bluuebunny/crossref_metadata_2025 huggingface dataset:
2187. Earliest Description of Mobile Genetic Elements (MGEs) Involved in Establishing blaNDM Persistence Following its Spread From Acinetobacter spp. to Enterobacterales
Authors: Touati Dalila , Grenier Frédéric , Lévesque Simon , Rodrigue Sebastien , Haraoui Louis-Patrick
Published: November 2023

Background

bla NDM is the most prevalent carbapenemase worldwide. It originated in Acinetobacter spp. and spread to Enterobacterales on MGEs despite bottlenecks in MGE transfers between, and persistence within, these phylogenetically distinct bacteria. To elucidate how this transfer and successful expansion were achieved, we investigated MGEs among the earliest NDM-positive Gram-negative bacteria (GNB), isolated in India in 2007.

Methods

Thirteen polymerase chain reaction-confirmed NDM-positive GNB underwent whole-genome sequencing (Illumina NovaSeq and Oxford Nanopore Technologies MinION) and computational analyses: assembly (Unicycler and Trycycler), annotation (RAST), identification (Kraken2), plasmid incompatibility (PlasmidFinder).

Results

Single copies of blaNDM-1 were found in 12 Enterobacterales (6 K. pneumoniae; 3 E. coli; 2 E. cloacae; 1 E. hormaechei) and 1 A. baumannii (Ab), located on plasmids in 11/13 strains: 6 IncC, 3 IncFII, 2 IncFIB (Figure 1). Partial or complete ISAba125 was found upstream of all blaNDM, with a second complete downstream copy forming Tn125 only in Ab. blaNDM's genetic environment was highly diverse including the earliest evidence of its association with MGEs that participated in its global dissemination: insertion sequence common region 1 (ISCR1, n=5) and Tn3000 (n=4). IS3000, present in 2 copies bracketing Tn3000, was also found in single copies in 4 strains at varying distances upstream of blaNDM. In 3/4 of these, ISCR1 was downstream of blaNDM. These hybrid constructs may represent precursors leading to the formation of these MGEs, or degenerate structures.

Figure 1: Genetic environment surrounding blaNDM in 13 Gram-negative bacteria isolated in India in 2007.

Acibau: Acinetobacter baumannii; Entclo: Enterobacter cloacae; Enthor: Enterobacter hormaechei; Esccol: Escherichia coli; Klepne: Klebsiella pneumoniae.

Conclusion

We present evidence of early, rapid and diverse adaptation of blaNDM’s genetic environment following its transfer from Acinetobacter spp. to Enterobacterales. We identify for the first time potentially intermediate genetic structures in the transition between the ancestral Tn125 structure from Acinetobacter spp., and both ISCR1 and Tn3000, which overtook Tn125 as the predominant MGEs among NDM-positive Enterobacterales. Additional sequencing of early NDM-positive isolates could shed more light on the genetic events leading to the formation of MGEs associated with blaNDM, furthering our understanding of the emergence of MGEs carrying antibiotic-resistance genes.

Disclosures

All Authors: No reported disclosures
2943. Hazardous Alcohol Use and Direct-acting Antiviral Therapy Initiation Among People Who Inject Drugs with Current Hepatitis C Infection
Authors: Karimi-Sari Hamidreza , Falade-Nwulia Oluwaseun , Zook Katie , Page Kathleen R , Lucas Gregory
Published: November 2023

Background

People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, HCV treatment rates among PWID remain low. Previous data suggest that hazardous alcohol use is negatively associated with direct-acting antiviral (DAA) therapy initiation in the general population. We aimed to evaluate the effect of hazardous alcohol use on DAA therapy initiation among PWID.

Methods

PWID were recruited through street outreach in Baltimore, Maryland 2018–2019. Participants completed a study survey and HCV testing (antibody reflex to RNA) at study visits. DAA initiation (self-report) was assessed at study follow-up in 6-month increments. Hazardous alcohol use was defined as Alcohol Use Disorders Identification Test-C (AUDIT-C) ≥4 for men or ≥3 for women. Frequency of injection drug use was categorized as ≤3 vs. >3 times/day. Longitudinal data were analyzed using descriptive statistics and multivariable logistic regression analyses with generalized estimating equations (GEE).

Results

Among 720 PWID, 291 (40.4%) had current HCV infection evidenced by detectable HCV-RNA. Among 134 people with HCV viremia and awareness of their HCV infection, the mean age (± standard deviation) was 48.7 ± 10.3 years, 53% were males, 64.9% were African-American, 59.7% had hazardous alcohol use and 60.4% reported >3 injections per day. DAA therapy was initiated in 16 (11.9%) PWID within 6 months (Table 1). In univariate analysis, DAA treatment was not associated with hazardous alcohol use (OR=1.84, 95%CI=.67–5.06) or injection frequency (OR=.54, 95%CI=.21–1.40) but was associated with Black race (OR=4.48, 95%CI=1.27–15.73) and age ≥50 years old (OR=7.17, 95%CI=2.04–25.26). In multivariate analysis, hazardous alcohol use (aOR=1.20, 95%CI=0.41–3.48), injection frequency (aOR=.84, 95%CI=.32–2.24), and Black race (aOR=1.88, 95%CI=.64–5.55) were not associated with DAA treatment initiation. Older age ≥50 vs. < 50 years was positively associated with HCV treatment initiation (aOR=4.79, 95%CI=1.61–14.22).

Conclusion

Among our sample of PWID with HCV infection, oral DAA treatment was not associated with self-reported hazardous alcohol use. The overall very low rates of HCV treatment are concerning and need to be addressed by effective interventions, especially for younger PWID.

Disclosures

Oluwaseun Falade-Nwulia, MBBS ,MPH, Abbvie Inc: Grant/Research Support|Gilead Sciences: Advisor/Consultant
2198. Assessing Strengths and Opportunities of Antibiotic Stewardship Programs in Philadelphia Skilled Nursing Facilities
Authors: Menanno Mariah , Gould Jane , Peritz Tiina , Welsh Elizabeth , Heisey Deborah , Jacob Jerry
Published: November 2023

Background

Skilled nursing facilities (SNFs) have significant opportunity to improve antibiotic use and reduce multidrug-resistant organism transmission. In the summer of 2022, the Southeast Pennsylvania Long-Term Care Resiliency, Infrastructure Supports, and Empowerment (LTC-RISE) team and the Philadelphia Department of Public Health (PDPH) distributed a survey to all Philadelphia SNFs to understand strengths and opportunities for improvement of antibiotic stewardship programs (ASPs).

Methods

A REDCap survey was distributed via phone or video call to 47 SNFs addressing all elements in the CDC's Checklist for Core Elements of Antibiotic Stewardship in Nursing Homes. SNFs self-reported survey responses. Survey results were used to provide individualized feedback highlighting SNF performance against peers, and to implement broad-based interventions to strengthen ASPs.

Results

Thirty-eight SNFs (81%) responded to the survey. All 7 ASP core elements were reported present by 55% of respondents. Only one SNF did not have any core elements present. The elements most commonly reported present and absent were tracking measures of antibiotic use (97%), and monitoring outcomes of antibiotic use (79%), respectively. The ASP lead(s) most commonly identified was the Infection Preventionist (66%), Director/Assistant Director of Nursing (55%), or Medical Director (37%). Infection-specific interventions and resident educational materials were provided in only 42% and 34% of SNFs, respectively. Customized ASP reports were sent to all participating SNFs, with feedback obtained at 3 months after distribution. Survey results were used to create an educational webinar and UTI-focused resource package.

Conclusion

A majority of Philadelphia SNFs reported having ASPs with all CDC core elements in place, and almost all facilities tracked at least one measure of antibiotic use. Opportunities for improvement included tracking outcomes of antibiotic use, providing infection-specific interventions, and providing educational materials to residents. Insights provided from the survey helped to guide individualized and broad-based ASP interventions across facilities.

Disclosures

All Authors: No reported disclosures
2206. Using Day-Level Registry Data on Patients in OPAT to Assess Heterogeneous Patterns of Time-Varying Antimicrobial Exposure and Unplanned Stopping across Multiple Infection Diagnoses, 2015-2022
Authors: Ponder Madison , Boerneke Renae , Schranz Asher J , Swartwood Michael , Farel Claire E , Kinlaw Alan C
Published: November 2023

Background

Patients receiving outpatient parenteral antimicrobial therapy (OPAT) are often medically complex and require carefully tailored treatments to address severe and often concomitant infections.

Methods

We conducted a cohort study of patients enrolled in the University of North Carolina Medical Center OPAT program between March 2015 and December 2022 (2358 OPAT courses among 2072 unique patients). Patients were followed from OPAT regimen initiation (day 0) until observed treatment stop date, based on a grace period of 5 days to confirm discontinuation. Using hierarchical and mutually exclusive categorization schema, we classified patients into 1 of 10 infection diagnosis groups (Figure 1A), and classified all observed antibiotic cocktails (64 distinct antimicrobial medications comprising 520 distinct cocktails) into 18 treatments (Figure 1B). For each patient, we assessed their planned OPAT duration to classify their observed discontinuation as “planned,” “unanticipated early stop,” or “unanticipated prolonged treatment.” Stratified by infection diagnosis and treatment classifications, we used stacked bar charts to describe treatment heterogeneity, and Aalen-Johansen-based cumulative incidence curves to estimate occurrence of each type of discontinuation amid competing events.

Results

The cohort was 59.7% male with median age 56 years (IQR 45-66); the most common infection diagnosis was osteomyelitis +/- diabetic foot infection (28.1%, Figure 1A). Medication exposures were heterogeneous within and across infection diagnoses (Figure 1A and 1B). Median planned OPAT duration was 36 days (middle 90% 15-44). Overall cumulative incidence of unanticipated early discontinuation was 11.9%; overall incidence of unanticipated prolonged treatment was 22.9% (Figure 2).

Conclusion

Day-level data on medication use in this registry provided evidence of heterogeneity in medication exposure and unplanned discontinuation from OPAT, within and across infection diagnoses. These data highlight the need for multi-layered ascertainment of medication exposure, microorganisms, and infection diagnosis in this medically complex patient population to inform surveillance for adverse effects and comparative effectiveness research for post-discharge antibiotic treatment.

Disclosures

Asher J. Schranz, MD, MPH, WoltersKluwer: Honoraria Alan C. Kinlaw, PhD, MSPH, Genentech: Grant/Research Support
2207. Impact of an Intervention Bundle on Azithromycin Use and 5-Day Durations of Therapy for Ambulatory Pediatric Community Acquired Pneumonia
Authors: Weber Matthew J , MacBrayne Christine , Birkholz Meghan C , Poole Nicole M
Published: November 2023

Background

Amoxicillin for a 5-day duration is the first-line recommended treatment for pediatric uncomplicated community acquired pneumonia (CAP). This project sought to identify the impact of a bundled intervention on first-line treatment for pediatric CAP in ambulatory settings.

Methods

The bundled intervention included (1) an electronic medical record (EMR) order set that preselected a 5-day duration of therapy for patients prescribed an antibiotic for CAP (8/2020) and (2) revision of an existing clinical pathway for CAP (4/2021) that removed amoxicillin-clavulanate and azithromycin as recommended antibiotics.

A retrospective review was conducted between July 2018 and July 2022. Patients ages 60 days to 18 years with an in-person or remote ambulatory encounter and validated ICD10 diagnosis code of pneumonia were included. Hospitalized patients and those with complex chronic conditions were excluded. Data was extracted from EPIC EMR.

Primary outcomes were rates of amoxicillin and azithromycin use (encounters receiving the antibiotic of interest out of all encounters receiving an antibiotic) and 5-day duration prescriptions (encounters receiving a 5-day prescription [excluding azithromycin] out of all encounters receiving an antibiotic). Receipt of an antibiotic by demographic categories were compared by chi-squared test. Statistical process control charts with upper and lower control limits and identified “special cause” variation were used to analyze outcomes.

Results

A total 18,839 pneumonia encounters were included with 3,723 (19.7%) prescribed at least one antibiotic. After pathway implementation, the amoxicillin prescribing rate rose from 72 to 80% (p < 0.01) and the azithromycin prescribing rate decreased from 13% to 4% (p = 0.01) (Graphs 1,2). Special cause variation was identified in 5-day prescriptions, which increased from 15% to 58% post-intervention (p < 0.01) (Graph 3).

Conclusion

Implementation of a revised clinical pathway substantially increased the rate of 5-day prescriptions for uncomplicated CAP. An EMR order set did not change durations of therapy, likely impacted by the COVID pandemic. Amoxicillin prescribing increased and azithromycin prescribing was negligible after the pathway implementation.

Disclosures

All Authors: No reported disclosures
2944. Comparative Effectiveness and Safety of 5-7 days versus 10 days of Antibiotics for Acute Bacterial Sinusitis in Children
Authors: Savage Timothy J , Kronman Matthew , Kattinakere Sreedhara Sushama , Huybrechts Krista F
Published: November 2023

Background

Acute bacterial sinusitis accounts for 5 million pediatric antibiotic prescriptions in the United States each year, with 65% amoxicillin or amoxicillin-clavulanate. More than 90% of pediatric patients are prescribed 10+ days of antibiotics. No study has compared shorter to longer treatment. This study compares 5-7 days versus 10 days of treatment in children and adolescents.

Methods

This cohort study included patients < 18 years with an outpatient encounter for acute sinusitis and a same-day dispensation of either a 5–7 day supply or a 10 day supply of amoxicillin or amoxicillin-clavulanate between January 1, 2017 and December 31, 2020 in the MarketScan Commercial Claims and Encounters database. Treatment failure, defined as a new antibiotic dispensation, an ED or inpatient encounter for acute sinusitis, or an inpatient complication of acute sinusitis, was assessed in the first 5, 10, and 30 days after cohort entry. Adverse and control outcomes were captured. We used Cox proportional hazards regression with propensity score (PS) overlap weights for confounding control.

Results

The initial cohort included 254,629 patients, among which 19,627 patients were prescribed a 5-7-day treatment (exposure) and 235,002 patients were prescribed a 10-day treatment (referent). After PS overlap weighting, groups were balanced on all measured covariates (Table 1). The rate of 30-day treatment failure was 167.77 per 1,000 person-years (95% CI, 155.94, 180.49) among patients dispensed 5-7 days of treatment and 150.19 per 1,000 person-years (95% CI, 145.54, 154.99) among patients dispensed 10 days of treatment (hazard ratio 1.12 [95% CI, 1.03,1.21]) (Table 2). Adverse events were rare, and there was no difference between groups in a negative control outcome (Table 3).Table 1:Patient and treatment characteristicsTable 2:Treatment FailureTable 3:Adverse and control outcomes

Conclusion

The absolute risk of treatment failure was very low. Children and adolescents dispensed 5-7 days of antibiotic treatment had a slightly higher rate of treatment failure compared to 10 days of antibiotic treatment. Adverse effects were rare, with a potentially lower rate of yeast infections following shorter treatment. The marginal benefit and increased risk of side effects with longer treatment indicates that shorter treatment of acute bacterial sinusitis, 5-7 days, may be a reasonable initial approach in some populations.

Disclosures

Timothy J. Savage, MD, MPH, MSc, UCB: Contract to Brigham and Women's Hospital Krista F. Huybrechts, PhD, MS, Takeda: Grant/Research Support|UCB: Grant/Research Support
2211. Nursing Home Infection Preventionists are Leading Antimicrobial Stewardship Programs – Should They Be? A Statewide Survey of Stewardship Leadership Roles in Nursing Homes
Authors: Zering Jessica , Kamenar Katarina , D’Angeli Marisa A , Delmer Samantha
Published: November 2023

Background

The Centers for Disease Control’s Core Elements (CEs) of Antibiotic Stewardship for Nursing Homes is the best-practice guideline for developing a nursing home (NH) antibiotic stewardship program (ASP). The CEs recommend that NHs select a medical director, director of nursing, and/or consultant pharmacist to lead the ASP. The Centers for Medicare and Medicaid Services’ State Operations Manual currently suggests an ASP leader and defines pharmacist involvement in ASPs as the performance of a medication regimen review at least once monthly. A survey was conducted of NHs in Washington State to assess implementation of ASP leadership best practices.

Methods

Infection Preventionists (IP) in licensed NHs in Washington State were contacted via email and asked to complete an online REDCap survey on their ASP. Non-responder facilities were contacted via phone and asked that the employee most knowledgeable about their ASP complete the survey. Responses were collected between February 15th, 2022, to May 2, 2023.

Results

A total of 101 Washington NHs out of 198 contacted (51%) responded to the survey. Approximately 90% of respondents reported that IPs led or co-led their antibiotic stewardship program (Figure 1). In comparison, directors of nursing were identified as leaders or co-leaders by 50% of respondents, medical directors by 37%, and consultant pharmacists by 34%. Subgroup analyses by number of facility licensed beds, corporate association, and hospital affiliation demonstrated that IPs were the staff primarily responsible for antibiotic stewardship efforts in NHs across Washington State (Figure 2). Common barriers reported to identifying an ASP lead were competing demands, lack of prioritization by leadership, staffing shortages and lack of expertise.

Conclusion

There is a discrepancy between NH ASP best practice recommendations and on-the-ground implementation. NH administrators can ensure alignment with best practices by putting dedicated time and responsibilities for stewardship into the job descriptions of medical directors and directors of nursing. Regulators can promote pharmacy leadership of NH ASPs by requiring greater clinical expertise and involvement of pharmacists beyond once-monthly medication regimen reviews.

Disclosures

All Authors: No reported disclosures
2216. Orthopedic Provider Adherence to American Academy of Orthopedic Surgeons (AAOS) Guidelines for Dental Prophylaxis in Total Joint Replacement
Authors: Escaler Patricia , Myers Thomas , Quartuccio Katelyn , Munsiff Sonal , Ted Louie
Published: November 2023

Background

Antibiotic prophylaxis before dental procedures (DP) in patients with prosthetic joints has not been shown to decrease the risk of prosthetic joint infections (PJI). Current American Academy of Orthopedic Surgeons (AAOS) guidelines do not recommend DP in low-risk patients, and no longer mention clindamycin for penicillin allergic patients. The CDC recently prioritized antimicrobial stewardship (AS) for dental procedures. Orthopedic provider compliance with AAOS guidelines is unknown.

Methods

This was a single-center, retrospective study of patients who underwent primary hip or knee replacement (TJR) from January to October 2019, and received DP prescribed by an orthopedic provider from the time of TJR through August 2021. DP was determined by chart review. Appropriateness was assessed according to 2016 AAOS guidelines. Further data was recorded, including demographics, pertinent orthopedic history, risk factors for PJI, and possible adverse effects from DP.

Results

Of 1800 patients that were evaluated, 250 patients (13.9% of TJR) were given 258 prescriptions for DP. 64.8% were prescribed by advanced practice providers. Of the patients who received DP, 66.8% were female, and 22.5% were obese. There were slightly more hip replacements than knee replacements. 2.7% of patients were immunocompromised per AAOS definitions. Of the 33 diabetic patients, 87.9% were well-controlled, and thus considered low- risk. 240/258 prescriptions for DP (93%) were inappropriate, with the great majority of those in low-risk patients. Five patients inappropriately received clindamycin. Two patients received the incorrect dosage of antibiotic. Within 6 months of DP, C. difficile was diagnosed in 0.4% of patients, and resistant organisms from any source were cultured in 0.4% of patients. One patient developed PJI within one year of TJR, despite receiving DP.

Conclusion

Though only a minority of patients undergoing TJR received DP, most were low-risk patients and thus considered inappropriate per 2016 AAOS guidelines. Further study is warranted, including analysis of dentists and other providers’ prescribing of DP, use of targeted educational materials, and utility of electronic health record order sets.

Disclosures

All Authors: No reported disclosures
2217. Evaluation of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab Screening in Patients with Cancer at a Large Comprehensive Cancer Center
Authors: Herrington Mark , Vuong Nancy N , Feng Chun , Hwang Hyunsoo
Published: November 2023

Background

Methicillin-resistant Staphylococcus aureus (MRSA) nasal screening has a high negative predictive value (NPV) in immunocompetent patients with infections and is widely utilized as a tool for antibiotic discontinuation. The data applying nasal swab screening in patients with cancer is limited, particularly for those that are immunocompromised and in the setting of neutropenic fever. The aim of this study is to determine the predictive values of MRSA swabs screenings in patients living with cancer.

Methods

This is a retrospective cohort observational study of adult patients admitted to The University of Texas MD Anderson Cancer Center between January 2019 through October 2022. Data from patients with documented MRSA nasal swab screenings and clinical cultures taken within 7 days was collected. The first documented MRSA swab screening and culture results from unique patients were included for analysis to calculate sensitivity, specificity, positive predictive value, and NPV.

Results

A total of 6,475 patients with MRSA swab screenings had 13,129 clinical cultures taken from different anatomical sites. Of the patients included, 57% had a solid tumor and 37% had a hematological malignancy, with 82% of patients receiving an anti-MRSA antibiotic agent within 90 days of the MRSA nasal swab. There were 167 documented positive MRSA cultures, most commonly from a wound (41.3%) or respiratory source (24%). Overall sensitivity and specificity for all culture sites were 50.9% and 98.4%, respectively, with an overall NPV of 99.4%. The NPV was 99.8% for bloodstream infections, 98.5% for respiratory infections, 92.6% for wound infections, and greater than 99% for other culture sites.

Conclusion

The specificity and negative predictive value of MRSA swab screenings in patients with cancer was high overall and consistent with the literature in immunocompetent patients. These results can help guide in the discontinuation of empiric antibiotics in patients living with cancer.

Disclosures

All Authors: No reported disclosures
2222. A study of the role of trimethoprim-sulfamethoxazole in opportunistic infection prevention in lupus patients taking low-level immunosuppressive treatment: An open-labeled, randomized controlled trial
Authors: Munthananuchat Paopat , Ngamjanyaporn Pintip , Pisitkun Prapaporn , Rotjanapan Porpon
Published: November 2023

Background

Individuals with lupus are at risk of opportunistic infections (OIs), especially pneumocystis pneumonia and nocardiosis. The current recommendation to prevent OIs is to take trimethoprim-sulfamethoxazole (TMP/SMX) regularly while on treatment for lupus. However, there has yet to be a standard recommendation on whether TMP/SMX prophylaxis is necessary and when prophylaxis can be discontinued.

Objectives

To assess the role of TMP/SMX in primary prophylaxis of OIs and to study the incidence of TMP/SMX sensitive OIs and the adverse events of TMP/SMX in the real-world setting among lupus patients taking low-level immunosuppressive therapy.

Methods

An open-label, randomized controlled trial was conducted among lupus patients taking low-level immunosuppressive at Ramathibodi Hospital between May 2021 and April 2023. The patient's demographic and relevant data were retrieved. The patients were randomized to receive or not receive TMP/SMX in a 1:1 ratio. The dose of TMP/SMX was adjusted based on renal function. The incidence of TMP/SMX-sensitive OIs was monitored until one year from enrollment, and the adverse events were assessed.

Results

The study was terminated prematurely due to an exceedingly high rate of adverse events secondary to TMP/SMX use. The analysis was made for the enrolled 138 lupus patients at six months, and OIs were monitored until one year. The mean ages were 45.4 in both groups. Most patients (98.4%) had SLEDAI-2K score < 4. The doses of immunosuppressive therapy were adjusted in six patients due to active disease and therefore excluded from the study. No TMP/SMX sensitive OIs documented in 114 lupus patients who completed follow-ups over nine months since enrollment. Eight from 10 patients had grade 1, whereas 2/10 patients had grade 3 adverse drug reactions, and all declined to resume prophylaxis. There was no mortality in the study.

Conclusion

The incidence of TMP/SMX-sensitive OIs among lupus patients taking low-level immunosuppressive was not a significant concern after a one-year follow-up, and high rates of adverse events with TMP/SMX prophylaxis were documented. Therefore, TMP/SMX primary prophylaxis may not be justified in this population.

Disclosures

All Authors: No reported disclosures
2226. Trough- Versus AUC-Based Vancomycin Monitoring for Treatment of Acute Pulmonary Exacerbations of Adult Cystic Fibrosis Patients
Authors: Smith Darrell , Monogue Marguerite , Sanders James
Published: November 2023

Background

Therapeutic drug monitoring (TDM) for IV vancomycin (VAN) in adults with cystic fibrosis (CF) historically has utilized trough concentrations. Recent VAN TDM guidelines recommend area under the curve (AUC)-monitoring to reduce the risk of vancomycin-induced kidney injury. However, limited data is available in adult CF patients to support this practice. The aim of the study was to determine the safety and efficacy of VAN AUC-monitoring in adult CF patients.

Methods

This single-center, retrospective, observational cohort study included adult CF patients admitted from July 1, 2017 to July 1, 2022 with an acute pulmonary exacerbation that received VAN for at least 72 hours with available VAN plasma concentrations for TDM. Eligible patients with multiple hospital admissions during the study period were incorporated as separate encounters. The primary outcome was incidence of acute kidney injury (AKI). A subgroup efficacy analysis was performed in patients with methicillin-resistant S. aureus (MRSA) in the sputum 3 months prior to or 3 weeks after hospitalization.

Results

One hundred forty-three patients were included in the study [AUC cohort (n=39) and trough cohort (n=104)]. Concurrent nephrotoxins was more common in the AUC cohort than in the trough cohort (97% vs 81%; p = 0.01), but rate of AKI was similar (7.7% vs 10.6%, respectively; p = 0.76). No significant differences were seen in achievement of TDM goal, incidence of supratherapeutic exposure or vancomycin accumulation, duration of vancomycin, length of stay, or number of vancomycin concentrations. AUC monitoring was associated with earlier achievement of TDM goal [median 0 days (0-2) vs 2 days (0-4); p < 0.01], lower total daily doses to achieve TDM goal [38.6 ±13 mg/kg/day vs 58.4 ±18.7mg/kg/day; p < 0.01], and fewer regimen changes [median 1 change (0-2) vs 2 changes (1-3); p < 0.01] compared to trough monitoring. In patients with MRSA, pulmonary function recovery, readmission, and mortality was similar.

Conclusion

In adult CF patients, the rates of AKI were similar between VAN TDM methods, but VAN AUC monitoring resulted in a therapeutic regimen sooner at lower total daily VAN doses and fewer number of regimen changes without significantly increasing the number of concentrations compared to trough monitoring.

Disclosures

James Sanders, PhD, PharmD, Merck & Co., Inc.: Grant/Research Support|Shionogi Inc.: Grant/Research Support
2227. Assessing Clinicians' and Trainees' Knowledge and Practice of the IDSA Asymptomatic Bacteriuria Guidelines in the Elderly
Authors: Smith Eleanor E A , Nachimuthu Nagakrishnal , Negrete Jose A , Flynn John , Al Mohajer Mayar
Published: November 2023

Background

Asymptomatic bacteriuria (ASB) is common in the elderly; however, its treatment in this population is not beneficial. Older individuals are also more susceptible to the adverse effects of antibiotics. In practice, many older patients with ASB and new delirium or a fall are empirically treated for presumed UTI, despite a 2019 update to the Infectious Disease Society of America (IDSA) ASB guidelines that recommends against this practice. We aimed to identify self-reported familiarity with the IDSA ASB guidelines, gaps in knowledge, and cognitive-behavioral constructs (CBCs) relevant to treating ASB in older patients.

Methods

This cross-sectional study included advanced practitioners, physicians, residents, and medical students at one academic medical center with affiliated community practices in Southeast Texas. Compared to previous studies, this sample included a greater variety of practitioners from both academic and community settings. The main outcomes were self-reported guidelines familiarity, knowledge score, and behavior score. Chi-squared, one-way ANOVA, and two multivariable linear regressions were performed to assess the relationship between outcomes and categorical variables.

Results

154 out of 1,305 participants (11.8%) responded. The mean knowledge score was 64.87 (SD 23.65), and the mean behavior score was 2.73 (SD 0.91, Table 1). Higher knowledge scores were significantly associated with better antibiotic stewardship practices (P< 0.001) and a better understanding of risks associated with treating ASB (P=0.019, Table 2). Self-reported familiarity with the guidelines did not correlate with knowledge scores (P=0.807). Higher behavior scores were significantly associated with better familiarity (P=0.002), workplace social norms (P< 0.001), knowledge scores (P< 0.001), and risk perceptions (P< 0.001).

Multivariable analysis assessing relationship between knowledge and behavior scores and cognitive constructs, guidelines familiarity, and other categorical variables

Conclusion

There is a gap in knowledge and practice related to antibiotic use for ASB in elderly patients. To optimize antibiotic stewardship, efforts should focus on improving knowledge, familiarity with guidelines, social norms, and risk perceptions.

Disclosures

All Authors: No reported disclosures
2228. Knowledge, Attitudes, and Practices Regarding Antibiotic Use during the COVID-19 Pandemic: A Comparison of United States (US) Survey Respondents Living in the US-Mexico Border Region with those Living in Non-border Regions
Authors: Subelj Maja , Camarena Jose Luis , Hawkes Brooke A , Ellingson Katherine
Published: November 2023

Background

Inappropriate use of antibiotics is a driver of antimicrobial resistance globally. The US-Mexico border region is medically underserved and socially vulnerable. This study aimed to assess knowledge, attitudes and practices (KAP) regarding antibiotic use during the COVID-19 pandemic among US residents, and to compare KAPs for those living in border versus non-border regions.

Methods

A cross-sectional online survey with monetary incentive was deployed to a sample of adults ≥18 years old through Amazon Mechanical Turk with enriched sampling in the US-Mexico border region (defined as residency within 100 km of the border). Surveys were completed from 8/8/2020 to 8/4/2021. KAP questions were aligned with published tools and COVID-19-specific questions were added. Of 602 respondents from the US, 590 (98%) had complete KAP data and were included in this analysis. Chi-square tests were performed to examine the association between KAPs related to antibiotic use and border residency status.

Results

Overall, for 6 of 8 knowledge items about antibiotic use, fewer than 50% of survey respondents answered correctly (Table 1). 50% of border residents versus 71% of non-border residents (p< 0.01) correctly agreed that “antibiotics should never be saved for the next time you get sick.” Conversely 44% of border residents, versus 31% of non-border residents (p=0.03), correctly disagreed with the statement “when I have a cold, I should take antibiotics to avoid getting a more serious illness.” There was no difference in knowledge about causes of antibiotic resistance by region of residency. Overall, 40% of respondents believed that their personal antibiotic use did not affect antibiotic resistance (Table 2). Finally 37% all respondents said they tried to obtain antibiotics, and 31% tried to obtain chloroquine or hydroxychloroquine, because of concerns about COVID-19 with no difference by region of residency.

Table 1: Number and percentage of survey respondents answering correctly to knowledge questions regarding antibiotic use, stratified by residency within 100 kilometers of the US-Mexico border. Table 2: Number and percentage of survey respondants with attitudes consistent with antibiotic stewardship among United States (US) residents, stratified by residency within 100 kilometers of the US-Mexico border.

Conclusion

KAP findings from this survey suggest that knowledge about antibiotic use is low regardless of proximity to the US-Mexico border. Further, practices related to antibiotic and chloroquine or hydroxychloroquine seeking in the context of COVID-19 suggest a role for public-facing information campaigns regarding medication seeking during public health emergencies.

Disclosures

All Authors: No reported disclosures
2230. Consumption of Quinolones, Macrolides, and Beta-Lactam Antibiotics at a Tertiary Care Veterans Affairs Medical Center (VAMC) during COVID-19 Pre-pandemic and Pandemic periods: A 4-year Analysis and Implications for Antimicrobial Stewardship
Authors: Ali Sajjad , Kuhn Ryan , Khaja Sumaiya F , Natesan Suganthini Krishnan
Published: November 2023

Background

During the coronavirus disease 2019 (COVID-19) pandemic, antimicrobial use increased tremendously. Evidence suggests that the pandemic has resulted in an increased rate of AMR due to inadvertent antibiotic use. This likely reflects difficulties in distinguishing COVID-19 from community-acquired pneumonia when patients first arrive at a hospital. Strengthening antimicrobial stewardship (AMS) efforts by formulating policies for the use of antibiotics is crucial to prevent emergence of AMR.

Methods

A retrospective analysis to assess changes in antibiotic use during the pandemic and pre-pandemic patterns was done.

Results

: In the inpatient setting, there was an overall decrease in antibiotic use (all units that follow are in DOT/1000 BDOC) from an average of 380 to 300, vancomycin from 90 to 62, cefazolin from 30 to 17, Linezolid from 5 to 2, Zosyn from 57 to 30 from pre-pandemic period (Jan 2019) to pandemic period (Dec 2022). Antimicrobials that showed an increase during the pandemic included ceftriaxone from 70 to 82, Cefepime from 5 to 8, Levofloxacin from 2 to 5, and fluconazole from 4 to 10 compared to pre-pandemic use. In the outpatient settings (units are in fills/1000 unique patients), levofloxacin use doubled from 3 to 6, cefuroxime use increased from 0.5 to 2 and Azithromycin use dropped from 80 to < 20, with concomitant increase in doxycycline use from 45 to 60. Outpatient antibiotic prescriptions were high for levofloxacin, doxycycline and cefuroxime and increases corresponded to peaks in cases of COVID-19.

Conclusion

Our analysis demonstrates that COVID-19 had shifted the antibiotic consumption curve towards treatment of pneumonia and invasive fungal infections (in seriously ill patients) which has key implications for AMS. Implementation of stringent AMS and mandatory Infectious disease consultation for all COVID 19 infections helped keep our antibiotic consumption well below the national average and curtail AMR.

Disclosures

All Authors: No reported disclosures
2232. Comparison of Empiric Vancomycin Prescribing in Response to Gram Positive Cocci Alerts on Blood Cultures Between Primary and Overnight Physicians on General Medicine Services: A Retrospective Study
Authors: Almulhim Abdulaziz , Cox Heather L , Mathers Amy , Park Stacy
Published: November 2023

Background

Blood culture contamination is associated with unnecessary antibiotic use, increased length of stay, and increased costs. Assessing the likelihood of true bacteremia versus contamination requires consideration of clinical context and microbiologic data. This may be more difficult for covering physicians overnight, who typically cover more patients and may not know patients’ clinical history as well. We compared rates of vancomycin (VAN) initiation in response to microbiology alerts for gram-positive cocci (GPC) in blood cultures during primary team shifts versus overnight.

Methods

We queried the University of Virginia Clinical Data Repository for blood culture results positive for GPC from 07/01/2021 to 12/30/2022 in inpatient general medicine patients. Cultures were stratified by time of the initial positive gram stain alert, which is called as a critical result to the team. All new positive blood cultures are run on a rapid molecular diagnostic (ePlex GenMark Diagnostics) with speciation results passively entered into the chart 2 hours after gram stain. Results were excluded if the patient was already on VAN or daptomycin at the time of gram stain or if the gram stain resulted during hours when the physician coverage (primary vs covering) was not consistent. The primary outcome was the rate of VAN initiation within 2 hours of gram stain with GPCs. Secondary outcomes were number of repeat blood cultures, length of stay (LOS), and incidence of acute kidney injury (AKI).

Results

320 instances of positive blood cultures were reviewed. 141 were excluded. Of 179 included instances, there was no significant difference in VAN initiation by overnight physicians compared to primary teams (21% vs 26%; p=0.418). There was no significant difference in repeat cultures or incidence of AKI.

Comparison of primary and overnight physicians

Blood culture speciation

Conclusion

There was no difference in VAN use, repeat blood cultures, or AKI when positive gram stain alerts were received by overnight physicians versus primary teams. Stewardship interventions targeting VAN prescribing in the setting of a rapid diagnostic workflow may not need to be specifically adapted to covering physicians or teams.

Disclosures

Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant
2235. Characterization of the Adult Sepsis Treatment Guideline Utilization Within the Emergency Department at an Academic Medical Center
Authors: Berg Deanna M , Maguire Christina , Binkley Amanda , Hinton Matthew , Foster Sean , Dutcher Lauren
Published: November 2023

Background

The early initiation of antibiotics in patients with sepsis has been identified as the most effective intervention in reducing mortality. Screening tools have been developed for the early identification of sepsis. This study characterized Emergency Department (ED) patients initiated on antibiotics for suspected sepsis of urinary or abdominal sources to identify opportunities to improve institutional sepsis guidelines.

Methods

A retrospective chart review was performed of patients initiated on empiric antibiotics in the ED for sepsis with a suspected source of urinary tract infection (UTI) or intraabdominal infection (IAI) from September 2021 to September 2022. Epic SlicerDicer, an electronic medical record (EMR) data extraction tool, identified ED patients with an order for broad-spectrum antibiotics. Patients less than 18 years or initiated on antibiotics prior to arrival were excluded. The EMR was utilized to assess the signs of organ dysfunction, antibiotic regimen, EMR-based sepsis pathway use, and patient-specific risk factors. Institutional guidelines defined antibiotic regimen appropriateness. Descriptive statistics were used to characterize the results.

Results

Among the 6869 patients screened, 190 patients were included. The provider initiated the sepsis pathway in 141 (74.2%) patients, and 21 (14.9%) were initiated on empiric antibiotics determined to be congruent with institutional guidelines. The most common deviation from institutional guidelines was the addition of anti-methicillin-resistant Staphylococcus aureus (MRSA) treatment. Anti-pseudomonal therapy was used in 165 (86.8%) patients and anti-MRSA coverage in 117 (61.6%) patients. Of patients with MRSA coverage, 36 (30.8%) had community-acquired infections. An organism was isolated in 113 (59.5%) patients, and Enterobacterales were most commonly isolated (65.5%). P. aeruginosa was isolated in 15 (7.9%) patients, and no patients had MRSA.

Conclusion

Most antibiotic regimens used in ED patients for the treatment of sepsis with suspected urinary or abdominal sources of infection were contrary to institutional guidelines. This may be a result of an overestimation of MRSA or P. aeruginosa in community-acquired infections, highlighting an opportunity for education and stewardship.

Disclosures

Christina Maguire, PharmD, Viiv: Advisor/Consultant Amanda Binkley, PharmD, BCIDP, AAHIVP, Viiv: Advisor/Consultant
2240. Breaking Dogmas: A Single Center Evaluation of Empiric Vancomycin Use Among Intensive Care Unit Patients with Suspected Pneumonia, Bacteremia or Sepsis
Authors: Xie Christina Y , Walsh Ashton , Campion Maureen , Foong Kap Sum , Doron Shira , Vazquez Gabriela Andujar
Published: November 2023

Background

Augmented concern for methicillin-resistant Staphylococcus aureus (SA) infections in intensive care units (ICU) has led to increased empiric vancomycin use (EVU) in patients with suspected pneumonia, bacteremia, and/or sepsis. At Tufts Medical Center, vancomycin is prescribed at clinician discretion without restrictions. We aimed to evaluate the impact of cultures on EVU and identify predictors associated with prolonged EVU among ICU patients with cultures negative (CN) for SA.

Methods

A retrospective study from April 2022 to January 2023 of ICU adult patients with EVU for suspected pneumonia, bacteremia, or sepsis was conducted. ICU service, length of stay (LOS), duration of EVU, blood & respiratory cultures, mechanical ventilation (MV), central line presence, and vasopressor use were collected. Prolonged EVU was defined as vancomycin use for more than 2 days despite CN for SA. The primary outcome was the rate of prolonged EVU discontinuation. Linear regression included demographics, ICU service, LOS, indication, Charlson Co-morbidity Index, lactate, MV, and 0.5 mg/dL serum creatinine change. Logistic regression included the same variables plus age, positive respiratory cultures and MV interaction.

Results

A total of 165 ICU patients had EVU. Of these, 132 (80%) had cultures collected before EVU vs. 33 (20%) that did not. Blood cultures were collected in 117 (88.6%); 66 (49.6%) had respiratory cultures; 51 (38.6%) had both collected. Median vancomycin duration was 2 days (1-3). Prolonged EVU was observed in 47 (46.1%) patients, while 55 (53.9%) had EVU discontinued within 2 days with CN for SA. On average Cardiac Surgery (CS) spent 2 days longer on vancomycin compared to Surgical (p=0.037) and Pulmonary (p=0.01) patients. MV among ICU patients was less likely to be associated with vancomycin discontinuation within 2 days with CN for SA (aOR [adjusted odd ratio] 0.12, 95% CI 0.03, 0.50; p=0.003).

Conclusion

EVU discontinuation was more likely within 2 days in ICU patients with CN for SA, but less likely for MV or CS patients. In a substantial proportion of patients, cultures were not collected. Our findings highlight the importance of diagnostic testing in ICU settings to help reduce EVU.

Disclosures

Maureen Campion, PharmD, Shinoigi: Speaker
2242. Leveraging the McGeer criteria to Determine the Frequency of Potentially Inappropriate Antibiotic Prescribing for Urinary and Respiratory Tract Infections Prior to and During the COVID-19 pandemic at a Skilled Nursing Facility
Authors: Colombo Paulina M , Ramadan Ferris A , Kaur Dilsharan , Ellingson Katherine
Published: November 2023

Background

Considerable reductions in antimicrobial stewardship efforts have been attributed to the COVID-19 pandemic, especially among low-resourced healthcare facilities, such as long-term care settings. Our study objectives were to (1) assess the appropriateness of antibiotic prescriptions for urinary (UTI) and respiratory tract infections (RTI) using standardized infection definitions, known as the McGeer criteria, and (2) to determine whether the prescribing practices differed prior to and during the COVID-19 pandemic.

Methods

We employed a HIPPA-compliant REDCap data collection tool to abstract Electronic Medical Record data from an Arizona-based, Skilled Nursing Facility between March 2019 and January 2022. Clinical and microbiologic infection characteristics were abstracted to determine whether indications for antibiotic prescriptions met the McGeer criteria for UTI and RTI. The frequency and proportion of antibiotic prescriptions for suspected infections that did not meet McGeer criteria were compared for the time period prior to and during the COVID-19 pandemic.

Results

388 total antibiotic events prescribed for UTI and RTI infections between March 2019 – January 2022 were analyzed (Figure 1). 61% (n=14) and 78% (n=154) of UTI prescriptions did not meet McGeer criteria prior to and during the COVID-19 pandemic, respectively. 70% (n=14) of RTI antibiotic prescriptions prior to the pandemic and 60% (n=89) of antibiotic events during the pandemic were not in accordance with McGeer criteria (Table 1) (Figure 2).

Flow diagram to demonstrate Electronic Medical Record abstraction analysis inclusion criteria

Note: a suspected infection was defined as a laboratory order (e.g., urine analysis, chest x-ray), or an antibiotic prescription

Frequency and percent of UTI and RTI antibiotic prescriptions that did not meet McGeer criteria, prior to and during the COVID-19 pandemic

Note: suspected infections from March 01, 2019 - January 25, 2020 are considered “pre-pandemic,” and January 26, 2020 – January 23, 2022 are considered “during pandemic” *The McGeer criteria differentiate infection definitions based on the presence or absence of an indwelling catheter

Antibiotic prescription accordance with McGeer criteria from March 2019 – January 2022

Conclusion

Despite consorted efforts to improve antimicrobial stewardship infrastructure, the majority of antibiotic prescribing for UTIs and RTIs prior to the pandemic did not meet McGeer criteria. This trend also persisted during the pandemic, indicating a need for increased stewardship practices that can operate concurrently with future public health threats.

Disclosures

All Authors: No reported disclosures