bluuebunny/crossref_metadata_2025 huggingface dataset:
1736. Xeruborbactam (QPX) Potentiates the Activity of Multiple β-Lactams Against Highly Resistant Pseudomonas aeruginosa to a Greater Degree than Other β-Lactamase Inhibitors
Authors: Fleres Giuseppe , Newbrough Anthony , Hao Binghua , Chen Liang , Shields Ryan K , Clancy Cornelius J , Nguyen Minh-Hong
Published: December 2022

Background

Pseudomonas aeruginosa (PA) is an important pathogen notorious for antibiotic resistance. Xeruborbactam (QPX) is a potent ultra-broad-spectrum boronic acid β-lactam inhibitor (BLI) that, in combination with selected BL antibiotics, has excellent in vitro activity against carbapenem-resistant Enterobacterales (CRE), and Acinetobacter baumanii or PA producing class A/B or D carbapenemases. We evaluated QPX in combination with anti-pseudomonal BLs against clinical PA isolates from tertiary care US hospitals.

Methods

We tested PA clinical isolates resistant to ≥1 BL (imipenem (IMP), meropenem (MEM), cefepime (FEP), piperacillin-tazobactam (PIP-TAZ), aztreonam (ATM), ceftolozane-tazobactam (TOL-TZP), ceftazidime-avibactam (CZA), IMI-relebactam (IMI-REL), MEM-vaborbactam (MVB)) against QPX (in fixed concentration of 8 µg/mL) combined with anti-pseudomonal BLs. We performed whole-genome sequencing on isolates using the MiSeq platform (Illumina).

Results

Antibiograms and resistance determinants of 77 isolates tested to date are summarized in Figs 1, 2. 91% of isolates were CR; 43%, 58% and 61% were resistant to CZA, IMI-REL and MVB, respectively. No isolates produced class A/B/D carbapemases. All except 2 isolates carried PDC variants. 92% either had oprD porin single nucleotide polymorphism (SNP) or deletions. mutS mutations (present in 23% of isolates) were associated with resistance to IPM/QPX (p=.04), but not TOL-QPX or PIP-QPX. Addition of QPX significantly reduced MIC50 of IPM (32-fold), PIP (16-fold), FEP and ATM (4-fold) (all p< .0001, Fig 3). Addition of QPX to MEM or TOL reduced MIC50 by 2-fold (p=.02, p< .0001). QPX reduced IMP and PIP MICs more than did REL (32 vs 8-fold, p< .0001) or TZP (16 vs nil, p=.0007), respectively. Addition of QPX reduced BL resistance, especially for TOL, PIP and IMP (Fig 4). We identified factors associated with BL/QPX resistance by logistic regression; for IMP/QPX: IMP resistance (p=.001), SNP in mexB (p=.01); for TOL/QPX: TOL resistance (p=.02); for PIP/QPX (SNP in mexR and mexB (p=.03).

Conclusion

QPX enhanced the activity of BLs, especially TOL and PIP, against PA with baseline resistance to BL, more so than other BLIs. TOL/QPX and PIP/QPX are less impacted by PA efflux and porin mutations than IMP/QPX.

Disclosures

Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham & Associates: Advisor/Consultant.
1746. Electronic medical record-embedded clinical decision support decreases inappropriate duration of antibiotics for outpatient pediatric skin and soft tissue infections
Authors: Lloyd Elizabeth C , Dillman Nicholas O , Tribble Alison C , Wu Lei , Seidl Stephannie , Burrows Heather L , Petty Lindsay A
Published: December 2022

Background

Most antibiotics are prescribed outside of the hospital, and up to 50% are unnecessary or inappropriate. Studies of ambulatory stewardship interventions have primarily targeted respiratory infections. We investigated the impact of an electronic medical record (EMR)-embedded clinical decision support tool on antibiotic duration for outpatient pediatric skin and soft tissue infection (SSTI).

Methods

Institutional SSTI treatment guidelines for pediatric and adult patients were developed in 7/2019, followed in 5/2020 by dedicated education for primary care pediatricians. In 12/2020, a SmartSet (EMR-embedded tool with a templated progress note and antibiotic guidance) was created for pediatrics only. In this quasi-experimental pre-post study, we included adult and pediatric patients who were prescribed antibiotics for SSTI at a primary care or surgery clinic (in person, virtual, or phone) from 7/2019 to 12/2021. Inappropriate pediatric antibiotic duration ( >7 days) was compared pre- and post-intervention with interrupted time series (ITS) analysis of aggregate quarterly data. The trend in adult antibiotic duration was modeled with linear regression.

Results

We included 3,786 (948 pediatric and 2,838 adult) pre-intervention and 2,122 (469 pediatric and 1,653 adult) post-intervention visits. Pre-intervention, the percentage of inappropriate duration for pediatric patients was decreasing 1.6 percentage points per quarter (p < 0.01). After SmartSet implementation, there was an immediate decrease of 10.3 percentage points (p < 0.01), a relative decrease of 40% from the modeled percentage just prior to intervention (Figure 1). Inappropriate antibiotic duration for adults averaged 22.9% over the same period and did not change (p = 0.88). Figure 1Figure 1. Raw and modeled percentages of inappropriate antibiotic duration for skin and soft tissue infection before (quarters -6 to 0, encompassing Q3 2019 through Q4 2020) and after (quarters 0 to 4, encompassing Q1 2021 through Q4 2021) implementation of an EMR-embedded clinical decision support tool for pediatric patients. Time is represented in 3-month intervals, with quarter 0 being indicating the intervention at the end of December 2020.

Conclusion

Following guideline implementation and education, inappropriate antibiotic duration for ambulatory pediatric SSTI declined only modestly. An EMR-embedded clinical decision support tool was associated with an additional relative decrease of 40% in inappropriate antibiotic duration. In the same health system with comparable adult SSTI guidelines, the percentage of inappropriate antibiotic duration for adults was unchanged, suggesting timely EMR nudges can provide additional benefit over guidelines alone.

Disclosures

All Authors: No reported disclosures.
1753. Impact of a Pharmacist-Driven Home Hospital Antimicrobial Stewardship Program Pilot within a Large Community Health System
Authors: Nguyen Van , Wankum Michael , Gens Krista , Hirsch Elizabeth B
Published: December 2022

Background

Home Hospital (HH) is a unique and rapidly expanding care model that allows patients to receive medical therapy and monitoring through telehealth communication and nursing visits, and there are currently no published studies evaluating antimicrobial stewardship interventions in the HH setting. The goal of this study is to evaluate the impact of a pharmacist-driven antimicrobial stewardship pilot for the HH program.

Methods

This was a pre-post quasi-experimental study of adult patients enrolled in HH program between January through March in 2021 (control cohort) and in 2022 (intervention cohort), who received antibiotics (oral/intravenous) during their HH admission. Patients on long-term prophylactic antimicrobials, antifungals, external antimicrobials, or mycobacterial treatment were excluded. The antimicrobial stewardship pharmacist performed prospective audit and feedback and provided recommendations to clinicians through the electronic medical record. The primary endpoint was antibiotic use (days of therapy per 1000 patient-days). Secondary endpoints included broad-spectrum antibiotic usage; appropriateness of antibiotic indication, dosing, and duration; compliance with the institution’s outpatient antibiotic reference guide or outpatient intravenous antibiotic therapy (OPAT) monitoring; treatment failure; antibiotic-associated adverse effects; and cost of antibiotic therapy.

Results

The study included 73 and 127 patients in the control and intervention group, respectively (Figure 1). On average, the pharmacist reviewed 8 eligible patients/day. Interventions were generally well received by HH providers (Figure 2). There was no significant difference in the primary outcome. More inappropriate antibiotic indication was identified in the intervention group (46 [36%] vs. 15 [19%], p=0.01), associated with post-surgical infection prophylaxis after orthopedic procedures (Figure 3). Other secondary outcomes did not vary significantly between the groups. Figure 1:Study inclusion flowchartFigure 2:Intervention breakdownFigure 3:Infection types

Conclusion

The pilot allows for better understanding of outpatient and HH antibiotic prescribing practices to provide targeted interventions, and suggests the need for additional antimicrobial stewardship involvement to optimize antibiotic therapy in this novel care setting.

Disclosures

Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.
1755. Interactive Provider Dashboards for Comparison of Outpatient Antimicrobial Prescribing for Respiratory and Otic Conditions in Urgent and Quick Care Clinics
Authors: Percival Kelly M , de Blois Michael R , Kinn Patrick M , Weiner Lukasz , Ince Dilek
Published: December 2022

Background

Due to antibiotic overutilization, development of antimicrobial stewardship (AMS) in the outpatient setting has become a necessary focus for AMS programs. The cornerstone of AMS is utilization of antimicrobial prescribing data to provide feedback to individual providers and compare providers to each other in order to promote improved prescribing practices. Respiratory infections, especially conditions that never require antimicrobials, are a common target for this feedback. We aimed to create interactive data visualization dashboards of end-users prescribing for these respiratory and otic conditions in order for AMS and urgent/quick care program staff to identify potential areas of intervention.

Methods

A multidisciplinary work group consisting of data analysts, infectious diseases physicians, urgent/quick care physicians, and infectious diseases pharmacists determined dashboard content, layout, and comparison charts. Graph types were tested to determine optimal visual output. Using the electronic medical record ICD10 and antimicrobial prescription data was extracted for the encounter with focus on ICD10 codes for respiratory and otic conditions which never require antimicrobials. Rates were calculated as number of antimicrobial prescriptions over total number of visits for these conditions.

Results

A multi-faceted dashboard was developed in Tableau® to view antimicrobial prescribing rates. Dashboard capabilities include the option to view individual provider prescribing rates compared to other de-identified providers, overall clinic prescribing rate, or individual rate compared to clinic rate. This allows for quick direct comparison of antimicrobial prescribing on the same graph by clinic to identify outliers (Figure 1) and allows visualization of trends in prescribing rates by clinics and providers over time (Figures 2,3).

Never Antimicrobial Prescribing Rate Comparison

Scatter plot comparing individual prescribers rate of prescribing for never antimicrobial events

Clinic Antimicrobial Prescribing Rate Trend

Clinic prescribing rate trend over time for never antimicrobial events

Prescriber and Clinic Antimicrobial Prescribing Rate Trend

Individual prescriber rate compared to clinic rate over time for never antimicrobial events

Conclusion

We developed an interactive outpatient AMS dashboard to visualize prescribing of antimicrobials for never respiratory and otic conditions. These dashboards can be used by providers along with AMS and clinic leadership to determine areas of intervention in the urgent/quick care setting.

Disclosures

Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant Patrick M. Kinn, PharmD, MPH, Gilead Sciences: Advisor/Consultant Dilek Ince, MD, Evergreen: Member of data monitoring board|Gilead Sciences: Grant/Research Support|Leidos: Grant/Research Support|Moderna: Grant/Research Support.
1759. Risk Factors for OPAT-Related Adverse Drug Events: A Case-Control Study
Authors: Burke Elysia , Croteau Desiree , Dutcher Lauren , Hamilton Keith W , Degnan Kathleen , Lee Tiffany , Saw Steve , Patel Sonal , Binkley Shawn , Athans Vasilios
Published: December 2022

Background

Outpatient parenteral antimicrobial therapy (OPAT) offers numerous clinical advantages, though adverse drug events (ADEs) are a common and potentially preventable challenge that may contribute to 30-day readmissions and other negative outcomes. In January 2021, our OPAT program began documenting all significant ADEs using an electronic template. The purpose of this study was to characterize significant OPAT ADEs and to identify potential risk factors for their development.

Methods

Outpatient parenteral antimicrobial therapy (OPAT) offers numerous clinical advantages, though adverse drug events (ADEs) are a common and potentially preventable challenge that may contribute to 30-day readmissions and other negative outcomes. In January 2021, our OPAT program began documenting all significant ADEs using an electronic template. The purpose of this study was to characterize significant OPAT ADEs and to identify potential risk factors for their development.

Results

Cumulative ADE incidence was 11%, and median time-to-ADE was 13 days after discharge. During the study period, 54 ADE patients vs. 100 control patients were identified. The most common ADEs attributed to OPAT were kidney injury (50%), rash (10%), and leukopenia (9%) (Table 1). Most ADEs resulted in an OPAT regimen change (33%), dosage adjustment (29%), or early cessation of OPAT (21%) (Table 2). In the final logistic regression model, receipt of vancomycin, use of empiric therapy for culture-negative infection, and OPAT duration ≥ 28 days were associated with increased ADE risk, whereas African American race and receipt of ceftriaxone were protective (Table 3).

Conclusion

Several modifiable risk factors may increase the likelihood of an ADE during OPAT and should be carefully considered prior to hospital discharge. Based on these data, OPAT programs should consider employing vancomycin alternatives, diagnostic stewardship, and strategies to minimize duration of therapy.

Disclosures

Kathleen Degnan, MD, Gilead: Grant/Research Support.
1765. Antibiotic Consumption in a Healthcare System in Bolivia During the First Wave of COVID-19 Pandemic
Authors: Quiros Rodolfo E , Escobar Elvio D , Tapia Juan Carlos , Fabre Valeria
Published: December 2022

Background

Several countries in Latin America reported an increase in antibiotic use during the first wave of the COVID-19 Pandemic.

Methods

We retrospectively evaluated antibiotic use among 10,752 members of a private healthcare system in Santa Cruz de la Sierra, Bolivia, between Jan-Dec 2019 (pre-pandemic) and Jan-Aug 2020 (pandemic). Antibiotic use was calculated as daily defined doses (DDD) per 1,000 member-days, per 100 ambulatory visits, and per 100 inpatient-days, and categorized using the World Health Organization classification (Access, Watch, and Reserve), based on the impact of different antibiotics on antimicrobial resistance. In April 2020, the antibiotic stewardship team developed COVID-19 treatment guidelines for ambulatory and hospitalized patients and provided recommendations on all patients hospitalized due to COVID-19. Due to the nature of the network, guideline use is usually high. During the pandemic period and due to local restrictions, patient interactions were mostly limited to COVID-19 presentations. Differences with 95% confidence intervals (CI) between groups were estimated.

Results

Pandemic and pre-pandemic antibiotic use in DDD/1,000 member-days was 8.48 and 18.37, respectively (diff. –8.89, 95%CI –10.11 to –9.67). Outpatient DDD/100 ambulatory visits was 67.68 vs. 86.20 (diff. –18.52, 95%CI –19.94 to –17.1), and hospital DDD/per 100 inpatient-days was 39.79 vs. 61.71 (diff. –21.92, 95%CI –26.2 to –17.68) for pandemic and pre-pandemic periods, respectively. During the pandemic period, an overall reduction in macrolides use was also observed (–3.13 DDD/100 ambulatory visits, 95%CI –3.84 to –2.44, and –2.05 DDD/per 100 inpatient-days, 95%CI –2.88 to –1.26). Additionally, an increase in Access antimicrobials (83.3% vs. 79.5%; diff. 3.8%, 95%CI 0.3% to 7.4%) and a reduction in the Watch group (16.7% vs. 20.5%; diff. –3.7%, 95%CI –7.4% to –0.1%) were observed for pandemic and pre-pandemic periods, respectively.

Conclusion

In this closed network, we observed a reduction in antibiotic use both in ambulatory and inpatient settings. Although, multifactorial, we believe the enhanced antibiotic stewardship approach on COVID-19 patients played a role in limiting antimicrobial use in this private healthcare system.

Disclosures

All Authors: No reported disclosures.
1767. Because I Could Not Stop for Death, They Gave Me Antibiotics? Perceptions And Reality of Antibiotic Prescribing When Patient Care Is Transitioned to CMO at an Academic Medical Center
Authors: Larnard Jeffrey , Blackshear Leslie , Lee Matthew S , Buss Mary , Stead Wendy
Published: December 2022

Background

Little is known about antimicrobial prescribing when patient care is transitioned to comfort measures only (CMO). We used a multi-disciplinary survey and retrospective chart review to gain insight into antimicrobial prescribing in this population at an academic medical center.

Methods

A survey focusing on antimicrobial prescribing during the transition to CMO was electronically distributed to providers in Infectious Disease, Pulmonary/Critical Care, Hematology/Oncology, Palliative Care, and Hospital Medicine, and responses were compared across divisions. A retrospective chart review was performed of patients admitted to Beth Israel Deaconess Medical Center in 2020 who were on antimicrobials in the 48 hours prior to CMO. We investigated the frequency of patients on antimicrobials after the transition to CMO and provider rationale for continuing antimicrobials.

Results

We received 113 survey responses for a response rate of 35%; 111 were included for analysis. 41% of respondents indicated that they “sometimes” or “often” continued an antimicrobial during the transition to CMO. Of the 546 patient charts reviewed, 140 (26%) patients were alive 48 hours after CMO order, and 19 (14%) of those patients remained on antimicrobials (Figure 1).

Patient/family preference was the most common factor when deciding whether to continue antimicrobials in patients on CMO, identified by 77% of respondents (Figure 2). 5/19 (26%) patients who were alive on antimicrobials 48 hours after CMO had documentation that antimicrobials were continued due to patient/family preference.

Symptom palliation was the second most common factor when deciding whether to continue antimicrobials in patients on CMO, identified by 62% of respondents. For patients already on symptom directed medications, many providers perceived antibiotics to be helpful to palliate symptoms, though there were inter-division differences (Table 1). 5/19 (26%) patients who were alive on antimicrobials 48 hours after CMO had documentation that antimicrobials were continued for palliation of symptoms.

Perceived Helpfulness of Antimicrobials for Specific Symptoms by Division

Number/percentage of survey responses indicating antimicrobials were at least somewhat helpful for specified symptoms in patients already on symptom directed medications. Divisions compared using Kruskal-Wallis Tests.

Conclusion

Even after transition to CMO, a substantial number of patients remain on antimicrobials. Patient/family preference and symptom palliation are important factors when continuing antimicrobials in this population.

Disclosures

All Authors: No reported disclosures.
1773. Evaluation of Fluoroquinolone Prophylaxis in Preventing Bacterial Infection in Neutropenic Afebrile Patients Without Leukemias or HSCT: A Systematic Review
Authors: Yazdi Mona T , Avula Divya
Published: December 2022

Background

Per 2010 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer, routine use of fluoroquinolone (FQ) chemoprophylaxis in low-risk populations (defined as those with solid tumors or lymphoma undergoing chemotherapy) is not recommended to prevent febrile neutropenic episodes as it was not found to impact all-cause mortality. Since these guidelines were published, there have been additional randomized trials (RCTs) of FQ chemoprophylaxis in patients with cancer.

Our objective was to assess the efficacy of FQ vs placebo in preventing probable or confirmed bacterial infection in patients with cancer who did not have leukemias or hematopoietic stem cell transplant (HSCT). Secondary outcomes of interest included febrile episodes, mortality, and adverse effects of antibiotic use.

Methods

Medline via PubMed, The Cochrane Central Register of Controlled Trials, and SCOPUS from inception through 2/17/2022 were searched. We included RCTs in English comparing FQ to placebo in preventing neutropenic fever and bacterial infections in patients with cancer who did not have leukemias or HSCT.

Results

We included 5 RCTs (N= 3158). The rates of probable or confirmed bacterial infection in patients with cancer revealed 541/1562 (34.6%) infections in the FQ group and 679/1560 (43.5%) in the placebo group (OR: 0.68, 95% CI:0.59,0.79, I2 = 57%, p=0.002). In evaluating development of febrile episodes, 300/1566 (19.2%) events were noted in the FQ group and 407/1555 (26.2%) in the placebo group (OR: 0.58, 95% CI:0.41,0.83, I2 = 0%, p< 0.001). Mortality events in the FQ group were 113/1597(7.1%) and 124/1508 (8.2%) in the placebo group (OR: 0.76, 95% CI:0.53,1.1, I2 = 7%, p=0.15). Adverse events associated with antibiotic use in the studies were more frequent in the FQ group. Figure 1Forest Plot of Mortality in included studiesFigure 2Results on Development of Fevers in included studies.Figure 3Forest plot of Probable or Proven Infection in included studies.

Conclusion

Although evidence does not show that FQ prophylaxis provides mortality benefit, it did show a decrease in development of bacterial infections and febrile episodes. This suggests that treatment may still provide clinical benefit to this population of patients, but must be weighed against risks and consequences of long-term antibiotic use, which were not reported by the included studies.

Disclosures

All Authors: No reported disclosures.
2311. Long-term prognosis and risk factors for overall mortality in patients with progressive multifocal leukoencephalopathy
Authors: Kim Jinnam , Kim Chang Hyup , Lee Jung Ah , Lee Se Ju , Lee Ki Hyun , Kim Jung Ho , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Choi Jun Yong , Yeom Joon-sup , Song Young Goo
Published: December 2022

Background

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period.

Methods

We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first.

Results

The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality.

Conclusion

With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis.

Disclosures

All Authors: No reported disclosures.
1800. Impact of Updated ATS/IDSA CAP Guidelines on Duration of Antibiotics
Authors: Petty Lindsay A , Vaughn Valerie , Malani Anurag N , Younas Mariam , Osterholzer Danielle , Bernstein Steven , Ratz David , McLaughlin Elizabeth , Czilok Tawny , Horowitz Jennifer , Flanders Scott A , Gandhi Tejal N
Published: December 2022

Background

In 10/2019, revised ATS/IDSA community-acquired pneumonia (CAP) guidelines removed healthcare-associated pneumonia (HCAP), expanding patients eligible for a 5-day antibiotic course. Using data from 46 hospitals in the Michigan Hospital Medicine Safety Consortium, we quantified the impact of removing HCAP on antibiotic duration for CAP.

Methods

From 11/2017 to 1/2022, data were abstracted from medical records of adult non-ICU medical patients admitted with pneumonia. Our primary outcome was percentage of patients who received 5-days of antibiotics out of those who, under the new CAP guidelines would be eligible for 5-days (including patients defined as HCAP prior to the 2019 guideline) [Table 1]. We evaluated using Chi-square, if the effect of the guidelines differed for patients defined as CAP based on the 2007 CAP guideline (pCAP) vs. HCAP. To assess the effect of the new guideline on 5-day therapy, we used segmented logistic regression accounting for hospital level clustering to look at changes at baseline and overtime before and after 10/2019.

Results

When applying the 2019 CAP definition to 34,810 patients admitted with pneumonia over the entire period, 41.2% (N=14,358) of patients were eligible for 5-day duration. Applying pre-2019 categorization to the entire period, 46.4% of pCAP (N=10,565/22,757) and 31.5% of HCAP (N=3793/12,053) were eligible for 5-day duration. Of those 5-day eligible, 34.4% (N=4,936) received 5 days (pCAP 35.5% N=3750; HCAP 31.2% N=1186, P< .001). Before 10/2019, 29.5% (N=2,018) of patients with pCAP who were eligible received 5 days vs 23.6% (N=548) of HCAP (P< .001). Post 10/2019, 46.5% (N=1,732) of patients with pCAP eligible received 5 days vs 43.5% (N=638) of HCAP (P=0.049). The improvement rate in 5-day therapy decreased after 10/2019, with similar decrements for both pCAP and HCAP [Figure 1].

Conclusion

Among patients hospitalized with pneumonia, two thirds received an excess antibiotic duration, with similar proportions for pCAP and HCAP. Prior to the new guidelines, the 5-day treatment rate was improving for HCAP and pCAP. However, the rate of improvement decreased after 10/2019 for both pCAP and HCAP, suggesting the 2019 guidelines did not have an added effect on improving antibiotic duration.

Disclosures

Valerie Vaughn, MD, MSc, Thermo Fisher Scientific: Honoraria.
1801. LVAD antimicrobial prophylaxis and infections, a 12-year experience
Authors: Mendoza Maria A , Ranganath Nischal , O’Horo John C , Stulak John , Shah Aditya
Published: December 2022

Background

The incidence of end-stage heart failure necessitating advanced cardiac therapy continues to increase in the United states. Implantable left ventricular assist devices (LVADs) represent an important modality that is utilized both as a bridge to heart transplant or as destination therapy. LVAD-associated infections, ranging from driveline exit site or pocket infections to endovascular infections, are a major complication with high mortality. Antibiotic prophylaxis at time of LVAD implantation is therefore an important strategy to mitigate infections. However, a clear surgical infection prophylaxis regimen and associated outcomes have not been reported.

Methods

We performed a single center, retrospective cohort study evaluating the impact of antimicrobial prophylaxis on risk of infection in patients who underwent LVAD implantation between February 2007 and June 2019 at Mayo Clinic. LVAD-specific and related infections were defined according to the International Society of Heart Lung Transplantation criteria. Single drug prophylaxis (SDP) included cefazolin only, vancomycin only, or cefazolin and vancomycin; multidrug (MDP) regimen includes either of the SDP regimens plus another antibiotic. We compared incidence of infection within 90-day and within one-year of implantation, as well as risk of C. difficile infections between the SDP and MDP cohorts.

Results

We reviewed 403 patients who received LVAD implantation (Table 1), 402 of had information on surgical prophylaxis. 307 (76%) patients received SDP and 95 patients (24%) received MDP. 14 patients developed an infection within 1 year of implantation (Table 2). There was no difference in the incidence of infections between SDP and MDP arms both at 90 days and 1-year post-implantation (p=0.11). The median time of infection since LVAD implantation was similar between SDP and MDP (p=0.37) arms. Incidence of C. difficile infection was not different between groups (p=0.10) (Table 3).

Conclusion

There was no significant difference in incidence or time to first infection, within 90-day and 1-year of implantation, between single- and multidrug antibiotic surgical prophylaxis regimens administered at the time of LVAD implantation. Future prospective trials are needed to develop a clear LVAD antibiotic prophylaxis protocol.

Disclosures

John C. O'Horo, Sr., MD, MPH, Bates college: Advisor/Consultant|MITRE corporation: Grant/Research Support|nferenec, Inc: Grant/Research Support.
1817. Characteristics and Outcomes in Patients with Staphylococcus lugdunensis Bacteremia Compared with Staphylococcus aureus and Staphylococcus epidermidis Bacteremia
Authors: Yukawa Satomi , Noguchi Taro , Shinohara Koh , Tsuchido Yasuhiro , Yamamoto Masaki , Matsumura Yasufumi , Nagao Miki
Published: December 2022

Background

Staphyococcus lugudnensis (SL) is a coagulase negative Staphylococcus species with a potential to cause invasive infection. Few studies have evaluated characteristics and outcomes of SL bacteremia (SLB) compared with Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE).

Methods

We performed a single center retrospective case-control study of patients > =18 years of age with SLB with at least two sets of positive blood cultures at Kyoto University Hospital, Japan from January 2005 to December 2021. Patients who had SA bacteremia (SAB) with at least one set of positive blood culture and those who had SE bacteremia (SEB) with at least two sets of positive blood cultures were randomly selected in a 1:5:5 (SL:SA:SE) ratio during the same period. Characteristics and clinical outcomes of SLB were compared with those of SAB and SEB.

Results

A total of 24 patients with SLB, 120 patients with SAB, and 120 patients with SEB were included. Patients’ median age (interquartile range) was 69 (60, 75), 68 (49, 77) and 65 (51, 73) in order of SL, SA, and SE. The rate of hospital-acquired infection in SL was similar to that of SA (54% vs 64%; p=0.86), lower than that of SE (54% vs 91%; p< 0.01). Rates of methicillin resistance and intravascular catheterization were higher in SE (83% and 92%, respectively). Patients with SLB were more likely to be on hemodialysis (25%). Rates of polymicrobial bacteremia and blood cancer was lower in SA (7% and 8%, respectively). Echocardiography was done for 14 patients in SL, lower than in SA (58% vs 82%; p=0.01). The rate of infective endocarditis (IE) (primary and secondary) was not significantly different among three groups (SL 8.5%, SA 6.5%, SE 2%). There was no significant difference in rate of metastatic lesions between SL and SA (17% vs 20%, p=0.9), statically lower in SE than in SL (17% vs 4%; p< 0.01). Seven-day mortality was similar between SL and SA (8% vs 7%; p=0.77), lower in SE than in SL (8% vs 0.5%; p=0.02). Thirty-day mortality in SL was not significantly different in other groups (SL 17%, SA 18%, SE 10%).

Conclusion

The rates of metastatic lesions and 7-day mortality in SL were similar to that of SA, higher than that of SE. Appropriate evaluation and treatment that are recommended for SAB may be warranted for patients with SLB.

Disclosures

All Authors: No reported disclosures.
1826. Comparative Use of Vancomycin versus Ampicillin for Blood Stream Infections Caused by Ampicillin-susceptible Enterococcus faecalis
Authors: Phan Michaele , Meredith Jacqueline , Ackley Renee , Ebeid Alex , Goodrich Kristen , Sampson Mindy
Published: December 2022

Background

Available studies assessing the efficacy of beta-lactam antibiotics compared to vancomycin (VAN) in the treatment of Enterococcal blood stream infections (BSI) have varying results and have not assessed the impact of rapid diagnostic testing. We aimed to compare clinical outcomes of ampicillin (AMP) vs. VAN for E. faecalis BSI treatment.

Methods

A multisite, retrospective evaluation of adults with E. faecalis BSI between 2017 to 2021 was performed. Patients who received at least four days of AMP or VAN as definitive therapy were analyzed; only initial episodes were included. All positive blood cultures underwent multiplex polymerase chain reaction blood culture identification (BCID). Patients with polymicrobial BSI were excluded, or if they received ≥ 50% concomitant use of AMP and VAN. The primary outcome was 30-day all-cause mortality. Secondary objectives included 90-day all-cause mortality, hospital length of stay, incidence of treatment failure, persistent BSI, change from initial definitive therapy, and adverse drug reactions (ADRs). Other microbiology endpoints included time to active treatment, BCID, beta-lactam coverage, definitive therapy, and culture clearance. A sample size of 208 patients was estimated to provide a 15% mortality difference with 80% power.

Results

In total, 123 patients with E. faecalis BSI were analyzed (AMP, n = 92; VAN, n = 31). Baseline characteristics were similar among both groups except gender and baseline penicillin allergy (p < 0.001) (Table 1). All-cause 30-day mortality was not significantly different between patients treated with AMP and VAN (10.8% vs. 22.6%, p = 0.130). No difference was found in secondary objectives except time to definitive therapy was longer for the AMP treatment arm (56.7 hours vs. 15.8 hours, p < 0.001) (Table 2). The incidence of ADRs were similar between the two groups (Table 3).

Conclusion

No difference in mortality was observed in the treatment with AMP or VAN for patients with E. faecalis BSI, but the study was not sufficiently powered. Despite the use of rapid BCID testing, earlier initiation of AMP was not observed. AMP or VAN may be reasonable options for treatment of E. faecalis BSI, but further research is warranted.

Disclosures

All Authors: No reported disclosures.
1833. Evaluating the Impact of Reported Beta-Lactam Allergies on Clinical Outcomes in Gram-Negative Bloodstream Infections: A Retrospective Cohort Study
Authors: Uzoma Joy , Patel Sonal , Athans Vasilios , Binkley Shawn , Degnan Kathleen , Dutcher Lauren , Hamilton Keith W , Lee Tiffany , Saw Steve
Published: December 2022

Background

Approximately 15% of hospitalized patients are labeled as beta-lactam (BL) allergic. Despite this, it is estimated that > 90% of patients do not have clinically significant hypersensitivity reactions and are BL-tolerant. The BL allergy label is associated with a host of downstream consequences, including receipt of suboptimal antibiotic therapy, healthcare-associated infections, and bacterial resistance. There are limited data investigating the impact of this allergy label on clinical outcomes in bloodstream infections caused by Gram-negative pathogens (GN-BSI).

Methods

This was a retrospective, single center, cohort study evaluating the impact of BL allergies on clinical outcomes in patients with GN-BSI from January 2017 to August 2021. Adult inpatients with index blood cultures positive for Pseudomonas species or Enterobacterales who received intravenous antibiotics with Gram-negative activity were included. The primary endpoint was time to effective therapy (defined as treatment with in vitro activity against a causative pathogen, as determined by phenotypic susceptibilities) and the key secondary endpoint was 30-day all-cause mortality.

Results

Overall, 120 patients were included, representing 30 BL-allergic (BL-A) and 90 BL-non-allergic (BL-NA) patients. Blood cultures positive for Pseudomonas species or Enterobacterales were evenly distributed (Table 1). Among Enterobacterales, Escherichia coli was implicated in 25% of cases overall. The most common source of infection was intra-abdominal infection. Across groups, median quick Pitt Bacteremia Score was 1 (IQR 0-2). Infectious Diseases was consulted in 37% of BL-A patients vs. 29% of BL-NA patients. Of BL allergies reported, 86% were classified as likely immunoglobulin E (IgE) mediated reactions. Allergy was not consulted in any of these cases. Median time to effective therapy was 162 minutes (IQR 20-824 minutes) vs. 103 minutes (IQR 27-775 minutes) in the BL-A and BL-NA groups, respectively. Thirty-day mortality occurred in 31% of BL-A and 21% of BL-NA patients.

Conclusion

Increased time to effective therapy and mortality rates were observed among patients with reported BL allergies. These findings highlight the importance of allergy clarification in antibiotic stewardship.

Disclosures

Kathleen Degnan, MD, Gilead: Grant/Research Support.
1844. Mortality associated with Stenotrophomonas maltophilia bloodstream infection in patients with leukemia
Authors: Aitken Samuel L , Rudoni Joslyn , Marx Kayleigh R , Tverdek Frank P , Shelburne Samuel A , Okhuysen Pablo C
Published: December 2022

Background

Patients with leukemia are disproportionately vulnerable to infections caused by S. maltophilia and mortality approaches 100% in patients with hemorrhagic pneumonia. Trimethoprim-sulfamethoxazole (SXT) is the drug of choice for treatment of infections caused by S. maltophilia however allergies, toxicity, and resistance may preclude its use. We sought to characterize clinical outcomes of patients with leukemia and S. maltophilia bloodstream infection (BSI).

Methods

Patients with leukemia are disproportionately vulnerable to infections caused by S. maltophilia and mortality approaches 100% in patients with hemorrhagic pneumonia. Trimethoprim-sulfamethoxazole (SXT) is the drug of choice for treatment of infections caused by S. maltophilia however allergies, toxicity, and resistance may preclude its use. We sought to characterize clinical outcomes of patients with leukemia and S. maltophilia bloodstream infection (BSI).

Results

Ninety-six patients with leukemia and S. maltophilia BSI were identified. The most common diagnosis was acute myeloid leukemia (60%); 31% had prior stem cell transplant. The most common single identified source was respiratory (31%) followed by central venous catheter (CVC, 26%). A single clear source was unable to be identified in 33%.Overall 14-day mortality was 31%. After excluding eleven patients who died within 24 hours, most patients received SXT (72%), followed by ceftazidime (40%), tigecycline (TGC, 40%), and minocycline (26%). SXT was associated with reduced mortality (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.05 – 0.44, p < 0.01) while TGC was associated with increased mortality (HR 3.13, 95% CI 1.00 – 9.73, p = 0.05). All patients who died were neutropenic at baseline and none had a CVC infection.

Conclusion

S. maltophilia BSI is associated with high mortality in patients with leukemia, particularly those with neutropenia at baseline. CVC infection alone was not associated with mortality. SXT is associated with reduced mortality relative to other antimicrobials. Alternative agents should be used with caution in these vulnerable patients.

Disclosures

Samuel L. Aitken, PharmD, MPH, Entasis Therapeutics: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Melinta: Grant/Research Support|Shionogi: Advisor/Consultant Pablo C. Okhuysen, MD, AstraZeneca: Stocks/Bonds|Beam Therapeutics: Stocks/Bonds|Biontech: Stocks/Bonds|Deinove: Grant/Research Support|Ferring: Advisor/Consultant|Glaxo Smith Kleine: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Melinta: Grant/Research Support|Merck Sharp & Dohme Corp: Grant/Research Support|Moderna: Stocks/Bonds|Napo Pharmaceuticals: Advisor/Consultant|Napo Pharmaceuticals: Grant/Research Support|Novavax: Stocks/Bonds|Pfizer: Stocks/Bonds|Summit: Advisor/Consultant|Summit: Grant/Research Support.
1846. Outcomes in Intravenous to Oral Antimicrobial Therapy in Beta-Streptococcus Species
Authors: Keintz Mackenzie R , Torres Cristina J , Miller Molly M , Alexander Bryan T , Lyden Elizabeth , Lyden Elizabeth , Lyden Elizabeth , Ma Jihyun , Van Schooneveld Trevor C , Marcelin Jasmine R
Published: December 2022

Background

Uncomplicated bloodstream infections (uBSI) are common and often receive prolonged courses of intravenous (IV) antibiotics, increasing risk for catheter-associated complications and hospitalization costs. β-hemolytic Streptococcus spp. are a common cause of BSI and have reliable susceptibility to many oral antibiotics. Clinically improving patients without persistent BSI and a controlled source of infection are candidates for oral antimicrobial therapy (OAT) but despite anecdotal practice, there are few studies affirming the practice of OAT for gram-positive uBSI. We evaluated IV to OAT transitions for treating β-hemolytic streptococcal uBSI.

Methods

This retrospective cohort study included patients >18 years old hospitalized between 1/1/2013 and 12/31/2019 diagnosed with uBSI due to β-hemolytic Streptococcus. Patients were excluded if BSI was due to endovascular, central nervous, or bone/joint infection without source control. We compared outcomes in patients treated with IV only to those transitioned to OAT including: 30-day mortality, antimicrobial therapy, BSI relapse, 30-day rehospitalization, adverse drug events, and reversion to IV therapy. Fisher’s exact test was used for categorical variables; Mann-Whitney test and independent t-test for continuous variables.

Results

A total of 238 Streptococcus BSI (of 321 BSI screened) were included (83 excluded as complicated, pediatric, or outpatient). OAT was used in 153 (64%). Cohort demographics were similar (table 1). Infectious disease (ID) consultation was not statistically associated with OAT transition; in fact, ID consults tended to use less OAT (66% IV vs. 54% OAT p=0.10). Hospital length of stay was statistically shortened in the OAT cohort with a median of 5 (interquartile range 4) vs. 7.5 (10.5) (p< 0.0001). Patients transitioned to OAT were more likely to finish their antibiotic course outpatient (93 vs. 61% p< 0.001). Thirty-day mortality was decreased in the OAT cohort (2% vs. 13% p< 0.0001). Adverse events were not statistically significant between the groups.

Conclusion

Opportunities exist to modify practice management of uBSI. For β-hemolytic Streptococcus uBSI, OAT was associated with decreased length of stay without adverse clinical outcomes.

Disclosures

Bryan T. Alexander, PharmD, BCIDP, AAHIVP, Astellas Pharma: Advisor/Consultant Trevor C. Van Schooneveld, MD, bioMerieux: Advisor/Consultant|bioMerieux: Grant/Research Support|Insmed: Grant/Research Support|Merck: Grant/Research Support|Thermo-Fischer: Advisor/Consultant Jasmine R. Marcelin, MD, Pfizer (Grant reviewer): Honoraria.
1847. Overview of Infective Endocarditis in Patients with Enterococcus Bacteremia from National Standpoint
Authors: Patel Premalkumar M , Ostran Garrett Van , Camps Nicholas
Published: December 2022

Background

Enterococci are the third most common hospital-acquired infection responsible for high morbidity and mortality, and are associated with high-grade vascular infections like infective endocarditis (IE). Our objective of the study is to discuss the outcomes of IE among patients with Enterococcus Bacteremia (EB) using ICD-10 CM codes from the national database.

Methods

We conducted a retrospective cohort study using the publicly accessible National Inpatient Sample (NIS) database from October 2015 to December 2017. Adult patients ( >/=18), who developed EB were included in the study. SAS 9.4 was used for univariate and multivariate logistic regression analyses.

Results

There were a total of 75,465 patients included in the study who developed EB, among them 5440 (7.21%) patients with IE. In this cohort, 3,620 were males and 1,820 females, among them 3,955 (68.2%) were Caucasians, 620 (11.7%) were African Americans, 6,445 (8.80%) were Hispanic, 100 (1.9%) were Asian and 285 (5.4 %) were native Americans with IE. The majority of them were suffering from congestive heart failure (39.0%), valvular disease (22.0%), peripheral vascular disease (14.8%), chronic lung disease (16%) neurological complications (9.2%), diabetes mellitus with complications (13%) renal failure (32%), obesity (11.0%), and/or drug abuse (8%). In-hospital mortality was 13.7% (p< 0.0001), which was most likely due to the underlying co-morbidities, with an average length of stay of 15.8 (7-18) days and an economic burden of 48,850.3 (16,104–54,410) USD in comparison to patients without IE, who had in-hospital mortality 10.9%, average length of stay 13.6 (5-15) days, and economic burden 49,638 (11009-36665) USD. Age-adjusted mortality among the patients with Infective Endocarditis was 1.2 (1.07-1.28).

Conclusion

Based on the results from our study, we found that patients with enterococcus bacteremia in appropriate settings should be screened for infective endocarditis to decrease the in-hospital mortality, length of stay, and economic burden.

Disclosures

All Authors: No reported disclosures.