bluuebunny/crossref_metadata_2025 huggingface dataset:
582. Pediatric vaccine completion and compliance in the Military Health System, 2006–2016
Authors: Romano Celeste , Bukowinski Anna , Hall Clinton , Burrell Monica , Gumbs Gia , Conlin Ava Marie , Ramchandar Nanda
Published: December 2022

Background

Few studies have reported on pediatric vaccination trends among military beneficiaries, though some evidence suggests military dependents have lower vaccination rates than their civilian counterparts. No prior work has examined timeliness of vaccinations in this population. Here, we assessed completion of and compliance with rotavirus; inactivated polio virus (IPV); and diphtheria, tetanus, and acellular-pertussis (DTaP) vaccination among military beneficiaries.

Methods

Department of Defense Birth and Infant Health Research program data were used to identify infants born at military treatment facilities (MTFs), 2006–2016. Infants were required to be enrolled in TRICARE within the first year of life, continuously enrolled through 2 years of age thereafter, and have at least 1 immunization at an MTF and 1 well-child visit annually by age 2. Immunization status was assessed using vaccine administered and Current Procedural Terminology codes from MTF immunization records and outpatient health care records, respectively. Completion of rotavirus (2 doses), IPV (3 doses), and DTaP (4 doses) vaccination was assessed by 2 years of age. Vaccine compliance was assessed by additionally applying the Advisory Committee on Immunization Practices childhood immunization schedule.

Results

A total of 317,348 infants were identified for vaccination assessment. Completion and compliance for all vaccines increased between 2006 and 2016, though there were wide disparities between the two measures, particularly for the DTaP series. While 89.8% of infants born between 2009 and 2016 (n=228,641) received 2 doses of rotavirus, 3 doses of IPV, and 3 doses of DTaP by 2 years of age, only 80.5% received a fourth dose of DTaP. More than 40.0% of infants were undervaccinated for at least 1 day before age 2, 2014–2016.

Percent of infants born to military beneficiaries who complete and are compliant with vaccine recommendations, by vaccine series and overall, Department of Defense Birth and Infant Health Research program data, 2006–2016 (n=317,348).

Conclusion

Rotavirus, IPV, and DTaP vaccine coverage appeared higher in this population of military children than what has been reported nationally, but gaps remain. Providers serving military beneficiaries should ensure infants return for a care visit during the 15- to 18-month age window in order to remain compliant with the DTaP series and limit periods of undervaccination.

Disclosures

All Authors: No reported disclosures.
616. Pharmacodynamics (PD) of the lipopeptide QPX9003 Against Acinetobacter baumannii and Pseudomonas aeruginosa in the Neutropenic Mouse Thigh Infection Model
Authors: Tarazi Ziad , Roos Niki , Page Ted , Li Jian , Wang Jiping , Roberts Kade , Griffith David
Published: December 2022

Background

Acinetobacter baumannii and Pseudomonas aeruginosa are important pathogens in hospital-acquired infections and can be resistant to multiple classes of antibiotics. QPX9003 is a novel synthetic lipopeptide that is highly active in vitro against MDR Acinetobacter sp. and P. aeruginosa. The purpose of these studies was to determine the pharmacodynamic parameter that best described the bacterial killing of QPX9003 in vivo.

PK-PD of QPX9003 against A. baumannii

PK-PD of QPX9003 against P. aeruginosa

Methods

Seven A. baumannii and six P. aeruginosa isolates were used in these studies. Swiss-Webster mice were rendered neutropenic by 150 mg/kg IP injections of cyclophosphamide 4 and 1 days prior to infection. The bacterial inoculum was prepared from an overnight culture adjusted to 108 CFU/mL then further diluted for inoculation into the thighs. Various dose and dose regimens of QPX9003 were administered by the IP route starting 2 hours post infection and continuing for 24 hours. Untreated control groups were sacrificed at the start of treatment. Treated and untreated control groups were sacrificed 24 hours after the start of treatment, thighs harvested, homogenized and plated to determine colony counts. PK was conducted in neutropenic, infected mice at doses ranging from 3 to 50 mg/kg administered by the IP route. The relationship between PK-PD parameters and the reduction in the log number of CFU per thigh between time zero and 24 h after the start of treatment were analyzed by using the sigmoid maximum reduction (Emax) PD model.

Results

The activity of QPX9003 was best described by the 24h free AUC/MIC ratio, with stasis and 1 log kill targets of 47.1 and 67.1 for A. baumannii and 96.1 and 117 for P. aeruginosa, respectively.

Conclusion

The PD of QPX9003 was best described by the 24h free AUC/MIC ratio. Based on the QPX9003 MIC90 for P. aeruginosa (0.25 mg/L) and A. baumannii (1 mg/L), 24h free AUCs between 30 and 67 mg*h/L will produce 1-log of bacterial killing for ∼90% of P. aeruginosa and A. baumannii strains, respectively. QPX9003 is a potentially useful treatment for infections due to P. aeruginosa and A. baumannii, including MDR isolates, that is advancing in clinical studies.

Disclosures

Ziad Tarazi, Qpex Biopharma: Employee Niki Roos, n/a, Qpex Biopharma: Employee Ted Page, n/a, Qpex Biopharma: Employee David Griffith, n/a, Qpex Biopharma: Employee.
644. Activity of Meropenem-Vaborbactam and Comparators Against Isolates from Patients in Hematology/Oncology and Transplant Units in the United States
Authors: Shortridge Dee , Deshpande Lalitagauri M , Carvalhaes Cecilia G , Castanheira Mariana
Published: December 2022

Background

Patients undergoing treatment for cancer or an organ transplant are often immunosuppressed and particularly susceptible to infections caused by Gram-negative pathogens, including resistant isolates. Meropenem-vaborbactam is a combination of a carbapenem and a beta-lactamase inhibitor that is effective against serine-beta-lactamases, including KPC carbapenemase. We evaluated the activity of meropenem-vaborbactam (MEV) and comparators against Enterobacterales isolates collected in the US during 2014-2021 from patients in hematology, oncology, or transplant units (H/T).

Activity of meropenem-vaborbactam and comparator antimicrobial agents tested against Enterobacterales isolates and CRE collected from medical centers in the US

Methods

A total of 2,185 clinical isolates were consecutively collected from patients in H/T units in 33 hospitals in all 9 US Census Divisions. Isolates were tested using CLSI broth microdilution methodology. Results were interpreted using CLSI breakpoints. Carbapenem-resistant Enterobacterales (CRE) were characterized as having MIC values ≥ 4 mg/L to imipenem and/or meropenem (MER). A subset of CREs were genotypically characterized for carbapenemase genes by PCR or whole genome sequencing.

Results

The most common species isolated were Escherichia coli (n=863), Klebsiella pneumoniae (n=518), and Enterobacter cloacae complex (n=284). The most common infection type was bloodstream infection (n=1,057), followed by urinary tract infection (n=347). Susceptibility was 99.6% to MEV, 98.5% to MER, and 83.4% to piperacillin-tazobactam (Table). 28 isolates (1.3%) were CRE; the susceptibility of these isolates to MEV was 71.4% while their susceptibilities to levofloxacin and piperacillin-tazobactam were 25.0% and 0.0%, respectively (Table). Of the 28 CRE, 19 were genotypically characterized. 13 isolates produced KPC, 3 produced OXA-48/232, and 1 had NDM-5. All KPC-producing isolates were MEV susceptible, and the 3 OXA-48/232 and 1 NDM were resistant.

Conclusion

MEV was very active against isolates causing infections in H/T patients, including isolates that were KPC-producing CREs. These in vitro data suggest that MEV would be an effective treatment option for H/T patients with Gram-negative infections.

Disclosures

Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Pfizer: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.
647. Cefepime Versus Carbapenems for the Treatment of ESBL-producing Enterobacterales among Non-blood Isolates
Authors: Garcia Brandon , King Madeline , Kludjian Geena , Hanretty Alexandra
Published: December 2022

Background

The incidence of organisms with extended-spectrum beta-lactamases (ESBLs) is increasing. The data for using cefepime in ESBL-producing Enterobacterales infections is conflicting. More favorable outcomes are likely if minimum inhibitory concentrations (MICs) < 2 mcg/mL. The aim of this study is to compare the efficacy of cefepime versus carbapenems for ESBL-producing, non-bloodstream Enterobacterales infections.

Methods

This study was a single-center retrospective cohort study of patients who received cefepime or a carbapenem for at least 72 hours for the definitive treatment of an ESBL-producing Enterobacterales non-bloodstream infection between Jan. 1, 2011 and Sept. 30, 2021. ESBL production was identified if the isolate either had a positive confirmatory ESBL test from VITEK 2 (bioMérieux) or phenotypic resistance to ceftriaxone. Isolates had to have a MIC < 2 mcg/mL to cefepime or be susceptible to carbapenems. Isolates with a cefepime MIC 4-8 mcg/mL were not included due to likely higher rates of treatment failure. The primary endpoint was clinical failure, defined as persistence of symptoms requiring escalation of therapy or death. Descriptive statistics were used to compare groups. A univariate analysis and odds ratio was calculated for clinical outcomes.

Results

One hundred patients were included. Twenty-two patients received cefepime and 78 received a carbapenem. Table 1 describes patient characteristics and clinical outcomes. Most patients had a urinary tract infection (UTI) (94%). More patients receiving cefepime were admitted to the intensive care unit (40.9% versus 15.4%). Treatment with cefepime displayed higher rates of clinical failure when compared to treatment with carbapenems (13.6% versus 6.4%). Cohen’s d-test for clinical failure was 0.46, indicating a medium effect.

Conclusion

Based on our analysis, cefepime may have higher rates of clinical failure when compared to carbapenem treatment for ESBL-producing Enterobacterales. Most of our patients were treated for UTIs and the sample size for both arms were limited, particularly for the cefepime arm. Further research is needed to confirm the role of cefepime as a carbapenem-sparing option in the treatment of these drug-resistant infections.

Disclosures

Madeline King, PharmD, Shionogi: Honoraria|Tetraphase: speakers' bureau.
662. In vitro antibacterial activity of contezolid compared to linezolid and vancomycin in clinical isolates from China
Authors: Wang Shanmei , Li Hao , Cheng Jianjian
Published: December 2022

Background

Linezolid and vancomycin are insufficient in the treatment of drug-resistant Gram-positive bacteria due to adverse drug reactions and drug resistance, and new antibiotics are needed, especially for patients with myelosuppression and vancomycin-resistant Enteroccocus (VRE) infection. Contezolid (CZD) is a novel oral oxazolidinone with potent activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and VRE. We evaluate the in vitro antibacterial activity of contezolid compared to linezolid and vancomycin in Gram-positive clinical isolates.

Methods

176 clinical isolates were obtained from 176 sterile body fluids from patients at 3 tertiary care hospitals in China, and the minimal inhibitory concentrations (MICs) of contezolid, linezolid and vancomycin determined by broth microdilution assay.

Results

Contezolid exhibits excellent antibacterial activity against prevalent Gram-positive bacteria, Staphylococcus spp. and Enterococcus spp., including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant and coagulase-negative Staphylococcus (MRCNS), and vancomycin-resistant Enterococcus (VRE). MIC90 values of contezolid were 2 mg/L for all MRSA and VRE isolates and 1 mg/L for MRCNS isolates. The antibacterial activity of contezolid against Staphylococcus spp., including S. aureus, was essentially similar to linezolid, and slightly higher than or similar to vancomycin. Antibacterial activity of contezolid against Enterococcus, including VRE, was similar to linezolid, while being slightly lower than for vancomycin in vancomycin-susceptible isolates. Consistent with the shared antibacterial mode of action, bacterial strains resistant to linezolid were cross-resistant to contezolid. Table 1.Antimicrobial susceptibility testing results of clinical bacterial strains (MICs, mg/L)

Conclusion

Contezolid, a novel oxazolidinone drug, exhibits potent in vitro antibacterial activity against clinical isolates of common Gram-positive pathogens, including multidrug-resistant (MDR) Gram-positive bacteria, MRSA, MRCNS, and VRE. Contezolid has antibacterial activity similar to standard-of-care antibiotics linezolid and vancomycin. Results suggest that contezolid can play an important role in treatment of MDR Gram-positive bacterial infections. Figure 1.Distribution of MICs of CZD or LZD against 48 strains of MRSAFigure 2.Distribution of MICs of CZD or LZD against 29 strains of MRCNSFigure 3.Distribution of MICs of CZD or LZD against 17 strains of VRE

Disclosures

All Authors: No reported disclosures.
671. Relevance of Levofloxacin-Resistant MRSA and hVISA when utilizing directed antibiotic locks to treat stage 4 biofilm bone and joint infections
Authors: Vicent Martie , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , Daffinee Kathryn E , LaPlante Kerry L
Published: December 2022

Background

Directed antibiotic locks have the potential to treat orthopedic infections due to the ability to bypass specific systemic absorption allowing for higher antimicrobial concentrations. With limiting antimicrobial options to treat biofilm commonly associated with bone and joint infections, our aim is to understand and further test the relevance of utilizing standard systemic MIC values to direct therapy.

Methods

Using our previously described biofilm assay with six unique spa-type (t004, t018, t062, t064, t1340, t008) MRSA isolates, biofilm was grown for 4, 6, and 24hrs at 6 log10 CFU/mL in TSB per CLSI guidance adding dextrose 1.25% for biofilm promotion. MIC were run using CLSI guidance. Planktonic cells were removed by irrigation, simulating debridement. 24hr treatment assays, simulating antibiotic locks included levofloxacin (5 mg/mL) in d5W solution and vancomycin (5 mg/mL) in NS.

Results

Levofloxacin by definition of standard MIC values was found to be resistant in five out of the six MRSA isolates (MIC ranging from 1 – 312mcg.mL). However, at 16-25,000 times the MIC, levofloxacin demonstrated a decrease in biofilm growth on mature 24-hr established biofilm by 9-130%. Similarly, vancomycin heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), at 3000-6000 the MIC demonstrated a decrease of 53-190% mature biofilm growth.

Conclusion

All isolates produced consistent biofilm as previously tested as a low or high biofilm-producer when there was no antibiotic present. Levofloxacin and vancomycin at least 1000X the MIC nearly eradicated all established MRSA biofilm. Our next steps will be to evaluate if the MIC values have any effect on additional antibiotics in a lock solution.

Disclosures

Kerry L. LaPlante, Pharm.D., FCCP, FIDSA, FIDP, AbbVie Inc.: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Melinta Therapeutics, Inc.,: Grant/Research Support|Merck & Co., Inc.: Advisor/Consultant|Merck & Co., Inc.: Grant/Research Support|Nabriva Therapeutics US, Inc.,: Grant/Research Support|Ocean Spray Cranberries, Inc.: Grant/Research Support|Pfizer Pharmaceuticals: Grant/Research Support|Shionogi, Inc.: Grant/Research Support|Tetraphase Pharmaceuticals.: Grant/Research Support.
675. Sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: A detailed safety review from the pivotal phase 3, global, randomized, active-controlled trial (ATTACK)
Authors: Lewis Drew , Rana Khurram , Poirier Gabrielle , Altarac David
Published: December 2022

Background

SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. The primary efficacy endpoint, 28-day all-cause mortality, was achieved. The safety profile of SUL-DUR versus colistin is presented here.

Methods

ATTACK consisted of two parts. Part A was the randomized, non-inferiority portion in ABC hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; patients were randomized 1:1 to SUL-DUR or colistin for 7 to 14 days. Part B provided open label SUL-DUR for patients intolerant of colistin or with colistin-resistant ABC. Safety data presented here include both Part A and Part B. All patients received imipenem/cilastatin as background therapy. The primary safety objective was nephrotoxicity (RIFLE classification); other safety endpoints included treatment-emergent adverse events (TEAEs) and assessments of laboratory parameters.

Results

The safety population includes 203 unique patients. TEAEs were common reflecting the critical level of illness. More frequently reported with colistin treatment are severe, serious, and drug-related TEAEs (infections, renal and urinary disorders, and gastrointestinal) (Table 1). Nervous system, infections and renal disorders leading to discontinuation of study drug were more common in the colistin arm (Table 2). During treatment, liver-associated enzymes were similar between arms. Creatinine clearance measures of central tendency showed reduction during the trial in the colistin arm. Nephrotoxicity (RIFLE classification) occurred significantly less often with SUL-DUR: 13.2% (12/91) and 37.6% (32/85), difference -24.4% [p=0.0002].

Conclusion

SUL-DUR treated patients had reduced nephrotoxicity, fewer drug-related TEAEs, no safety signals, and fewer TEAEs leading to discontinuation of study drug. If approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains.

Disclosures

Drew Lewis, MD, MTM&H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.
889. Another Respiratory Culture Nudge Improves Pneumonia Prescribing
Authors: Langley Christen , Kenney Rachel M , Kendall Ronald , Tibbetts Robert , Veve Michael
Published: December 2022

Background

Nudging with purposeful, directed comments to microbiology results appears to improve antibiotic prescribing. The study objective was to assess prescribing before and after a β-lactamase interpretative comment for Haemophilus influenzae and Moraxella catarrhalis lower respiratory tract infections (LRTI).

Methods

IRB approved, quasi-experiment. Included: hospitalized adults prescribed antibiotics for H. influenzae or M. catarrhalis LRTI from 8/20/17-3/19/19 (pre-group) and 3/20/19-8/20/21 (post-group). Excluded: non-LRTI, polymicrobial infections, antibiotic prophylaxis, IgE-mediated β-lactam allergy. Intervention- automated comment for β-lactamase negative: “this organism is predictably susceptible to ampicillin or amoxicillin”; β-lactamase positive: “this organism is predictably susceptible to ampicillin-sulbactam or amoxicillin-clavulanate”. Primary endpoint: optimal de-escalation, defined as ampicillin, amoxicillin or aminopenicillins for β-lactamase negative; amoxicillin/clavulanate or ampicillin/sulbactam for β-lactamase positive. Secondary endpoints: clinical success, antibiotic duration, time to de-escalation. Sample size: 200 calculated for 30% difference in de-escalation, α=0.05, β=0.2.

Results

Enrolled 100 pre- and 101 post. 61% vs. 64% male; 63% vs. 73% community-acquired pneumonia; 20% vs. 15% hospital acquired pneumonia; 17% vs. 12% ventilator associated pneumonia; 81% vs. 77% H. influenzae; 46% vs. 52% β-lactamase positive; 4% vs. 7% non-IgE β-lactam allergy, respectively. Optimal de-escalation: 19 (19%) pre-, 51 (51%) post- (p< 0.001). After adjustment, post-group associated with 5-fold increased odds of optimal de-escalation (Table 1). Secondary endpoints pre and post: median (IQR) duration 7 (6, 8) and 7 days (6, 10); median time to de-escalation: 1 (0, 2) and 0 (0, 1) days; clinical success: 79 (79%) and 81 (80%).

Conclusion

An automated, β-lactamase nudge was associated with a reduction in definitive broad-spectrum antibiotics. Stewardship programs should continue to evaluate persuasive comments as an effective and efficient intervention.

Disclosures

All Authors: No reported disclosures.
901. Evaluation of Azithromycin Usage Following a Pharmacist Discontinuation Protocol
Authors: Percival Kelly M , Kinn Patrick M , Weiner Lukasz , Ince Dilek
Published: December 2022

Background

Azithromycin usage along with a beta-lactam is common in hospitalized patients with community-acquired pneumonia (CAP). The total recommended dosage is 1500mg as either 500mg on day one followed by 250mg daily for 4 days or 500mg daily for 3 days. It was observed that total doses of >1500mg were frequently administered at our institution. Institutional empiric treatment guidelines for CAP were updated and educational sessions were given for medicine providers in November 2019 to emphasize a total dose of 1500mg. This was further followed in April 2020 by the creation of a pharmacist collaborative practice agreement (CPA) to allow any unit-based clinical pharmacist to discontinue azithromycin for CAP after administration of a sum total of 1500mg.

Methods

A retrospective quasi experimental study was performed to evaluate the impact of implementing a pharmacist CPA for discontinuation of azithromycin for CAP. The primary objective was to compare the proportion of patients receiving greater than 1500mg of azithromycin during the pre-implementation period of April 2018-March 2020 to the post-implementation period of April 2020-March 2022. Pre- and post-implementation period rates were compared using a Chi-square test. Secondarily, utilization of CPA as the discontinuation method was evaluated.

Results

A total of 8,373 patients were included (5123 pre and 3250 post) in the analysis. The proportion of patients receiving >1500mg of azithromycin decreased from 29.32% pre-implementation to 20.22% post-implementation (P< 0.001). There was a decrease seen immediately after implementation that has been maintained over time, as shown in figure 1. The CPA was utilized for discontinuation in a minority of patients during the post-implementation period and the majority discontinued by pharmacists were per verbal order.

Percentage of Patients Receiving >1500mg Azithromycin

Conclusion

Implementation of a pharmacist driven CPA for discontinuation of azithromycin for CAP reduced excessive azithromycin usage with minimal time burden for the AMS team. To further meet the goal of decreasing excessive azithromycin usage additional interventions are needed, and low utilization of the CPA should be further evaluated.

Disclosures

Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant Patrick M. Kinn, PharmD, MPH, Gilead Sciences: Advisor/Consultant Dilek Ince, MD, Evergreen: Member of data monitoring board|Gilead Sciences: Grant/Research Support|Leidos: Grant/Research Support|Moderna: Grant/Research Support.
902. Evaluation of Post-Discharge Sterile-Site Positive Microbiology Results and the Impacts on Patient Care
Authors: LaPlante Reid L , Claeys Kimberly C , BORK J A C Q U E L I N E T , Banoub Mary , Noval Mandee
Published: December 2022

Background

Half of patients have cultures pending at discharge. Failure to address these results may delay diagnosis and time to appropriate antimicrobials. The purpose of the study is to evaluate appropriateness of antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge.

Methods

Retrospective cohort study of patients from 7/2019-12/2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥48 hours and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial intervention based on finalized culture results. Secondary objectives included incidence and timeliness of result documentation and rates of 30-day hospital readmission, among intervention warranted vs not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day hospital re-admission stratified by infectious disease (ID) team involvement.

Results

208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Antimicrobial intervention was warranted in 36.5% of patients (n=76). Rates of result documentation were overall low (35.5%). Time to documentation of results was significantly shorter in patients warranting intervention compared to those who did not, but hospital readmission was higher (Table 1). Finally, result documentation in patients not being followed by ID was associated with decreased odds of 30-day readmission (OR 0.19, 95% CI, 0.07-0.53) (Table 2).

Conclusion

A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of final culture data can decrease the risk of 30-day hospital readmission, especially in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and follow-up of pending cultures to improve patient outcomes.

Disclosures

Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria|La Jolla Pharmaceuticals: Advisor/Consultant.
910. Impact of Indication-based Antibiotic Order Sentences on Optimal Prescribing in the Emergency Department: A Quasi-experiment
Authors: Vuong Lisa , Kenney Rachel M , Thomson Julie , Faison Darius J , Veve Michael P
Published: December 2022

Background

A prior study demonstrated suboptimal antibiotic prescribing in the emergency department (ED) at 77.4% for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). This study measured the effect of indication-based antibiotic order sentences (AOS) on prescribing.

Methods

IRB-approved quasi-experiment of adults prescribed antibiotics in ED for uncomplicated LRTI, UTI, or ABSSSI from January - June 2019 (pre-group) or September - December 2021 (post-group). Exclusion: hospital admission, immunocompromised, active cancer, or prophylactic antibiotics. AOS are lean process, electronic discharge prescriptions retrievable by name or indication; AOS implementation occurred July 2021. Optimal prescribing was defined as the correct antibiotic selection, dose, and duration per local and national guidelines. Seven-day endpoints: antibiotic escalation, ED or hospital readmission, any outpatient contact, and reported adverse drug event (ADE). Descriptive and bivariate statistics performed. Variables considered for multivariable logistic regression had p< 0.2 or plausible association with optimal prescribing.

Results

294 patients included: 147-pre and 147-post. Patient characteristics are in Table 1. Overall optimal prescribing improved from 12 (8.2%) to 34 (23.1%) (p< 0.001). Breakdown of optimal prescribing in pre- and post-groups: selection 90 (61.2%) vs 117 (79.6%) (p< 0.001), dose 99 (67.3%) vs 115 (78.2%) (p=0.036), duration 38 (25.9%) vs 50 (34%) (p=0.126). After adjustment, AOS were independently associated with optimal prescribing (Table 2). Secondary endpoints: antibiotic escalation 10 (6.8%) vs 7 (4.8%) (p=0.662), hospital or ED readmission 12 (8.2%) vs 10 (6.8%) (p=0.658), outpatient contact 31 (21.1%) vs 28 (19%) (p=0.662), and ADE 2 (1.4%) vs 4 (2.7%) (p=0.684). Post-hoc analysis showed suboptimal uptake of AOS by ED prescribers. Table 1:Baseline and Clinical CharacteristicsTable 2:Bivariable and Multivariable Regression Analysis of Factors Associated with Optimal Prescribing†Covaries with intervention group; Hosmer and Lemeshow p = 0.68; Method: backwards logistic regression; No variables removed

Conclusion

AOS is an efficient and promising antimicrobial stewardship strategy; provider re-education is needed to increase AOS uptake.

Disclosures

All Authors: No reported disclosures.
913. Impact of BioFire® FilmArray® Blood Culture Identification Panels on Time to Optimal Antimicrobial Therapy
Authors: Vyas Shivam , Giordano Pamela , Patel Dimple , Bandali Aiman
Published: December 2022

Background

Bloodstream infections are associated with significant morbidity, mortality, and costs. Timely initiation of effective treatment is required for optimal outcomes. Conventional microbiological techniques require 72 hours for organism identification; however, rapid blood culture identification (BCID) polymerase chain reaction (PCR) panels have expedited this process. At Atlantic Health System, the BioFire® FilmArray® BCID panel was implemented June 2020 (BCID1), with subsequent upgrade to BCID2 March 2021. Notable features of the BCID2 panel include speciation of Enterococcus spp. and the addition of the CTX-M target. The purpose of this study is to assess time to optimal therapy (TTOT) with and without the BCID platforms for select organisms. Table 1:Select Primary and Secondary Endpoints

Methods

This retrospective study of hospitalized, adult patients was conducted at two community teaching hospitals from 5/2019 to 12/2021. Patients with a blood culture positive for Enterococcus faecalis, E. faecium, Proteus spp., Escherichia coli, or non-aerogenes Klebsiella spp. were included. Patients with polymicrobial or presumed polymicrobial source of bacteremia, recent positive blood cultures, PCR not performed in BCID arms, or who were deceased/comfort care at time of Gram stain were excluded. The primary endpoint was TTOT. Secondary endpoints included time to effective therapy, duration of vancomycin, therapy modification 24 hours after Gram stain result, and length of stay. All analyses compared PreBCID to either BCID1 or BCID2 arm.

Results

Three hundred patients (100 per arm) were included. Patient characteristics were similar across study arms. The median Pitt Bacteremia Score was 1, the most common organism identified was E. coli (65%), the most common source of bacteremia was genitourinary (65%), and 11% of isolates produced ESBL. TTOT (days) was similar in PreBCID compared to BCID1 and BCID2 [(2.48 vs. 2.65, p=0.10); (2.48 vs. 2.37 days, p=0.27)]. TTOT was significantly longer in the gram-negative subgroup of the BCID1 arm compared to PreBCID (2.62 vs 1.85 days, p=0.03). See Table 1 for full analyses.

Conclusion

Implementation of the BCID panels did not reduce TTOT in select organisms at our institution. Barriers to benefit may include limited education and lack of formal antimicrobial stewardship team involvement.

Disclosures

All Authors: No reported disclosures.
917. Infectious Diseases Consult Improves Management of Candidemia
Authors: Stornelli Nick , Everson Nathan , Everson Nathan , Everson Nathan , McDaniel Lauren , White Melissa
Published: December 2022

Background

Infectious Diseases consultations (IDC) have been associated with improved outcomes in multiple disease states with high morbidity/mortality like invasive candidiasis. This study evaluated management of candidemia at Carilion Clinic in patient with and without IDC.

Methods

A retrospective, observational cohort study was performed among hospitalized patients with candidemia who either received or did not receive an IDC between January 2014 and August 2020. Patients included had Candida species from at least one blood culture. Exclusions were death or transfer to a palliative care plan within 48 hours of culture, cultures from an outside facility, and patients that were pregnant or incarcerated. The primary outcome was a composite of all-cause mortality and recurrent candidemia within 90 days. Secondary outcomes included compliance with candidemia management bundle items such as echocardiography, ophthalmologic evaluation, receipt of susceptible antifungal, source control and repeated blood cultures.

Results

A total of 194 patients were included in the study. The population was 50.3% male sex and mean ± standard deviation age was 57.8 ± 17.2 years. In the study timeframe, 131 patients received an IDC while 62 did not receive an IDC. ICU level of care, vasopressor requirement and Candida Score ≥ 3 were all similar between the two groups. Candida albicans was the most common species in IDC and non-IDC groups (48.1% vs. 41.1%). Empiric therapy was more commonly an echinocandin in 138/194 (71.1%) and definitive therapy was fluconazole in 117/194 (60.3%). An improved primary composite outcome was observed in the IDC group (34.9% vs. 21.4%, p = 0.043). Patients receiving IDC had a higher rate of repeated cultures (100% vs. 92%) and ophthalmologic examination (54.2% vs. 20.6%). More patients in the IDC group were found to have infective endocarditis (10.7% vs. 1.6%, p = 0.04) as they were more likely to have echocardiographic imaging (86.2% vs. 57.1%, p< 0.0001). The median time to susceptible antifungal was 43 (27-61) hours without ICD and 35 (27-52) hours compared in those with IDC.

Conclusion

A more comprehensive workup by IDC was associated with more identification of endocarditis and less recurrence of candidemia within 90 days.

Disclosures

Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Lauren McDaniel, PharmD, BCIDP, Merck: Grant/Research Support.
921. Leveraging the Electronic Health Record for Antimicrobial Stewardship: Assessing the Impact of Antimicrobial Ordering Clinical Decision Support Tools on Duration of Therapy
Authors: Gerhardt Jenna , Cheatham Megan , Davis Christie M , Dine Serena , Erdman Sharon , Geik Katherine , Gerke Steven , Kressel Amy B , McIntire Allyson
Published: December 2022

Background

In an ideal state, the stewardship of antimicrobial agents would happen at the point of order entry. In June 2018, Eskenazi Health implemented a series of clinical decision support tools in the electronic health record (EHR), including required fields on all inpatient antimicrobial orders for indication, type of therapy (empiric or definitive), and duration. When empiric therapy is selected, providers receive a Best Practice Advisory (BPA) at 48 hours to re-evaluate therapy. Additionally, a side bar table was added to all antimicrobials orders that included drug-specific duration of therapy recommendations for common indications.

Methods

This is a single-center, retrospective, observational chart review that includes adult inpatients prescribed antibiotics for the treatment of CAP or UTI from July 2017 to December 2018. The primary outcome is the overall length of therapy between pre- and post-intervention groups for CAP and UTI. Secondary outcomes include duration of empiric/broad-spectrum therapy, duration of definitive therapy, time to de-escalation, length of hospital stay, C. difficile infections, 30-day readmission, and cost of antimicrobial therapy.

Results

A total of 541 orders were included for analysis. The composite overall duration of therapy decreased from 7 days to 5 days in the post-intervention group (p< 0.001). For CAP, the duration of therapy (5 days) was not different between groups. For UTI, the duration of therapy decreased from 11 days to 7 days in the post-intervention group (p< 0.001). The duration of empiric therapy decreased from 3 days to 2 days (p< 0.001) and the duration of definitive therapy decreased from 4 days to 3 days (p< 0.001). There was a 1 day longer length of stay for patients in the post-intervention group (p=0.038); however, there was a lower 30-day readmission rate in the post-intervention group (p=0.003). The rate of hospital-acquired C. difficile infections did not differ between groups (p=1.000). It was found that action was taken from the BPA 55.4% of the time after implementation.

Conclusion

The duration of therapy overall was shortened by 2 days, which was driven by the difference in duration for UTI. Incorporating antimicrobial stewardship principles at the point of order entry can result in fewer days of unnecessary therapy.

Disclosures

All Authors: No reported disclosures.
923. Providers’ Perception of CME Antimicrobial Stewardship Quizzes and Its Impact on Antibiotic Prescribing Practices
Authors: Chan Shannon , Harrington Nicole , Couch Kimberly A , Marcinak Rebecca , Shapiro Craig , Chasanov William M , Dressler Robert , Consiglio-Ward Loretta , Drees Marci
Published: December 2022

Background

A statewide antimicrobial stewardship (AS) collaborative across 5 health systems was formed with the mission to share best antibiotic prescribing. Recognizing that education is an important pillar of AS intervention, the statewide collaborative implemented a monthly CME quiz focusing on a wide range of clinical infectious diseases and AS topics. These quizzes consisted of 5-10 case-based and clinical pearl questions with evidence-based answers focusing on the adult and pediatric patient populations. Participants were awarded one hour CME credit. After 3 years of distributing the quizzes, we sought to assess the providers’ perceptions of the CME quizzes and their impact on clinical practice.

Methods

A nine-question survey was emailed to providers, pharmacists, and nurses. Questions regarding providers’ perceptions on the importance of antibiotic education and the impact that it has on their clinical practice were included.

Results

Among the 89 respondents, 50% were physicians, 25.6% were advanced practice providers, 14% were pharmacists and 3.5% were nurses. The most common practice setting was primary care (43.8%), followed by acute care (35.9%). The monthly ASP quizzes were considered helpful or very helpful in enhancing their practice in 95% of the respondents. More than half of the respondents believed that the ASP quizzes led to enhancement of their ASP knowledge (61.8%). Prescribing shorter duration and narrow spectrum antibiotic were reported by 48 (53.9%) and 28 (31.5%) respondents respectively. Twenty-three (25.8%) respondents reported that they prescribe less antibiotics because of the ASP quizzes and 28 (31.5%) reported that they became more aware of potential harm of antibiotics. The ASP quizzes did not influence, but rather reinforce current prescribing practice in 25% of the respondents.

Conclusion

Provider directed education is a core element of both ambulatory and acute care antimicrobial stewardship. Through a statewide initiative, using a monthly CME quiz circulated via email, prescribers were able to improve their knowledge and enhance their prescribing of antibiotics. Most providers perceive this format of education as helpful and describe it as having a positive impact on their prescribing behavior.

Disclosures

All Authors: No reported disclosures.
924. Reducing Rates of Hospital Acquired Clostridium Difficile Infection by Switching to Two-Step Testing
Authors: Barchuk Andriy , Dorobisz Monica , Oconnell Kathleen , Zainah Hadeel
Published: December 2022

Background

Clostridium difficile infection (CDI) tests have various degrees of sensitivity, making diagnosis challenging. Polymerase chain reaction (PCR) positive tests in colonized patients can impact rates of hospital-acquired CDI (HACDI). A negative toxin A/B enzyme immunoassay (EIA) as a second step can help determine colonization but is not as sensitive. We aimed to study the impact of a two-step testing strategy on rates of HACDI and CDI treatment outcomes.

Methods

Two-step testing consisted of C. difficle DNA PCR, which if positive, was followed by toxin A/B EIA (Figure 1). We conducted a retrospective study in a 359-bed hospital from March 2020 to July 2021. Patients with positive PCR and negative EIA results were included and further classified based on CDI treatment status. The primary outcome was the number of HACDI cases avoided. Secondary outcomes included location at the time of testing, symptoms, leukocytosis, discharge disposition and readmission.

Results

Ninety-six patients were included. Sixty-five patients (68%) were treated while 31 (32%) were not. HACDI was avoided in 18 cases (18.8%). There were more HACDI avoided in the non-treated group compared to the treated group (32.3% vs 12.3%; p=0.026). Most non-treated patients were tested on medical-surgical units (77.4%), whereas 49.2 % of the treated patients were tested in more acute areas such as emergency or intensive care. Treated patients were more likely to have leukocytosis and/or fever (66.2%) compared to non-treated patients (29%; p= 0.0009), while there was no difference in abdominal pain, diarrhea, bloody stool, or constipation (Table 1).

Most patients had an abdominal CT scan (70.8%). Of those that had a CT, colitis was found in 48.5%. Patients in the treated group were more likely to have had a CT completed that showed colitis vs the non-treated patients (43.1% vs 16.1%; p< 0.011).

Finally, compared to the non-treated patients, treatment did not affect home disposition on discharge or 30-day readmission rate (80% vs 71%, P=0.436) and (25 % vs 29%, P= 0.63) respectively.

Symptoms Associated with C. difficile infection.

Schematic of C. difficile test interpretation.

Conclusion

CDI two-step testing led to decreased HACDI rates without affecting discharge disposition or readmission rates in patients with PCR positive and toxin EIA negative results regardless of treatment status.

Disclosures

All Authors: No reported disclosures.
925. Remdesperate for Stewardship: Impact of a Remdesivir Stewardship Strategy on the Care of Patients with COVID-19 Admitted to a Community Teaching Hospital
Authors: Hayes Jillian , Ghonim Ahmed , Wooten Leslie , Sippel-Tompkins Jenny , Herrera Victor , Carr Amy L
Published: December 2022

Background

The use of remdesivir (RDV) in patients hospitalized with COVID-19 has resulted in a significantly shorter time to recovery, especially in patients receiving low flow oxygen. Despite the shortened time to recovery, concerns have been raised regarding the $3,120 cost of a five-day course. This price was originally justified by the suggestion that RDV would save hospitals approximately $12,000 per patient by shortening hospital length of stay (LOS) by four days, however, this has not been consistently demonstrated in clinical practice. A preliminary review of RDV orders at our facility revealed hospital discharges were being delayed to complete a five-day course of treatment in patients otherwise medically ready to discharge.

Methods

This single-center, retrospective, comparative study was conducted at AdventHealth Orlando, a 1,368-bed community teaching hospital in central Florida. In January 2021, the campus stewardship committee devised a RDV stewardship strategy including targeted education and escalation of orders not meeting institutional criteria at time of order verification. This study compared pre-intervention patients who received RDV from December 1, 2020, to January 7, 2021, to post-intervention patients who received RDV from January 8, 2021, to February 28, 2022. The primary objective of this study was to assess the impact of a pharmacist-driven RDV stewardship initiative on the duration of therapy in hospitalized patients with COVID-19.

Results

A total of 2104 remdesivir orders were included in the study (209 pre-intervention and 1895 post-intervention). Overall, patients had a median age of 59 years and 49% were male. Majority of patients in both groups required low flow supplemental oxygen at the time of RDV initiation. Significantly more orders in the intervention group aligned with institutional criteria at the time of order entry (47% vs 84%, p< .001). Patients completing the full 5-day course of remdesivir therapy decreased from 79 to 53% (p< .001). A decreased duration of therapy and length of stay were observed in the intervention group.

Conclusion

Pharmacist-driven RDV stewardship increased adherence to the institutional algorithm and reduced duration of therapy.

Disclosures

Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.