Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis

BACKGROUND AND OBJECTIVES: Multiple strategies are used to identify newborn infants at high risk of culture-confirmed early-onset sepsis (EOS). Delivery characteristics have been used to identify preterm infants at lowest risk of infection to guide initiation of empirical antibiotics. Our objectives were to identify term and preterm infants at lowest risk of EOS using delivery characteristics and to determine antibiotic use among them. METHODS: This was a retrospective cohort study of term and preterm infants born January 1, 2009 to December 31, 2014, with blood culture with or without cerebrospinal fluid culture obtained ≤72 hours after birth. Criteria for determining low EOS risk included: cesarean delivery, without labor or membrane rupture before delivery, and no antepartum concern for intraamniotic infection or nonreassuring fetal status. We determined the association between these characteristics, incidence of EOS, and antibiotic duration among infants without EOS. RESULTS: Among 53 575 births, 7549 infants (14.1%) were evaluated and 41 (0.5%) of those evaluated had EOS. Low-risk delivery characteristics were present for 1121 (14.8%) evaluated infants, and none had EOS. Whereas antibiotics were initiated in a lower proportion of these infants (80.4% vs 91.0%, P < .001), duration of antibiotics administered to infants born with and without low-risk characteristics was not different (adjusted difference 0.6 hours, 95% CI [−3.8, 5.1]). CONCLUSIONS: Risk of EOS among infants with low-risk delivery characteristics is extremely low. Despite this, a substantial proportion of these infants are administered antibiotics. Delivery characteristics should inform empirical antibiotic management decisions among infants born at all gestational ages.

Eliminating Contamination in Umbilical Cord Blood Culture Sampling for Early-Onset Neonatal Sepsis

Introduction: Despite the advantages of umbilical cord blood culture (UCBC) use for diagnosis of early onset sepsis (EOS), contamination rates have deterred neonatologists from its widespread use. We aimed to implement UCBC collection in a level III neonatal intensive care unit (NICU) and apply quality improvement (QI) methods to reduce contamination in the diagnosis of early onset sepsis.Methods: Single-center implementation study utilizing quality improvement methodology to achieve 0% contamination rate in UCBC samples using the Plan-Do-Study-Act (PDSA) model for improvement. UCBC was obtained in conjunction with peripheral blood cultures (PBC) in neonates admitted to the NICU due to maternal chorioamnionitis. Maternal and neonatal characteristics between clinical sepsis and asymptomatic groups were compared. Process, outcome, and balancing measures were monitored.Results: Eighty-two UCBC samples were collected in addition to peripheral blood culture from neonates admitted due to maternal chorioamnionitis. Ten (12%) neonates had a diagnosis of clinical sepsis. All PBCs were negative and 5 UCBCs were positive in the study period. After 2 PDSA cycles, there was special cause variation with improvement in the percent of contaminated samples from 7.3 to 0%. There was no change in antibiotic duration among asymptomatic neonates.Conclusions: Implementation of UCBC for the diagnosis of EOS in term infants is feasible and contamination can be minimized with the implementation of a core team of trained providers and a proper sterile technique without increasing antibiotic duration.

349. Diagnostic Testing and Antibiotic Utilization in Patients with COVID-19

Background Patients with COVID-19 receive high rates of antibiotic therapy, despite viral origin of infection. Reports of bacterial coinfection range from 3.5 to 8% in the early phase of infection. This study aimed to evaluate the relationship between diagnostic tests and antibiotic utilization in patients admitted with COVID-19 at the University of Maryland Medical Center to better inform future prescribing practices. Methods Retrospective cohort study of adult patients with a positive SARS-CoV-2 PCR on admission from March 2020 through June 2020. Associations between diagnostic tests employed and antibiotic initiation and duration were explored using bivariate analysis (SPSS®). Results Baseline characteristics of 224 included patients are reported in Table 1. Excluding SARS-CoV-2 PCRs, most frequently performed diagnostic tests included blood cultures (65.6%), MRSA nasal surveillance (45.1%), respiratory cultures (36.2%), respiratory viral panel (RVP) (33.0%), and Legionella (28.6%) and pneumococcal (26.3%) urine antigens. Positivity of RVP, Legionella, pneumococcus, blood, and respiratory tests were low (1.3%, 0.4%, 0.9%, 1.8%, and 6.7%, respectively). A total of 62% of patients were initiated on antibacterial therapy with a median cumulative antibiotic duration of 77.9 hours (IQR 41.4, 111.8). History of chronic respiratory disease (76% vs. 58.6%; P=0.025), any degree of oxygen requirement on admission (72% vs. 42.6%; P=0.006), and performance of blood cultures (70.7% vs. 46.8%, P< 0.0001) were associated with antibiotic initiation. Positive bacterial diagnostic respiratory culture (median duration 72.8h [IQR 46.7, 96.6] vs. 97.3h [IQR 79.8, 194.1]; P=0.027) and positive blood culture (median duration 80.1h [IQR 42.1, 111.7] vs. 97.5h [IQR 71.8, 164.8]; P=0.046) were associated with longer antibiotic duration. Patients who did not have respiratory cultures performed had similar antibiotic durations as those with negative respiratory cultures. Table 1. Baseline Characteristics Conclusion Despite low coinfection rates, negative diagnostic tests did not result in shorter empiric antibacterial duration. These findings highlight the ongoing need for both diagnostic and antimicrobial stewardship in COVID-19. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

111. Duration of Antibiotic Therapy after Debridement and Implant Retention in Patients with Periprosthetic Joint Infections

Background Debridement, antibiotics, and implant retention (DAIR) is appropriate for select acute postoperative and hematogenous periprosthetic joint infections (PJIs). However, the optimal duration of antimicrobial therapy in patients treated with DAIR has not been defined. Therefore, we aimed to identify the ideal duration of parenteral and oral antibiotics after DAIR. Methods We performed a retrospective study of patients >18 years of age with hip or knee PJI managed with DAIR between January 1, 2008, and December 31, 2018, at Mayo Clinic. PJI was defined using criteria adapted from the International Consensus Meeting on PJI. The outcome was defined as either PJI recurrence or unplanned reoperation due to infection. Joint-stratified Cox proportional hazards regression models with time-dependent covariates were used to assess nonlinear effects of antibiotic duration. Hazard ratios were computed based on prespecified time points for comparison, whereas p-values represented the overall effect across the entire range of durations. Results There were 247 unique episodes of PJI in 237 patients during the study period. Parenteral antibiotics were given in 99.2% of cases (n=245). This was followed by chronic oral antibiotic suppression in 92.2% (n=226) with a median duration of 2.2 years (1.0-4.1). DAIR failed in 65 cases over a median follow-up of 4.4 years, with a 5-year cumulative incidence of 28.1%. After adjustment for risk factors, there was no significant association between duration of parenteral antibiotics and treatment failure (p=0.203), with no difference between four versus six weeks (HR 1.11; 95% CI 0.71-1.75) (Figure 1). However, both use and longer duration of oral antibiotic therapy was associated with a lower risk of failure (p=0.006). To account for the possibility that this association was driven by results during early follow-up, conditional analyses at one- and two-year follow-up were performed. Both showed a significantly lower risk for a longer duration of antibiotics (Figure 2). Figure 1. Time-Dependent Analysis of Parenteral Antibiotic Duration Figure 2. Time-Dependent Analysis of Oral Antibiotic Suppression Duration Conclusion After DAIR, efficacy from four weeks of parenteral antibiotics was no different from six weeks when followed by chronic oral antibiotic suppression. Our results could not establish an optimal duration but suggested that continuing suppression portends a lower risk of failure of DAIR. Disclosures Elie Berbari, MD, Uptodate.com (Other Financial or Material Support, Honorary unrelated to this work) Matthew P. Abdel, MD, Stryker and AAOS Board of Directors (Board Member, Other Financial or Material Support, Royalties) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing)

613. Clinical Outcomes Following Dalbavancin Administration during Outpatient Parenteral Antimicrobial Therapy

Background Dalbavancin, a lipoglycopeptide with prolonged half-life targeting Gram-positive organisms, is approved for treatment of acute bacterial skin and soft tissue infection. It reduces hospital duration in patients with barriers to short-term rehabilitation or outpatient parenteral antimicrobial therapy (OPAT). Increasing evidence supports the off-label use of dalbavancin to treat other types of infection. We conducted a quality improvement study to evaluate outcomes following dalbavancin administration. Methods We performed a cohort study of recipients of ≥1 dose of dalbavancin from 1/31/2016-1/31/2021 at the Veterans Affairs Connecticut Healthcare System. Demographic, comorbidity, microbiological, antibiotic duration prior to dalbavancin, indication for dalbavancin, and type of infection data were collected. Outcomes included 1) lab abnormalities: hepatotoxicity within 2 weeks of dalbavancin; 2) clinical cure: resolution of symptoms of infection within 90 days; 3) all-cause readmission within 90 days; and 4) all-cause mortality within 90 days. Results 42 patients met criteria. Median age was 69 years (range, 32-91), 100% were male, 55% (n=23) had diabetes, 31% (n=13) had liver disease, 36% (n=15) had other immunosuppressive conditions, and 12% (n=5) had substance use disorder (SUD). All received their first dose as inpatients. Median hospital duration was 8 days (range, 1-32). 4 (10%) required critical care. Median antibiotic duration prior to dalbavancin was 7 days (range, 1-42). Indications included ineligibility for OPAT (n=21, 50%), pharmacologic reasons (n=10, 24%), ineligibility for peripherally inserted central catheter (n=6, 14%), or SUD (n=5, 12%). Common microorganisms were Staphylococcus spp. (n=22, 52%), polymicrobial (n=13, 31%), and Corynebacterium spp. (n=10, 24%). 93% (n=39) had clinical cure of infection; readmissions and mortality were rare (Table 1). Conclusion Dalbavancin was associated with clinical cure for diverse infections with low rates of adverse events, readmission and mortality in patients ineligible for traditional OPAT. Although confirmatory data are needed from larger studies, dalbavancin appears to be a versatile therapeutic agent for Gram-positive infections. Disclosures All Authors: No reported disclosures

162. Duration of Antibiotics Through Care Transitions: A Quality Improvement Initiative

Background Antibiotic resistance is increasing worldwide, largely driven by excessive antibiotic use. Antibiotic stewardship (AS) interventions have traditionally focused on acute care, long-term care, and ambulatory settings. However, as patients transition from one care setting to another, AS interventions should address antibiotic orders (agent, dose, duration) between the hospital and the home. The purpose of this study is to determine the appropriateness of a total course of antibiotics, including inpatient and outpatient prescriptions, to aid in prioritizing AS interventions. Methods A single-center, retrospective study was performed to evaluate antibiotic duration for adult patients discharged from a large quaternary-care academic hospital. All antibiotic prescribing data, including pre-admission, during admission, and after hospital discharge, as well as information on indication, was collected from the electronic medical record. Descriptive statistics were used to summarize the data collected. Results 196 patients were included in the study. There were 100 instances of disagreement on antibiotic indication between the discharge summary and reviewer. However, 70% of patients were discharged on an appropriate antibiotic. The majority of patients (75%) were prescribed excess antibiotic days beyond guideline recommended total duration, and 68% of patients did not have appropriate duration of antibiotics post-discharge. Of those with excess duration, 31% were prescribed penicillins, 23% were prescribed cephalosporins, and 20% were prescribed trimethoprim/sulfamethoxazole. Excess antibiotic duration was associated most commonly with an unknown diagnosis (23%), a skin and soft tissue infection diagnosis (16%), and antibiotic prophylaxis (12%). Conclusion The results of this study showed that patients were often prescribed excess antibiotics at discharge, and the total duration of antibiotics from pre-admission to post-discharge were prolonged beyond guideline-recommended duration. Understanding the total duration of antibiotic prescription, including post-discharge and pre-admission durations, is key in assessing risk from antibiotics and targeting AS interventions. Disclosures Kate Dzintars, PharmD, Nothing to disclose

109. Evaluating Predictive Value of Surgical Resected Proximal Bone Margins in Diabetic Foot Osteomyelitis with Clinical Outcomes at One Year

Background Diabetic foot osteomyelitis (DFO) remains a significant comorbidity in diabetes and often requires both surgical and medical interventions. Surgical bone resection with proximal margins is performed for treatment at our institution to guide antimicrobial therapy. Optimal antibiotic duration often remains unclear, along with clinical outcomes with negative margins. We evaluate if negative bone margins predict outcomes of DFO at one year in our county hospital. Methods A retrospectively cohort study assessed adult patients undergoing DFO amputations between 9/2016 to 9/2019. Patient data collected included demographics, smoking history, hemoglobin A1c (HbA1c), basic labs, microbiology, antibiotic duration, bone margin pathology. Physician review of records determined if intervention was successful. Primary outcome was met if no further amputation at the same site was required in the following 12 months. Results Of 92 patients, 57 had negative margins and 35 had positive margins for pathology confirmed osteomyelitis. Smoking history was significant in positive margins (35.1% vs 57.1%; p=0.038). Patients with negative margins had a successful outcome at 12 months compared to positive margins (86% vs 66%; p=0.003), but no significant differences in outcome at 6 months. Antibiotic days was reduced in negative margin individuals (mean 18 vs 30 days; p=0.001). Negative margins also demonstrated significant lower rates of readmission at 12 months (p=0.015). Staphylococcus aureus was notable in positive vs negative margins (57.1% vs 29.8%; p=0.017). MSSA was significantly noted in positive margins (45.7% vs 14%; p=0.001). MRSA was similar regardless of margin results (15.8% vs 11.4%; p=0.399). Initial ESR, CRP and HbA1c were similar between groups. Conclusion Our study noted that negative proximal bone margins resulted in more successful outcomes at 12 months and less days of antimicrobial therapy. Patients with negative margins had lower rates of readmission at 12 months for surgical site complications. Negative proximal bone margins results can guide antibiotic therapy and improve outcomes of resections. Presence of S. aureus was significant in positive margins and likely warrant consideration for further aggressive intervention. Clinical Characteristics of Patients with Diabetic Foot Osteomyelitis Clinical demographics, antibiotic usage, microbiology and results of patients presenting for diabetic foot osteomyelitis needing surgical amputation intervention. Abbreviations: HbA1c - Hemoglobin A1c; MSSA - methicillin-susceptible Staphylococcus aureus; MRSA - methicillin-resistant Staphylococcus aureus; CRP -C-reactive protein; ESR - erythrocyte sedimentation rate Disclosures All Authors: No reported disclosures

9. The Skip Phenomenon in Staphylococcus aureus Bacteremia: Clinical Associations

Background Serial blood cultures are integral in managing Staphylococcus aureus bacteremia (SAB) as clinicians rely on the results to determine infectious complication risks and antibiotic duration. Current IDSA guidelines suggest a single set of negative blood cultures is adequate evidence of SAB clearance. Several studies, however, have identified the skip phenomenon (SP), which is the occurrence of intermittent negative blood cultures, and have recommended obtaining additional blood cultures to document bacterial clearance (Table 1). We therefore examined patients who manifested the SP to determine its clinical significance and to study this, associations were tested for SP in relation to various baseline factors as well as clinical outcomes. Methods We performed a retrospective, multicenter study of all patients with a positive blood culture for S. aureus from January 2019 to December 2019 using data collected from electronic health records and the clinical microbiology laboratory. Results A total of 602 patients with SAB were identified and 495 patients were included in the investigation (Figure 1). Overall, 25 (5.1%) patients had the SP. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use, automatic implantable cardioverter defibrillator, and community onset of infection in the SP cohort (Table 2). Moreover, the median duration of SAB was longer (3.2 [2.3-5.4] vs 1.90 [1.2-2.9] days, p=0.002), and high-grade SAB, (88.0% vs 58.7%, p=0.004), complicated bacteremia (92.0% vs 67.9%, p=0.011) and IE diagnosis (28.0% vs 11.3%, p=0.013) were all more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached statistical significance (p=0.055). Analysis of 435 hospital survivors revealed no significant differences in rates of 1-year mortality or 90-day relapse between the two groups (Table 3). Conclusion Findings of the current investigation demonstrates an increased risk of SAB complications in patients with the SP and support the notion that serial negative blood cultures are needed to document clearance of SAB. Disclosures Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)

180. Duration of Therapy and Clinical Outcomes in Adult Oncology Patients with Uncomplicated Coagulase Negative Staphylococcal Bacteremia

Background Although they are often considered contaminants, coagulase negative staphylococci (CoNS) can be pathogens especially in immunocompromised patients. National and local guidelines recommend treatment durations of 7 to 14 days, depending on specific clinical scenarios. The objective was to characterize the duration of treatment for CoNS bacteremia and clinical outcomes at our cancer center. Methods We conducted a retrospective chart review of adult patients ≥18 years old with ≥1 blood culture with growth of CoNS between 1/1/17 and 12/31/19 at our cancer center. Patients with complicated CoNS bacteremia and polymicrobial infections were excluded. Results Among 128 patients identified during the study period, 98 met inclusion criteria (Figure 1). Most patients (N= 92; 94%) had a hematologic malignancy as the underlying oncologic diagnosis, and 68 (69%) were hematopoietic stem cell transplant recipients. The median total antibiotic duration was 13 days, and median duration from the date of 1st negative blood culture was 12 days; 29 (30%) patients were treated for a total duration of >14 days (Figure 2). The catheter was retained in 67 (68%) and exchanged in 4 (4%) of the cases. Three (3%) patients had recurrence of bacteremia within 30 days of treatment completion, and 8 (8%) patients were transferred to the ICU within 7 days of the index blood culture. The 30-day crude mortality rate was 10%. The most commonly used antibiotic for treatment was vancomycin (N= 95; 97%), and 32 (34%) patients on vancomycin had an increase in serum creatinine of ≥ 50% from baseline. Five (5%) patients discontinued vancomycin due to nephrotoxicity, and 4 (4%) patients required hemodialysis. Figure 1. Results Overview Among 128 patients identified during the study period, 98 met inclusion criteria. Of those included, 36 had one set of blood cultures that were positive for CoNS and 62 patients had at least two sets of blood cultures that were positive for CoNS. Figure 2. Duration of Antibiotic Treatment We evaluated duration of treatment based on total antibiotic duration and duration from date of 1st negative blood culture. The number of patients is noted above each bar. Conclusion Although the majority of patients were treated for ≤14 days for uncomplicated CoNS bacteremia, nearly 1/3 of patients were treated for > 14 days. Recurrent bacteremia was uncommon despite catheter retention in most patients. Relatively high rates of vancomycin associated nephrotoxicity highlight opportunities for antimicrobial stewardship to limit duration of vancomycin therapy among cancer patients with uncomplicated CoNS bacteremia. Disclosures All Authors: No reported disclosures

95. Reduced Antibiotic Duration Defaults in Outpatient Automated Dispensing Cabinets Change Antibiotic Prescribing Habits in a Tertiary VA Healthcare System

Background Ten percent of adult, outpatient visits result in an antibiotic prescription (Rx). At the start of our intervention, our VA healthcare system consisted of 13 community-based outpatient clinics (CBOCs), 9 of which did not have an onsite pharmacy but utilized automated dispensing cabinets (ADCs) for prepackaged outpatient Rxs. ADC antibiotic orders are generated from electronic medical record (EMR) order sets. The stewardship team shortened the durations of 5 antibiotics in the ADC order sets to make them consistent with current literature and guidelines. We assessed the impact of these changes on antibiotic prescribing habits. Methods We compared outpatient antibiotic Rx data between 10/1/2018-9/30/2019 (pre-intervention) and 10/1/19-9/30/20 (post-intervention) from 8 CBOCs with ADCs (1 closed during the pandemic). Amoxicillin-clavulanate 875/125mg (AMC), cephalexin 500mg (CPH), levofloxacin 500mg and 750mg (LEV 500 and LEV 750), and sulfamethoxazole-trimethoprim 800/160mg (SXT) prescription durations were all reduced by 3 days. Process metrics included days supplied/1000 prescriptions (DS/1000 Rx), median DS, and ADC utilization rates. We used Mann-Whitney U and correlation statistical analyses to assess differences and associations. Results The DS/1000 Rx of antibiotics with a default duration change decreased in the post-intervention phase for CBOCs with ADCs (AMC, -25.4%; CPH, -21.1%; LEV 500, -18.9%; LEV 750, -28.0%; SXT, -27.4%). The median DS for these antibiotics all reduced by 3 days in concordance with new ADC prescriptions defaults (AMC, 10 vs 7 days, P< 0.001; CPH, 10 vs 7 days, P< 0.001; LEV 500, 8 vs 5 days, P< 0.001; LEV 750, 8 vs 5 days, P< 0.001; SXT 10 vs 7 days, P< 0.001). Due to COVID-19, 7/8 ADC CBOCs closed for in-person visits from 3/20/20-5/4/20. ADC utilization was inversely proportional to DS/1000 Rx for most antibiotics (R: -0.51 to -0.77) except SXT. Conclusion EMR-driven reductions in ADC default Rx durations led to a corresponding decrease in overall outpatient antibiotic prescribing. Higher DS/1000 Rx were often associated with lower ADC utilization. Informatics-driven antibiotic interventions may be potential outpatient stewardship tools to increase guideline-concordant prescribing across multisite healthcare systems. Disclosures Sharanie Sims, PharmD, AbbVie (formerly Allergan) (Speaker’s Bureau)