant enough to represent new Bartonella species. We report, for the first time, the detection of Bartonella alsatica in North America in Sylvilagus audubonii and expand the known host range of Bartonella washoensis to include Otospermophilus variegatus. Interpretation and Conclusion: This work broadens our knowledge of the hosts and geographic range of bacterial pathogens that could guide future surveillance efforts and improves our understanding of the dynamics of Bartonella infection in wild small mammals.

Gram-negative septic thrombosis in critically ill patients: A retrospective case–control study

BackgroundData on septic thrombosis caused by Gram-negative bacilli (GN-ST) in intensive care unit (ICU) patients are currently limited. MethodsThe aim of this retrospective case–control study (matched 1:3) performed over a 15-month period on ICU patients with bacteraemia, associated (cases) or not (controls) with GN-ST, was to assess 30-day mortality and clinical/microbiological features of GN-ST. ResultsDuring the study period, 16 patients with GN-ST and 48 controls were analyzed. Polytrauma was the cause of ICU admission in 12 (75%) cases and 22 (46%) controls (p = 0.019). In no case of septic thrombosis was surgical debridement performed. The site of venous thrombosis was more frequently in the lower limbs, associated with bone fracture in nine out of 12 (75%) cases. The median duration of bacteraemia (22 days vs 1 day; p < 0.001) and time to clinical improvement (15 days vs 4 days; p < 0.001) were significantly longer in cases than in controls. On analysis of the receiver operating characteristics (ROC) curve, bacteraemia >72 h was significantly associated with GN-ST (area under the curve (AUC) 0.95, sensitivity 0.996 and specificity 0.810; p < 0.001). Finally, 30-day mortality was 20% in cases and 67% in controls (p < 0.001). ConclusionsCritically ill patients with GN-ST showed specific clinical features. Despite delayed bacteraemia clearance, targeted antibiotic therapy plus anticoagulation usually provided clinical improvement and a low 30-day mortality rate.

Follow-up blood cultures in Gram-negative bacilli bacteremia: are they needed for critically ill patients?

Gram-negative bacilli bacteremias (GNB-Bs) represent a major cause of morbidity and mortality in Intensive Care Unit (ICU) patients. Aim of this study was to investigate the role of follow-up blood cultures (FUBCs) and the clinical significance of persistent bacteremia (PB) in these settings. We retrospectively analyzed clinical data and outcome of GNB-Bs that occurred in ICU patients over a span of 1 year. In particular we sought information on development and clinical details of PB, defined as repeatedly positive FUBCs after ≥96 hours of appropriate antibiotic treatment and ≥48 hours after removal of endovascular devices. Among 307 ICU patients, 69 (22.4%) developed 107 GNB-Bs. Of these, 78 (73%) could be eventually analyzed: 50 of 78 (64.1%) were non-PBs from 26 patients and 28 of 78 (35.9%) were PBs from 23 patients. Duration of fever and bacteremia, time to procalcitonin normalization and weaning from vasopressors were longer in episodes of PBs than non-PBs (P=0.04, P<0.001, P=0.02 and P=0.004, respectively). Primary bacteremia was more frequent in non-PBs than in PBs (29 of 50, 58% vs. 3/28, 10.7%, P=0.0001), whereas septic thrombus infection (STI) was the source of infection in 14 of 28 (50%). Finally, clinical features and 30-day mortality did not differ between patients with PB and those who developed only non-PB episodes. Among our ICU patients, more than one third of GNB-Bs for which FUBCs were performed resulted PB. This condition is often associated with the presence of STI; therefore, FUBCs seem useful for the optimal management of GNB in this clinical setting.

Intermittent Negative Blood Cultures in Staphylococcus aureus Bacteremia; a Retrospective Study of 1071 Episodes.

BackgroundRecommended management of Staphylococcus aureus bacteremia (SAB) includes follow-up blood culture sets (BCs) to determine the duration of bacteremia. Duration of bacteremia is an important prognostic factor in SAB, and follow-up BCs have a critical role in differentiation of uncomplicated and complicated SAB. However, intermittent negative BCs occur in SAB. Clinical guidelines for SAB management do not specify an approach to follow-up BCs’ collection or define the number of negative BCs required to demonstrate resolution of bacteremia. This study assessed the frequency of intermittent negative BCs in SAB and used these findings to formulate a recommendation for collection of follow-up BCs.MethodsThis retrospective study reviewed 1071 episodes of SAB. Clinical and microbiological data including the duration of bacteremia and the occurrence of intermittent negative BCs (those preceded and followed by positive cultures) were considered.ResultsIntermittent bacteremia occurred in 13% (140/1071) of episodes. A single negative BC on days 1–3 had a predictive value of 87%–93% for resolution of bacteremia, although this was improved if all BCs collected within the same day were considered.ConclusionsIntermittent negative BCs are common in SAB. Given this, we would not recommend accepting a single negative BC as demonstrating resolution of the bacteremia. This is particularly important if a patient is to be classified as having uncomplicated SAB.

177. Clinical Outcomes of Daptomycin vs. Anti-Staphylococcal β-Lactams in Definitive Treatment of Methicillin-Susceptible Staphylococcus aureus (MSSA) Bloodstream Infections

BackgroundThe preferred management of patients with MSSA bacteremia includes definitive therapy with intravenous anti-staphylococcal β-lactam antibiotics. In β-lactam allergic or intolerant patients, daptomycin has been targeted as a viable alternative. The objective of this study was to assess clinical outcomes of daptomycin compared with nafcillin or cefazolin for the treatment of MSSA bacteremia.MethodsThis was a retrospective cohort study of patients hospitalized from November 1, 2011 to October 31, 2018 at The Ohio State University Wexner Medical Center with MSSA bacteremia. Patients treated with nafcillin, cefazolin or daptomycin were included with 1:1:1 random selection. The primary outcome was a composite of clinical failure, defined as a change in therapy due to persistent/worsening signs and symptoms, bacteremia recurrence or persistence, or inpatient infection-related mortality. Secondary endpoints included 30-day infection-related mortality, duration of bacteremia, 30-day all-cause mortality and adverse events (AEs) necessitating a change in therapy.ResultsAmong patients with MSSA bacteremia, 162 received at least one dose of daptomycin. Of those, 29 received at least 14 days of daptomycin and/or received daptomycin as definitive therapy and thus were included in the analysis. There was no difference in the primary outcome of composite clinical failure comparing daptomycin vs. nafcillin/cefazolin (P = 0.71). In addition, no difference was observed in 30-day infection-related mortality (P = 0.51), duration of MSSA bacteremia (P = 0.9), or 30-day all-cause mortality (P = 0.64). A higher number of AEs necessitating change in therapy were seen in the daptomycin group (P = 0.0002), reflecting initial β-lactam intolerance.ConclusionNo difference in clinical failure was identified in patients treated with daptomycin vs. nafcillin/cefazolin suggesting that daptomycin may serve as a non-inferior alternative for treatment of MSSA bacteremia. A higher number of AEs occurred in the daptomycin group indicating β-lactam intolerance as a primary indication for daptomycin therapy. Given the small sample size, subsequent studies are needed to further evaluate the use of daptomycin in the treatment of MSSA bacteremia.Disclosures All authors: No reported disclosures.

854. Impact of Antimicrobial Stewardship and Rapid Diagnostics in Children with Staphylococcus aureus Bacteremia

BackgroundRapid diagnostic testing (RDT) in combination with antimicrobial stewardship programs (ASPs) has been associated with improved outcomes in adults with Staphylococcus aureus bacteremia (SAB). Data in children are lacking. In January 2017, Atrium Health implemented a pediatric ASP with blood culture RDT. The objective of this study was to determine the impact of those interventions.MethodsThis was a retrospective, multicenter, quasi-experimental study of children ≤18 years with monomicrobial SAB from March 2015 to August 2016 (pre-intervention; PRE) and March 2017 to August 2018 (post-intervention; POST). The primary outcome was time to an optimal antibiotic. Secondary outcomes included time to effective antibiotic, total antibiotic exposure in the first 5 days, duration of bacteremia, infectious diseases (ID) consultation, time to central line removal, hospital and pediatric ICU length of stay (LOS), need for vasopressors or intubation, recurrence of SAB within 90 days, and inpatient mortality.ResultsOf 101 patients with SAB, 32 and 36 met inclusion criteria for the PRE and POST groups, respectively. The median time to optimal antimicrobial therapy decreased by 23 hours (PRE 44.3 hours vs. POST 21.3 hours; P = 0.008). Duration of bacteremia (65h vs. 40.9 hours; P = 0.028) and mortality (12.5% vs. 0%; P = 0.044) was also significantly reduced. Differences in median time to effective therapy (7 hours vs. 5.1 hours; P = 0.74), total antibiotic exposure in the first 5 days (160.4 hours vs. 152 hours; P = 0.4), hospital LOS (9.9 vs. 8.5 days; P = 0.25), and pediatric ICU LOS (7 vs. 4 days; P = 0.11) did not meet statistical significance, but trended downward. The POST group had more patients with ID consultation (78% vs. 89%, P = 0.23) and shorter time to central line removal (68 hours vs. 20 hours; P = 0.037). There was no difference in the need for vasopressors (3 vs. 3 patients; P = 0.99) or intubation (2 vs. 4 patients; P = 0.68). Throughout the study period, recurrence of SAB only occurred in one patient (PRE).ConclusionConcurrent implementation of RDT and an ASP in pediatric patients with SAB decreased time to optimal antimicrobial therapy, duration of bacteremia, and mortality. RDT coupled with timely feedback from an ASP contributed to improved SAB management and clinical outcomes in children.Disclosures All Authors: No reported Disclosures.

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.

575. Evaluation of Risk Factors and Clinical Outcomes of Patients with Vancomycin-Resistant Enterococcus Infections

BackgroundVancomycin-resistant Enterococci (VRE) occurs with enhanced frequency in hospitalized patients and are usually associated with poor clinical outcomes. The purpose of this study was to evaluate the risk factors and clinical outcomes of patients with VRE infections.MethodsThis study was an IRB-approved multi-center retrospective chart review conducted at a three-hospital health system between August 2016-November 2018. Inclusion criteria were patients ≥18 years and admitted for ≥24 hours with cultures positive for VRE. Patients pregnant or colonized with VRE were excluded. The primary endpoint was to analyze the association of potential risk factors with all-cause in-hospital mortality (ACM) and 30-day readmission. The subgroup analysis focused on the association of risk factors with VRE bacteremia. The secondary endpoint was to evaluate the impact of different treatment groups of high dose daptomycin (HDD) (≥10 mg/kg/day) vs. low dose daptomycin (LDD) (< 10 mg/kg/day) vs. linezolid (LZD) on ACM and 30-day readmission. Subgroup analysis focused on the difference of length of stay (LOS), length of therapy (LOT), duration of bacteremia (DOB) and clinical success (CS) between the treatment groups.ResultsThere were 81 patients included for analysis; overall mortality was observed at 16%. Utilizing multivariate logistic regression analyses, patients presenting from long-term care facilities (LTCF) were found to have increased risk for mortality (OR 4.125, 95% CI 1.149–14.814). No specific risk factors were associated with 30-day readmission. Patients with previous exposure to fluoroquinolones (FQ) and cephalosporins (CPS), nosocomial exposure and history of heart failure (HF) showed association with VRE bacteremia. ACM was similar between HDD vs. LDD vs. LZD (16.7% vs. 15.4% vs. 0%, P = 0.52). No differences were seen between LOS, LOT, CS, and DOB between the groups.ConclusionAdmission from LTCFs was a risk factor associated with in-hospital mortality in VRE patients. Individuals with history of FQ, CPS and nosocomial exposure as well as history of HF showed increased risk of acquiring VRE bacteremia. There was no difference in ACM, LOS, LOT, and DOB between HDD, LDD and LZD.Disclosures All authors: No reported disclosures.

1511. Effect of Discharge Antibiotic Route on Clinical Outcomes in Children with Methicillin-Resistant Staphylococcus aureus (MRSA) Osteomyelitis with Bacteremia

BackgroundChildren with osteomyelitis transitioned to oral step-down therapy experience similar outcomes to those treated with outpatient parenteral antibiotic therapy (OPAT). Compared with OPAT, oral therapy has lower costs and avoids catheter complications. However, few studies have specifically compared patient outcomes between those receiving oral therapy vs. OPAT for osteomyelitis with associated bacteremia caused by MRSA.MethodsWe performed a retrospective cohort study comparing early oral therapy (EOT), defined as transition to oral therapy at or prior to discharge vs. use of OPAT at discharge. We identified hospitalized children <19 years of age with MRSA osteomyelitis with bacteremia between 2007 and 2014 from three children’s hospitals. The primary outcome was treatment failure within 6 months of discharge, defined as unplanned change in antibiotic after discharge, development of chronic osteomyelitis, need for an operative procedure after discharge, or recrudescence of bacteremia. The secondary outcome was treatment-related events, defined as documented adverse drug events in the medical record and/or central venous catheter complications. Between-group comparisons were made using Fisher exact test for binomial distributions and the Wilcoxon rank-sum test for continuous variables.ResultsWe included 61 patients with MRSA osteomyelitis with bacteremia. Twenty-five patients (41%) received EOT and 36 (59%) received OPAT. Duration of bacteremia and hospital length of stay was similar between groups (Table 1). Clindamycin was the most commonly used antibiotic in both the EOT (24/25; 96%) and OPAT (22/36; 61%) groups. Clinical failure occurred in 1/25 (4%) children receiving EOT and in 5/36 (14%) in the OPAT group (95% CI of difference: −29 to 6%; P = 0.38, Table 1). Treatment-related adverse events occurred in 1/25 (4%) children receiving EOT compared with 9/36 (25%) receiving OPAT (95% CI of difference: −49 to –7%; P = 0.04, Table 1).ConclusionChildren receiving EOT for MRSA osteomyelitis with bacteremia did not experience higher rates of clinical failure and had fewer treatment-related complications compared with OPAT. Oral step-down therapy can be considered for children with MRSA osteomyelitis with bacteremia. Disclosures All authors: No reported disclosures.

178. Evaluation of Oral Antibiotic Stepdown Therapy for the Management of Gram-Negative Rod Bacteremia in a Tertiary Care Medical Center

BackgroundTreatment strategies surrounding bacteremia are constantly changing as new data emerges. Transition from intravenous (IV) to oral (PO) antibiotics in patients with Gram-negative rod bloodstream infections (GNR BSI) remains controversial. The objective of this study was to characterize clinical outcomes in patients who received early (≤72 hours) vs. late (>72 hours) stepdown therapy (ES vs. LS, respectively) for GNR BSIs.MethodsA single-center, retrospective cohort study was conducted including adults with GNR BSIs admitted to a 610-bed tertiary care academic medical center between January 1, 2016 and December 31, 2017 who were transitioned from IV to PO antibiotics. Patients with severe renal impairment, inadequate source control, prolonged antibiotic course, HIV/AIDS, and pregnancy were excluded. The primary endpoint was clinical failure and secondary endpoints were 30- and 90-day all-cause mortality, duration of bacteremia, and adverse events.Results164 patients (ES = 61; NS = 103) were included. Population median age was 63 years, 56% were male, and 19% were immunocompromised. Genitourinary source was most common (48.7%), while the most common organism isolated was Escherichia coli (52.4%). Most infections were community-acquired (70.1%) and the most common step-down therapy choice was ciprofloxacin in 75% of patients. There were no major differences in baseline demographic and clinical characteristics between groups except for the greater presence of central venous catheters (16.4% vs. 35.9%; P = 0.006) in the LS group. Overall clinical failure was 9.8% vs. 13.6% between the ES and LS groups, respectively. The LS group had a higher rate of clinical failure defined by escalation from PO to IV antibiotics (1.6% vs. 10.7%; P = 0.03). Patients who failed therapy tended to be immunocompromised and/or have an intra-abdominal source of infection. Secondary endpoints did not differ between groups.ConclusionHigher clinical failure rates in the LS group indicate that these patients may have underlying clinical characteristics not amenable to stepdown therapy. Choice of step-down therapy was not driven by the source of infection or patient acuity. Further analysis and studies are needed to determine optimal time and population for stepdown.Disclosures All authors: No reported disclosures.

1430. The Hidden Costs of Vancomycin Use During the Treatment of Staphylococcus aureus Bacteremia Concurrent with Acute Hematogenous Osteomyelitis

BackgroundCurrent guidelines recommend the use of parenteral vancomycin for children with acute hematogenous osteomyelitis and concurrent Staphylococcus aureus bacteremia (SAB) due to Methicillin-Resistant Staphylococcus aureus (MRSA), despite vancomycin’s slow bactericidal activity. This study explores the hidden costs of this approach.MethodsChildren with AHO and concurrent SAB, treated from 2009 to 2018, who had received vancomycin at some point during their treatment course were studied. Data collected included antibiotic susceptibilities; duration of bacteremia, blood culture results, duration of vancomycin; number of dose/interval changes; vancomycin trough and creatinine levels; rate of achieving target trough; use of other nephrotoxic agents; occurrence of acute kidney injury (AKI); and length of stay.Results130 children diagnosed with AHO and concurrent SAB received vancomycin. Isolates were CR MSSA (3 or 2.3%), CR MRSA (5 or 3.8%), CS MSSA (35 or 26.9%), and CS MRSA (87 or 66.9%). Mean LOS was 14.6 days. 1,312 blood cultures were obtained (503 positive cultures and 809 negative cultures). Bacteremia persisted an average of 3.6 days. Target trough level (15–20 µg/mL) was achieved in 65 children (50%) within an average of 3.4 days of initial dosing. Attempts to reach therapeutic levels were abandoned in 32 children (24.6%) as MSSA was isolated before the trough. There were 319 vancomycin dose and/or interval changes, 1,192 serum creatinine levels, and 689 vancomycin trough levels obtained. Fourteen children (10.8%) experienced AKI. Additional nephrotoxicity exposure included: NSAIDs (127), IV contrast (100), loop diuretics (37), and aminoglycosides (11).ConclusionThis study exposes and quantifies a substantial amount of resources devoted to dosing adjustments and serum level monitoring for vancomycin use in children with AHO and concurrent SAB. The cost differential in comparison to that of newer antibiotic alternatives is undermined by the effort to attain therapeutic target levels, resolve bacteremia, and address episodic AKI. If vancomycin is utilized, a deliberate approach should be taken to minimize risk of toxicity, including AUC/MIC ratio calculation, as opposed to therapeutic level monitoring, and avoid the concurrent use of other nephrotoxic agents. Disclosures All authors: No reported disclosures.

412. Host Response Biomarkers Predict Clinical Failure in Patients with Staphylococcus aureus Bacteremia (SAB) Treated with Flucloxacillin (FLU) or Vancomycin (VAN)

BackgroundImbalance among innate mediators such as IL-1β, IL-10, and TNF-α portends poor outcomes of persistence and death in patients with SAB. Previous studies did not consider the role of antibiotic treatment in this important host–pathogen relationship. In this study of SAB, we determined cytokine signatures that correlate with the composite endpoint of clinical failure (bacteremia duration >4 days or 30-day mortality) in Australian patients treated with FLU or VAN.MethodsSera from 86 patients with SAB (24.4% MRSA) were obtained from a clinical study of patients treated with FLU or VAN. All of the patient samples were collected at clinical presentation (day 0 or day 1 of infection) and were treated with FLU or VAN throughout. Patients were classified into either clinical success (CS = 68) or clinical failure (CF = 18), defined as death or prolonged bacteremia >4 days. Patient demographic and infection characteristics were collected. A 10-multiplex TH1/TH2 cytokine analysis was performed using electrochemoluminescence with the Meso-Scale Discovery platform analyzed by Mann–Whitney U.ResultsPatients’ median values were significantly elevated and above the normal range in CF for IL-1β (P = 0.029), IL-10 (P = 0.018), TNF-α (P = 0.042), and IL-6 (P = 0.006) (figure). Epidural abscess source was associated with CF, but no other host or pathogen characteristics correlated to outcome. Patients infected with isolates with VAN MIC = 2 mg/L (by Etest and broth dilution) had lower concentrations of IL-1β and IL-10 (P = 1.5 mg/L. In ROC analysis, IL-1β, IL-10, TNF, and IL-6 were higher sensitivity and specificity predictors of CF (AUC 0.65–0.71; P = 0.05).ConclusionA suboptimal host immune response to SAB at presentation predicts adverse clinical outcomes. IL-10, TNF-α, and IL-6 serum concentrations appear to reflect immunopathology in patients with SAB. These predictive markers may be considered in therapeutic clinical decision-making, such as escalation of alternative therapies in high-risk patients and/or de-escalation treatment in low-risk patients. These data offer steps toward further refining therapeutic precision for patients with SAB beyond the standard clinical or microbiological metrics that are employed in current practice. Disclosures All authors: No reported disclosures.