Changes In Antimicrobial Therapy Research Articles

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study.

Bloodstream infection (BSI), a frequent cause of severe sepsis, is a life-threatening complication in critically ill patients and still associated with a high mortality rate. Rapid pathogen identification from blood is crucial for an early diagnosis and the treatment of patients with suspected BSI. For this purpose, novel diagnostic tools on the base of genetic analysis have emerged for clinical application. The aim of this study was to assess the diagnostic value of additional next-generation sequencing (NGS) pathogen test for patients with suspected BSI in a surgical ICU and its potential impact on antimicrobial therapy. In this retrospective single-centre study, clinical data and results from blood culture (BC) and NGS pathogen diagnostics were analysed for ICU patients with suspected BSI. Consecutive changes in antimicrobial therapy and diagnostic procedures were evaluated. Results: 41 cases with simultaneous NGS and BC sampling were assessed. NGS showed a statistically non-significant higher positivity rate than BC (NGS: 58.5% (24/41 samples) vs. BC: 21.9% (9/41); p = 0.056). NGS detected eight different potentially relevant bacterial species, one fungus and six different viruses, whereas BC detected four different bacterial species and one fungus. NGS results affected antimicrobial treatment in 7.3% of cases. Conclusions: NGS-based diagnostics have the potential to offer a higher positivity rate than conventional culture-based methods in patients with suspected BSI. Regarding the high cost, their impact on anti-infective therapy is currently limited. Larger randomized prospective clinical multicentre studies are required to assess the clinical benefit of this novel diagnostic technology.

555. Clinical impact and real-life utilization of Karius testing: a retrospective analysis of cases from an urban, academic medical center

Abstract Background Metagenomic next-generation sequencing (NGS) of microbial cell-free DNA is a relatively novel diagnostic technique that may potentially expedite and/or supplement pathogen-specific infectious disease diagnoses, minimize the time to appropriate antibiotic therapy, and reduce unnecessary and invasive testing. However, careful diagnostic stewardship is necessary to ensure that such tests are being ordered in the appropriate patient population. Methods A retrospective chart review of all patients for whom the Karius NGS test was sent at our institution between Jun 13, 2020-Jul 22, 2022 was performed. Clinically relevant pathogens were defined as diagnoses that led to change in antimicrobial therapy. Stata statistical software (version 17.0, College Station TX) was used to analyze patient and hospitalization risk factors associated with Karius testing. Results Thirty cases among 29 unique patients for whom Karius testing was performed were included in our review. Patient characteristics are shown in Table 1. Twenty-one patients (72%) were immunocompromised, including 14 (47%) with solid organ transplant (SOT) and 9 (30%) with malignancy. Mean hospital length of stay (LOS) prior to Karius test collection was 15.8 days (+/- 21.6 days, range 1-120). Reasons for sending Karius are shown in Fig 1. Three patients (10%) had tissue-specific NGS testing performed in addition to Karius. On average, patients received 13.9 days of antibiotics prior to Karius (+/-10.11, range 0-37). Mean turnaround time for Karius results was 38.3 hours (+/- 16.5, range 23-79). Ten (34.5%) Karius results identified no pathogens. Karius identified fungal organisms in 3 (10%) tests, one of which correlated with true infection. Karius results correlated with other infectious diagnostics (such as viral PCR or cultures) in 10 (33%) cases. Clinically relevant pathogens (not identified by other testing) were identified by Karius in only 3 (10%) cases. There was no statistically significant correlation between pathogen detection by Karius and history of HIV (p=0.27), transplant (p=0.70), malignancy (p= 0.21), or number of days from admission to test (p=0.66) Table 1 Patient characteristics (N=29 unique patients, 30 tests) Figure 1 Reasons for Karius test Conclusion Metagenomic NGS is an exciting area of diagnostic innovation, but more studies are needed to determine when and where this test is best utilized. Disclosures All Authors: No reported disclosures

Change in Antimicrobial Therapy Based on Bronchoalveolar Lavage Data Improves Outcomes in ICU Patients with Suspected Pneumonia.

Flexible bronchoscopy (FB) is often performed in critically ill patients with suspected pneumonia. It is assumed that there will be an association with improved outcomes when bronchoalveolar lavage (BAL) data lead to a change in antimicrobial therapy. Methods. This study included a retrospective cohort of intensive care unit (ICU) patients who underwent FB for a diagnosis of suspected pneumonia. The study compared the outcome of patients in whom antimicrobial modification was carried out based on BAL reports versus those in whom it was not carried out. Cases where the procedure could not be completed or had incomplete records were excluded. The FB reports were accessed from the register maintained in the Department of Respiratory Medicine. The demographic details, clinical symptoms, laboratory investigations, and microbiological and radiology reports were recorded. Data on the antmicrobial therapy that the patients received during treatment and the outcome of the treatment were obtained from the case records and noted in the data collection form. Results. Data from a total of 150 patients admitted to the ICU, who underwent FB, were analyzed. The outcomes in the group where antimicrobial modification based on bronchoalveolar lavage (BAL) fluid reports was carried out versus the no-change group were as follows: expired 23, improved 82, unchanged 8 versus expired 12, improved 18, and unchanged 7 (p = 0.018); total duration of ICU stay 13.12 ± 10.61 versus 19.43 ± 13.4 days (p = 0.012); and duration from FB to discharge from ICU 6.33 ± 3.76 days versus 8.46 ± 5.99 (p = 0.047). The median total duration of ICU stay and clinical outcomes were significantly better in the nonintubated patients in whom BAL-directed antimicrobial modification was implemented. Distribution of microorganisms based on BAL reports was as follows: Acinetobacter baumanii 45 (30%), Klebsiella pneumoniae 37 (24.66%), Escherichia coli 9 (6%), and Pseudomonas aeruginosa 9 (6%). Conclusion. A change in antimicrobial therapy based on BAL data was associated with improved outcomes. The commonest bacterial isolate in the BAL fluid was Acinetobacter baumanii.

The Dynamics of the Results of Bacteriological Studies Obtained from Clinical Samples in a Multidisciplinary Surgical Hospital Converted for the Treatment of Patients with COVID-19

Nosocomial infections remain a serious problem and are one of the main causes of unfavorable outcomes.
 Local microbiological monitoring of the etiological structure and the level of antibiotic resistance is necessary for the
 development and improvement of surgical, anesthetic and intensive care and for the prevention of nosocomial infection.
 Goal of the study: To evaluate the changes of the microorganisms’ structure and their resistance to antimicrobial drugs
 after conversion of a multidisciplinary surgical hospital into an infectious diseases hospital due to COVID-19 pandemic.
 The study included the patients who were treated at the «City Clinical Hospital» named after Professor A.M. Voino-
 Yasenetsky from 2006 to 2020, including the period of conversion of a multidisciplinary surgical hospital into an
 infectious diseases hospital due to COVID-19 pandemic. 8 411 positive bacteriological tests were studied.
 For 15 years, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Staphylococcus aureus dominated in the
 structure of causative agents of purulent-infl ammatory diseases.
 In 2020, the overwhelming majority of K. pneumoniae isolates were resistant to ampicillin, cefuroxime, cefotaxime,
 ceftazidime, and cefi pime, while maintaining the activity of amoxicillin with clavulanic acid up to 50 % that indirectly
 indicates the production of expanded spectrum of activity (ESBL) plasmid β-lactomases. The increase in K. pneumoniae
 strains resistant to carbapenems to 33,4 % is very alarming, because this is an unfavorable prognostic sign.
 Hospital conversion leads to a change in the microbial landscape and requires a change in antimicrobial therapy
 algorithms. A modern epidemiological feature in patients with COVID-19 is the predominance of spp. Candida (32,8 %)
 and Str. pneumonia (36,4 %) in the structure of microorganisms. The increase of multi-resistant strains of microorganisms
 is associated with respiratory support. It is necessary to monitor the level of resistance of key microorganisms to
 antimicrobial drugs in every hospital.

Diagnostic Yield of Bronchoscopy in Children with Leukemia or Post Hematopoietic Stem Cell Transplant

This project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute funded, in part by UL1TR002529 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
 Background: The utilization and diagnostic yield of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised children is not well understood. We aim to describe bronchoscopy use and complication rates and to investigate diagnostic yield.
 Project Methods: This is a retrospective cohort study of 60 children with leukemia or post hematopoietic cell transplant who had a bronchoscopy with BAL at Riley Hospital for Children between 2017 and 2021. Existing datasets and the electronic medical record were used to collect data on demographics, transplant and diagnosis information, as well as respiratory and bronchoscopy data. Inferential statistics were used. Comparisons were done with regression analysis.
 Results: Of the 60 bronchoscopies performed, 48 (80%) revealed diagnostic information: 41 (68%) identified a pathogen, 14 (23.3%) found significant secretions/mucus plugging, and 6 (10%) found pulmonary hemorrhage. BAL results led to a change in antimicrobial therapy in 27 (45%) cases. Blood cultures, respiratory viral panels and serum pathogen testing did not always correlate with BAL results. In patients with other infectious workup, 53% of bronchoscopies found a new infectious diagnosis. Of this cohort, 39 (65%) received supplemental oxygen for a median of 3 (IQR: 1-7) days prior to the bronchoscopy. Most patients, 58 (96.7%), had respiratory symptoms for a median of 5 (IQR: 2-18) days prior to bronchoscopy. Antibiotic use prior to bronchoscopy was common with use in 56 (93.3%) patients for a median length of 6 (IQR: 3-14) days. None of these factors were associated with the diagnostic yield. No patient required an escalation of respiratory support post-bronchoscopy. For the 25 (41.7%) children on mechanical ventilation when the bronchoscopy was performed, there was no difference in ventilator settings pre and post-bronchoscopy.
 Conclusion and Implications: Bronchoscopies with BAL are useful, safe, and important in the diagnostic management of pulmonary complications in this cohort of children.

536. Evaluation of the Clinical Utility of Universal Polymerase Chain Reaction Testing

Abstract Background Despite advances in microbiologic techniques, for patients with complex infections it often remains a challenge to identify the causative infectious pathogen. Traditional cultures (Cx) may fail to grow microorganisms due to inadequate sampling, prior antibiotic use, or the inherent insensitivity of culture methods for fastidious pathogens. Molecular tests allow for the detection of microbial nucleic acids directly from clinical specimens and do not require the presence of viable organisms for identification. Universal polymerase chain reaction testing (UPCR) is offered though the University of Washington Department of Laboratory Medicine and Pathology as a metagenomic approach using broad-range PCR primers followed by sequencing to hypothetically identify any pathogen present. The testing is composed of 3 separate tests for bacterial (BUPCR), fungal (FUPCR), and acid-fast (AFUPCR) organisms. The utility of UPCR has not been formally evaluated. Our objective is to describe the diagnostic utility of UPCR by comparing Cx and UPCR results, and their impact on management. Figure 1:Introduction - Types of Universal PCR Testing Methods We retrospectively collected data on UPCR and culture results and changes in antimicrobial therapy based on UPCR results for all patients with at least 1 UPCR test done during the 2-year study period. Results 367 UPCR tests were performed over 24 months on 155 patients. From 367 tests, 119 were FUPCR, 111 AFUPCR, and 137 BUPCR. 32/155 (20.6%) patients had positive UPCR. 25/32 were BUPCR and 7/32 were FUPCR. No AFUPCR was positive. In 8/155 (5.2%) patients management was changed based on UPCR results: Positive UPCR results directed treatment in 5 patients: 4 patients had positive UPCR and negative culture, and 1 had both UPCR and Cx positive but for different organisms. In all 5 therapy was changed in favor of UPCR result. All 5 tests were BUPCR.Negative UPCR led to antimicrobial discontinuation in 3 patients. 11/155 (7.1%) patients had negative UPCR and positive Cx, 10 of which were BUPCR and 1 AFUPCR. These results did not change management. Figure 2:Results – Type of Tissue and Test ResultsFigure 3:Results – Universal PCR Test Type and ResultsFigure 4:Results - Summary Conclusion Based on the real-world experience, UPCR results have limited impact on antimicrobial management in our institution. Further studies may try to identify clinical scenarios where UPCR may be of better clinical utility. Disclosures All Authors: No reported disclosures.

877. Synovial Fluid Testing Using the BioFire® Joint Infection (JI) Panel Potentially Decreases Time to Antibiotic Optimization for Acute Joint Infections

Abstract Background Traditional synovial fluid culture for acute joint infection (AJI) is time-consuming, potentially delaying initiation of targeted antimicrobial therapy. The BioFire® Joint Infection (JI) panel, a multiplex PCR for synovial fluid, has been shown to have 90.2% sensitivity and 99.8% specificity for diagnosis of AJI. We sought to determine the potential impact of the JI panel on antimicrobial use for AJI at our institution. Methods Antimicrobial use was retrospectively reviewed in a cohort of adult inpatients who underwent synovial fluid culture and were diagnosed with septic arthritis or periprosthetic joint infection from Sept 2021-Apr 2022. Patients were excluded if there was an alternative source of infection or septic shock. Synovial fluid specimens were tested using the JI panel, and results were compared to those of traditional culture methods. Patients who were initially treated with broad-spectrum antimicrobials for AJI were included in a review of antimicrobial prescribing. Records were reviewed to determine the time at which a transition to targeted therapy was made when using culture. This was compared to the time at which panel results could be available and acted upon, in this study presumed to be 12 hours after culture collection. Results 42 inpatients met study criteria for comparison of culture and JI panel results. The panel identified the organism that was grown in culture in 21 cases while detecting an organism in 5/16 culture-negative cases (table 1). In 5 cases, culture identified an organism not included on the JI panel. 29 patients met criteria for review of antimicrobial prescribing. Of these, therapy in 14/16 with positive cultures could have been changed earlier (table 2), resulting in an average reduction of time to targeted therapy of 57 hours (range 27–107 h, median 50.5 h) per patient. Targeted therapy could have occurred in 5/13 culture-negative cases. Summary of comparison of culture and BJI panel results. *Organisms identified by culture: Coagulase-negative staphylococci (n=4), Pasteurella multocida (n=1) **Organisms detected by JI panel: Streptococcus pyogenes (n=2), Streptococcus agalactiae (n=1), Finegoldia magna (n=1), Enterobacter cloacae (n=1) Proportion of patients eligible for a change in antimicrobial therapy. Conclusion Use of the JI panel could have prompted earlier optimized therapy in approximately two-thirds of patients. In 5 instances where cultures were negative, important AJI pathogens were identified. Another potential benefit includes reduced exposure to unnecessary broad-spectrum antimicrobials. Future study should evaluate the actual impact of the JI panel in practice. Disclosures All Authors: No reported disclosures.

203. When rapid molecular blood culture testing fails to identify the organism: microbiology and patient outcomes

Abstract Background Verigene™ is a rapid nucleic acid test used to optimize antibiotic selection on positive blood cultures but it does not detect all pathogens. The purpose of this project was to describe the organisms Verigene™ could not identify as well as the clinical outcomes of the patients. Methods This was a single-center, retrospective cohort study of patients who received a Verigene™ non-detected result from 5/19/20-6/30/21. The primary objective of this study was to identify the organisms and secondary objectives included any changes in antimicrobial therapy after the test result, appropriateness of change in therapy, discharge disposition, and 30-day readmission rate. Results A total of 85 of 958 (8.9%) Verigene results were non-detected during the time period. Among the 85 results included for the primary objective, six were determined to be contaminants by the clinicians. Among the remaining 79 results, 44 were anaerobic bacteria, 11 Serratia species, and 24 were other miscellaneous bacteria. Therapy was changed in 62 (78.5%) after the Verigene result. Overall antibiotic regimens were deemed appropriate after antibiotic changes were made from the final culture result in 70 of 79 (88.6%) cases. Twenty five of 79 (31.6%) patients died in the hospital. Among the 54 patients discharged, 11 (20.3%) were readmitted within 30 days including five (9.2%) due to infection. No cases of infectious readmission were due to the prior episode of bacteremia. Conclusion The majority of Verigene results that were not able to be identified were later identified to be anaerobic bacteria and Serratia species which are known limitations of the test. While most patients received appropriate therapy, there was a high mortality and readmission rate. Further studies should be performed to confirm this observation. Disclosures All Authors: No reported disclosures.

Epidemiology, Outcomes and Tolerability of Protracted Treatment of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States.

Nontuberculous mycobacterial (NTM) infections present a treatment challenge for clinicians and patients. There are limited data about current susceptibility patterns and treatment outcomes in U.S. adults. This was a 10-year, single-center, retrospective, observational cohort study of adults with a positive NTM culture and clinical suspicion of infection between 1 January 2010 and 30 June 2020. The primary objective was to identify predictors for favorable treatment outcomes. Key secondary objectives were characterization of NTM epidemiology, susceptibility profiles, and safety and tolerability of treatment, including the proportion of subjects with an antimicrobial change and the reasons for the change. Of 250 subjects diagnosed with NTM infection, the most prevalent NTM isolates were Mycobacterium avium intracellulare complex (66.8%) followed by Mycobacterium abscessus (17.6%). Antimicrobial susceptibility data were available for 52.4% of the cohort (45.8% slow growers; 54.2% rapid growers). Only 88 (35%) subjects received treatment with evaluable clinical outcomes. The proportion of subjects with a favorable outcome was 61.4%. More subjects in the unfavorable outcome group experienced a change in antimicrobial therapy (73.5% vs. 51.9%, p = 0.043). The most common reason for antimicrobial change was adverse drug events (n = 36, 67.9%). In the regression model, private insurance was associated with a favorable outcome, whereas having multiple antimicrobial changes was associated with an unfavorable outcome. The complexity of NTM treatment and high incidence of medication-related issues suggest the necessity of interdisciplinary collaboration to improve overall treatment outcomes in NTM infections.

Evaluation of the Potential Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients With Hospital-Acquired Pneumonia.

BackgroundRapid diagnostic tools have emerged as valuable assets assisting clinicians in decision-making regarding patient management in the hospital setting. Our study sought to identify the potential impact of the BioFire® FilmArray® Pneumonia Panel (FP Panel) (BioFire Diagnostics, Salt Lake City, UT, USA) in patients with hospital-acquired pneumonia (HAP).MethodsRespiratory samples obtained by bronchoalveolar lavage (BAL) or tracheal aspiration (TA) from ICU patients with a diagnosis of HAP were tested by the FP panel in addition to routine bacterial cultures. In addition, the electronic health records of these patients were reviewed to determine what potential changes in antimicrobial therapy could have been implemented if the panel results were known to the treatment team in real-time. A cost analysis was also performed incorporating the cost of the pneumonia panel and the savings associated with the potential decrease of antibiotic use and avoidance of the rapid viral diagnostic panel. ResultsFifty-six patients met the study criteria. The FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with an anticipated mean reduction in time to optimized therapy of approximately 51 hours. In addition, the panel identified three cases where antimicrobials should have been altered because patients were not receiving empiric therapy with activity against the causative pathogen and 34 opportunities for antibiotic de-escalation. The cost analysis calculated an additional cost of $10 per patient associated with using the FP panel. ConclusionsThe FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include a more rapid time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.

1032. Evaluation of a Multiplex Rapid Diagnostic Panel in Respiratory Specimens from Critically Ill Patients with Hospital-Acquired Pneumonia

BackgroundRapid diagnostic tests can be a valuable aide in clinical decision-making but often cost more than traditional cultures. Prior to its implementation at our institution, we sought to evaluate the potential clinical and financial impact of using the FilmArray® Pneumonia Panel® (FP panel) in patients with hospital-acquired pneumonia (HAP). MethodsThis was a retrospective, observational, comparative study conducted at an 885-bed academic medical center. Respiratory samples obtained by bronchoalveolar lavage or tracheal aspiration from adult intensive care unit (ICU) patients with a diagnosis of HAP from Nov 2019 – Feb 2020 were tested by the FP panel in addition to routine cultures. Medical records were reviewed to determine potential changes in antimicrobial therapy if FP panel results were known by the treatment team in real time. A cost analysis was also performed incorporating the cost of the FP panel and the savings associated with the potential avoidance of antibiotics and other rapid diagnostic tests normalized per patient. Results56 patients met study criteria. FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with a mean reduction in time to optimized therapy of approximately 51 hours. The panel identified 3 cases where the causative pathogen was not treated by empiric therapy and 34 opportunities for antibiotic de-escalation, the most common being the discontinuation of empiric vancomycin. 36 patients had been tested with a Respiratory Virus Panel, which could have been avoided if the FP panel was used. The potential therapy impact based on specific ICU and respiratory culture results is summarized in Table 1. The cost analysis calculated an additional cost of &10 per patient associated with using the FP panel. Table 1. Potential Changes in Therapy Based on Patient Location and Culture Result ConclusionThe FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include quicker time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.Disclosures James Johnson, PharmD, FLGT (Shareholder) Vera Luther, MD, Nothing to disclose

138. Implementation of an Antimicrobial Stewardship Order Set in the Emergency Department at a Quaternary Care Facility

BackgroundImplementation of antimicrobial stewardship (AS) interventions in the emergency department (ED) has been associated with improved patient outcomes. One potentially promising AS strategy is the implementation of an ED-specific, evidence-based antimicrobial order set. In this study, we aimed to examine the impact of implementing an ED-specific order set (EDOS) on the appropriateness of empiric antimicrobial therapy.MethodsWe conducted a pre-post quasi experimental study on 160 adult patients presenting to the ED with suspected or confirmed common infections at our quaternary healthcare facility. The EDOS was implemented in December 2020, providing evidence-based recommendations for the management of common infectious diseases. Data was collected between September 2019 and March 2020 for the pre-EDOS implementation group and between January 2021 and April 2021 for the post-EDOS implementation group.Pregnant women and patients with suspected or confirmed COVID-19 infection were excluded. Data were analyzed using two-sample T-test and mixed effects logistic regression. The primary study outcome was the appropriateness of antimicrobials selected, and the secondary outcomes were clinical and microbiologic cure, length of hospital stay, Clostridioides difficile infection, and the number of changes in antimicrobial therapy on transition to inpatient setting.ResultsA total of 100 ED patients pre-EDOS implementation and 60 patients post-EDOS implementation were compared. At baseline, patients in the post-EDOS group were older (59.83±20.30 years vs. 50.17±19.97 years, P=0.0037). A higher number of patients in the post-EDOS group had a history of multiple comorbidities (76.67% vs. 54%, P=0.0039). There was a higher rate of appropriate antimicrobial use in the post-EDOS group as compared to the pre-EDOS group (88.3% vs. 50%, P< 0.001). Longer hospital stays were observed in the post-EDOS group (P=0.0005). Clinical cure was similar between the two groups (96.6% vs. 94%, P=0.4568). ConclusionIn our study, we observed higher rates of appropriate antimicrobial selection after implementation of an EDOS. Use of an EDOS may represent a valuable AS intervention to guide appropriate antimicrobial prescribing in the ED, and larger studies are needed to confirm those findings.Disclosures All Authors: No reported disclosures

A retrospective observational study of the impact of 16s and 18s ribosomal RNA PCR on antimicrobial treatment over seven years: A tertiary hospital experience.

BackgroundAlthough culture-based methods remain a staple element of microbiology analysis, advanced molecular methods increasingly supplement the testing repertoire. Since the advent of 16s and 18s ribosomal RNA PCR in the 2000s, there has been interest in its utility for pathogen detection. Nonetheless, studies assessing the impact on antimicrobial prescribing are limited. We report a single-centre experience of the influence of 16s and 18s PCR testing on antimicrobial treatment, including a cost-analysis.MethodsData were collected retrospectively for all samples sent for 16s and 18s PCR testing between January 2014 and December 2020. Results were compared to any culture-based result. Assessment focused on any change of antimicrobial treatment based on PCR result, or use of the result as supportive evidence for microbiological diagnosis.Results310 samples relevant to 268 patients were referred for 16s/18s rRNA PCR testing during the period. Culture was performed for 234 samples. Enrichment culture was performed for 83 samples. 82 of 300 samples sent for 16s PCR had positive results (20.8%). When culture was performed, enrichment reduced the outcome of 16s PCR only positive results (4/36 [11.1%] versus 14/35 [40.0%], p = 0.030 where a pathogen found). 18s PCR yielded 9 positive results from 67 samples. The 16s PCR result influenced antimicrobial change for 6 patients (2.2%). We estimated the cost for 16s PCR testing to result in one significant change in antimicrobial therapy to be €3,340. 18s PCR did not alter antimicrobial treatment.ConclusionThere was limited impact of 16s PCR results on antimicrobial treatments. Relevance to practice was affected by relatively long turn-around-time for results. Utility may be increased in specialised surgical centres, or by reducing turn-around-time. Enrichment culture should be considered on samples where 16s PCR is requested. There remains limited evidence for use of 18s PCR in clinical management, and further studies in this area are likely warranted.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Retrospective analysis of 34 febrile neutropenia episodes - therapeutic implication of multiplex polymerase chain reaction in infection diagnosis

Hemato-oncologic patients on chemotherapy or undergoing bone marrow transplantation are susceptible to infections due to neutropenia. Incidences of febrile neutropenia (FN) in these patients are common, contributing to high mortality and morbidity. Lack of diagnosis of pathogens responsible for infections in these patients is a major healthcare challenge. Newer molecular diagnostics are increasingly becoming relevant. The objective of this retrospective study was to evaluate the effectiveness of Syndrome Evaluation System (SES), a multiplex molecular diagnostic platform for diagnosis of pathogens, and its impact on the management of FN. In total, 34 neutropenic episodes from 21 patients admitted during September 2013 to April 2015 were analyzed in this study. Clinical samples from patients were tested on SES and routine culture. Treatment was as per standard of care. SES showed a 5-fold higher clinical sensitivity (55.9%) as compared to automated culture (11.1%). SES results were available within 14 hours as compared to >72 hours for culture, and elucidated change in antimicrobial therapy in 50% of episodes. Mortality rates were lower when SES was used early in the episode. De-escalation of antimicrobials according to SES results was possible, which translated into substantial cost saving. Newer non-culture-based molecular technologies like SES are changing the way we manage FN. It is faster, has a higher diagnostic yield as compared to traditional culture, and helps in making rapid, evidence-based therapeutic decision-making including de-escalation of antimicrobials. It would potentially lead to a reduction in mortality and healthcare cost in the long run.

213. An Analysis of the Impact of Gastrointestinal Polymerase Chain Reaction Panel Use on Antimicrobial use at a Tertiary Care Academic Medical Center

BackgroundGastrointestinal Polymerase Chain Reaction (GI PCR) panels are increasingly utilized in place of conventional stool testing methods. Several studies have noted GI PCR testing is associated with a reduction in antibiotic prescribing. As it relates to the appropriate timing to order this test in hospitalized patients, one study showed decreased utility when ordered more than 72 hours into admission. At Tampa General Hospital, we utilize the BioFire® FilmArray® GI PCR panel. Since implementation in March 2015, its impact on antimicrobial use has not been formally assessed. Our aim was to evaluate the impact of the GI PCR panel and determine its usefulness as a potential tool for antimicrobial stewardship.MethodsWe conducted an IRB approved retrospective chart review in adult patients admitted to our institution who were ordered the GI PCR panel between 1/1/2018 and 12/31/19. Our primary objective was to assess antimicrobial prescribing patterns; secondary objectives included determining the quantity of tests ordered after 72 hours of admission and inpatient length of stay.ResultsOur initial chart review of 50 patients who were ordered the GI PCR panel revealed 60 % (n = 30) females with an overall median age of 55 years (interquartile range (IQR): 40.75,66.75). GI PCRs were ordered a median of 1 day into the hospital admission (IQR: 1,3) with 6 patients having a test ordered longer than 72 hours into their admission. The median length of stay was 5 days (IQR: 3,7). Testing was negative for 82 % of patients. For patients with positive tests, the most common pathogen identified was E coli (EPEC). Five out of 50 patients (10%) had antimicrobial therapy modified after GI PCR results. Internal medicine providers ordered the majority of tests in these patients (n = 26 (52 %)).ConclusionOur findings suggest the majority of GI PCRs were ordered within 72 hours of admission. However, changes in antimicrobial therapy were minimal. A limitation of our study includes patients who were on antimicrobials for other indications.Disclosures All Authors: No reported disclosures

Gallium-67 Single-Photon Emission Computed Tomography Affects Management of Infections of Left Ventricular Assist Devices.

Our institution employs gallium-67 single-photon emission computed tomography low-dose CT (Ga-SPECT-CT) to determine the presence and extent of left ventricular assist device (LVAD) infections. We present a retrospective single-center study of 41 LVAD recipients who underwent Ga-SPECT-CT from January 2011 to June 2018 to determine whether Ga-SPECT-CT led to changes in antimicrobial therapy, LVAD revision or exchange, or application for 1A exception. The average age was 56.6 years, predominantly male (80.5%) and diabetic (68.3%), divided between ischemic (48.8%) and nonischemic (51.2%) cardiomyopathy. The majority had HeartMate II devices (82.9%). Device-related infections were classified as possible (12.2%), probable (36.6%), proven (36.6%), or rejected (14.6%). Sensitivity was 68.6% and specificity was 100%. Most VAD-specific infections were percutaneous deep driveline infections (DRIs) (34.1%), and VAD-related infections were primarily bloodstream infections (31.7%). Staphylococcus aureus was the major pathogen isolated. Gallium-67 single-photon emission computed tomography low-dose CT resulted in changes in management in more than half (53.7%) of patients: starting (24.4%) or stopping (17.1%) antimicrobial therapy, LVAD revision (22.0%) or exchange (12.2%), and the application for 1A exception for transplant listing (17.1%). We conclude that Ga-SPECT-CT is an effective modality for determining the presence and extent of LVAD DRIs, and contributed to a change in management in more than half of cases.

Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case–control study

BackgroundThe Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. MethodA retrospective case–control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011–April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. ResultsThe derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65–0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0–1.3), medium- (1.4–2.3) and high-risk (2.4–4.3) patients for RGNB infection (P<0.001) in a UK setting. ConclusionA simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.

Role of Image-Guided Biopsy in the Diagnosis and Antimicrobial Management of Vertebral Osteomyelitis

Purpose The aim of this study was to evaluate the role of fluoroscopy-guided vertebral biopsy in vertebral osteomyelitis and determine if it results in a change in antimicrobial management based on bone culture yield. Materials and Methods This study is a retrospective chart review of 83 patients (49 men, 34 women; age range, 28–92 years; mean age, 56.9 years) with a diagnosis of vertebral osteomyelitis on imaging (computed tomography or magnetic resonance imaging) who underwent a fluoroscopy-guided biopsy from January 2010 to May 2015. Data collection included patient demographic information; etiology/risk factors for vertebral osteomyelitis; antibiotic exposure within 30 days before biopsy; blood, urine, and bone culture results; and any postprocedural change in antibiotic therapy. The primary outcome is culture yield from biopsy, whereas the secondary outcome is to determine if a change in antimicrobial therapy occurred based on biopsy results. A change in antimicrobial management is defined as transitioning from empiric antibiotic coverage to narrow-spectrum antibiotics based on positive bone culture yield or discontinuation of empiric antibiotic coverage based on negative culture yield. Biopsy culture yield was tested against a change in antimicrobial management with statistical analysis including the Fisher exact test. Results Positive bone culture yields were obtained in 22 (27%) of the 83 cases. Of the 22 that were positive, only 11 resulted in a change in antimicrobial management where broad empiric coverage was switched to narrow-spectrum organism-specific coverage. Of the remaining 61 negative cultures, only 2 (3%) had a change in management where the empiric antibiotic treatment was discontinued. Whether the culture results were positive or negative, 70 patients (84%) did not have any change in antimicrobial management after biopsy with the results being statistically significant (odds ratio, 27.3; 95% confidence interval, 5.25–141.82; P &lt; 0.0001). Conclusions Vertebral biopsies do not cause a significant change in antimicrobial management in the majority of cases.

Commercial bacterial and fungal broad-range PCR (Micro-Dx™) used on culture-negative specimens from normally sterile sites: diagnostic value and implications for antimicrobial treatment

The aim of this study was to evaluate the clinical value of partial 16S/18S rRNA gene sequencing with the commercial kit Micro-Dx™ used with the SelectNA™plus instrument on culture-negative samples. A retrospective study of microbiological and clinical data from a 2.5-year period was performed. Assessment of the clinical relevance of the 16S/18S rRNA gene sequencing results was based on evaluation of the results in the clinical context and changes in antimicrobial therapy. Included were 529 samples from 223 patients, representing 251 episodes. In 191 samples (36.1%), bacterial/fungal DNA was detected. Positive results were judged clinically relevant in 79 (31.5%) episodes. Antimicrobial treatment was adjusted according to the 16S/18S rRNA gene sequence analysis result in 42 (16.7%) episodes. The results from 16S/18S rRNA gene sequence analysis were highly clinically relevant. These findings support the use of this analysis in a routine setting.