Antibiotic Escalation Research Articles

Long-term Outcomes of Direct Endoscopic Necrosectomy for Complicated or Symptomatic Walled-Off Necrosis: A Korean Multicenter Study

Background/AimsThe endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis.MethodsThe data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected.ResultsSixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites).ConclusionsConsidering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Healthcare-Associated Viral Respiratory Infections in a Pediatric Intensive Care Unit and Cardiovascular Intensive Care Unit

Background: Healthcare-associated infections (HAIs) affect patient health and are tracked closely by infection prevention. Patients in a pediatric intensive care unit (PICU) acquired viral respiratory infections had longer use of respiratory support. We sought to determine the types of viral respiratory HAIs (VR-HAIs) acquired in the PICU and the characteristics of those affected. Methods: CHOC Children’s Hospital is a 334-bed tertiary-care center. Charts were reviewed on patients with VR-HAIs from fiscal years (FY) 2005–2020. High-risk VR-HAI (HR-VR-HAI) were influenza A and B, respiratory syncytial virus (RSV), adenovirus, parainfluenza, and human metapneumovirus (hMPV, added in FY 2014). Patients in the PICU, cardiovascular ICU (CVICU), and oncology ICU (OICU) with HR-VR-HAIs were reviewed. Patients were categorized according to underlying pathology, immunosuppression, and isolation prior to HR-VR-HAI. Increased respiratory support was defined as any increase from a patient’s baseline support ±24 hours of viral diagnosis: increase in oxygen flow or transition from nasal cannula to high-flow nasal cannula or ventilator support. Antibiotic escalation, defined as initiation of antibiotic therapy for ≥2 days ±24 hours of viral diagnosis or broadening the spectrum of antimicrobials for ≥2 days ±24 hours of viral diagnosis. Results: During FY 2005–2020, there were 204 VR-HAIs: 143 HR-VR-HAIs (70%), of which 39 (27.2%) occurred in ICUs (Figure 1). Most of the HR-VR-HAIs were RSV, parainfluenza, and hMPV (Figure 2). Of 39 patients, 10 (25.6%) had underlying oncologic conditions, 9 of whom were immunosuppressed. Of 39 patients, 16 (41%) had structural cardiac disease, 4 (10.3%) had pulmonary disease, 5 (12.8%) had neurologic disease, and the remaining 4 (10.3%) had other comorbidities. Of 39 patients, 12 (31%) required an increase in respiratory support and 13 (33%) had escalation of antibiotics. Of 39 HR-VR-HAI patients, 2 died within 2 weeks of acquisition. Conclusions: HR-VR-HAIs are uncommon in ICUs. RSV, parainfluenza, and hMPV are the most common, and 1 of 3 of patients required escalation in respiratory support and/or escalation in antibiotics. All patients had underlying comorbidities. In our series, there were 2 deaths within 2 weeks of infection.Funding: NoDisclosures: None

Descriptors of Sepsis Using the Sepsis-3 Criteria: A Cohort Study in Critical Care Units Within the U.K. National Institute for Health Research Critical Care Health Informatics Collaborative.

To describe the epidemiology of sepsis in critical care by applying the Sepsis-3 criteria to electronic health records. Retrospective cohort study using electronic health records. Ten ICUs from four U.K. National Health Service hospital trusts contributing to the National Institute for Health Research Critical Care Health Informatics Collaborative. A total of 28,456 critical care admissions (14,332 emergency medical, 4,585 emergency surgical, and 9,539 elective surgical). Twenty-nine thousand three hundred forty-three episodes of clinical deterioration were identified with a rise in Sequential Organ Failure Assessment score of at least 2 points, of which 14,869 (50.7%) were associated with antibiotic escalation and thereby met the Sepsis-3 criteria for sepsis. A total of 4,100 episodes of sepsis (27.6%) were associated with vasopressor use and lactate greater than 2.0 mmol/L, and therefore met the Sepsis-3 criteria for septic shock. ICU mortality by source of sepsis was highest for ICU-acquired sepsis (23.7%; 95% CI, 21.9-25.6%), followed by hospital-acquired sepsis (18.6%; 95% CI, 17.5-19.9%), and community-acquired sepsis (12.9%; 95% CI, 12.1-13.6%) (p for comparison less than 0.0001). We successfully operationalized the Sepsis-3 criteria to an electronic health record dataset to describe the characteristics of critical care patients with sepsis. This may facilitate sepsis research using electronic health record data at scale without relying on human coding.

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ~48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (~50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.

Fever and Abdominal Pain in Acute Pancreatitis

Question: A 44-year-old man with diabetes and a history of severe acute pancreatitis with encapsulated pancreatic necrosis in the context of hyperlipemia requiring admission to the intensive care unit. He was admitted for a second episode of acute pancreatitis. He initially presented renal failure and metabolic acidosis requiring admission to the intensive care unit with the need for vasopressors and the initiation of broad-spectrum antibiotic coverage. Despite antibiotic treatment, on day 7 of admission a high fever occurred, requiring antibiotic escalation with no microbiological findings.

Antibiotic prescribing patterns in patients hospitalized with COVID-19: lessons from the first wave.

BackgroundA high proportion of hospitalized patients with COVID-19 receive antibiotics despite evidence to show low levels of true bacterial coinfection.MethodsA retrospective cohort study examining antibiotic prescribing patterns of 300 patients sequentially diagnosed with COVID-19. Patients were grouped into 3 sub-cohorts: Group 1 received no antibiotics, Group 2 received antibiotics for microbiologically confirmed infections and Group 3 was empirically treated with antibiotics for pneumonia. The primary aim was to identify factors that influenced prescription and continuation of antibiotics in Group 3. Secondary aims were to examine differences in outcomes between groups.ResultsIn total, 292 patients were included (63 Group 1, 35 Group 2, 194 Group 3), median age was 60 years (IQR 44–76) and the majority were ethnically Irish (62%). The median duration of antibiotics was 7 days (IQR 5–10). In Group 3, factors associated with prescription IV antibiotics on admission were raised C-reactive protein (CRP) (P = 0.024), increased age (P = 0.023), higher quick SOFA (P = 0.016) score and fever >37.5 °C (P = 0.011). Factors associated with duration of antibiotic course were duration of hypoxia (P < 0.001) and maximum respiratory support requirement (P = 0.013). Twenty-one patients in Group 3 had one or more antibiotic escalation events, most (n = 139) had no escalation or de-escalation of therapy.ConclusionsDuration of hypoxia and need for respiratory support may have acted as surrogate measures of improvement where usual response measures (CRP, neutrophilia, culture clearance) were absent. Continuous review of antibiotic prescriptions should be at the forefront of clinical management of hospitalized patients with COVID-19.

Updates on bacterial resistance and empirical antibiotics treatment of complicated acute appendicitis in children

Objective: Through historical comparison with our previous study published 10 years ago, this paper aims to provide latest analysis of local bacteriology of acute complicated appendicitis and evaluate the effects of early escalation of potent antibiotics on course of postoperative recovery.Methods: A 5-year retrospective review of all children receiving emergency laparoscopic appendicectomies for acute appendicitis from December 2014 to November 2019 was conducted.Results: 257 cases of acute appendicitis were included, 126 were complicated appendicitis (38 gangrenous, 88 ruptured). 96 had positive peritoneal swab culture, 53 (42.1%) grew resistant bacterial strains, including extended spectrum beta-lactamase producing E. coli (ESBL E. coli), Pseudomonas aeruginosa, against traditional empirical triple antibiotics. The prevalence had significantly increased over the past decade (p = 0.008). In our patients, piperacillin/tazobactam, ertapenem, gentamicin provided coverage of 69.8%, 45.3% and 45.3% respectively. For patients with early escalation of postoperative antibiotics, no statistical significance was identified in terms of postoperative complications (p = 0.883), or duration of antibiotics (p = 0.0615).Conclusion: Growing prevalence of resistant strains were observed over the decade. Piperacillin/tazobactam provided the best coverage (69.8%) against resistant bacterial strains in our patients. Early escalation of antibiotics failed to reduce postoperative complications and antibiotics duration.Type of Study: Clinical Research, Retrospective Historical Comparative StudyLevel of Evidence: Level III

Tracheostomy in Postoperative Pediatric Cardiac Surgical Patients—The Earlier, the Better

AbstractObjectives This study was aimed to assess the benefits of early tracheostomy (ET) compared with late tracheostomy (LT) on postoperative outcomes in pediatric cardiac surgical patients.Design Present one is a prospective, observational study.Setting The study was conducted at a cardiac surgical intensive care unit (ICU) of a tertiary care hospital.Participants All pediatric patients below 10 years of age, who underwent tracheostomy after cardiac surgery from January2019 to december2019, were subdivided into two groups according to the timing of tracheostomy: “early” if done before 7 days or “late” if done after 7 days postcardiac surgery.Interventions ET versus LT was measured in the study.Results Out of all 1,084 pediatric patients who underwent cardiac surgery over the study period, 41 (3.7%) received tracheostomy. Sixteen (39%) patients underwent ET and 25 (61%) underwent LT. ET had advantages by having reduced risk associations with the following variables: preoperative hospital stay (p = 0.0016), sepsis (p = 0.03), high risk surgery (p = 0.04), postoperative sepsis (p = 0.001), C-reactive protein (p = 0.04), ventilator-associated pneumonia (VAP; p = 0.006), antibiotic escalation (p = 0.006), and antifungal therapy (p = 0.01) requirement. Furthermore, ET was associated with lesser duration of mechanical ventilation (p = 0.0027), length of ICU stay (LOICUS; p = 0.01), length of hospital stay (LOHS; p = 0.001), lesser days of feed interruption (p = 0.0017), and tracheostomy tube change (p = 0.02). ET group of children, who had higher total ventilation-free days (p = 0.02), were decannulated earlier (p = 0.03) and discharged earlier (p = 0.0089).Conclusion ET had significant benefits in reduction of postoperative morbidities with overall shorter mechanical ventilation, LOICUS, and LOHS, better nutrition supplementation, lesser infection, etc. These benefits may promote faster patient convalescence and rehabilitation with reduced hospital costs.

Protocol for an international, multicentre, prospective, observational study of nosocomial pneumonia in intensive care units: the PneumoINSPIRE study

Background: Nosocomial pneumonia in the critical care setting is associated with increased morbidity, significant crude mortality rates and high health care costs. Ventilator-associated pneumonia represents about 80% of nosocomial pneumonia cases in intensive care units (ICUs). Wide variance in incidence of nosocomial pneumonia and diagnostic techniques used has been reported, while successful treatment remains complex and a matter of debate. Objective: To describe the epidemiology, diagnostic strategies and treatment modalities for nosocomial pneumonia in contemporary ICU settings across multiple countries around the world. Design, setting and patients: PneumoINSPIRE is a large, multinational, prospective cohort study of adult ICU patients diagnosed with nosocomial pneumonia. Participating ICUs from at least 20 countries will collect data on 10 or more consecutive ICU patients with nosocomial pneumonia. Site-specific information, including hospital policies on antibiotic therapy, will be recorded along with patient-specific data. Variables that will be explored include: aetiology and antimicrobial resistance patterns, treatment-related parameters (including time to initiation of antibiotic therapy, and empirical antibiotic choice, dose and escalation or de-escalation), pneumonia resolution, ICU and hospital mortality, and risk factors for unfavourable outcomes. The concordance of ventilator-associated pneumonia diagnosis with accepted definitions will also be assessed. Results and conclusions: PneumoINSPIRE will provide valuable information on current diagnostic and management practices relating to ICU nosocomial pneumonia, and identify research priorities in the field. Trial registration:ClinicalTrials.gov identifier NCT02793141.

Impact of Next-Generation Sequencing Cell-free Pathogen DNA Test on Antimicrobial Management in Adults with Hematological Malignancies and Transplant Recipients with Suspected Infections

Infections in adult patients with hematological malignancies (HM) and stem cell transplant (SCT) recipients are a significant cause of morbidity and mortality. A timely diagnosis of infections can have a major impact on outcomes. Tools that help rule out infectious causes of fever can decrease antibiotic use, toxicities, hospitalization costs, and potentially decrease antibiotic resistance in the long term. We retrospectively evaluated the ability of cell-free DNA next-generation sequencing (NGS) testing in the timely identification of pathogenic microorganisms and its impact on the antimicrobial management of immunocompromised patients with hematologic malignancies. In the period between 2018 to 2020, 95 samples were reviewed, of which 31 adult patients (32 tests) had hematologic malignancies or were recipients of SCT. The NGS tests were performed in the following patients: (a) patients with prolonged fever and negative conventional tests, (b) persistent fever despite positive conventional test and appropriate antimicrobials, and (c) fever-free patients with imaging suspicious for infection. The median time from fever to NGS sampling was 5 days (range, 1-28). The median time to NGS results was 2 days (range, 1-6). The NGS resulted in an escalation of antibiotics in 28% of cases (9/32) and de-escalation of antibiotics in 31% of cases (10/32). Overall, NGS testing changed management in nearly 59% (19/32) of patients. The sensitivity and specificity of NGS to detect clinically significant infection was 80% and 58%, respectively. The test identified uncommon and difficult to diagnose organisms such as Nocardia, Legionella, Toxoplasma and Pneumocystis jirovecii resulting in rapid antimicrobial interventions. In conclusion, in patients with HM or SCT recipients, microbial cell-free DNA sequencing allowed rapid and actionable treatment. This strategy can target appropriate antibiotic use, avoid overtreatment, and potentially decrease the hospital length-of-stay.

EUCAST rapid antimicrobial susceptibility testing (RAST): analytical performance and impact on patient management.

The emergence of antibiotic-resistant species calls for fast and reliable phenotypic susceptibility testing to adapt clinical management as fast as possible. We assessed the real-life performance of EUCAST rapid antimicrobial susceptibility testing (RAST) and analysed its impact on patient management. RAST was performed on clinical blood cultures containing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii complex. Categorical agreement with VITEK2 was analysed. A pre-post quasi-experimental observational study was designed to compare antibiotic treatment in sepsis patients in the RAST patient group (n = 51) and a historical control cohort (n = 54). In total, 436 isolates, corresponding to 2314 disc diameters, were measured; 18.4% of these measurements were in the area of technical uncertainty. For the 81.6% categorical results, which could be compared, 94.7% were in agreement, whereas 5.3% of the results were not. In the RAST group, optimal therapy was initiated on the same day as blood culture positivity, while this was the case in the historical group after 24 h. In six cases, RAST allowed for rapid antibiotic escalation. The 30 day mortality rate was lower in the RAST group, although this was not statistically significant. RAST provides a reliable tool to improve clinical management of sepsis patients by providing rapid phenotypic susceptibility data. While not necessarily being an instrument for de-escalation, especially in areas of low prevalence, early detection allows for timely coverage of resistant isolates. Thus, RAST significantly adds to successful antibiotic stewardship programmes.

Evaluation of antibiotic escalation in response to nurse-driven inpatient sepsis screen.

To determine the frequency and predictors of antibiotic escalation in response to the inpatient sepsis screen at our institution. Retrospective cohort study. Two affiliated academic medical centers in Los Angeles, California. Hospitalized patients aged 18 years and older who had their first positive sepsis screen between January 1, 2019, and December 31, 2019, on acute-care wards. We described the rate and etiology of antibiotic escalation, and we conducted multivariable regression analyses of predictors of antibiotic escalation. Of the 576 cases with a positive sepsis screen, antibiotic escalation occurred in 131 cases (22.7%). New infection was the most documented etiology of escalation, with 76 cases (13.2%), followed by known pre-existing infection, with 26 cases (4.5%). Antibiotics were continued past 3 days in 17 cases (3.0%) in which new or existing infection was not apparent. Abnormal temperature (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.91-4.70) and abnormal lactate (aOR, 2.04; 95% CI, 1.28-3.27) were significant predictors of antibiotic escalation. The patient already being on antibiotics (aOR, 0.54; 95% CI, 0.34-0.89) and the positive screen occurred during a nursing shift change (aOR, 0.36; 95% CI, 0.22-0.57) were negative predictors. Pneumonia was the most documented new infection, but only 19 (50%) of 38 pneumonia cases met full clinical diagnostic criteria. Inpatient sepsis screening led to a new infectious diagnosis in 13.2% of all positive sepsis screens, and the risk of prolonged antibiotic exposure without a clear infectious source was low. Pneumonia diagnostics and lactate testing are potential targets for future stewardship efforts.

Direct Detection of Extended Spectrum β-Lactamases from Positive Blood Cultures by using Aztreonam and Clavulanate

Introduction: Bacterial Sepsis by Multidrug Resistant Gram Negative Bacilli (MDRGNB) producing Extended Spectrum β-Lactamases (ESBL) is one of the major causes of mortality and morbidity in hospitals. Early detection of ESBLs directly from positive blood cultures can reduce mortality. The phenotypic detection of ESBLs is difficult as they may be masked by the co-production of additional enzymes like AmpC. This can be overcome by using an Aztreonam Discs With and Without Clavulanate (AO/CL) method. Aim: To identify ESBLs directly from the positive blood cultures by using AO/CL disc diffusion method and to detect the genes coding for ESBL enzymes by conventional Polymerase Chain Reaction (PCR). Materials and Methods: A prospective study was conducted over a period of five months (October 2020-February 2021). A total of 100 positive blood cultures showing Gram-negative bacilli on Gram stain was subjected to direct detection of ESBLs by using Cefotaxime (CTX), Ceftazidime (CAZ) discs with and without clavulanate and AO/CL. Isolates from positive blood culture were identified to genus and species level by VITEK-2 compact. Isolates were tested for ESBL production by CAZ/CTX with and without clavulanate disc diffusion method as recommended by CLSI. PCR was carried out to detect target genes responsible for ESBL production such as CTX–M, TEM, SHV genes. Statistical analysis was done by using MS Excel sheet. Descriptive statistics like percentage calculation was done in the study. Results: Out of 100 positive blood cultures showing Gram Negative Bacteria (GNB) on Gram stain, 33 were positive for ESBL production by direct disc diffusion method. Out of these, 27 ESBL producers were detected by CAZ/CTX with and without clavulanate disc diffusion method and AO/CL method whereas six ESBL producers were detected by AO/CL disc diffusion method only. A 27 culture isolates were found positive for ESBL production by CAZ/CTX with and without clavulanate disc diffusion method as recommended by Clinical and Laboratory Standards Institute (CLSI). Out of 33, 28 (85%) isolates possessed one of the target genes for ESBL production such as 10TEM (36%), 10CTX-M (36%), 07TEM+CTX M (25%), 01SHV (3%). Conclusion: Direct detection of ESBLs plays a significant role in management of sepsis. It helps the clinician in escalation and de-escalation of antibiotics and prevents the development of antimicrobial resistance. It contributes towards antibiotic stewardship and better compliance to infection prevention and control protocols. AO/CL method is preferred to detect ESBL producers directly from positive blood culture bottles.

98. Clinical and Pharmacoeconomic Impact of Rapid Diagnostic Pneumonia Panel in Critically Ill Patients Admitted with Nosocomial Pneumonia

BackgroundRapid identification of causative organisms and tailored antibiotic therapy is essential to improving patient outcomes in critically ill patients with nosocomial pneumonia (NP). The BioFire ® FilmArray ® Pneumonia Panel (BFPP) can identify and semi-quantify the causative organisms via PCR. However, there is limited evidence of its implementation and utility within antimicrobial stewardship program (ASP) in managing NP.MethodsThis was an IRB-approved retrospective pre- and post-interventional study at an acute care hospital. Critically ill patients were included in the intervention group (IG) with a confirmed diagnosis of NP and had BFPP performed. Patients in IG were matched on a 2:1 ratio to a comparator group (CG) who did not receive BFPP. The primary endpoint was clinical cure (CC), defined as: 1) resolution of symptoms and/or leukocytosis; or 2) radiographic improvement; or 3) expression of CC noted by infectious disease physician. Secondary endpoints include time to escalation, de-escalation, or discontinuation of antibiotics, and inpatient mortality (IM). In addition, a pharmaco-economic analysis of the utilization of this panel was conducted.ResultsThere were 52 patients evaluated, of which 26 were included in IG and 13 were matched to be included in CG. Demographics were similar between the two groups. No difference in CC was observed between IG and CG (38.5% vs 38.5%, p = 1). However, when evaluating ASP interventions, more patients in IG had de-escalation (53.8% vs 15.4%, p = 0.01) and discontinuation (50% vs 7.7%, p = 0.003) performed compared to CG. No difference was seen in escalation of therapy (34.6% vs 30.8%, NS) and IM (26.9% vs 46.2%, p = 0.27). Time to ASP intervention was quicker by 24 hours in IG vs CG (24 vs 48 hours, p = 0.01). No difference was seen in total cost of therapy between the two groups ($289,500 vs $243,705, p = 0.6). However, cost savings of $31,000 was seen in total cost of ICU care in IG vs CG ($144,000 vs $175,000, p = 0.032).Figure 1: ASP Intervention ConclusionThere was no observed impact of BFPP on CC and IM in critically ill patients. However, utilization of BFPP led to faster time to ASP interventions and higher rates of de-escalation and discontinuation of antibiotics. When utilized as part of ASP, BFPP can serve to be a cost-effective option for critically ill patients.Disclosures All Authors: No reported disclosures

Impact of FilmArray Pneumonia Panel on Early Targeted Antibiotic Therapy

Background: Patients with pneumonia are frequently recipients of broad-spectrum antibiotics while awaiting maturation of respiratory cultures. FilmArray pneumonia panel (FPP) is an option for more expeditious identification of pathogen(s). We evaluated the utility of FPP in early de-escalation or escalation of antibiotics. Methods: FPP tests were performed on adults hospitalized with pneumonia. The microbiologist directly communicated the organisms, colony counts, and resistance patterns to the infectious disease physician or pharmacist. These results were also compared with pathogen identification and resistance patterns from a VITEK-2 system. The primary objective of this analysis was to evaluate the rates of de-escalation, escalation, and discontinuation of therapy and their impact on inpatient mortality. The secondary objective of the analysis was to evaluate the confirmation of detected organisms and resistance patterns by FPP. Results: In total, 26 patients included in the analysis. The median age was 70 years and 62% of patients were men; 50% of these patients were critically ill. In the cohort, the most commonly identified organisms were Pseudomonas aeruginosa (31%) and Staphylococcus aureus (30%). Other common organisms were Moraxella catarrhalis (23%) and influenza A (15%). The CTX-M resistance gene was seen in 30% of Enterobacteriaceae cultures, and the MecA/C and MREJ genes were detected in 75% of Staphylococcus aureus cultures. As a result of FPP, de-escalation occurred at a rate of 62%; discontinuation occurred at 42%; and escalation occurred 23%. Inpatient mortality was similar among the 3 groups: de-escalation, 37.5%; discontinuation, 45.5%; escalation, 50%. Notably, 82% of patients received comfort care. Organisms and resistance rates were confirmed with respiratory cultures in 54% of patients. Conclusions: Utilizing FPP yielded high rates of de-escalation, discontinuation, and escalation of antibiotics. No impact noted on inpatient mortality was noted; most of these patients were managed by comfort care. Culture confirmation rates were low due to the variety of sample types. We believe that the use of FPP for bronchoscopy and endotracheal cultures would have the highest impact on antibiotic stewardship efforts.Funding: NoneDisclosures: None

S2648 Spontaneous Peritonitis and When to Escalate Therapy From Bacterial to Fungal: A Case Report and Review of the Literature

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a disease seen in patients with decompensated liver cirrhosis and can be deadly. Clear diagnostic criteria have been established with ascites showing >250 PMNs/mm at which point of time empiric antibiotic therapy should be initiated. Spontaneous fungal peritonitis (SFP) can present similarly to SBP, yet the diagnosis is often delayed and outcomes are poor. We present a case of a patient with SFP was misdiagnosed as SBP, followed but criteria that can distinguish those at high risk for SFP for whom early antifungal therapy could be considered. CASE DESCRIPTION/METHODS: A 67 yr old man with a history of decompensated NASH cirrhosis, CKDIII and diabetes presented to our hospital with acute kidney injury and abdominal pain, after having been discharged 2 weeks prior for a C. difficile infection and ascites requiring paracentesis. Signs and symptoms on arrival suggested spontaneous bacterial peritonitis with abdominal distension and tenderness and ceftriaxone was started empirically. Nephrology was consulted for kidney injury and diagnosed hepatorenal syndrome type 1. His initial paracentesis ascites fluid showed >4000 PMNs/mm3, confirming SBP. On day 2 he underwent hemodialysis and developed altered mental status, respiratory distress and hypotension and was emergently transferred to the ICU for intubation and antibiotic escalation to vancomycin, cefepime and metronidazole for septic shock. At 48 hours he underwent second paracentesis for which ascites fluid showed 3600 PMNs/mm3, suggesting failure of SBP therapy. Candida glabrata grew from initial paracentesis culture on day 3 and empiric micafungin was initiated. By day four with worsening clinical status and dismal prognosis, he was made comfort care after discussion with family. DISCUSSION: Effective medical therapy has been established for SBP, but such is lacking for spontaneous fungal peritonitis (SFP). In cases where SBP therapy fails, SFP should be seriously considered. Mortality for SFP remains significant at 50–100%, thought to be due to the delay in culture-based fungal therapy initiation. Literature suggests antifungal initiation at 48 hours does little to change initial prognosis and thus earlier initiation should be sought when possible. Ascitic fluid fungal PCR should be pursued for early diagnosis when SFP is suspected. We will present criteria that can delineate patients at high risk for SFP so that early empiric antifungal therapy can be initiated in attempt to improve overall prognosis.

Antibiotic modification versus withhold in febrile patients without evidence of bacterial infection, unresponsive to initial empiric regimen: a multicentre retrospective study conducted in Israel.

Prescribing antibiotics for febrile patients without proof of bacterial infection contributes to antimicrobial resistance. Lack of clinical response in these patients often leads to antibiotic escalation, although data supporting this strategy are scarce. This study compared outcomes of modifying, withholding, or continuing the same antibiotic regimen for such patients. Febrile or hypothermic stable patients with suspected infection, unresponsive to empiric antibiotic treatment, admitted to one of 15 internal medicine departments in three hospitals during a 5-year study period, were included. Patients with a definitive clinical or microbiological bacterial infection, malignancy, immunodeficiency, altered mental status, or need for mechanical ventilation were excluded. Participants were divided into groups based on treatment strategy determined 72h after antibiotic initiation: antibiotic modified, withheld or continued. Outcomes measured included in-hospital and 30-day post-discharge-mortality rates, length of hospital stay (LOS) and days of antimicrobial therapy (DOT). A total of 486 patients met the inclusion criteria: 124 in the Antibiotic modified group, 67 in the Antibiotic withheld group and 295 in the Initial antibiotic continued group. Patient characteristics were similar among groups with no differences in mortality rates in-hospital (23% vs. 25% vs. 20%, p= 0.58) and within 30days after discharge (5% vs. 3% vs. 4%, p= 0.83). Changing antibiotics led to longer LOS (9.0 ± 6.8 vs. 6.2 ± 5.6days, p = 0.003) and more DOT (8.6 ± 6.0 vs. 3.2 ± 1.0days, p < 0.001) compared to withholding treatment. Withholding as compared to modifying antibiotics, in febrile patients with no clear evidence of bacterial infection, is a safe strategy associated with decreased LOS and DOT.

Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN.

Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID). Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P < .001) and AST (13.5 [56] vs 44.9 [12.1] hours; P < .001). Median (interquartile range [IQR]) time to first antibiotic modification was faster in the RAPID arm vs the SOC arm for overall antibiotics (8.6 [2.6-27.6] vs 14.9 [3.3-41.1] hours; P = .02) and gram-negative antibiotics (17.3 [4.9-72] vs 42.1 [10.1-72] hours; P < .001). Median (IQR) time to antibiotic escalation was faster in the RAPID arm vs the SOC arm for antimicrobial-resistant BSIs (18.4 [5.8-72] vs 61.7 [30.4-72] hours; P = .01). There were no differences between the arms in patient outcomes. Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs. NCT03218397.

EP05 The wolf finds unusual prey

Abstract Background Systemic lupus erythematosus (SLE) or lupus (Latin for wolf) is a rare multi-system autoimmune disease that has usually presented by the fifth decade, with a seven-fold higher incidence in females, especially of Afro-Caribbean descent. It is a recognised cause of pyrexia of unknown origin (PUO) though infection and malignancy are far commoner causes. Lupus nephritis (LN) can be life-threatening and affects nearly one-third of patients. We highlight a surprising case of late-onset SLE in a 65-year-old Caucasian man that presented with PUO and early LN. Methods Our patient was known to have atrial fibrillation, hypertension and previous obstructing renal calculus and presented to the Emergency Department with two weeks of right flank pain and fevers. He required critical care admission due to haemodynamic instability. CT excluded obstructive uropathy but a complex right renal cyst was present with mild inflammatory stranding. Bloods showed new neutrophilia (8.31-9.50 x 109/L), anaemia (haemoglobin 93 g/L), thrombocytopenia (platelets 90 x 109/L) and acute kidney injury (creatinine 128 μmol/l from 90 μmol/l baseline). CRP persisted above 110 mg/L. Liver function and ferritin were normal. Despite escalation of antibiotics he remained febrile, creatinine peaked at 291 μmol/L with raised urine protein:creatinine ratio (PCR) of 384 mg/mmol. Repeated septic screens and blood-borne virus tests were negative. Further CT showed mild ascites and pleural effusions. Transthoracic echocardiogram revealed a small pericardial effusion only, and pleural aspirate was a transudate, without malignant cells. Results There was clinical improvement after three weeks despite persistent fevers and he was discharged. However, readmission within three days necessitated inotropic support. After stabilisation, he was transferred under Infectious Diseases in a tertiary hospital. Shortly afterwards, the autoimmune screen showed positive anti-nuclear antibody (ANA), with positive Crithidia luciliae IgG double-stranded DNA (dsDNA) and titres &amp;gt;379 IU/mL. Concurrent hypocomplementaemia (C3 0.22 g/L, C4 0.03 g/L) raised the possibility of LN with SLE and renal biopsy demonstrated class 3 LN. Prompt treatment with intravenous glucocorticoids and mycophenylate mofetil (MMF) resulted in an excellent recovery. Almost a year later, he is taking MMF 1g twice daily with prednisolone 10mg daily. His creatinine is stable at 110 μmol/L, urine PCR around 300 mg/mmol and complements have normalised, despite persistent dsDNA titre of 150 IU/mL. He continues driving taxis and reports a good quality of life. Conclusion There was low suspicion of SLE in this case given the absence of typical symptoms and considering his age, gender and ethnicity. A literature review of male patients with SLE suggested tendency for later-onset and a worse prognosis. There appears to be less LN but when present requires prompt immunosuppression as occurred in this case. Currently, the oldest documented male patient with both SLE and biopsy-proven LN at diagnosis was 74 years old. Disclosures M. Chakravorty None. R. Sandler None. A. El-Nayal None.

784 Automated SIRS Alert Systems Are Ineffective at Predicting Sepsis in Burn Patients

Abstract Introduction Burn injury patients represent a population at particularly high risk for sepsis and sepsis mortality due to the severe immunological insult. Because of the unique nature of burn injury, this population has largely been excluded from studies developing protocols for identification and treatment of sepsis. In our institution, the protocolized approach to sepsis starts with an alert if two SIRS criteria are met, regardless of the patient’s diagnosis. We examined whether the SIRS alert was an effective way to identify and treat sepsis in burn patients. Methods Patients admitted to the burn surgery service at an academic regional burn center were identified by querying the “SIRS alert” dashboard from the hospital’s quality and safety department. The dashboard is a record of every patient whose clinical status triggered a SIRS alert during hospital admission, and whether a screening order set was opened. The SIRS alert and order set usage data were analyzed directly from the dashboard. Each patient’s chart was then reviewed to decide whether there was clinical suspicion of sepsis at the time an order set was released. We determined that there was clinical suspicion of sepsis if antibiotics were initiated or escalated within 6 hours of a SIRS screening order set being opened. Results From January 1, 2019 until September 14, 2019 there were 225 patients admitted to the burn surgery service at an academic regional burn center. 70 patients, specifically receiving treatment in the burn ICU, met the criteria to trigger a SIRS alert at least once in that time. Across those 70 patients, a total of 1381 SIRS alerts were acknowledged by the nursing staff. Due to a lack of clinical suspicion for sepsis, the SIRS screening order set was opened 8.5% of the time an alert was acknowledged. Only two times in the 1381 alerts was an order set opened and then followed by the initiation or escalation of antibiotics within 6 hours. Conclusions SIRS criteria appear to be ineffective at helping clinicians to identify and treat sepsis in the burn patient population. This is consistent with the fact that burn patients are in a virtually constant state of inflammation, making SIRS alerts futile at picking up subtle changes that could indicate early sepsis. Applicability of Research to Practice Hospitals should abandon the use of the standard SIRS criteria as a starting point for sepsis protocols when treating burn patients. There does not yet exist a validated criteria set to replace the standard SIRS criteria. In the meantime, the Burn Sepsis Consensus Conference definitions could be used as a guideline to modify the criteria, and future research should continue seeking to identify early predictors of sepsis in the burn population.