bluuebunny/crossref_metadata_2025 huggingface dataset:
139. Development of cefiderocol resistance in an Enterobacter hormaechei strain following prolonged antibiotic exposure
Authors: Medernach Rachel , Moore William J , Nozick Sophia , Alamri Maha M , Kling Kendall , Ison Michael G , Chao Qi , Bachta Kelly E R , Rhodes Nathaniel J , Ozer Egon A , Hauser Alan R
Published: December 2022

Background

Cefiderocol (FDC) is a novel antimicrobial agent used for multi-drug resistant Gram-negative pathogens. To date, reports of mutations in β-lactamase and siderophore complex genes have been described and may contribute to FDC resistance. This case describes a New Dehli metallo-β-lactamase (NDM)-producing strain of Enterobacter hormaechei that developed FDC resistance following antibiotic exposure.

Methods

Serial respiratory and blood cultures were collected from a lung transplant recipient throughout 72 days of hospitalization. Confirmatory susceptibility and combination minimal inhibitory concentration (MIC) testing were performed using broth dilution and E-test assays. Short-read sequencing libraries were prepared using a seqWell plexWell 96 kit, and whole-genome sequencing was performed using the Illumina NovaSeq platform. Reads from the sample genomes were aligned to the chromosome and three plasmid sequences of reference genome ENCL48880.

Results

Four serial respiratory E. hormaechei isolates and one blood isolate were evaluated. Although initial isolates were susceptible to FDC (MICs 1-2 µg/mL), two respiratory isolates cultured after 41 days of FDC therapy had MICs of 128 µg/mL. The blood isolate remained FDC susceptible despite respiratory resistance. The combination of ceftazidime/avibactam and aztreonam was determined to be active via synergy MIC testing in all isolates, and aztreonam therapeutic drug monitoring confirmed an adequate dosing strategy. Whole-genome sequencing revealed no nonsynonymous single nucleotide variants (SNVs) within the chromosomes but identified a deletion of a large urease island in the resistant isolates. In four of the five isolates, a plasmid (p48880_mcr) was identified and analyzed for possible contributions to FDC resistance.

Enterobacter Isolate Assemblies

This figure demonstrates genomic assemblies from the five Enterobacter clinical isolates, noting an absence of sequence from ECResp2.

Conclusion

This case demonstrates development of FDC resistance in E. hormaechei isolates during a 41 day course of FDC therapy. Possible causes of resistance include a large chromosomal deletion and plasmid alleles, demonstrating a potential novel mechanism for FDC resistance. Partnering molecular testing and enhanced antimicrobial stewardship should be encouraged to optimize selection of regimens and durations to prevent resistance to FDC.

Disclosures

Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant Nathaniel J. Rhodes, PharmD, MSc, American Academy of Colleges of Pharmacy: Grant/Research Support|Paratek: Grant/Research Support|Third Pole Therapeutics: Advisor/Consultant.
141. Evaluating Cefepime And Alternative Beta-lactams For The Treatment Of Serratia marcescens Blood Stream Infections
Authors: Vicente-Lopez Natcha , Patel Radha , Stock Kent J
Published: December 2022

Background

AmpC β-lactamase enzymes can be produced by a number of Enterobacterales. Due to its inducible chromosomal resistance, cefepime is often preferred. In vitro analysis and clinical reports have shown AmpC expression can occur less than 5% among S. marcescens. Locally, there has been a rise in beta-lactam resistant S. marcescens, however guidelines and small clinical trials have suggested treatment according to susceptibility testing. This study aimed to evaluate the use of cefepime vs. alternative beta-lactams like third generation cephalosporins or piperacillin-tazobactam as treatment of S. marcescens.

Overall treatment Failure

Methods

This is a single-center, retrospective review of adult hospitalized patients with S. marcescens BSIs over a five-year period. Patients who received more than 24 hours of susceptible antibiotics were included. Patients who received at least 72 hours of antibiotics from index blood culture were divided into definitive cefepime (DCEF) or definitive alternative beta-lactams (DBLA) groups. Composite outcome of 30-day re-admission, 90-day reinfection rates, and mortality was used to evaluate treatment failure.

Results

A total of 53 patients were enrolled. Common sources of infection include genitourinary (12), bone and joint (6), and skin and soft tissue (6). DCEF and DBLA groups included 35 and 18 patients, respectively. Most DBLA patients received piperacillin-tazobactam (9/18). Median Charlson Comorbidity Index (CCI) was 6 for DCEF and 4.5 for DBLA. 11 patients in the DCEF group were readmitted, vs 2 patients in the DBLA group. One patient in each group had reinfection within 90 days. In-hospital mortality occurred in 4 and 1 patients in the DCEF and DBLA groups, respectively. Overall treatment failure was observed in 15 patients in the DCEF group and 3 patients in the DBLA group. Median hospital length of stay was 10.1 days for DCEF and 9.5 days for DBLA.

Conclusion

More patients received DCEF compared to DBLA, potentially related to acuity evidenced by higher CCI and ICU admissions. Results showed a higher rate of overall treatment failure among DCEF group. Due to the retrospective design and small sample size, it is difficult to infer clinical significance. These findings prompt further investigation into the difference in treatment failure between these groups.

Disclosures

All Authors: No reported disclosures.
145. Harnessing the Inoculum Effect to Diagnose Molecular Mechanisms of Carbapenem Resistance
Authors: Cartagena Alexis Jaramillo , Taylor Kyra , Bhattacharyya Roby P
Published: December 2022

Background

The global spread of carbapenem-resistant Enterobacterales (CRE) presents a major threat to public health. CRE employ two molecular mechanisms to evade carbapenems: 1) expression carbapenemases (CPases), which efficiently hydrolyze carbapenems or 2) disruption of porins, which reduces carbapenem influx to levels that can be hydrolyzed by certain beta-lactamases. Diagnosing mechanisms underlying carbapenem resistance is important for infection control and to administer appropriate treatments.

Methods

We measured Meropenem and Ertapenem minimum inhibitory concentrations (MICs) for 103 clinical Enterobacterales isolated from hospitals in Massachusetts and California using broth microdilution assays at 14 inocula spanning four orders of magnitude. They represented 30 isolates encoding CPases and intact porins, 46 isolates with disruptions in one or both of the porins responsible for carbapenem influx (OmpC and OmpF), 25 encoding CPases with disrupted porins, and two controls encoding intact porins and no CPases.

Results

We observed that the two mechanisms result in distinct profiles; first the carbapenem MICs of CPase-encoding strains show a strong inoculum dependence (Fig 1.A), whereas the MICs of porin deficient strains remain largely constant at all inocula (Fig 1.B). The synergistic action of these two mechanisms leads to high-level resistance that we termed “hyper-CRE” (Fig 1.C). Together these factors explain the level of resistance in nearly all our CRE isolates. To validate the hyper-CRE phenotype, we successfully employed CRISPR-based gene editing to show that knocking out the major porin in CPase-producing strains elevates their carbapenem resistance to hyper-CRE levels.

We also determined 18% of our isolates changed susceptibility classification within the Clinical Laboratory and Standards Institute (CLSI) recommended inoculum range. This is worrisome for the treatment of infections with strains that are deemed susceptible via in vitro AST assays but are truly resistant in vivo.

Conclusion

Overall, our approach has demonstrated that measuring MICs at different inoculum can yield crucial diagnostic information about mechanisms of resistance which has important implications for patient care, infection control, and surveillance of emerging CPases.

Disclosures

All Authors: No reported disclosures.
158. Adherence to use of blood cultures according to current national guidelines and their impact in patients with community acquired pneumonia: A retrospective cohort
Authors: Ruiz Gaviria Rafael E , Rivera Arturo Marroquin , Pardi Maria D , Ross Robert W
Published: December 2022

Background

Community acquired pneumonia(CAP) is one of the highest infectious causes of mortality. Recommendations about the use of blood cultures in the diagnosis and treatment of CAP has been a continuous topic of debate. Current guidelines specify the situations when blood cultures should be ordered.

Methods

A retrospective cohort in a teaching hospital in Baltimore USA was conducted that include all the patients that were admitted with diagnosis of CAP as per the International Disease Classification 10 ( ICD 10) between January 1, 2019, and December 31, 2019. Socio demographic and clinical characteristics were obtained, as well as length of hospital stay and mortality. Blood cultures were classified as positive or negative and at the same time it was evaluated if they were done in compliance with current recommendations of Infectious Disease Society of America ( IDSA)

Results

721 patients had CAP and were included in the study. Median age was 68 years and almost 50% of the patients were male (n= 293). Most of the patients were from home (84%) and the most common comorbidities were hypertension and diabetes ( 68% and 31 % respectively). 96 patients had positive blood culture and 34% (n= 247) of all the blood cultures were adequately ordered as per current IDSA guidelines. 80 patients died or went to hospice and the median length of stay in our cohort was of 7 days. The multivariate model showed that mortality was associated with positive blood cultures ( OR= 3.1 95%CI 1.63- 5.87)and appropriateness of blood cultures ( OR=2.96 95% CI 1.25.7). Length of hospital stay did not show any association with positive blood cultures, but it was associated with blood culture appropriateness (OR= 1.63 95% CI 1-2.65).

Relation bewteen BC and LOS

Relationship between appropriateness of BC and length of stay according to the positivity of the BC

Multivariate with final disposition

Multivariate logistic regression to assess the association with mortality

Multivariate length of stay

Multivariate logistic regression to assess the association with extended length of stay

Conclusion

Adequate use of blood cultures in patients with CAP might have some association in the outcomes of patients suffering from this condition. However, a prospective study evaluating the utility of this test following current IDSA recommendations is needed to understand their impact in mortality and morbidity of CAP

Disclosures

All Authors: No reported disclosures.
160. Antimicrobial Prescribing Patterns in Bloodstream Infections Caused by Cefepime-Susceptible Extended Spectrum β-lactamase Enterobacterales
Authors: O’Rourke Emerald , Binkley Amanda , Talati Naasha J , Patel Sonal , Maguire Christina
Published: December 2022

Background

The reliability of piperacillin-tazobactam (TZP) and cefepime (FEP) breakpoints for extended spectrum β-lactamase Enterobacterales (ESBL-E) isolates remains controversial. The Infectious Diseases Society of America recommends against the use of TZP and FEP for the treatment of bloodstream infections (BSIs) caused by ESBL-E, even when in-vitro susceptibility is demonstrated. The University of Pennsylvania Health System microbiology laboratory suppresses TZP susceptibilities on Escherichia coli and Klebsiella pneumoniae blood isolates nonsusceptible to ceftriaxone (CRO) or ceftazidime (CAZ) and specifies the presence of a multidrug resistant organism. However, FEP susceptibilities are reported. The objective of this study was to assess appropriate antimicrobial prescribing for the treatment of FEP-susceptible ESBL-E BSIs with our institution’s current susceptibility reporting practices.

Methods

This multicenter retrospective observational study included patients with blood cultures positive for E. coli, K. oxytoca, K. pneumoniae, and Proteus mirabilis nonsusceptible to CRO or CAZ but susceptible to FEP from August 1, 2018 through August 1, 2021. Patients with a concominant gram-negative infection or true beta-lactam allergy were excluded. Patients were assessed for appropriate therapy (demonstrated susceptibility to and administration of carbapenems fluoroquinolones, novel beta-lactam/beta-lactamase inhibitors, or sulfamethoxazole-trimethoprim) within 24 h following the availability of susceptibility results.

Results

During the study period 38 patients were included. Of the 38 patients, 52.6% (n=20) received appropriate therapy with an average time to appropriate therapy of 3.7 (SD 2.1) h. Among patients receiving inappropriate therapy (n=18), 50% (n=9) were changed to appropriate therapy >24 h after susceptibility results, with an average time to appropriate therapy of 46.5 (SD 44.4) h. The remaining 9 patients (23.7%) did not receive appropriate therapy beyond 24 h.

Conclusion

Reporting FEP susceptibility results on ESBL-E blood isolates may contribute to the prescribing of FEP for the treatment of ESBL-E BSIs and delay appropriate antimicrobial therapy. Given these findings, cefepime will now be suppressed on ESBL-E blood isolates.

Disclosures

All Authors: No reported disclosures.
168. Closing Time: A Quasi-experiment Comparing Time to Optimal Therapy using Traditional Identification and Susceptibility Methods, Rapid Identification, or Rapid Identification with Phenotype for Gram-negative Bloodstream Infections
Authors: Perry Rachel , Mercuro Nicholas J , Mercuro Nicholas J , Connolly Kristina Rokas , Dollard Eliza W , Stogsdill Patricia , Wungwattana Minkey
Published: December 2022

Background

Bloodstream infections (BSI) are a major cause of morbidity and mortality. Compared to traditional microbiology methods, rapid diagnostic testing (RDT) provides prompt organism identification and antibiotic susceptibility results. This leads to earlier opportunities to optimize therapy, which may improve patient outcomes.

Methods

This was a single center quasi-experimental study of hospitalized adults with Gram-negative (GN) BSI, comparing the management and outcomes across three periods: pre-RDT (traditional identification and susceptibilities with BD Phoenix®, December 2014 to September 2016), RDT1 (Nanosphere Verigene®, December 2016 to December 2019), and RDT2 (Accelerate Pheno™, February 2020 to September 2021). The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to oral antibiotic step-down, hospital length of stay (LOS), incidence of Clostridioides difficile infection, and 30-day inpatient mortality. Chi-squared and Kruskal-Wallis tests were used to compare categorical and continuous variables. Significance values for the primary endpoint were adjusted with Bonferroni correction to account for multiple pairwise comparisons.

Results

Of 296 included patients, 100 were in the pre-RDT, 98 in the RDT1, and 98 in the RDT2 arms. The most common organisms were Escherichia coli (64.5%) and Klebsiella species (20.3%). The TTOT (median, interquartile range) in the pre-RDT, RDT1, and RDT2 groups were 46 (7-61), 30 (0-53), and 12 (0-28) hours (P< 0.001), respectively. The time to oral antibiotic step-down and hospital LOS was similar between groups. There was no difference in C. difficile infection or 30-day inpatient mortality (Table 1). Table 1.Comparison of Outcomes

Conclusion

In patients with GN BSI the TTOT in RDT1 was shorter when compared to traditional susceptibility methods. Compared to both rapid identification alone and traditional identification and susceptibility methods, RDT2 improved time to optimal therapy. Larger, controlled studies are needed to examine the clinical impact of different RDT methods for Gram negative bloodstream infections.

Disclosures

Rachel Perry, PharmD, Accelerate Diagnostics: Investigator initiated funding for research presentation; no funding for study design or data analysis Minkey Wungwattana, PharmD, BCIDP, Accelerate Diagnostics: Investigator initiated funding for research presentation; no funding for study design or data analysis.
171. Diagnostic stewardship to limit repeat plasma cytomegalovirus viral load testing
Authors: Trirattanapikul Akeatit , Pasomsub Ekawat , Siriyotha Sukanya , Pattanaprateep Oraluck , Phuphuakrat Angsana
Published: December 2022

Background

Serial monitoring of plasma cytomegalovirus (CMV) viral load monitoring with intervals of less than five days or using different assays for monitoring may cause unnecessary budgets for laboratory testing without changes in treatment, morbidity, and mortality.

Methods

The pre-intervention retrospective study and post-intervention prospective cohort study were performed. In 2021, the inpatient electronic pop-up and telephone interview and feedback were used to limit unnecessary plasma CMV viral load testing. The rate of plasma CMV viral load testing being performed with intervals of less than five days was compared before and after protocol implementation using the Poisson regression model. The cost-effectiveness of plasma CMV viral load testing after protocol implementation was also studied.

Results

After protocol implementation, there was a significant decrease in the rate of plasma CMV viral load test requests with intervals of less than five days from 11.8% to 6.2% [Incident rate ratio (IRR) 0.50, p-value < 0.001]. Of these, 38.9% was due to unintentional requests. After telephone interviews the rate of plasma CMV viral load test requests with intervals of less than five days decreased further to 4.7% (IRR 0.37, p-value < 0.001). The costs of plasma CMV viral load testing performed with intervals of less than five days and anti-CMV drugs were reduced significantly. (822,500 to 345,000 Thai Baht, p < 0.001 and 12,327,436 to 7,860,187 Thai Baht, p = 0.001)

Incidence of plasma CMV viral load testing performed with intervals of less than five days

Costs of plasma CMV viral load testing, anti-CMV drug, bronchoscopy, and gastrointestinal endoscopy

Conclusion

The diagnostic stewardship program is helpful to reduce unnecessary plasma CMV viral load testing and costs without increasing CMV viremia and CMV diseases. This program should be maintained, and an electronic hard stop alert program should be developed.

Disclosures

All Authors: No reported disclosures.
172. Does Passive Reporting of Streptococcus spp Identified by Rapid Molecular Assay Change Antibacterial Prescribing Compared to Gram Stain (GS) Alone?
Authors: Archer Adam W , Cox Heather L , Donohue Lindsay E , Mathers Amy J
Published: December 2022

Background

At University of Virginia Health, the detection of Streptococcus spp via rapid molecular assay from blood cultures (BCx) was not historically reported in the EMR until the isolate was further identified. However this was reconsidered following anecdotal observation of inappropriate vancomycin (VAN) prescribing with GS alone. The purpose of this study was to investigate the impact of implementing passive reporting of Streptococcus spp on antibacterial prescribing patterns with a focus on VAN.

Methods

This was a single-center, pre-post quasi-experimental study of adult inpatients with non-duplicate Streptococcus spp identified via rapid molecular assay (ePlex®; GenMark Diagnostics) from BCx before (pre-intervention, Jul 2020 – Sep 2021) and after (post-intervention, Oct 2021 - Apr 2022) implementing passive reporting of Streptococcus spp. The primary outcome was any antibacterial switch within 24 hours of GS. VAN days of therapy (DOT) within 7 days and rates of Streptococcus spp deemed contamination by the primary team were also assessed.

Results

A total of 83 patients were included (58 pre- and 25 post-intervention). Baseline characteristics were similar including immunocompromised status (45% vs 52%), febrile neutropenia (28% vs 28%), and admission to a medical service (90% vs 96%). An antibacterial switch occurred within 24 hours of GS in 59% and 64% of the pre- and post-intervention groups, respectively, and was most commonly the addition of VAN (66% [25/38] vs 40% [8/20]; p=0.09). Fewer post-intervention patients continued VAN beyond 24 hours (66% vs 48%; p=0.15), but this was not statistically significant. The median VAN DOT remained unchanged at 2 days. A non-significant decrease in Streptococcus spp deemed contaminants was noted in the post-intervention arm (28% vs 16%; p=0.16). Finally, a non-streptococcal organism was isolated from concomitant BCx in approximately one-third of patients in each arm.

Conclusion

Passively reporting Streptococcus spp identified by rapid molecular assay without paired stewardship intervention did not impact antibacterial prescribing. The identification of Streptococcus spp may be characterized by heterogeneous circumstances requiring nuanced real-time stewardship intervention.

Disclosures

All Authors: No reported disclosures.
173. Evaluating Respiratory Tract Culturing in Mechanically Ventilated Patients: Opportunity for Diagnostic Stewardship
Authors: Tripathi Ravi , Kenaa Blaine , Claeys Kimberly C , Patel Meghana , Maldarelli Mary , Newman Michelle , Leekha Surbhi
Published: December 2022

Background

Overdiagnosis of ventilator associated pneumonia (VAP) is common and may be due, in part, to excessive culturing of the respiratory tract in ventilated patients. We sought to evaluate the appropriateness of these cultures based on clinical characteristics leading to culture acquisition, and the relationship with antibiotic use.

Methods

We included mechanically ventilated adult patients in the Neuroscience and Cardiac Surgery Intensive Care Units at an academic medical center in Baltimore, MD, who had respiratory tract cultures obtained from March 1 to June 30, 2021. The appropriateness of respiratory cultures was evaluated by chart review in a standardized manner using a published algorithm (Figure 1). Clinical characteristics of patients with appropriate vs. inappropriate cultures were compared using Fisher’s exact test.

Results

98 respiratory tract cultures (58 endotracheal aspirates, 25 mini bronchoalveolar lavages (BAL), 13 BALs, and 2 bronchial washings) were evaluated. Of these, 19 (19%) were deemed appropriate and 79 (81%) were inappropriate. Compared to patients with inappropriate cultures, those with appropriate cultures were more likely to demonstrate worsening oxygenation, new or increasing infiltrate on chest x-ray, or hemodynamic instability. The groups did not significantly differ with respect to fever or changes in WBC count (Figure 2). Of 79 inappropriate cultures, 31 (39%) received a clinical diagnosis of VAP from their provider. In 23 (29%) instances, antibiotics were started or changed based on culture results, and 9 (11%) were on empiric therapy for VAP that was continued unchanged. An additional 24 (30%) continued antibiotics not directed toward VAP. Excluding those on antibiotics not directed towards index respiratory culture results, patients received a median of 6 (IQR 2.5, 7) days of therapy.

Conclusion

A large majority of lower respiratory tract cultures in mechanically ventilated patients are potentially inappropriate and associated with overdiagnosis of VAP and unnecessary antibiotic exposure. Incorporating respiratory tract specific attributes into clinical decision making rather than “pan-culturing” for fever or leukocytosis may be an opportunity for diagnostic stewardship in this setting.

Disclosures

Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria.
177. Follow-up Respiratory Cultures in Suspected Ventilator-associated Pneumonia: An Opportunity for Diagnostic Stewardship
Authors: Gomez Cyndi Gonzalez , Albin Owen
Published: December 2022

Background

Ventilator-associated pneumonia (VAP) is overdiagnosed in intensive care units (ICUs) and contributes to antibiotic overuse. Follow-up/test-of-cure culturing practices have garnered stewardship attention in urinary tract infections and gram-negative bacteremia but remain unexplored in suspected VAP. We aimed to ascertain the stewardship implications of repeat respiratory culturing practices in ICU patients.

Methods

Retrospective descriptive cohort study of adult patients in Michigan Medicine ICUs requiring invasive mechanical ventilation in 2019 who had repeat respiratory cultures (RCx) performed within 72 hours after an index respiratory culture. Relevant patient demographics, comorbidities, culture indications and consequent antimicrobial modifications based on RCx were captured.

Results

Of 2340 total respiratory cultures performed, 286 (12%) were RCx. Patient characteristics and indications for culture collection are shown in Figures 1 and 2, respectively. Only 12 patients (4%) had antimicrobial agents modified based on growth of a pathogenic organism from a RCx not covered by the prior antimicrobial regimen. In cases where RCx grew an identical organism with an identical susceptibility profile to the initial respiratory culture, existing antibiotic treatment durations were extended for microbiologic positivity in 12% of cases. Notably, 94 patients (33%) had RCx performed for persistent fevers or leukocytosis, without corresponding changes in ventilator requirements, changes in endotracheal secretions or worsening appearance on chest imaging.

Conclusion

RCx performed within 72 hours of an initial respiratory culture in mechanically-ventilated patients was both common and low-yield. RCx not uncommonly precipitated unnecessary prolongation in antimicrobial treatment durations, and nearly one-third of patients had RCx obtained for persistent fevers or leukocytosis without other signs of VAP treatment failure, a suspect indication for culture collection given that the median time to clinical improvement in VAP clinical trials in 4-5 days. Limiting repeat respiratory cultures in ICU patients represents a potentially valuable opportunity for diagnostic stewardship.

Disclosures

Owen Albin, MD, Charles River Laboratory: Advisor/Consultant|Cipla Pharmaceuticals: Advisor/Consultant|Shionogi Inc: Advisor/Consultant.
178. Impact of a microbiology comment nudge on the diagnostic evaluation of Staphylococcus aureus bacteriuria
Authors: Patel Dimple , Bandali Aiman , Giordano Pamela , Kessler Jason , Roland Robert
Published: December 2022

Background

Staphylococcus aureus is a relatively uncommon cause of urinary tract infections. S. aureus bacteriuria is thought to result most commonly from urinary tract instrumentation (ascending infection) or via hematogenous seeding of the genitourinary tract (descending infection). Given the devastating impact of invasive S. aureus infection and awareness that S. aureus bacteriuria is often a marker for S. aureus bacteremia, growth of S. aureus from urine cultures should prompt urgent clinical assessment, including blood culture collection. In April 2021, a comment nudge was added to the microbiology culture and susceptibility report for all S. aureus isolated from urine cultures performed at the Atlantic Consolidated Laboratory (ACL) at Atlantic Health System. The purpose of this study is to assess the impact of a comment nudge on the diagnostic evaluation of S. aureus bacteriuria.

S. aureus bacteriuria comment nudge

Methods

All patients with S. aureus bacteriuria were retrospectively identified from the ACL microbiology database. The primary endpoint was collection of blood cultures within 96 hours of positive urine culture during the 6-month period pre-comment (October 2020 – April 2021) compared to 6-month period post comment (May 2021 – November 2021). In addition, incidence of S. aureus bacteremia among the patients with collected blood cultures was also evaluated.

Results

S. aureus bacteriuria was identified in 122 patients during the Pre-Comment period and 188 patients in the Post-Comment period. Blood cultures were collected more frequently in the Post-Comment period compared to the Pre-Comment period (64% vs. 51%, p=0.018). Among patients for whom blood cultures were collected, 29% had concomitant S. aureus bacteremia in the Pre-Comment period compared to 16% in the Post-Comment period (p=0.03).

Conclusion

The addition of a comment nudge to the microbiology report of urine cultures growing S. aureus significantly improved follow-up blood culture collection. Health systems may consider implementation of similar interventions, particularly in resource-limited settings, to avoid delayed recognition of S. aureus bacteremia.

Disclosures

All Authors: No reported disclosures.
179. Impact of a Nurse-Pharmacist Driven Antimicrobial Stewardship: Redefining the Team
Authors: Brooks Aislinn , Elarabi Salwa
Published: December 2022

Background

The Centers for Disease Control and Prevention have recognized the worldwide emergence of antimicrobial resistance. The Joint Commission mandated acute care hospitals to implement antimicrobial stewardship (AMS) programs. Core elements were developed to help hospitals achieve this goal. Core elements were updated incorporating nursing-based actions such as optimizing microbiology cultures.

Methods

The aim is ≥20% of ICU C. difficile, respiratory, and urine culture interventions made by the Nurse-Infectious Diseases (ID) Pharmacist AMS team will be accepted by March 4th, 2022. The ID Pharmacist engaged front line nurses in the AMS program by creating algorithms to guide nursing to appropriate culturing practices. Nurses utilized the algorithms to assess appropriateness of the cultures ordered. If deemed inappropriate, nurses contacted the ID Pharmacist and/or ordering physician to intervene. The outcome measure assessed was the percentage of interventions accepted for inappropriate C. difficile, respiratory, and/or urine cultures weekly. Process measures included time (in hours) to discontinue inappropriate cultures and the type of culture addressed. The balancing measure was the average time the Nurse/ID Pharmacist spent to assess appropriateness of ordered cultures.

Results

A total of 69 interventions were made by the Nurse/ID Pharmacist AMS team. Due to a high intervention acceptance rate, the target was changed from 20% to 60% at week 8. Out of the 69 interventions, 91% (n=63) were accepted and resulted in the discontinuation of the culture. The majority of accepted interventions were among urine cultures. The average time to discontinue inappropriate cultures was 2 hours and the average time the Nurse/ID Pharmacist spent to assess appropriateness of cultures was 15 minutes.

Percentage of Interventions Accepted

Data shown reflects the weekly percentage of accepted interventions recommended by the nurse/ID Pharmacist AMS team. Due to the high intervention acceptance rate, target was changed from 20% to 60% in week eight.

Intervention Type

This data reflects the number of accepted interventions for each culture type made by Nurse/ID Pharmacist AMS team resulting in the discontinuation of the inappropriate culture.

Conclusion

The implementation of a Nurse/ID Pharmacist AMS collaboration resulted in a high acceptance of culture interventions leading to discontinuation of inappropriate cultures. AMS nurse champions expanded SEMC’s AMS team and led to improved microbial culture practices in the ICU.

Disclosures

All Authors: No reported disclosures.
182. Impact of Rapid Identification and Phenotypic Results on Clinical, Economic, Antimicrobial Stewardship Outcomes in Patients with Gram-Negative Bacteremia
Authors: Shoop Harold , Fabian Amy , Doyen Shaina
Published: December 2022

Background

Timely and effective antibiotic therapy is a critical determinant of clinical outcome in Gram-negative bacilli (GNB) bloodstream infections (BSI). Conventional antimicrobial susceptibility testing (AST) remains a rate-limiting step in determining targeted therapy. Accelerate Pheno™ (AP) is a novel system providing both identification (ID) and AST results within 8 hours. The primary objective of this study was to determine the impact of rapid ID and AST with AP on time to achieving targeted therapy (TTT).

Methods

This single center, quasi-experimental study compared outcomes with AP (POST; November 2020 to July 2021) versus a historical standard (PRE; November 2019 to July 2020) of rapid diagnostic testing (BioFire® FilmArray®BCID) and conventional AST (VITEK®2) with pharmacist-driven antimicrobial stewardship (AMS) intervention. PRE and POST BSI were retrospectively identified by positive blood culture (BCx) with an on-panel GNB. Inpatients were excluded if less than 18 years of age, pregnant, polymicrobial BCx, BCx with the same organism and source within 7 days, or if died or transitioned to palliative or hospice care before final AST results. Secondary outcomes included inpatient all-cause mortality, hospital and ICU length of stay, hospital-acquired Clostridioides difficile infection, antibiotic and microbiologic costs, days of anti-pseudomonal therapy, antibiotic intensity score, and time to first intervention following Gram stain, ID, and AST results.

Results

Overall, 373 BSI were screened and 294 were included [161 PRE vs 133 POST]. Baseline demographics and characteristics were similar between groups. Median TTT was shorter POST [50 hours (IQR 44–92) vs 28 hours (IQR 14–55), p < 0.05]. Median microbiology testing costs per episode were higher POST [Δ$40.33 (32%), p < 0.05]. Other secondary outcomes did not differ significantly between groups. Pharmacists intervened more POST [69 (43%) vs 77 (58%), p < 0.05]. AP completed ID and AST in 155 of 205 (76%) BSI. Off-panel GNB occurred in 26 (13%) BSI POST.

Conclusion

Implementing the AP system together with an established AMS program resulted in a shorter TTT and a higher cost to test. Clinical, AMS, and other economic outcomes were not impacted by the addition of AP.

Disclosures

All Authors: No reported disclosures.
183. Impact of Revised Piperacillin/Tazobactam Clinical Breakpoints on Enterobacterales Isolates Identified in Blood Cultures
Authors: Moore Nicholas M , Houlihan Joyce H , Varughese Christy A , Hodgson Hayley A , Shankaran Shivanjali , Won Sarah Y , Hayden Mary K
Published: December 2022

Background

Enterobacterales are a significant cause of bloodstream infections (BSI) in hospitalized patients. Prior evidence suggests that treatment with piperacillin/tazobactam may not be ideal for BSI. Piperacillin/tazobactam clinical breakpoints were recently updated by the Clinical and Laboratory Standards Institute (CLSI).

Methods

We retrospectively evaluated Enterobacterales blood isolates identified by MALDI-TOF (Vitek MS, bioMérieux) between January 1, 2017 through December 31, 2021 at Rush University Medical Center in Chicago, Illinois. Antimicrobial susceptibility testing was performed using NM43 or NM56 panels on the MicroScan WalkAway 96 (Beckman Coulter). The range of dilutions of piperacillin/tazobactam included on both panels was 8/4 to 64/4 μg/mL. Minimal inhibitory concentrations (MIC) were interpreted using current CLSI breakpoints.

Results

We evaluated 1597 Enterobacterales isolates. Most isolates identified were Escherichia coli [n=806 (50%)] and Klebsiella pneumoniae [n=358 (22%)]. The majority of isolates (90.4%) were susceptible; 28 (1.8%) isolates were susceptible-dose dependent and 125 (7.8%) were resistant to piperacillin/tazobactam using the new CLSI breakpoints (Table). 236 isolates had a multidrug-resistant phenotype, of which 216 (92%) were confirmed as an ESBL. Among ESBL-producing isolates, the majority (81%) were susceptible [MIC ≤ 8 µg/mL) to piperacillin/tazobactam. Isolates with confirmed carbapenemase production had off-scale MICs ( > 64 µg/mL) (Figure).

Piperacillin/Tazobactam Breakpoint Revision Table

Overall changes in piperacillin/tazobactam interpretations using revised breakpoints.

MDR-Enterobacterales piperacillin/tazobactam MIC distributions

Piperacillin/tazobactam minimal inhibitory concentration distributions among multidrug-resistant Enterobacterales isolates.

Conclusion

While there was an increase in resistance, our results indicate that most Enterobacterales isolates tested susceptible to piperacillin/tazobactam using the revised CLSI breakpoints.

Disclosures

Nicholas M. Moore, PhD, D(ABMM), Abbott Molecular: Grant/Research Support|Cepheid: Grant/Research Support.
187. Nasopharyngeal Testing to Individualize Management of Acute Otitis Media
Authors: Sebastian Thresia , Toseef Mohammad , Kurtz Melanie , Frost Holly M
Published: December 2022

Background

There are > 10 million antibiotics prescribed yearly for acute otitis media (AOM). The associated organism can influence the likelihood of antibiotic benefit and optimal treatment. A rapid diagnostic test (RDT) for AOM could prevent unnecessary antibiotic use, while assuring those likely to benefit from antibiotics receive the appropriate agent. Nasopharyngeal (NP) polymerase chain reaction can effectively exclude the presence of organisms in middle ear fluid and may be useful to individualize care.

Objective: To explore the potential cost-effectiveness and reduction in antibiotics with NP RDTs to direct AOM management.

Methods

We developed two algorithms for AOM management based on NP bacterial otopathogens (Figure1). The algorithms provide recommendations on prescribing strategy (immediate, delayed, or observation) and antimicrobial agent. We utilized a tiering system based on expected pathogen-associated severity and resistance. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality adjusted life day gained (QALD). We used a decision-analytic model to evaluate the cost-effectiveness of the RDT algorithms compared to usual care from a societal perspective over a 30-day time horizon. Secondary outcomes included the (1) cost at which a RDT would be cost-effective and (2) potential reduction in annual antibiotics used.

Flow diagram Figure 1:Flow diagram for management of AOM including RDT-DP and RDT-OBS algorithms

Results

An RDT algorithm that used immediate, delayed prescribing, and observation based on pathogen (RDT-DP) had an ICER of $1336.15/QALD compared with usual care and strongly dominated the RDT that used only immediate prescribing and observation (RDT-OBS). At an RDT cost of $278.56, the ICER for RDT-DP exceeded the willingness to pay threshold ($274 per QALD gained); however, if the cost of the RDT was < $212.10, the ICER was below the threshold. Both algorithms reduced annual antibiotic use, including broad-spectrum use, compared to usual care (RDT-DP 4.7 million (56% reduction), RDT-OBS 5.4 million (49% reduction), usual care 10.5 million).

Conclusion

The use of a NP RDT for AOM is likely to be cost-effective and substantially reduce unnecessary antibiotic use. These iterative algorithms could be modified to guide AOM management as scientific knowledge evolves.

Disclosures

All Authors: No reported disclosures.
191. Predictive Value of Procalcitonin across Disease States within an Inpatient Veteran Population
Authors: Bowden Jarred , Davis Kelly W , Bennett Jessica G , Eason Jane V , Callicott William , Dash Anwesh , Minrath Rachel , Stearns Evan , Thomas-Gosain Neena , Thomas-Gosain Neena
Published: December 2022

Background

Procalcitonin (PCT) can be elevated with certain bacterial infections. Debate continues as to how to best use this biomarker to guide antibiotic use. The primary objective of this study was to evaluate the correlation of PCT levels and the presence of bacterial infection on admission in the total population and in different disease states.

Methods

This was a multicenter retrospective cross-sectional study of patients admitted with specified infectious diagnoses to two VA Medical Centers from 4/1/2019 to 7/1/2021. Patients were stratified into 4 cohorts for analysis; those with COVID-19, sepsis from respiratory source_(S-R), sepsis from non-respiratory source (S-NR), and respiratory source without sepsis (R). Electronic medical records were reviewed to collect the following: initial procalcitonin, cultures, SIRS criteria, comorbidities (CKD, ESRD, HF, immunosuppressed, surgery within the 7 days), and c-reactive protein. PCT elevation was defined as ≥0.25 ng/mL. The frequency of positive cultures within 72 hours was evaluated for patients with elevated and normal PCT levels to determine the diagnostic performance of PCT overall and for each cohort.

Results

632 of 664 patients were evaluated in this study. PCT is elevated twice as often in the septic groups as compared to the non-septic groups (figure 1). Positive predictive value (PPV) varies from 27% to 63% as compared to negative predictive value (NPV) 53%-79% among the disease state groups (figure 2). Although small numbers, the NPV of PCT improves to 83% in patients with elevated temperature and white blood cells (WBC) (figure 3). Figure 1Figure 2Figure 3

Conclusion

The findings that NPV of PCT appears to be better than PPV, support current recommendations against using this as a diagnostic tool, but rather as a tool to assist with antibiotic de-escalation. Further studies are necessary to confirm whether there are specific markers such as temperature or WBC which may improve the NPV. Our data suggests PCT is less helpful in identifying the presence or absence of bacterial infection in septic versus non-septic patients.

Disclosures

All Authors: No reported disclosures.
193. Rapid Diagnostic Testing and Vancomycin Utilization for Contaminated Blood Cultures
Authors: Lockridge Connor , Paciullo Kristen , Trible Ronald
Published: December 2022

Background

Bacteremia is a prevalent hospital acquired infection that affects nearly one in ten hospitalized patients. Rates of contaminated blood cultures have ranged from 0.6% to 6% in the literature. Vancomycin is often chosen as empiric coverage for gram positive organisms while awaiting bacterial identification. The purpose of this study was to evaluate the impact of GenMark ePlex Blood Culture Identification Panel (BCID) implementation on the duration of vancomycin therapy for blood cultures contaminated with coagulase negative staphylococci (CoNS).

Methods

A retrospective chart review was conducted on patients meeting inclusion criteria during a six month period prior to BCID implementation and post BCID implementation, from 03/01/2019 to 08/31/2019 and 03/01/2021 to 08/31/2021. The primary outcome analyzed was the duration of vancomycin therapy, in hours, in patients with a contaminated blood culture. Contaminated blood cultures was defined as a single blood culture growing CoNS. Secondary outcomes included hospital length of stay, readmission for treatment of contaminated blood cultures, and nephrotoxicity.

Results

This IRB-approved study included 190 patients, 75 in the pre-BCID group and 115 in the post-BCID group. The average duration of vancomycin therapy was 53.7 hours in the pre-BCID group and 20.5 hours in the post-BCID group (p = 0.04). Time to organism identification was reduced from 22.8 hours in the pre-BCID group to 12 hours in the post-BCID group (p = 0.5). Additionally, our study did not find a difference in nephrotoxicity, hospital length of stay, or readmissions between the two groups.

Conclusion

Following implementation of the GenMark ePlex Blood Culture Identification Panel (BCID), there was a reduction in both duration of vancomycin therapy and time to culture identification for blood cultures contaminated with CoNS. Rapid diagnostic testing is helpful in clinical decision-making and can lead to earlier discontinuation of empiric antibiotics, such as vancomycin.

Disclosures

All Authors: No reported disclosures.
194. Rapid diagnostic testing to improve management of suspected chlamydia and gonorrhea in adolescents in a Pediatric Emergency Department
Authors: Frost Holly M , Wilson Michael L , Roosevelt Genie D
Published: December 2022

Background

Standard turnaround times for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) testing result in unnecessary antibiotic use for patients without infection and undertreatment of patients with infection(s). We aimed to determine the impact of rapid CT/GC testing on reducing unnecessary antibiotic use, undertreatment of CT and/or GC, and length of stay in an urban safety-net pediatric emergency department (PED).

Methods

Before 2020, testing for CT/GC was performed using a batched nucleic acid amplification test (NAAT; Hologic Aptima Combo2) with results available the following day. Starting January 2020, the GeneXpert rapid NAAT (Cepheid Xpert CT/NG) with turnaround time between 90-120 minutes was available. Our primary outcome variables were under- and over-treatment. Undertreatment was defined as GC and/or CT positive patients who did not receive appropriate antibiotic treatment in the PED. Overtreatment was defined as GC or CT negative patients who received antibiotic treatment in the PED. Under- and over-treatment percentages were plotted on Statistical Process Control p charts. The balancing measure was length of stay (LOS).

Results

There were 739 patients evaluated in the baseline period (2019), 631 in the intervention period (2020) and 626 in the post-intervention period (2021). There were no differences in gender, race, ethnicity, and insurance across the 3 time periods. After introduction of the GeneXpert, over-treatment decreased from 18.4% to 8.1% (Figure). Under-treatment did not differ. Median turnaround for the GeneXpert was 119 minutes. Median LOS in minutes increased from 165 minutes (baseline) to 182 minutes (intervention) and 202 minutes (post-intervention; p< .001).

Percentage of patients over-treated for chlamydia and gonorrhea.

Conclusion

Rapid CT/GC testing substantially reduced unnecessary antibiotic use but increased LOS. Given the rapid increases in CT/GC rates and antimicrobial resistance health systems should consider implementation of rapid testing to appropriately direct antimicrobials to patients most likely to benefit. A more rapid test would likely increase appropriate antibiotic use and limit impact on LOS.

Disclosures

All Authors: No reported disclosures.