bluuebunny/crossref_metadata_2025_split huggingface dataset:
668. Presence of the Narrow-Spectrum OXA-1 Beta-Lactamase Enzyme is not Associated with Elevated Ceftolozane-Tazobactam MIC Values among ESBL-Producing Escherichia coli Clinical Isolates (CANWARD, 2011-2018)
Authors: Walkty Andrew , Karlowsky James , Golden Alyssa , Lagace-Wiens Philippe , Baxter Melanie , Denisuik Andrew , McCracken Melissa , Mulvey Michael , Adam Heather , Zhanel George 
Published: December 2022

Abstract

Background
Beta-lactam-beta-lactamase inhibitor combinations have been proposed as an alternative to carbapenems for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli as an antimicrobial stewardship initiative. However, in a recent randomized trial evaluating patients with bacteremia, presence of the narrow spectrum OXA-1 beta-lactamase enzyme among ESBL-producing Enterobacterales was associated with higher piperacillin-tazobactam MICs, and in turn excess mortality among patients treated with piperacillin-tazobactam relative to meropenem. The purpose of this study was to determine whether the in vitro activity of ceftolozane-tazobactam versus ESBL-producing E. coli is similarly compromised by the presence of OXA-1.

Methods
E. coli clinical isolates were obtained from patients evaluated at hospitals across Canada (January 2011 to December 2018) as part of an ongoing national surveillance study (CANWARD). ESBL production was confirmed using the Clinical and Laboratory Standards Institute phenotypic method. Susceptibility testing was carried out using custom broth microdilution panels, and all isolates underwent whole genome sequencing for beta-lactamase gene detection.

Results
In total, 485 ESBL-producing E. coli identified as part of the CANWARD study were included. The majority of isolates (91.3%; 443/485) harbored a CTX-M ESBL enzyme. OXA-1 was present in 39.6% (192/485) of isolates. OXA-1 was detected in 62.5% (187/299) of isolates with a CTX-M-15 ESBL enzyme versus only 2.7% (5/186) of isolates with other ESBL enzyme types. Ceftolozane-tazobactam MIC50 and MIC90 values were identical (0.25 µg/mL and 1 µg/mL, respectively) for the isolate subsets with and without OXA-1. Overall, 97.4% and 96.9% of isolates with and without OXA-1 remained susceptible (CLSI breakpoint) to ceftolozane-tazobactam.

Conclusion
The presence of OXA-1 among ESBL-producing E. coli clinical isolates was not associated with an elevation in MIC values for ceftolozane-tazobactam. These data support further evaluation of ceftolozane-tazobactam as an alternative to carbapenems for the treatment of infections caused by ESBL-producing E. coli, as is being done with the MERINO-3 trial.

Disclosures
George Zhanel, PhD, Merck: Grant/Research Support.
670. Real-life Experience of Imipenem-cilistatin-relebactam for the Treatment of Extensively Drug-resistant and Difficult-to-treat Pseudomonas Infections
Authors: Vu Christine A , Bec Elizabeth , Deronde Kailynn , Rosa Rossana , Abbo Lilian M 
Published: December 2022

Abstract

Background
Imipenem-cilistatin-relebactam (Recarbrio) is recommended to treat extensively drug-resistant (XDR) and difficult-to-treat (DTR) Pseudomonas aeruginosa (PA). Since approval in 2019, there remains limited literature describing real-world use. We describe our experience and evaluate the efficacy and safety of Imipenem-cilistatin-relebactam for the treatment of XDR and DTR Pseudomonas infections.

Methods
This was a retrospective, observational study at a 1,550 licensed-bed academic hospital. Adults receiving ≥72 hours of Imipenem-cilistatin-relebactam for Pseudomonas infections between January 2020-February 2022 were included. The primary outcome was clinical success. Secondary outcomes included 30-day all-cause mortality, 30-day recurrence, 60-day infection-related hospital readmission, and adverse effects. Descriptive statistics were used to analyze our findings.

Results
Ten patients were included, with 60% being male and a median age of 63 years (range 31-85). The median duration of treatment was 7 days (range 4-14). Sources of infection included ventilator-associated pneumonia (70%), empyema (20%), and bacteremia (20%). Two isolates were XDR, and seven DTR, including an isolate positive for Verona-integron-borne Metallo-β-lactamase (VIM). At the time of index culture, the median APACHE II score was 25.5 and 60% had at least one concomitant infection. For our primary outcome, 7 patients (70%) achieved clinical success. All-cause mortality at 30 days was 30% and 3 out of 8 patients had recurrent infection within 30 days.

Conclusion
Our study demonstrates the real-life use of Imipenem-cilistatin-relebactam for the treatment of XDR and DTR Pseudomonas infections. While the majority of patients achieved clinical success, a high mortality and recurrence rate was still observed. Larger studies are needed to validate our initial findings.

Disclosures
All Authors: No reported disclosures.
680. Utility of Cefoxitin for the Treatment of ESBL-producing E. coli Urinary Tract Infections
Authors: Nathan Ramesh V , Tran Diem 
Published: December 2022

Abstract

Background
Carbapenems are regarded as first-line agents for the treatment of ESBL-producing bacterial infections, even when in vitro activity to other beta lactams is demonstrated. However, overuse is associated with the selection of beta-lactamases that can hydrolyze carbapenems. Patients with isolated urinary tract infections due to ESBL–producing E. coli potentially have a lower burden of infection ("low inoculum"). These patients are frequently less ill and may benefit from non-carbapenem therapy. Cephamycins have in vitro activity against ESBL–producing Enterobacterales, and may be useful in the treatment of ESBL E. coli urinary tract infections as a carbapenem sparing agent.

Methods
Patients 18 years of age and older, hemodynamically stable with negative blood cultures and who demonstrated signs and symptoms of a urinary tract infection with a urine culture showing ESBL E. coli, were eligible to participate. Patients were started on initial antimicrobial therapy at the discretion of the admitting physician, and if the urine culture showed ESBL E. coli with an MIC of less than 8, the antimicrobial stewardship team requested to switch the patient to Cefoxitin 2 g intravenously every 6 hours, via extended infusion. The dose was renally adjusted as appropriate, and patients with beta-lactam allergies were excluded.

Results
46 patients were evaluated between May 2017-April 2022. Patients received antibiotics for 2.6+1 day before the switch to Cefoxitin. The mean duration of therapy with Cefoxitin was 4.5+2.2 days. All 46 patients had resolution of fever and dysuria. Six patients were readmitted within 30 days, but none were due to a urinary tract infection. 30 patients had a repeat urinalysis at 48 hours, and all demonstrated reduction in pyuria. 39 patients had a repeat urine culture following completion of therapy, and 36 had converted to culture-negative status.

Conclusion
Cefoxitin is a useful agent for the treatment of ESBL E. coli urinary tract infections. The optimal dose appears to be 2 g intravenously every 6 hours, via extended infusion, in patients with normal creatinine clearance. Further larger studies, involving patients with pyelonephritis, are needed to validate these findings.

Disclosures
Ramesh V. Nathan, MD, Eli Lilly: Grant/Research Support|PPD: Grant/Research Support.
888. A Predictive Model for Subtherapeutic Vancomycin Troughs in Adults
Authors: Crisp Sarah , Shrestha Nabin K , Pallotta Andrea , Wu Janet , Ahrens Christine , Cerrato Pooja 
Published: December 2022

Abstract

Background
Vancomycin is a first line agent in the treatment of methicillin-resistant Staphylococcus aureus infections. The ability to predict sub-therapeutic troughs would limit potential for development of resistance. The purpose of this study was to develop a predictive model for sub-therapeutic vancomycin troughs in adults.

Methods
This retrospective cohort study included adults 18 years and older ordered a pharmacy to dose vancomycin consult. Exclusion criteria included patients with cystic fibrosis, pregnancy, no steady-state trough, or required dialysis during therapy. Patients with sub-therapeutic vancomycin troughs (&lt; 10 mg/L) were compared to patients with therapeutic troughs (10-20 mg/L). A K-nearest neighbors (KNN) regression model to predict an initial sub-therapeutic vancomycin level based on age, gender, race, BMI, loading dose, frequency, creatinine clearance, and institutional vancomycin dosing guideline adherence was developed and validated using 10-fold cross validation. The association of vancomycin dosing guideline adherence with initial sub-therapeutic vancomycin trough was evaluated in a multivariable logistic regression model adjusted for age and creatinine clearance.

Results
A total of 1,615 subjects were included; 494 (30.5%) subjects experienced a sub-therapeutic trough. A KNN regression model to predict an initial sub-therapeutic vancomycin level had an area under the ROC curve of 0.82, and an accuracy of 0.77 (95% CI 0.75-0.79, baseline accuracy 0.69). After adjusting for age and creatinine clearance, guideline dosing adherence was associated with significantly lower odds of an initial sub-therapeutic vancomycin level compared to guideline dosing non-adherence (OR 0.37, 95% CI 0.20-0.66, p-value 0.001).

Conclusion
A predictive model, based on readily available data points, for an initial sub-therapeutic vancomycin level was reasonably accurate. Adherence to the institutional vancomycin dosing guideline was associated with greater than 60% lower odds of an initial sub-therapeutic vancomycin level.

Disclosures
All Authors: No reported disclosures.
904. Impact of a Pharmacist-driven Antimicrobial Stewardship Program on Prescribing Practices by Intensive Care Physicians in a Latin American Hospital.
Authors: Díaz-Madriz José Pablo , Zavaleta-Monestel Esteban , Chaverri-Fernandez José Miguel , Arguedas-Chacón Sebastián , Arguedas-Herrera Raquel , Leiva-Montero Brayan , Vásquez-Mendoza Ana Fernanda , Muñoz-Gutierrez Gabriel 
Published: December 2022

Abstract

Background
In a recent report from Latin American hospitals, only 59.7% of the prescriptions of patients admitted to the ICU followed treatment guidelines. Implementation of antimicrobial stewardship programs (AMS) have proven to be an effective tool for the rational use of antimicrobials, but their implementation has been a challenge in this region due to resources limitations. One significant barrier is the lack of clinical pharmacists with specialized training in infectious diseases. This study aims to determine the impact of a pharmacy driven AMS on the optimal prophylactic and empirical therapy prescription by intensive care physicians (ICP) in a Latin American hospital.

Methods
A retrospective observational study that compared the optimal selection and the consumption (DOTs/1000 ICP patient days) of antibiotics in patients treated by intensive care physicians before and after the implementation of the AMS at Clínica Biblica Hospital, Costa Rica. The comparison was made from January to December 2014 (preAMS) and from January 2020 to March 2021 (postAMS). Bacterial resistance patterns before and after AMS implementation were also compared.

Results
A total of 333 patients met the inclusion criteria (52% preAMS and 48% postAMS). After a five-year intervention, the optimal antibiotic selection prescribed by ICP was 43.1% (n=75) in the preAMS period and 86.8% (n=138) in the postAMS period (43.7% absolute improvement, p &lt; 0.001). The prescription of most antibiotics showed an improvement (Fig 1), such as ertapenem in 45% (p&lt; 0.001) and levofloxacin in 59% (p&lt; 0.001). Similarly, there was a trend towards improvement of the prescription by diagnosis (Fig 2), including an increase of 32% (p&lt; 0.001) in CAP. There was a reduction of the consumption of most antimicrobials (Fig 3) including a decrease of 66.9% (p =0.017) for vancomycin and 64.7% (p =0.033) for meropenem. Regarding bacterial resistance, there was found a decrease of 11% (p=0.048) of P. aeruginosa resistant to meropenem and a reduction in the detection of ESBL in E. coli (11% decrease; p=0.007).

Conclusion
The AMS implementation showed an overall positive impact on antibiotics selection and consumption. In addition, is thought that the intervention could had a positive effect on antibiotic resistance.

Disclosures
José Pablo Díaz-Madriz, PharmD, MSc, Eli Lilly: Stocks/Bonds|Pfizer: Advisor/Consultant.
907. Impact of Antimicrobial Stewardship Prospective Audit and Feedback on Antibiotic Utilization in Hospitalized COVID-19 Patients
Authors: Shafiq Ashfaq , Hori Taylor , Pham Selena 
Published: December 2022

Abstract

Background
Studies have consistently shown a high proportion of antimicrobial usage in hospitalized COVID-19 patients despite low prevalence of bacterial co-infection. Improving antibiotic utilization is one of the main goals of antimicrobial stewardship program (ASP). This study aimed to determine the impact of prospective audit and feedback intervention (PAF) performed by ASP pharmacists on antibiotic utilization in hospitalized COVID-19 patients.

Methods
A retrospective chart review was conducted at a 90-bed Veteran Affairs hospital. This study included patients who were admitted to the hospital due to laboratory confirmed COVID-19 infection from November 1, 2020 to January 31, 2021. The primary outcome of this study was to evaluate the impact of ASP PAF on avoiding the unnecessary use of antibiotics in hospitalized patients with acute COVID-19. The secondary outcomes included the prevalence of bacterial co-infection in hospitalized COVID-19 patients and the clinical outcomes.

Results
A total of 199 patients were included in this study. Sixty-one patients (30.7%) had antibiotics started empirically upon hospital admission. Fifty (82%) out of 61 patients had antibiotics discontinued due to the lack of indication for antibiotics during their hospital admission, with 47 (94%) was done by ASP team versus 3 of them (6%) was done by Internal Medicine. Fifty-eight of these patients were followed by ASP team, with 28 patients (48.3%) met SIRS criteria upon admission and 25 (43.1%) with elevated procalcitonin level. The overall readmission rate was 5.8%, with readmission rate of the intervention group to be 6.4% and the non-intervention group to be 5.6% (p = 0.29). The overall mortality rate was 13.1% in hospitalized COVID-19 patients, with 19% reported in the intervention group and 10.1% in the non-intervention group (p = 0.09). Overall, only 5 patients (2.5%) had laboratory-confirmed bacterial co-infection upon admission. Sixteen patients (8%) were found to have microbiologically confirmed nosocomial infection.

Conclusion
The findings suggested that ASP PAF safely and effectively avoided the unnecessary use of antibiotics in hospitalized patients with acute COVID-19 infection. In addition, low prevalence of microbiologically confirmed bacterial co-infection was observed.

Disclosures
All Authors: No reported disclosures.
915. Implementation of Face-to-Face Antimicrobial Stewardship Rounding at a Veterans Affairs Hospital
Authors: Malepsy Jon , Atluri Vidya 
Published: December 2022

Abstract

Background
The Veterans Affairs Central California Healthcare System (VACCHCS) antimicrobial stewardship program primarily utilizes prospective audit-feedback. Initially, antimicrobial recommendations were communicated to medicine and surgery teams exclusively through chart notes. Beginning September 2021, a new process was initiated whereby all antibiotic recommendations were communicated to care teams during daily face-to-face rounds. This pre-post cohort study is an assessment of the changes in antimicrobial use, inpatient mortality and 30-day readmissions that occurred with the intervention.

Methods
Both pre- and post- intervention, all admitted patients with active antibiotic orders were reviewed for antibiotic optimization by an ID team and a chart note was written to document recommendations. Post-intervention, recommendations were communicated via daily face-to-face rounds with medicine and surgery services. Total antibiotic use was collected from the National Healthcare Safety Network’s Antimicrobial Use and Resistance (NHSN-AUR) Module as antibiotic days-of-therapy per 1000 patient days (DOT/1000). Monthly in-hospital mortality and 30-day readmission data were collected from the VA’s Corporate Data Warehouse. Median monthly amounts of each measure were compared pre- and post-intervention. Antibiotic use was compared monthly for 2 years prior and 3 months post intervention, whereas mortality and readmission outcomes included 2 years prior and 6 months post-intervention.

Results
Pre and post-intervention median monthly antibiotic use was 728 and 741 DOT/1000, respectively. Median monthly mortality was seven deaths pre-intervention and six post-intervention. Median monthly 30-day readmissions were 48 pre-intervention and 36 post-intervention.

Conclusion
Total antibiotic use slightly increased after the intervention. Further post-intervention observation is needed in order to better characterize impact on antimicrobial use. Monthly in-hospital mortality and 30-day readmission data were decreasing prior to our intervention and continued to decrease post-intervention.

Disclosures
All Authors: No reported disclosures.
918. Influence of a hospital-based antimicrobial stewardship program on clinical and economic outcomes. The experience from a referral center in Mexico.
Authors: Molina-Jaimes Aaron , del Carmen Gonzalez-Sanchez M , Molina Mariana 
Published: December 2022

Abstract

Background
Antibiotic stewardship programs (ASP) are relatively new in Mexico. It was until May 2018 that it was established as a public health policy in the country. Few hospitals have acknowledged the mandate and started an ASP despite the efforts. Besides, little has been done to evaluate the efficacy of the program in terms of antibiotic expenditure and the incidence of associated infections. Therefore, the main objective was to evaluate antibiotic expenditure before and after the ASP in a third-level hospital in Mexico. As a secondary analysis, the relationship with Clostridioides difficile infections was explored.

Methods
This is a retrospective and descriptive study from January 2017 to February 2020 (pre-COVID-19 pandemic). First, the mean antibiotic expenditure (adjusting for DDD/patient days-costs in USD) was evaluated before and after (June 2018 as the first month of implementation) the ASP. Statistical difference of the means was evaluated. It was also performed an exploratory analysis between the prescription of Clindamycin and Levofloxacin with the number of cases and deaths related to C. difficile infection.

Results
The average antibiotic expenditure before ASP was US$13,468 ± 3,267, and US$8,193 ± 2,574 (p&lt; 0.001) after. Graph 1 presents the changes in trend. Specifically, caspofungin, ciprofloxacin, clindamycin, fluconazole, levofloxacin, linezolid, piperacillin/tazobactam, and tigecycline showed statistically significant reduction after June 2018. Graph 2 displays the descriptive relationship between the prescription of levofloxacin and clindamycin, the cases of C. difficile infection, and the elimination of all associated mortality.
Graph 1.
Antibiotic expenditure. Before and after AMS
Graph 2.
Relationship between monthly consumption of clindamycin and levofloxacin and the number of cases/deaths secondary to Clostridioides difficile infections, before and after ASP.

Conclusion
The ASP has significantly reduced the antibiotic expenditure in the hospital. Besides reducing the prescription of associated antibiotics, a possible reduction in C. difficile infections and associated deaths were observed.

Disclosures
All Authors: No reported disclosures.
926. Shorter. Safer. Better. Pledge Campaign to Increase Uptake of Shortest Effective Durations of Antimicrobial Therapy
Authors: Doughman Danielle , Marx Ashley H , Mavrogiorgos Nikolaos 
Published: December 2022

Abstract

Background
Patients often receive longer-than-needed antimicrobial treatment for common infections, when a shorter duration would be equally effective. To promote use of evidence-based durations, the University of North Carolina Medical Center’s (MC) Carolina Antimicrobial Stewardship Program (CASP) developed best practices (BPs) in 2020 to inform prescribing. CASP conducted a signature pledge campaign to encourage nurses, pharmacists, prescribers, and allies to know, use, and share BPs.

Methods
CASP developed a pledge form on a password-protected MC intranet site. Participants selected way(s) to “action” their pledge from a pre-filled list. CASP delivered coordinated messages to nurses, pharmacists, prescribers, and allied groups using multiple platforms: tiered safety huddles, leadership meetings, MC news, email, social media, and the CASP website over a 35-day campaign period that culminated with Antibiotics Awareness Week.
Measures of campaign effectiveness included number of pledgers, intranet views of BPs, reported awareness and use of BPs by pledgers at the time of pledge and in a 90-days post-campaign electronic survey, and pledge actions fulfilled.
Survey responses were cross-tabulated and analyzed using descriptive statistics.

Results
238 MC staff signed the pledge; nurses comprised 21%, pharmacists 24%, prescribers 48%, and allies 7%. At time of pledge, 39% reported prior awareness of BPs (Figure 1); 39% reported prior use of BPs. 99% selected at least one action at time of pledge. 116 (49%) responded to the 90-day post campaign survey. 84% reported taking at least one action. The most common action reported among nurses was patient education (36%); among pharmacists, identifying too-long durations for query (78%); among prescribers, BP use and patient education were tied at 60%. The BPs page was viewed 323 times during campaign, compared to 153 total pre-campaign views. Prescribers’ BP use increased 66% from time of pledge.
90 days post-pledge, all groups except allies reported increased use of BPs since pledging (Figure 2).
Awareness of CASP Best Practices for Durations of Therapy resource among pledgers at time of signature.
Reported use of CASP Best Practices for Duration of Therapy resource at the time of pledge and at time of survey, 90-days post campaign.

Conclusion
A pledge campaign to increase awareness and uptake of shortest effective durations was effective except among allies. Further analysis is needed to determine if durations for common infections are similar to the BP ranges post-campaign.

Disclosures
All Authors: No reported disclosures.