bluuebunny/crossref_metadata_2025 huggingface dataset:
86. Effect of Oral Fosfomycin Compared to the Intravenous Beta Lactam/Beta-Lactamase Inhibitor or Carbapenem in Step-down Treatment of Patients with Complicated Urinary Tract Infection due to Extended-Spectrum Beta-Lactamase (ESBL) Producing Enterobacteriaceae: A Multicenter, Open-label, Randomized Controlled, Non-inferiority Trial
Authors: Seo Jun-won , Young Kim Da , Yoon Youngmin , Sang Lyu Young , Sub Na Yong , Sik Moon Do , Ra Yun Na , Seok Kim Min , Kim Jeong-Han , Woon Bae Sang , Hur Jian , Hyung Kim Min , Soo Park Yoon , Kim Heejung , Lee Hyungdon , Jang Hee-Chang , Kim Dong-Min
Published: November 2023

Background

The widespread use of carbapenem in the treatment of UTIs caused by ESBL-producing enterobacteriaceae has led to the emergence of carbapenem resistant enterobacteriaceae. In this randomized controlled trial, we aimed to determine whether oral fosfomycin was inferior to carbapenems or beta-lactamase inhibitors (BL/BLIs) in treatment of complicated UTIs caused by ESBL-producing enterobacteriaceae.

Methods

This study was a multicenter, randomized, controlled, open-label, non-inferiority trial conducted at four tertiary hospitals in South Korea. Eligible patients were randomly assigned 1:1 at the time of step-down therapy, to continue carbapenem or BL/BLIs already in use or to switch to oral fosfomycin (Figure 1). The antibiotic treatment period was set to 10 days in total. The primary end point was clinical resolution of UTIs related symptom and signs within 4 days after the end of treatment. This trial is registered with cris.nih.go.kr (KCT0007669).

Results

Between Nov 1, 2022, and Apr 30, 2023, 250 patients were screened for eligibility. 96 patients were randomly allocated to receive oral fosfomycin or maintain empirical carbapenem or BL/BLIs, of whom 93 were analyzed (Figure 2). Most of demographic and baseline characteristics showed no statistically significant difference between the two groups (Table 1). The primary endpoint was achieved by 45 (93.8%) of 48 patients in the oral fosfomycin group and 43 (95.6%) of 45 patients in the carbapenem or BL/BLIs group (Figure 3). As a result of the subgroup analysis, there was no statistically significant difference between the two groups for all subgroup items (Figure 4). Microbiological cure in urine specimen was met in 47 of 48 (97.9%) assigned to oral fosfomycin and 44 of 45 (97.8%) assigned to carbapenem or BL/BLIs (Table 2). Side effects were observed in both groups during the treatment period, but the serious adverse events were not observed in both groups (Table 3).

Conclusion

Oral fosfomycin is not inferior to carbapenem or BL/BLIs for the step-down treatment of complicated UTIs caused by ESBL-producing enterobacteriaceae. Therefore, it is one of the optimal treatment options applicable to the strategy of changing to early oral antibiotics in the step-down treatment of complicated UTIs caused by ESBL-producing enterobacteriaceae.

Disclosures

All Authors: No reported disclosures
974. Real World Experience of Posaconazole Therapeutic Drug Monitoring in Oncology Patients: Clinical Implications of Hypoalbuminemia as a Predictor of Subtherapeutic Posaconazole Levels
Authors: Pasikhova Yanina , Greene John , Morrison Austin R , Handley Guy
Published: November 2023

Background

Posaconazole (POS) is utilized for prophylaxis or treatment of invasive fungal infections (IFI) in patients with malignancies or following stem cell transplant (SCT). Subtherapeutic levels may be associated with breakthrough infection and therapeutic drug monitoring (TDM) is recommended. Timely measurements are not available at most institutions. We sought to identify factors associated with subtherapeutic POS levels in high-risk patients for IFI.

Methods

Patients at an NCI designated cancer center with POS level from 06/2021 to 07/2022 were evaluated for risk factors associated with subtherapeutic levels. Only patients with at least one level receiving oral delayed release tablets or IV formulations were included.

Results

A total of 66 patients were identified with 61 included. 46 had hematologic malignancies, 27 underwent SCT, 4 were treated with chimeric antigen receptor T cell therapy. Majority were male with a median age of 64 years old, a median BMI of 26.26 and a weight of 75.9 kilograms.

POS was used for treatment of IFI in 53 patients. Median time from initiation to level was 13 days. The median level was 1.74mcg/mL. whereas for patients with a BMI above 30 (17/61), median level was 1.17mcg/mL. Hypoalbuminemia, defined as ≤ 3g/dL, was seen in 28 patients and was associated with statistically higher rates of sub-therapeutic levels for target levels reported for treatment of 1.25mcg/mL (18/28; p=0.004), 1.5mcg/mL (20/28; p=0.012) and 1.8mcg/mL (22/28; p=0.016).

Only one breakthrough IFI occurred on patients receiving POS for prophylaxis compared to two patients receiving POS for treatment: both with subtherapeutic levels. Only one patient discontinued the drug due to intolerance. No discontinuations occurred due to liver toxicity or QTc prolongation.

Conclusion

Therapeutic levels are critical for treatment and prophylaxis of IFI in oncology patients and delays in accurate measurements are common. In our analysis, hypoalbuminemia was associated with subtherapeutic levels at standard dosing, and higher initial dosing may be considered in high-risk patients with hypoalbuminemia particularly for treatment of IFI.

Disclosures

All Authors: No reported disclosures
982. A Comparison of Decolonization Methods and Impact on MRSA Infection in a Neonatal Intensive Care Unit
Authors: Hiermandi Nahid , Foster Catherine , Purnell Krystal , Campbell Judith R , Marquez Lucila
Published: November 2023

Background

Infection due to methicillin-resistant Staphylococcus aureus (MRSA) causes morbidity and mortality in premature hospitalized neonates. MRSA colonization is a risk factor for transmission and outbreaks within neonatal intensive care units. Decolonization aims to stop MRSA transmission and infection. National guidelines lack recommendations for which decolonization practices are the most effective in neonates. We hypothesize that both topical mupirocin and chlorhexidine (CHG) is more effective than mupirocin alone at preventing MRSA infection in neonates.

Methods

In this retrospective study, we compared the rates of MRSA infection among all colonized neonates admitted to a 42 bed NICU at Texas Children’s Hospital from 2012 to 2020. Our surveillance and decolonization protocol (Figure 1) was introduced in October 2016. The MRSA screening methodology initially consisted of culture, then was changed to PCR (reflexed to culture if MRSA was detected). We grouped colonized neonates as those who underwent no decolonization, partial decolonization (mupirocin only), and full decolonization (CHG+ mupirocin) and compared the rates of infection in each. Infection was defined by isolation of MRSA from any specimen in the context of illness. This study was approved through the Baylor College of Medicine Institutional Review Board.

Figure 1

MRSA surveillance and decolonization protocol

Results

7,980 neonates were admitted to the NICU from 2012-2020. Of those screened, 128 were MRSA-colonized. Eighteen were fully decolonized, 76 partially decolonized and 34 received neither (Table 1). Zero infants who underwent full decolonization had MRSA infection. Decolonized infants were less likely to develop infection (OR 0.56, 95% C.I. 0.2-1.58) compared to infants who did not undergo any decolonization. Neonates who received only mupirocin (due to age) were less likely to develop infection (OR 0.72, 95% C.I. 0.26-2.04), however this reduction was not as impactful as with the combination of CHG and mupirocin (Figure 2).

Table 1

MRSA infection rates by category of decolonization

Figure 2

Comparison of MRSA infection between decolonized vs not decolonized and mupirocin vs no mupirocin with odds ratio and relative risk

Conclusion

Neonates who received CHG and mupirocin did not develop MRSA infection, and decolonization with mupirocin alone provides some but not as much protection from MRSA disease as does both mupirocin and CHG. Further studies should evaluate the safety of CHG wipes in neonates less than 36 weeks gestation/4 weeks chronologic age.

Disclosures

All Authors: No reported disclosures
985. Pooled RNA Metagenomics to Enable Scalable, Unbiased Pathogen Detection and Surveillance
Authors: Messer Katelyn S , Adams Gordon , Paull Jillian S , Livny Jonathan , Lemieux Jacob , Park Daniel J , Sabeti Pardis C , Siddle Katherine J
Published: November 2023

Background

As disease patterns shift with changing demographics and climate, developing comprehensive and scalable tools for tracking and identifying emerging pathogens is an increasingly critical component in mounting a robust public health response. Metagenomic next-generation sequencing (mNGS) provides unbiased detection of etiological agents from diverse types of clinical specimen and has great potential to aid in the prediction and prevention of future outbreaks. However, available protocols are unsuitable for widespread and routine use, due to high cost and extended hands-on time required for sample processing. Thus there is a need for faster, cheaper, and more automatable sequencing methods that retain the accuracy and breadth of current protocols.

Methods

Here we develop Pooled RNA Metagenomics; a cost-effective and highly-multiplexed method that accelerates the processing of RNA samples by barcoding individual samples early in the pipeline allowing for parallel preparation. We benchmark this method by comparing the output from clinical samples to that from other established mNGS methods. Additionally, the protocol is designed to preserve the RNA sense information in the resulting sequencing data, and we incorporate unique molecular identifiers upstream of amplification; two features that enhance the utility and flexibility of the method for downstream applications.

Pooled RNA Metagenomics Overview

Schematic overview of the pooled mNGS workflow: RNA samples are ligated to uniquely barcoded adapters before being pooled together for cDNA synthesis with UMI incorporation and subsequent library construction PCR.

Results

We found that early pooling of barcoded RNA samples can reduce reagent costs by up to 80% and processing time by up to 60%. We demonstrate that pooling up to 32 samples in a single well results in similar recovery of complete viral genomes to those produced by other mNGS methods where each RNA is processed separately.

Conclusion

Pooled RNA Metagenomics provides an innovative, cost-effective, scalable, and pathogen-agnostic approach to outbreak monitoring and prevention. The high throughput enabled by this method can be augmented by incorporating automation, which in tandem increases speed and scale. The protocol is also amenable to miniaturization, which can further reduce costs and is of particular interest for low input clinical specimens. In summary, Pooled RNA Metagenomics dramatically lowers the barrier to high throughput mNGS, making it a viable option for enhanced pathogen surveillance.

Disclosures

Pardis C. Sabeti, MD, PhD, Danaher Corp: Board Member|Danaher Corp: Stocks/Bonds|Delve Bio: Advisor/Consultant|Delve Bio: Stocks/Bonds|NextGen Jane: Advisor/Consultant|Sherlock Biosciences, Inc: Advisor/Consultant|Sherlock Biosciences, Inc: Stocks/Bonds
1034. COVID-19 Bloodstream Infection Outcomes Stratified by Social Determination Index (SDI) in NYC Public Hospital System
Authors: Yao Lim Chee , Johan Kenneth , Gutierrez Jorge , Romero Garcia Alberto , Afzal Afsheen , Al-Khateeb Mohannad Al-Khateeb , Yankulova Boyana , Yusuf Mubarak , De Castro Yinelka Silverio , Venugopal Usha , Feinstein Addi , La Fortune Alexander , Sittler Daniel , Menon Vidya
Published: November 2023

Background

Impact of socioeconomic factors on outcomes was significant during the COVID-19 pandemic. We aim to study disparities in outcomes among hospitalized COVID-19 patients with bloodstream infection (BSI) stratified by SDI in the NYC Public Health System.

Methods

Retrospective multicenter study of hospitalized patients with COVID-19 in 11 acute care hospitals in the NYC public health system from March 2020 to May 2020 was collected. Hospitals are further stratified according to the median household income of NYC using their zip code area into high (≥$65,000), medium ($40,000-64,999) and low income (< $40,000). Descriptive statistics were used to compare baseline patient characteristics including COVID-19 severity and BSI features. The primary outcome was in-hospital mortality. Logistic regression models were used to adjust for potential confounders.

Inclusion Process of Study Population

Results

Eleven hospitals were stratified based on SDI (high income: 2, medium income: 4, low income: 3), 2 were excluded as they lie on zip codes with overlapping income. Patients’ baseline and BSI characteristics are described in Table 1. For every change in income group: high-middle and middle-low, the odds of mortality increased by 1.33 times (p=0.048). Additionally, for every increase in 1 year of age above 23, the risk of mortality from BSI increased by 2.2% (p=0.004).

Baseline Characteristics of Subjects Stratified by Household Income Status

Bloodstream Infection Characteristics Stratified by Household Income Status

Conclusion

The study shows the impact of health disparities during COVID-19 among hospitals with the same standard of care, where higher mortality rates were observed in low and middle-income zip code areas in NYC, likely due to the burden of social determinants of health. Hospital acquired BSI was uniformly high in all income groups, compared to primary BSI. Nonetheless, it provided an insight about the need for further investigation about the impact of socioeconomic factors on mortality and for strategies to address disparities in access to healthcare.

Disclosures

All Authors: No reported disclosures
1103. Endemic Coronavirus Infections in a US Cohort of Children from Birth to 4 Years
Authors: Payne Daniel C , Morrow Ardythe L , Conrey Shannon C , McMorrow Meredith L , McNeal Monica , Niu Liang , Burrell Allison , Schlaudecker Elizabeth P , Mattison Claire , Burke Rachel M , DeFranco Emily A , Teoh Zheyi , Wrammert Jens , Atherton Lydia J , Thornburg Natalie J , Staat Mary A
Published: November 2023

Background

Endemic coronaviruses (“CoVs”) OC43, HKU1, NL63 and 229E are “common cold viruses” related to SARS-CoV-2, but their natural histories are poorly understood. We documented endemic CoV infections in a prospective cohort of US infants and children to determine the extent to which natural infection protects against subsequent homotypic and heterotypic endemic CoV infections and SARS-CoV-2 infections.

Methods

Cincinnati mother-child pairs were enrolled in the third trimester of pregnancy in 2017-18 and children were followed from birth to 4 years with weekly collection of mid-turbinate nasal swabs. Blood was collected at 6 weeks; 6, 12, 18, 24 months; and annually thereafter. Mothers reported on socio demographics, risk factors, and the child’s weekly symptoms. Medical visits were documented from pediatric care providers.

CoV infections were followed for the first 4 years of life (focusing on the most compliant subset of 116 children having >70% weekly sample collection). Infections were identified through nasal swabs tested using a RT-PCR multiplex pathogen panel, and by serum IgG responses using a validated kit at CDC and interpreted using classification and regression tree (CART) analysis.

Results

We detected 398 endemic CoV infections over 317.5 child-years of follow-up (1.1 infections/child-year). Endemic beta-coronaviruses, OC43 and HKU1, were associated with statistically significant homotypic protection (77% and 84%, respectively) after a single infection. Similarly protective homotypic associations (73%) were elicited by NL63, the dominant alpha-coronavirus, after two infections. 229E infections were uncommon. No heterotypic protective association was found for any of the endemic CoVs or for SARS-CoV-2 infections from June 2020 to Nov 2021. The majority of endemic CoVs and SARS-CoV-2 infections were asymptomatic, but this proportion varied by CoV strain. Symptomatic infections were mild for all CoV strains with no hospitalizations.

Conclusion

Natural infection resulted in homotypic immunity but not heterotypic immunity against other CoVs to the 4th birthday. Children were not protected against SARS-CoV-2 by prior endemic CoV infections. CoV infections in these young children were largely asymptomatic or mild.

Disclosures

Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
1931. Real-world evaluation of adequacy of empiric and definitive therapy in carbapenem susceptible and non-susceptible Enterobacterales and Pseudomonas aeruginosa by time to culture result: A multicenter analysis
Authors: Riccobene Todd , Ai ChinEn , Yu Kalvin , Gregory Sara , Lock John L , Kim Brooke , Gupta Vikas
Published: November 2023

Background

Infections caused by multi-drug resistant (MDR) Gram-negative pathogens are increasingly problematic in healthcare settings and are associated with worse clinical outcomes in critically ill patients. We conducted a multicenter real-world evaluation of culture turn-around time (TAT), associated inadequate empiric (IET) and definitive therapy (IDT) in carbapenem susceptible (Carb-S) and non-susceptible (Carb-NS) Enterobacterales (ENT) and P. aeruginosa (PSA).

Methods

Hospitalized adults (≥ 18 years old) with facility reported antibiotic susceptibility from 2018-2022 across 161 facilities (BD Insights Research Database, Franklin Lakes, NJ) were identified for non-contaminant Carb-S/Carb-NS ENT and PSA across respiratory, blood, urine, intra-abdominal, skin/wound, and other sources. We evaluated antibacterial therapy as IET (prior to first susceptibility result) and IDT (48hrs post first susceptibility result & not discharged) by culture TAT (date/time first susceptibility results – date/time culture collection).

Results

We identified 345,245 ENT of which 1.8% (6,174) were Carb-NS and 60,143 PSA of which 17.2% (10,357) were Carb-NS. IDT was lower than IET in Carb-S ENT (12.9% vs. 5.1%), Carb-NS ENT (53.5% vs. 25.2%), Carb-S PSA (28.4% vs. 11.0%), and Carb-NS PSA (53.5% vs. 26.0%) pathogen results. IDT was also lower than IET at each 12-hour increment of availability of susceptibility results (Figure 2) and overall IDT was 25.2% and 26.0% in Carb-NS ENT and Carb-NS PSA, respectively. Median time to positive susceptibility result was longer in Carb-NS ENT vs. Carb-S ENT (67 vs. 53 hrs) and longer in Carb-NS PSA vs. Carb-S PSA (68 vs. 62 hrs) (Table 1, Figure 1).

Conclusion

There was a reduction in inadequate therapy prescribed once cultures were available (IET to IDT) overall and across each of the 12-hr TAT to susceptibility results periods evaluated in Carb-S and Carb-NS ENT and PSA positive cases. Both IET and IDT were higher in patients with either Carb-NS ENT or Carb-NS PSA than Carb-S patients. However, more than 25% of patients with Carb-NS ENT/PSA were prescribed IDT within 48 hours of a susceptibility result. These data support efforts to improve TAT to susceptibility results and can inform protocols and workflow that guide empiric and definitive therapy.

Disclosures

Todd Riccobene, PhD, AbbVie: Employee salary|AbbVie: Stocks/Bonds ChinEn Ai, MPH, Becton, Dickinson and Company: Employee Kalvin Yu, MD, FIDSA, BD: Stocks/Bonds Sara Gregory, PhD, Becton, Dickinson and Company: Employee John L. Lock, PharmD, AbbVie: Employee|AbbVie: Stocks/Bonds Brooke Kim, RN, BSN, MSM, AbbVie: Employee|AbbVie: Stocks/Bonds Vikas Gupta, PharmD, Becton, Dickinson and Company (BD): Employee of BD|Becton, Dickinson and Company (BD): Stocks/Bonds
1181. Evaluation of the Safety of a Beta-Lactam Allergy Protocol
Authors: Sakowski Alexandra K , Borkowski Jaime , Rhodes Karen
Published: November 2023

Background

Beta-lactam allergies (BLA) pose a challenge to the optimization of antibiotic therapy as some of these are not true allergies, are minor reactions, or instead may be adverse effects. This issue is further complicated by the fact that traditional methods of challenging allergies can be costly or time-consuming. The purpose of this study was to evaluate the safety of a protocol which directly challenges patients with a BLA via full dose administration of the challenge antibiotic based on the risk of cross-reactivity.

Methods

This retrospective, observational, case-control study compared the incidence of hypersensitivity reactions following the administration of a beta-lactam antibiotic in patients with a reported BLA to that of those without a reported BLA. It included adults in the community hospital setting who received a beta-lactam antibiotic for any indication during an inpatient admission between March 2018 and October 2022. The treatment groups were separated by the presence or absence of a documented BLA. The primary outcome was the occurrence of a hypersensitivity reaction following the administration of a beta-lactam antibiotic.

Results

A total of 910 out of 1000 patients were eligible for evaluation, and 116 of those patients had a history of a BLA documented on the chart whereas 794 did not. The primary outcome of an IgE-mediated hypersensitivity reaction occurred in 1 out of 116 in the BLA group and 4 out of 794 in the non-BLA group (OR 1.72; 95% CI 0.19-15.5) (see table).

Results

Conclusion

No significant increase in the incidence of IgE-mediated allergic reactions was noted in the patients with a history of a BLA, however, the study was not powered to detect a difference due to the rarity of IgE-mediated reactions. Despite a trend towards an increased risk of reactions in patients with a history of a BLA, the majority of the few reactions that occurred were non-severe in nature. The benefits of challenging a BLA outweigh the risks in this setting.

Disclosures

All Authors: No reported disclosures
1187. Evaluation of an Antimicrobial Stewardship (AS) Bundle for Uncomplicated Gram-Negative Bloodstream Infections (GN-BSI) in Adults at a Large Academic Health System
Authors: Dipietro Juliana M , Dubrovskaya Yanina , Marsh Kassandra , Decano Arnold , Mazo Dana , Major Vincent J , So Jonathan , Yuditskiy Samuel , Papadopoulos John , Siegfried Justin
Published: November 2023

Background

AS bundles provide concise steps to clinicians at the point of care to guide antibiotic decision-making. At NYULH GN-BSI bundle was implemented in the electronic health record of the microbiology report. The purpose of this project was to evaluate the impact of the bundle on patient outcomes and prescribing.

Methods

This was a multicenter, retrospective review of patients with GN-BSI in the pre-bundle group (preBG, 3/2019-2/2020) and post-bundle group (postBG, 3/2021 to 2/2022). The primary outcome was the composite of in-hospital mortality, infection-related readmission, and GN-BSI recurrence.

Results

Out of 1097 patients screened, 225 patients met inclusion criteria n=101 in preBG, n=124 in postBG. Baseline characteristics were similar between groups, including Charlson Comorbidity Index [4 (IQR 3-6) vs. 4 (2-5); p=NS] and Modified PITT Bacteremia Score [1 (0-2) vs. 1 (0-2); p=NS]. The most common sources of GN-BSI were urinary (59 vs 59%, p=NS) and intra-abdominal (29 vs 23%, p=NS). E. coli (62 vs 61% p=NS) and K. pneumoniae (30 vs 21%, p=NS) were the most common organisms. There was no difference in the primary composite outcome (13 vs 7%; p=NS) and its individual components of in-hospital mortality, 30-day infection related readmission and GN-BSI recurrence (2 vs 0%, 10 vs 7%, 1 vs 1.6%). The median hospital length of stay (HLOS) from GN-BSI onset and days of therapy were also similar between the pre- and postBG [5 vs 5 days, p=NS; 14 vs 15 days, p=NS]. There was no difference between pre- and postBG in empiric vancomycin (VAN) initiation (57 vs 61%) and median VAN days (2 vs. 2 days). VAN discontinuation (DC) was done more frequently by the primary team in postBG group (67 vs. 38% preBG; p< 0.01). Numerically more patients were de-escalated in postBG (81 vs 73% preBG, p=NS) with 9% increase in the use of ampicillin/sulbactam or amoxicillin/clavulanate, p=0.043 and no difference in time to de-escalation. In postBG, de-escalation by the primary team and ASP increased numerically by 8.8%, p=NS and 4.4%, p=NS with a decrease in ID recommendations related to de-escalation by 13.6%, p=NS.

Conclusion

GN-BSI bundle worked as a nudge-based tool to guide providers in VAN DC, de-escalation to more narrow antibiotics and decreasing amount of ID consults without negative impact on HLOS and patient outcomes.

Disclosures

All Authors: No reported disclosures
1189. The Impact of Clinical Staff Pharmacist Driven Weekend Antimicrobial Stewardship Coverage in a Quaternary Hospital in UAE
Authors: Elrefaei Hazem , Al Quteimat Osama , Ismail Rami , Nasef Rama , Hisham Mohamed , El Nekidy Wasim S , ElLababidi Rania
Published: November 2023

Background

Pharmacy antimicrobial stewardship services were extended to cover the weekends, incorporating a clinical staff pharmacist with infectious disease (ID) training to cover antimicrobial stewardship program (ASP) activities on weekends is an opportunity. The aim of this study is to assess the impact of integration ASP clinical staff pharmacist into an ASP on weekends by collecting and analyzing the documented pharmacists’ ASP interventions before and after implantation of the service.

Methods

A single center, pre-post quasi-experimental study. Data were collected retrospectively from the electronic medical record (EMR). The study included at 2 sets of data: pre-implementation (2020) and post-implementation (2021) of an ASP weekend pharmacist,

The primary outcome is to evaluate pharmacist ASP Interventions through prospective audit and feedback review analysis. Secondary outcomes include antibiotics days of therapy (DOT), length of hospital stay (LOS), healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 1:Characteristics of the pre-and post-intervention group

Results

During the study, an increase in the number of documented interventions was observed with 452 interventions were documented on 362 patients during the post-implementation period compared to 114 interventions were documented on 108 patients during the pre-implementation period (p = 0.04).

A reduction in the LOS was observed with a median (IQR) of 16 days (8-34) during the post-implementation period compared to 27.5 days (10-56) during the pre-implementation period (p = 0.001), while the median (IQR) total DOT was increased during the post-implementation period 8 (6-11) versus 7 (4-11) during the pre-implementation period (p = < 0.001). No differences were observed in healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 2:Pharmacist interventions on the pre-and post-intervention groupTable 3:Outcome of pharmacists driven weekend antimicrobial stewardship on the pre-and post-intervention group

Conclusion

The pharmacists driven weekend antimicrobial stewardship is an opportunity for the pharmacists to intervene and optimize patients’ treatment plan and contributed towards a significant shortened length of hospital stay. Therefore, healthcare facilities should prioritize the involvement of pharmacists in weekend ASPs to ensure consistent, high-quality care throughout the week.

Disclosures

All Authors: No reported disclosures
1203. Impact of Antimicrobial Stewardship Interventions on Hospital-Onset Clostridioides difficile Infections
Authors: Kwon Taesung , Dillon Caroline E , Duggirala Madhuri , Berk Daniel , Barbour Tyler , Vasireddy Swati , Yablonski Bridget , Shelly Mark A
Published: November 2023

Background

We carried out a case control study to document the effect of antimicrobial stewardship interventions (ASI) on hospital-onset CDI.

Types of antimicrobial stewardship intervention and implementation rate

*Antimicrobial stewardship team reviews the case and recommends no change.

Methods

We identified cases of laboratory-identified CDI at a medical school-affiliated medical center. Cases were identified by PCR as laboratory identified hospital onset CDI. Each case was matched with 2 cases where a stool PCR on the same hospital day was negative in the same month. Cases were limited to adults without a history of CDI in the last 3 months. Charts were reviewed for CDI risk factors, antibiotic exposure, and ASI documentation and follow-through.

Results

From 2020 to 2021 there were 145 cases of HO-CDI, for which we assigned 125 cases with 250 in the matched referent group. A total of 323 ASIs were recorded in 184 charts. The ASI implementation rate was 87.2% with the lowest rate (77%) seen in “discontinue antibiotics” (Table). Of patients in the CDI group, 53.6% (67) had an ASI, compared to 47.2% (118) in the control (OR 1.29 (0.84 to 1.99), P = 0.25). Oftentimes (47.8%) these occurred on or after the day of the CDI test. Most risk factors for CDI were evenly distributed in both groups. Use of PPI/H2 blockers were seen more often in the cases (73.6% in cases vs 58.4% in controls, OR 2.00 (1.26 to 3.23), P = 0.004). The number of days with antibiotics and the cumulative number of antibiotic days was not different in patients tested for CDI. The median (IQR) of the number of days with antibiotic use in the 30 days prior to test was 6 (3.5 to 9) in the CDI and 7 (4 to 10) in the control. The total number of antibiotic days were 9 (5 to 14) in the CDI group and 10 (6 to 16) in the control group. No antibiotic class was seen more often in the CDI group. Macrolides, mostly azithromycin, were seen more often in the control group (OR 0.30 (0.09 to 0.82), P = 0.016).

Conclusion

We did not see a difference in the rate of ASIs in patients who tested PCR positive or negative for CDI. The rate of ASI was lower than we anticipated, reducing the chance for ASI to show an effect. Most ASIs were followed when directions were given (87.2%), leaving too few not followed (17) to meaningfully assess differences. Diarrhea and CDI often occurred before the ASI was completed, reducing the opportunity for impact. To influence this outcome, ASI need to be implemented early in the antibiotic course to see an impact.

Disclosures

Mark A. Shelly, M.D., Rebiotrix: Advisor/Consultant
1206. A Quality Improvement Project Utilizing Clinical Decision Support (CDS) to Optimize Outpatient Antibiotic Prescribing
Authors: Mason Matt , Shapiro Craig , Chan Shannon
Published: November 2023

Background

Antimicrobial resistance remains one of the greatest threats to public health. A major contributing factor is overuse of antibiotics, with most prescribing occurring in the outpatient setting. CDS in the outpatient setting can improve antibiotic use by optimizing durations of therapy. The primary objective of this study was to assess the impact of CDS on prescribing of amoxicillin (AMX) and amoxicillin-clavulanate (AMC) for treatment of acute otitis media (AOM). The secondary objective was to assess prescribers’ perception of the CDS.

Methods

The Nemours Children’s Health Antimicrobial Stewardship Program (ASP) developed antibiotic order panels (OPs) available for ambulatory care providers. The OPs provided guidance for drug formulation, dose, and duration. Providers were notified of implementation through email. Prescribed durations for AMC and AMX for AOM were compared for 3 months pre- and post-implementation. A 14-question survey was emailed to primary care providers to assess perceptions of the OPs and the impact on prescribing practices.

Results

The OP utilization rate for AMC from February to April 2022 was 27.7%. In patients ≥2 years, OP utilization resulted in a decreased average duration of therapy compared to no OP utilization, 7.6 vs 9.8 days, respectively. The OP utilization rate for AMX for AOM from April to June 2022 was 15% (342/2356). In patients ≥2 years old, 5-day and 7-day prescriptions increased from 1.7% (8/472) and 9.5% (45/472) to 11.4% (193/1688) and 12.3% (207/1688), respectively. There was a 40% response rate to the survey; 75% reported awareness of the OPs and 72.7% reported routine use. The OPs were most helpful in selection of correct dose (83.3%), duration of therapy (81.3%), and indication (77.1%). Most providers reported improved efficiency (77.1%) and agreed that the OPs led to shorter durations of therapy (81%).

Conclusion

Development of antibiotic specific OPs with defaulted durations can be an effective strategy to improve outpatient prescribing of antibiotics. Providers are open to CDS to improve prescribing practices. Education and evidence-based support for the recommended changes in prescribing could further maximize providers’ engagement and implementation of these changes.

Disclosures

All Authors: No reported disclosures
1218. Retrospective Audit of Vancomycin Utilization after Initiation of Methicillin Resistant Staphylococcus aureus (MRSA) Screening in Hematology and Bone Marrow Transplant (BMT) Patients.
Authors: Swaminathan Neeraja , Cowman Kelsie , McCort Margaret E , Nori Priya , McSweeney Terrence D , Guo Yi , Bartash Rachel
Published: November 2023

Background

Inappropriate vancomycin use in patients with febrile neutropenia (FN) can contribute to emergence of resistant organisms, acute kidney injury, and infusion related adverse effects. Methicillin resistant Staphylococcus aureus (MRSA) nares Polymerase Chain Reaction (PCR) testing has a high negative predictive value for invasive MRSA infections and therefore, offers a rapid tool to help avoid or de-escalate anti-MRSA therapy. In this study, we aimed to assess the impact of MRSA nares PCR on the utilization of vancomycin in a hematology/bone marrow transplant (BMT) unit.

Methods

Our hematology/BMT unit is a closed 32-bed unit with patients undergoing BMT, receiving care for complications related to BMT or undergoing chemotherapy for hematologic malignancies. Nasal MRSA PCR testing was added to our institutional FN treatment protocol in September 2021 to help guide antibiotic use for this patient population. As part of our antimicrobial stewardship program’s audit and feedback and antimicrobial utilization monitoring, we measured the use of intravenous (IV) vancomycin on the unit before (August 2020-August 2021) and after (October 2021-March 2023) updating our guidelines to include MRSA PCR. Vancomycin utilization, which was obtained from data submitted to National Healthcare Safety Network (NHSN), was measured using unit-level days of therapy (DOT) per 1000 days present. The incidence density rates were compared using the NHSN statistics calculator.

Results

Mean IV vancomycin use pre-MSRA PCR implementation was 91.27 DOT per 1000 days present, compared to 52.69 DOT per 1000 days present post MRSA PCR implementation (p < 0.001) (Figure 1). The monthly trend of vancomycin DOT per 1000 days present is shown in Figure 2.

Conclusion

Vancomycin utilization significantly decreased after the implementation of MRSA nares PCR as a part of the neutropenic fever workup. This study highlights its utility as a tool to guide therapy specifically in immunocompromised patients with significant antibiotic exposure.

Disclosures

All Authors: No reported disclosures
1225. Optimization of Antimicrobial Therapy for Extended-Spectrum β-Lactamase-Producing Enterobacterales (ESBL-E) Bloodstream Infections Through Laboratory-Based Interventions
Authors: Yazdi Mona , Wang Rebecca , Martin Isabella W
Published: November 2023

Background

In 2020, the Infectious Diseases Society of America (IDSA) published clinical practice guidance recommending up-front treatment with an IV carbapenem for severe infections with extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (EB).1 This single-center, observational study sought to optimize adherence to IDSA guidance through two laboratory-based interventions.

Methods

On 12/29/2021, the laboratory initiated the first intervention: suppression of piperacillin-tazobactam results for EB isolates with ceftriaxone resistance, a surrogate for ESBL production.2 On 5/16/2022, the laboratory adopted the second intervention: implementation of a new rapid sepsis diagnostic assay (from BCID to BCID2, BioMerieux). BCID2 detection of blaCTX-M was accompanied by a report footnote recommending up-front carbapenem therapy. To determine the impact of these interventions, patients with blood cultures positive for ceftriaxone-resistant EB between 1/1/2019 and 11/7/2022 were identified. Chart review was performed to determine demographic data, antimicrobial use, and clinical outcomes. The time period between the first and second interventions was excluded. The primary endpoint was use of an IV carbapenem within 24 hours of available phenotypic antimicrobial susceptibility test results.

Results

During this time period, a total of 44 unique ceftriaxone-resistant EB were isolated in blood culture. Of these, 34/44 (77.3%) were Escherichia coli, 6/44 (13.6%) were Klebsiella pneumoniae, and 4/44 (9.1%) were Klebsiella oxytoca. The primary endpoint was observed in 19/33 (57.6%) patients prior to the interventions and 11/11 (100%) patients after.

Conclusion

Through serial laboratory-based interventions, we successfully improved institutional adherence to IDSA guidance for treatment of ESBL-EB bloodstream infections. The findings of our study may inform collaborative microbiology-stewardship efforts at other facilities.

Disclosures

All Authors: No reported disclosures
1241. Outcomes of a Novel Antimicrobial Handshake Stewardship Service in the Immunocompromised Population at an Academic Medical Center
Authors: Gomez Keven , Guerrero-Wooley Richelle , McLeod Caleb C , Msdi Abdulwhab Shremo , Chang Sandy , Arcobello Jonathan T , Zhou Anna
Published: November 2023

Background

Prospective audit and feedback (PAF) is integral to antimicrobial stewardship programs (ASP) and is typically conducted electronically. Handshake stewardship (HS) is a form of in-person PAF advocated by the CDC and IDSA. There is scarce data regarding successful ASP interventions within the immunocompromised (IC) population, and even less data on the impact of HS. The objective of this study was to describe the outcomes of a novel HS service on the IC population and identify ASP interventions that may be generalizable.

Methods

This is a retrospective study of hospitalized adult patients (≥ 18 years old) with IC conditions on pre-determined antimicrobials for at least 72 hours between May 1st, 2022 and January 31st, 2023. IC patients included those with active malignancy on chemotherapy or with functional immunosuppression, solid organ transplant (SOT), and rheumatological conditions on active immunosuppressants. The ASP team comprised of 1 infectious disease (ID) physician and 1 ID pharmacist who provided all recommendations to the intensive care unit (ICU), transplant, and oncology services. Primary outcomes included recommendation acceptance and recommendation types. Additional outcomes included incidence of C. difficile, resumption of antibiotics after discontinuation, lengths of stay (LOS), and 60-day readmission and mortality. Descriptive statistics were performed.

Results

Twenty-nine patients with IC conditions were identified. Majority were White (41.4%) or Hispanic/Latino (44.8%). The median age was 57 years old (IQR 22-78). Fifteen patients had active malignancy, 11 were SOT recipients, and 3 had rheumatologic disorders. Primary teams accepted 45/51 (85%) of recommendations for 27/29 (93.1%) patients. Common recommendations included discontinuation of empiric therapy for febrile neutropenia or for non-infectious etiologies, de-escalation, or escalation to ID consults. Primary teams only resumed antibiotics in 1 patient after early discontinuation. The median LOS was 14 days with 2 patients testing positive for C. difficile and only 1 patient readmitted due to infection.

Conclusion

HS was well received and most recommendations targeting the IC population were accepted and did not lead to poor patient outcomes.

Disclosures

Anna Zhou, PharmD, BCIDP, Melinta Therapeutics: Honoraria
1245. Knowledge, Attitudes, and Practices of Healthcare Workers towards Antimicrobial Stewardship in Dr. Paulino J. Garcia Memorial Research and Medical Center: A Cross Sectional Study
Authors: Hernandez Maria Kim
Published: November 2023

Background

Antimicrobial resistance, a challenge faced by the public health sector, occurs when pathogens are no longer susceptible to common medicines used to treat them. Several studies have shown that reduction in antibiotic prescription could be done successfully through behavioral intervention. It is important to ensure that antimicrobials are prudently used to preserve its efficacy and enable maximum therapeutic effect. This study assessed the knowledge, attitudes, and practices of healthcare workers towards antimicrobial stewardship at Dr. Paulino J. Garcia Memorial Research and Medical Center in Nueva Ecija, Philippines.

Methods

Cross-sectional design was used in this study. Stratified random sampling and proportional allocation to each stratum was used. Healthcare workers including physicians who routinely prescribed antibiotics; nurses assigned at the wards, and pharmacists were included. Questionnaires were self-administered. Kruskal-Wallis H Test and Dwass-Steel-Critchlow-Fligner pairwise comparisons were used in data analysis.

Results

There were a total of 142 participants. Significant differences were noted on actual knowledge between physicians and nurses, on hand hygiene between physicians and nurses and nurses and pharmacists, on perceived knowledge between surgical area and family medicine and medical area and family medicine. There was also a significant difference between physicians and nurses on attitudes towards antimicrobial stewardship. There were no significant differences noted in the practices of healthcare workers.

Conclusion

Healthcare workers are essential in the fight against antimicrobial resistance. Physicians, nurses, and pharmacists had overall good knowledge, attitudes, and practices towards antimicrobial stewardship but despite this, attention must be given to subsets of the study garnering a poor or moderate level of knowledge. This must be addressed by reinforcing previous known concepts and conducting regular trainings and seminars. Factors affecting the knowledge and practice of antimicrobial stewardship program must also be explored.

Disclosures

All Authors: No reported disclosures
1247. Going Viral with Antimicrobial Stewardship
Authors: Jenkins Abi , Ahmed Jubeyr , Bosworth Andrew , Michael Kidd I , Osman Husam , Atabani Sowsan F
Published: November 2023

Background

Historically, antimicrobial stewardship (AMS) has considered the judicious use of antibiotics. AMS is widely adopted across Europe and the US; recently antifungal AMS is gaining momentum but antiviral AMS has been little described. Here we report findings following introduction of AMS virology reviews at University Hospitals Birmingham (UHB); a novel concept and an opportunity to broaden the beneficial aspects of AMS to virology.

Methods

In June 2022, a UK supply issue with aciclovir (ACV) injection was announced. In order to review and preserve ACV injection for those in greatest need, UHB virologists implemented a specialist review for all patients prescribed > 48 hours of treatment. Additionally, we collected data on the advice offered, whether it was accepted, and time required completing the review.

Results

ACV usage had no seasonal pattern. Over the shortage period of 10 weeks, AMS virology rounds were conducted twice weekly either face-to-face or remotely via the Electronic Patient Management System. During these 10 weeks, IV ACV administered to patients for more than 48 hours of treatment was reduced by 51%. Depending on the patient complexity, ward rounds lasted between 60 and 120 minutes (n=24) with advice given to cease treatment (n=8), IV-to-oral switch (n=5), to continue IV ACV (n=8) and/or to undertake further sampling and diagnostic testing (n=6). Advice offered by the clinical virologists to the host clinicians was accepted in all cases.

Conclusion

Antiviral AMS rounds halved IV ACV consumption, compared to pre or post intervention levels, with more than half of patients advised to stop or switch to oral therapy. Diagnostics and sampling guidance was offered in one quarter of reviews, whilst the remaining interventions were more stewardship focused. In all cases stewardship advice was readily accepted by clinical teams. Antiviral AMS rounds provide an opportunity to optimise sampling, diagnosis and improve patient management. Introduction of regular antiviral AMS rounds at UHB are at advanced planning.

Disclosures

All Authors: No reported disclosures
1982. GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV
Authors: Nguyen Quynh P , Wooten Darcy , Duren Kye , Moreno Manuel , Promer Katherine , Hien Tan Matthew , Tang Michael E , Rajagopal Amutha V , Hill Lucas , Yin Jeffrey , Toperoff Will
Published: November 2023

Background

Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH), especially those initiating second-generation integrase strand transfer inhibitors (INSTIs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are incretin-based therapies for diabetes that have been shown to result in substantial weight loss; however, studies of their efficacy in PWH are limited. We aimed to describe the prescribing practices and clinical outcomes of GLP-1 RA use among PWH.

Methods

We conducted a retrospective cohort study among PWH who were prescribed GLP-1 RAs at University of California, San Diego between 2/1/2021and 2/1/2023. Patients who were prescribed but never took GLP-1 RAs or those for whom weight data were not available after GLP-1 RA initiation were excluded. We collected baseline clinical data and calculated changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before and during receipt of GLP-1 RA. We conducted logistic regression to identify variables associated with more than 5% of total body weight loss.

Results

227 patients met our inclusion criteria. Baseline characteristics are shown in Table 1. Ninety-nine patients (43%) were prescribed GLP-1 RAs for weight management alone without concurrent diabetes. Patients had received on average 15.2 months of GLP-1 RA therapy, with 92 (40.5%) achieving the maximum GLP-1 RA dose. On average, GLP-1 RA therapy resulted in a loss of 12 pounds, decrease in BMI by 1.8, and decrease in A1C by 0.5 among all patients and by 1.2 among patients with an A1C > 6.5 at baseline. In the multivariable analysis, higher baseline BMI [OR 1.07 (1.02-1.3)] and longer treatment duration of GLP-1 RA therapy [OR 1.04 (1.01-1.07)] were significantly more likely to be associated with >5% weight loss, whereas receipt of dulaglutide significantly decreased the likelihood of >5% weight loss compared to other GLP-1 RAs [OR 0.33 (0.17-0.66)]. Age, sex assigned at birth, race, ethnicity, ART regimen, baseline CD4 cell count, HIV viral load, and presence of diabetes were not predictive of weight change.Table 1.Baseline Patient Characteristics (N = 227)Table 2.Mean weight, BMI, and A1C before and during GLP-1 RA therapy for PWH

Conclusion

Use of GLP-1 RAs led to improvements in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and related metabolic complications.

Disclosures

All Authors: No reported disclosures