Background: Accurate early identification of sepsis remains a major clinical challenge due to its heterogeneous presentation and overlap of clinical signs with the non-infectious systemic inflammatory response syndrome (SIRS). Timely differentiation is crucial for improving patient outcomes, meeting sepsis bundle requirements and reducing inappropriate antimicrobial use. We hypothesized that clinical and laboratory data available within the first 3 hours of patient presentation could be used to identify patients with sepsis to an actionable level of accuracy, in lieu of traditional microbiology results which would not become available until at least 12-24 hours. Data from two independent studies were used to quantify the diagnostic value of demographic, vital, clinical-laboratory, and microbiological data available at three time points for distinguishing retrospectively diagnosed critically ill patients with either sepsis or non-infectious SIRS. A particular focus of this work was an assessment of the utility of SeptiCyte RAPID (Immunexpress Inc., Seattle, Washington, USA) as an aid to sepsis diagnosis, producing actionable data within 1 hour. Methods: Data from two independent study cohorts were analysed. The 510k cohort consisted of 419 adult patients in intensive care (ICU) (MARS, VENUS, and NEPTUNE trials). The Andalusian cohort consisted of 353 ICU patients from the PANGEA study. Logistic regression models, selected by a greedy search algorithm and validated by repeated cross-validation, were used to determine the contributions of different variables to diagnostic accuracy. Diagnostic performance was quantified by area under the receiver operating characteristic curve (AUC). Results: For the 510k cohort, a baseline AUC of 0.69-0.73 was observed using 5-7 vital and demographic variables assessed immediately upon presentation (time T1). The addition of clinical-laboratory variables, in particular SeptiCyte RAPID, within 1-3 hours post-presentation (time T2) increased the AUC to 0.83-0.85). Finally, the addition of microbiological data 12-24 hours post-presentation (time T3) further improved the AUC to 0.90-0.91. Similar results were obtained for the Andalusian cohort. AUC values at the three time points were as follows: At time T1, AUC = 0.67 based solely on vital signs and demographics; at time T2, AUC = 0.87 based on vitals + demographics + SeptiCyte RAPID or other clinical laboratory data; at time T3, AUC = 0.93 based on vitals + demographics + SeptiCyte RAPID or other clinical laboratory data + microbiology results). For both cohorts, the most significant variables included temperature, mean arterial pressure, respiratory rate, suspected infection site; SeptiCyte RAPID, procalcitonin, confirmed bacterial infection and positive blood culture confirmation. Conclusions: Accuracy of identification of sepsis increases markedly as demographics and vital signs are supplemented with clinical-laboratory information, and ultimately with microbiological culture results. The AUC improves significantly from T1 to T2 as laboratory data, and in particular SeptiCyte RAPID results, become available. Integrating rapid host-response testing with SeptiCyte RAPID into time-based diagnostic frameworks may enhance early sepsis recognition, improve antimicrobial stewardship, and support guideline-driven clinical decisions. ### Competing Interest Statement K.A.N., T.D.Y., S.C., R.F.D., D.S. and R.B.B. declare that they are current or past employees or shareholders of Immunexpress, Inc. The remaining authors declare no competing interests. ### Clinical Trial NCT01905033, [NCT02127502][1] and [NCT05469048][2] ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board Statement: The studies were conducted in accordance with the Declaration of Helsinki and approved by Institutional Review Boards (see below). The primary cohort was drawn from retrospective ([NCT01905033][3] and [NCT02127502][1]; clinical-trials.gov (accessed on 17 February 2024)) and prospective trials ([NCT05469048][2]; clinicaltrials.gov (first submitted 15 July 2022, accessed on 17 February 2024)). The studies were named MARS, VENUS, and NEPTUNE. Ethics approval for the MARS trial was given by the Medical Ethics Committee of the Amsterdam Medical Center (approval 156 June 2010, # 10-056C). Ethics approvals for the VENUS trial were given by the relevant Institutional Review Boards as follows: Intermountain Medical Center/Latter Day Saints Hospital (approval, 21 February 2016, # 1024931); Johns Hopkins Hospital (approval 28 January 2016, # IRB00087839); Rush University Medical Center (approval 11 March 2016, # 15111104-IRB01); Loyola University Medical Center (approval, 10 March 2016, # 208291); Northwell Healthcare (approval 1 April 2016, #16-02-42- 03). Ethics approvals for the NEPTUNE trial were given by the relevant Institutional Review Boards as follows: Emory University (approval 4 December 2019, # IRB00115400); Grady Memorial Hospital (approval, 14 January 2020, # 00-115400); Rush University Medical Center (approval, 16 January 2020, # 19101603-IRB01); University of Southern California Medical Center (approval, 10 February 2020, # HS-19-0884-CR001). The secondary cohort was con-ducted in seven ICUs in Andalusia (Spain) and coordinated by the Virgen Macarena University Hospital in Seville. The study was approved by the Research Ethics Committees of the Virgen Macarena-Virgen Rocio University Hospitals (Certificate of Ethics Approval dated 23 Dec 2021. Trial name SEPT-ANC. Codigo Interno: 2662-N-21.) Informed Consent Statement: Informed consent was obtained from all subjects involved in the clinical studies. All methods used in this study were carried out in accordance with the relevant guidelines and regulations. For the secondary cohort blood sample extractions were permitted prior to obtaining written permission, if needed, to enable SeptiCyte RAPID results to be generat-ed as quickly as possible. Written consent from the patient, or next of kin, was obtained within 48 hours of ICU admission and the blood sample was discarded if written consent was not obtained. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02127502&atom=%2Fmedrxiv%2Fearly%2F2026%2F06%2F06%2F2026.05.27.26354135.1.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05469048&atom=%2Fmedrxiv%2Fearly%2F2026%2F06%2F06%2F2026.05.27.26354135.1.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01905033&atom=%2Fmedrxiv%2Fearly%2F2026%2F06%2F06%2F2026.05.27.26354135.1.atom

Candida auris is an emerging fungal pathogen associated with outbreaks in healthcare settings. We report a multiyear outbreak of C. auris in a burn intensive care unit in Illinois, USA, during 2021-2023. We identified 28 C. auris cases in the unit over a 2-year period, despite outbreak response and multimodal mitigation measures. Of the 28 case-patients, 15 (53.6%) were considered colonized and 13 (46.4%) had clinical infections. Phylogenetic analysis of whole-genome sequences revealed 4 distinct clusters of closely related (0-6 SNP differences) genomes containing 3-6 cases. Clusters generally contained temporally related isolates from patients with epidemiologic links; this finding suggests that multiple introductions and within-unit spread over a limited time were responsible for the outbreak, rather than transmission from a long-term source (e.g., persistent environmental contamination or staff carriage). Here, integrated traditional and genomic epidemiology supported C. auris outbreak investigation and response and informed targeted interventions.

The impact of chronic indwelling urinary catheters (IUCs) on the composition and stability of the urinary microbiota remains unknown. The primary aim of this study was to describe the urinary microbiomes of geriatric males with chronic IUCs. A secondary aim was to explore clinical catheter-associated urinary tract infection (CAUTI) courses of the participants. Geriatric male patients with chronic IUCs were followed longitudinally. Catheterized urine, catheter tips, and both urethral and periurethral swabs were collected from participants at monthly intervals. Microbes were isolated and identified from each specimen using an enhanced culture method called expanded quantitative urine culture (EQUC) and targeted 16S rRNA gene DNA sequencing. Microbial outcomes were examined both in the absence of urinary symptoms and in the context of clinical diagnosis of CAUTI. Ten male participants (mean age 86 years) were enrolled. Urinary microbiomes differed for each participant. However, within each individual, microbiomes were similar over time and across niches (bladder, catheter, urethra, and periurethra). Within-niche microbiomes differed across individuals, and this was observed over time. The most abundant bacteria isolated from all niches were known uropathogens. Six of 10 individuals met diagnostic criteria for CAUTI at least once during the 12-month observation period, but no evidence of this or antibiotic treatment/response was discernable in our monthly samples. The microbiomes of each participant were unique and remained similar over time and across niches. Longitudinal EQUC or 16S rRNA gene sequencing data could be useful to clinicians when diagnosing or treating possible CAUTI.IMPORTANCECatheter-associated urinary tract infections (CAUTIs) are serious but preventable nosocomial infections. The most common risk factor for developing CAUTI is prolonged use of indwelling urinary catheters (IUCs). This study provides the first longitudinal description of the urinary microbiomes of geriatric males with chronic IUCs, in the absence of urinary signs and symptoms, as a first step toward enhancing our knowledge of the impact of chronic IUCs on the composition and stability of the urinary microbiota. This is an understudied area, particularly for males.

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0–15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1–5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4–15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86–0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Background Persons with infectious Mycobacterium tuberculosis (MTB) pose a significant risk to others in crowded areas, such as emergency department (ED) waiting rooms. After a slow response to a first MTB exposure was associated with poor compliance with post-exposure MTB testing, we sought to determine if a more expedient response would improve compliance with post-exposure testing. Methods We compared two large MTB exposures occurring six months apart in the ED of an acute care academic hospital. Exposed patients and accompanying guests were contacted by phone and certified mail and offered baseline and follow-up QuantiFERON-TB Gold (QFT) tests, obtained 10-12 weeks apart. Results In the first exposure investigation, a positive MTB PCR test resulted three days after an infectious patient presented to the ED. Sixty-one non-staff were identified as potentially exposed (39 patients + 22 guests). Exposed persons were notified by telephone starting 16 days post-exposure. In the second exposure investigation, 90 non-staff exposures were identified (54 patients + 36 guests). Exposed persons were notified starting six days post-exposure. Baseline QFT testing was obtained by 30/61 (49%) and 39/90 (43%) persons in the first exposure and second exposures, respectively (p=0.48). Follow-up QFT testing was obtained by 13/61 (21%) and 17/90 (19%) in the first and second exposures, respectfully (p=0.68). 38/76 (50%) of exposed persons who were contacted directly by telephone obtained QFT testing, while 3/14 (21%) of persons only contacted indirectly (voicemail or certified mail) obtained QFT testing (p=0.049). Conclusions A more expedient response did not have an impact on post-exposure QFT test compliance. Direct communication was associated with a statistically greater likelihood of persons following through with post-exposure testing. A greater focus on initiating direct contact via telephone and communicating that two QFT tests are needed may be essential to compliance with post-exposure MTB testing. Persons with infectious Mycobacterium tuberculosis (MTB) pose a significant risk to others in crowded areas, such as emergency department (ED) waiting rooms. After a slow response to a first MTB exposure was associated with poor compliance with post-exposure MTB testing, we sought to determine if a more expedient response would improve compliance with post-exposure testing. We compared two large MTB exposures occurring six months apart in the ED of an acute care academic hospital. Exposed patients and accompanying guests were contacted by phone and certified mail and offered baseline and follow-up QuantiFERON-TB Gold (QFT) tests, obtained 10-12 weeks apart. In the first exposure investigation, a positive MTB PCR test resulted three days after an infectious patient presented to the ED. Sixty-one non-staff were identified as potentially exposed (39 patients + 22 guests). Exposed persons were notified by telephone starting 16 days post-exposure. In the second exposure investigation, 90 non-staff exposures were identified (54 patients + 36 guests). Exposed persons were notified starting six days post-exposure. Baseline QFT testing was obtained by 30/61 (49%) and 39/90 (43%) persons in the first exposure and second exposures, respectively (p=0.48). Follow-up QFT testing was obtained by 13/61 (21%) and 17/90 (19%) in the first and second exposures, respectfully (p=0.68). 38/76 (50%) of exposed persons who were contacted directly by telephone obtained QFT testing, while 3/14 (21%) of persons only contacted indirectly (voicemail or certified mail) obtained QFT testing (p=0.049). A more expedient response did not have an impact on post-exposure QFT test compliance. Direct communication was associated with a statistically greater likelihood of persons following through with post-exposure testing. A greater focus on initiating direct contact via telephone and communicating that two QFT tests are needed may be essential to compliance with post-exposure MTB testing.

Background Urine cultures (UCX) are frequently sent for diagnostic work-up of fevers, even when little else suggests there is a urinary tract infection (UTI). Yet, UCXs are very easily contaminated, often misleading caregivers. In normal hosts, it is very unlikely that a patient has a UTI, even if their UCX shows growth, unless there is concomitant inflammation/increased white blood cells (WBC) in the urine. Urinalysis (UA) measures urine WBCs and can be used to screen if urine should be reflexed for UCX. With rare exception, UA with ≤5 WBCs/high-powered field (HPF) need not be reflexed for UCX, while UA with>10 WBCs/HPF should be reflexed for UCX. We sought to determine if UAs with 6-10 WBCs/HPF were likely to have significant bacterial growth reflecting an underlying UTI. Methods We conducted a multicenter retrospective study of all UAs with reflex UCX from 10/01/2019-10/31/2020. All UAs found to have 6-10 WBCs per HPF and associated UCXs were examined. Clinical charts were reviewed for evidence to support/dismiss UTIs. Results 39,855 urine specimens were reviewed. 2,275 met inclusion criteria. Only 77 (3.4%) were flagged as "abnormal" UCXs. Chart review ruled out UTIs in all but 20 (0.9%) cases. 2,198 (99.6%) urines either had no growth (1,593 - 70.0%), scant growth (353 - 15.5%) or other findings consistent contaminated cultures (252 - 11.1%). Conclusions The overwhelming majority of urine specimens with 6-10 WBCs were unlikely to have an UTI and did not require reflex UCX. Decreasing the number of urine specimens that are reflexed to UCX would decrease unnecessary resource utilization in the lab and help reduce the number of misleading contaminated UCXs not from true UTIs. This could help to improve antibiotic stewardship, reduce antibiotic resistance pressures, reduce hospital onset C. difficile infection, and some cases with Foley catheters would no longer be reported as catheter-associated UTIs. Urine cultures (UCX) are frequently sent for diagnostic work-up of fevers, even when little else suggests there is a urinary tract infection (UTI). Yet, UCXs are very easily contaminated, often misleading caregivers. In normal hosts, it is very unlikely that a patient has a UTI, even if their UCX shows growth, unless there is concomitant inflammation/increased white blood cells (WBC) in the urine. Urinalysis (UA) measures urine WBCs and can be used to screen if urine should be reflexed for UCX. With rare exception, UA with ≤5 WBCs/high-powered field (HPF) need not be reflexed for UCX, while UA with>10 WBCs/HPF should be reflexed for UCX. We sought to determine if UAs with 6-10 WBCs/HPF were likely to have significant bacterial growth reflecting an underlying UTI. We conducted a multicenter retrospective study of all UAs with reflex UCX from 10/01/2019-10/31/2020. All UAs found to have 6-10 WBCs per HPF and associated UCXs were examined. Clinical charts were reviewed for evidence to support/dismiss UTIs. 39,855 urine specimens were reviewed. 2,275 met inclusion criteria. Only 77 (3.4%) were flagged as "abnormal" UCXs. Chart review ruled out UTIs in all but 20 (0.9%) cases. 2,198 (99.6%) urines either had no growth (1,593 - 70.0%), scant growth (353 - 15.5%) or other findings consistent contaminated cultures (252 - 11.1%). The overwhelming majority of urine specimens with 6-10 WBCs were unlikely to have an UTI and did not require reflex UCX. Decreasing the number of urine specimens that are reflexed to UCX would decrease unnecessary resource utilization in the lab and help reduce the number of misleading contaminated UCXs not from true UTIs. This could help to improve antibiotic stewardship, reduce antibiotic resistance pressures, reduce hospital onset C. difficile infection, and some cases with Foley catheters would no longer be reported as catheter-associated UTIs.

Objective: To determine the effectiveness of active, upper-room, germicidal ultraviolet (GUV) devices in reducing bacterial contamination in patient rooms in air and on surfaces as a supplement to the central heating, ventilation, and air conditioning (HVAC) air handling unit (AHU) with MERV 14 filters and UV-C disinfection.Methods: This study was conducted in an academic medical center, burn intensive care unit (BICU), for 4 months in 2022. Room occupancy was monitored and recorded. In total, 402 preinstallation and postinstallation bacterial air and non-high-touch surface samples were obtained from 10 BICU patient rooms. Airborne particle counts were measured in the rooms, and bacterial air samples were obtained from the patient-room supply air vents and outdoor air, before and after the intervention. After preintervention samples were obtained, an active, upper-room, GUV air disinfection system was deployed in each of the patient rooms in the BICU.Results: The average levels of airborne bacteria of 395 CFU/m3 before GUV device installation and 37 CFU/m(3) after installation indicated an 89% overall decrease (P < .0001). Levels of surface-borne bacteria were associated with a 69% decrease (P < .0001) after GUV device installation. Outdoor levels of airborne bacteria averaged 341 CFU/m(3) in March before installation and 676 CFU/m(3) in June after installation, but this increase was not significant (P = .517).Conclusions: Significant reductions in air and surface contamination occurred in all rooms and areas and were not associated with variations in outdoor air concentrations of bacteria. The significant decrease of surface bacteria is an unexpected benefit associated with in-room GUV air disinfection, which can potentially reduce overall bioburden.

Background Early recognition of infectious tuberculosis (TB) cases and use of appropriate precautions are essential to infection prevention. In late 2021, a patient with active pulmonary TB presenting with an abnormal x-ray and productive cough went unrecognized for nearly 20 hours in our emergency department. Methods Logs of patients' registration times and charts-reviews were used to determine patient and staff exposures. All potentially exposed patients were contacted by telephone, regular and certified mail and asked to present for free baseline interferon gamma release assay testing, followed by a free second test 10-12 weeks later. Patients were asked to provide information about anyone who accompanied them to the ED (visitors). The employee health service followed-up staff. Results 70 persons were recognized as potentially having TB exposure; including 9 staff and 39 patients. 32 patients reached by phone identified 22 additional visitors. Two staff wore N95s (considered not exposed). 5/7 (71.4%) staff, 17/39 (43.6%) patients and 13/22 (59.1%) visitors completed baseline post-exposure testing. 5/7 (71.4%) staff, 8/39 (20.5%) patients and 4/22 (18.2%) visitors completed follow-up testing. We estimate 17 additional visitors accompanied the patients never reached by phone. Conclusions A symptomatic smear-positive patient with active TB was not placed on appropriate precautions and ≥ 70 persons were potentially exposed to TB. No known TB conversions resulted from this event, but there was significant noncompliance with post-exposure testing, especially by non-staff. Hundreds of man-hours and thousands of resource dollars were spent on this investigation. Unnecessary staff exposures were identified, as only 2 staff used N95 respirators, although COVID-related precautions required N95 use by patient-facing staff. Non-staff reached directly by phone were more likely to come in for testing than those who only received mailings, underscoring the importance of personal direct communication. Names/contacts of all persons lost to follow up were provided to the department of public health. Early recognition of infectious tuberculosis (TB) cases and use of appropriate precautions are essential to infection prevention. In late 2021, a patient with active pulmonary TB presenting with an abnormal x-ray and productive cough went unrecognized for nearly 20 hours in our emergency department. Logs of patients' registration times and charts-reviews were used to determine patient and staff exposures. All potentially exposed patients were contacted by telephone, regular and certified mail and asked to present for free baseline interferon gamma release assay testing, followed by a free second test 10-12 weeks later. Patients were asked to provide information about anyone who accompanied them to the ED (visitors). The employee health service followed-up staff. 70 persons were recognized as potentially having TB exposure; including 9 staff and 39 patients. 32 patients reached by phone identified 22 additional visitors. Two staff wore N95s (considered not exposed). 5/7 (71.4%) staff, 17/39 (43.6%) patients and 13/22 (59.1%) visitors completed baseline post-exposure testing. 5/7 (71.4%) staff, 8/39 (20.5%) patients and 4/22 (18.2%) visitors completed follow-up testing. We estimate 17 additional visitors accompanied the patients never reached by phone. A symptomatic smear-positive patient with active TB was not placed on appropriate precautions and ≥ 70 persons were potentially exposed to TB. No known TB conversions resulted from this event, but there was significant noncompliance with post-exposure testing, especially by non-staff. Hundreds of man-hours and thousands of resource dollars were spent on this investigation. Unnecessary staff exposures were identified, as only 2 staff used N95 respirators, although COVID-related precautions required N95 use by patient-facing staff. Non-staff reached directly by phone were more likely to come in for testing than those who only received mailings, underscoring the importance of personal direct communication. Names/contacts of all persons lost to follow up were provided to the department of public health.

Abstract Background Identification of C. difficile infection (CDI) as community onset (CO) versus hospital onset (HO) is based upon the timing of the laboratory testing. Any lab diagnosis made after day 3 of hospitalization is classified as HO-CDI, even if there is clinical evidence that the patient had CDI before lab testing was sent on day 4 or later. Capturing CDI infection early in hospitalization is essential to proper diagnosis and management of CDI. Methods This is a single center retrospective study of all HO-CDI cases identified from January 2018 through January 2022. All cases were reviewed to determine if patients had loose stools during days 1-3 which were not tested, as these may have been missed opportunities to diagnose CO-CDI. We used nursing flowsheet determine if the patient had soft, loose, watery, liquid or pasty stool bowel movements (BM). Results We identified 302 unique patients diagnosed with HO-CDI during the 4 year study period. 181 (60%) were men. The mean age 57 (range 3-98 years), with increasing case numbers with increasing age groups: age 0-18 (19/6.3%), 19-39 (39/12.9%), 40-59 (73/24.2%), ≥ 60 (171/56.6%). Mean time of HO-CDI diagnosis was 12.4 days (range 4-122 days) with a skew towards early onset HO-CDI diagnosis as 86/302 (28.5%) testing positive on days 4-6. Overall, 119/302 (39.0%) of patients had identified missed opportunities for testing stools during days 1-3 of hospitalization. 38/86 (44.2%) of patients with HO-CDI diagnosed on days 4-6 had missed opportunities for testing. 40/302 (13.2%) patients expired during the index hospitalization. Conclusion Better tracking of patients' symptoms, number and consistency of BMs could improve recognition of patients presenting with CO-CDI. In turn, this would help to institute earlier isolation and treatment of these patients, as well as decreasing HO-CDI resulting from late recognition of CO-CDI which may falsely inflate HO-CDI case numbers, and/or lead to secondary hospital transmission from delayed isolation of patients with CDI. Our findings likely represent a significant under estimation of the magnitude of the errors of omission of missing opportunities for early diagnosis of CDI since it based on review of nursing flowsheets which often miss the number and consistency of patients' BMs. Disclosures Jorge Paiva Parada, MD MPH, Shionogi: Honoraria.

Abstract Background C auris is an emerging often multidrug resistant pathogen capable of causing severe morbidity and mortality. C auris has been increasingly isolated from patients in skilled nursing facilities and hospitals, and has been associated with facility outbreaks. A resilient pathogen, C. auris survives harsh disinfectants, desiccation and readily colonizes the environment posing an especially great risk to immunocompromised patients with large open wounds and long lengths of stay. Methods From 7/1/21 - 8/30/21 we noted a cluster of 4 patients with C auris in clinical cultures from the Burn ICU (BICU). A multidisciplinary team involving infection prevention, nursing/medical directors, health and safety, engineering, environmental services, and hospital leadership investigated the cluster as a potential outbreak. Mitigation measures involved a multi-modal response of C auris admission screening, weekly point prevalence testing of all BICU patients, environmental surface cultures, enhanced room cleaning, staff education, hand hygiene and personal protective equipment usage audits. Results 11 cases of C auris were identified on our BICU from 7/1/21 - 2/28/22. 5 (45.5%) cases from clinical isolates, 1 (9.1%) from a BICU point prevalence screen on 12/15/21, 5 (45.5%) as a part of weekly point prevalence screens started on 1/1/22. 6 (54.5%) patients were admitted for burn related injuries, 2 (18.2%) for Steven Johnson Syndrome, 2 (18.2%) for necrotizing wounds, and 1 (9.1%) for COVID-19 pneumonia. Cases occurred in 6/10 rooms in the Burn ICU. One (9.1%) patient expired during this outbreak (not deemed to be from C auris infection). Conclusion Resilient infections like C auris pose a risk of nosocomial transmission and potential high morbidity and mortality to burn patients with impaired immune defense and large open wounds. A multidisciplinary team using targeted interventions including screening, education, enhanced cleaning eradicated the outbreak in our BICU. As of 5/1/22, we went 13 + weeks without identifying a new case. The last patient with C auris was discharged 3/16/22. To prevent future outbreaks, we created a standardized response plan and instituted a universal screening protocol for C auris targeting all patient admissions from skilled nursing facilities and admissions to all ICUs. Disclosures Jorge Paiva Parada, MD MPH, Shionogi: Honoraria.

Background: Postoperative infectious complications after a pancreaticoduodenectomy remain a significant cause of morbidity. Studies have demonstrated that a preoperative biliary stent increases the risk of postoperative infectious complications. Few studies have investigated the specific preoperative biliary stent bacterial sensitivities to preoperative antibiotics and the effect on infectious complications. The goal of this study was to investigate if the presence of a preoperative biliary stent increases the risk of postoperative infectious complications in patients undergoing a pancreaticoduodenectomy. Additionally, we aimed to investigate biliary stent culture sensitivities to preoperative antibiotics and determine if those sensitivities impacted postoperative infectious complications after a pancreaticoduodenectomy. Methods: A retrospective chart review of patients who had undergone a pancreaticoduodenectomy at a single institution tertiary care center from 2007 to 2018 was performed. Perioperative variables including microbiology cultures from biliary stents were collected and analyzed. Results: A total of 244 patients underwent a pancreaticoduodenectomy. A preoperative biliary stent was present in 45 (18%) patients. Infectious complications occurred in 25% of those patients with a preoperative biliary stent, and 19% of those without (P = .37). Of those patients with a stent that was cultured intraoperatively, 92% grew bacteria and 61% of those were resistant to the preoperative antibiotics administered. Of the patients with a preoperative biliary stent and bacteria resistant to the preoperative antibiotics, 17% developed a postoperative infectious complication, compared with 20% if the bacteria cultured was susceptible to the preoperative antibiotics (P = .64). Conclusion: Infectious complications after pancreaticoduodenectomy are a significant cause of morbidity. Stent bacterial sensitivities to preoperative antibiotics did not reduce the postoperative infectious complications in the preoperative biliary stent group suggesting a multifactorial cause of infections. (C) 2020 Elsevier Inc. All rights reserved.

Abstract Background Clostridioides difficile can cause a severe infectious colitis and is often associated with significant morbidity and mortality. C. difficile infection (CDI) is defined as the presence of diarrhea plus a positive stool test, whereas C. difficile colonization is defined as a positive stool test in the absence of diarrhea or the presence of diarrhea attributable to causes other than CDI. Widespread use of stool polymerase chain reaction (PCR) testing, especially within the first 3 days of admission, has become common at our institution and has been associated with increased number of positive C. difficile tests results. However, C. difficile colonization rates may be 15% or higher. Oral (PO) vancomycin (vanc) is first line therapy for the treatment of CDI. We sought to evaluate the appropriateness of use of PO vanc in patients who tested positive for C. difficile via stool PCR within 3 days of admission. Methods We reviewed the clinical history, presence of diarrhea, risk factors for diarrhea, treatment and use of an infectious disease (ID) consultation for all patients 18 years of age or older found to test positive for C. difficile by PCR on stool assays during the first 3 days of admission from 07/01/18 to 12/31/18. Results A total of 228 patients met inclusion criteria. 183 (80%) received PO vanc while 45 (20%) did not. 131 (71.6%) of patients who received PO vanc had diarrhea, 39 (21.3%) did not have diarrhea, 13 (7.1%) the presence of diarrhea was unknown. 41 of 143 (28.7%) of patients without ID consults received PO vanc despite not having diarrhea, while 11 of 40 (27.5%) patients seen by ID received PO vanc despite not having diarrhea (p=0.888). Conclusion Most patients who tested positive for C. difficile received PO vanc had documented diarrhea, meeting the definition of CDI. However, over 1 in 5 (21.3%) of patients who received PO vanc did not have diarrhea and may have been colonized rather than have true CDI. ID consultation did not decrease the number of patients without diarrhea who received PO vanc or prevent treatment of colonized patients. This work reveals there may be an opportunity for improvement regarding management of CDI vs. C. difficile colonization which may enhance antibiotic stewardship and the appropriate use of PO vanc. Disclosures All Authors: No reported disclosures

Abstract Background Patient transportation for off unit procedures is associated with transfers from bed to chair to examination tables, frequent elevation of the urine collection bag (UCB) above the bladder and urinary reflux (UR) of bacteria-laden urine into the bladder, significantly increasing risks of catheter-associated urinary tract infection (CAUTIs). If UCBs were systematically emptied prior to transportation the likelihood of UR would be greatly diminished, potentially reducing CAUTIs. Methods During a 5-week period transportation services (TS) collected baseline data on UCB status of all ICU patients, classifying them as empty/good to go vs. full/not good to go (Phase 1). Then, TS were educated on the importance of reducing UR as part of CAUTI reduction and were empowered to request UCBs be emptied. In parallel, unit-based staff were instructed to drain CBs prior to patient transport off unit and to expect the TS would refuse transport if CB was not emptied (Figure 1). Wireless voice-activated communications devices were used to improve coordination between TS and unit staff. During a 3 month (Phase 2) period, TS again collected data on the UCB status of ICU patients while reinforcing the need to empty UCBs. Results At baseline it was a coin toss as to whether a patient’s UCB would be empty or full at the time of transportation, while over 90% of UCB were emptied in Phase 2 (47.1% and 52.9%, vs. 90.6% and 9.4%, empty and unemptied in Phase 1 and Phase 2, respectfully, P < 0.001) (Figure 2). Figure 3 shows the detailed UCB status (empty at TS arrival, emptied upon TS request, transported full, transport refused) during Phase 2, with significant month upon month improvements (P = 0.014). Conclusion Despite longstanding existing hospital policies promoting best practices, including the need to empty UCBs prior to transport, we found this was commonly ignored in usual practice. Recruiting the TS to enforce UCBs are empty at the time of transportation proved a very effective way to markedly improve best practices. If representative of general practices elsewhere, this suggests leveraging TS can help ensure UCBs are emptied prior to patient transport and reduce CAUTI risk. It also exemplifies how ancillary services can be recruited to play an active role in quality improvement/patient safety projects. Disclosures All authors: No reported disclosures.

Catheter-associated asymptomatic bacteriuria (CAABU) is frequent in intensive care units (ICUs) and contributes to the routine use of antibiotics and to antibiotic-resistant infections. While nurses are responsible for the implementation of CAABU-prevention guidelines, variability in how individual nurses contribute to CAABU-free rates in ICUs has not been previously explored. This study's objective was to examine the variability in CAABU-free outcomes of individual ICU nurses. This observational cross-sectional study used shift-level nurse-patient data from the electronic health records from two ICUs in a tertiary medical center in the US between July 2015 and June 2016. We included all adult (18+) catheterized patients with no prior CAABU during the hospital encounter and nurses who provided their care. The CAABU-free outcome was defined as a 0/1 indicator identifying shifts where a previously CAABU-free patient remained CAABU-free (absence of a confirmed urine sample) 24-48 hours following end of shift. The analytical approach used Value-Added Modeling and a split-sample design to estimate and validate nurse-level CAABU-free rates while adjusting for patient characteristics, shift, and ICU type. The sample included 94 nurses, 2,150 patients with 256 confirmed CAABU cases, and 21,729 patient shifts. Patients were 55% male, average age was 60 years. CAABU-free rates of individual nurses varied between 94 and 100 per 100 shifts (Wald test: 227.88, P<0.001) and were robust in cross-validation analyses (correlation coefficient: 0.66, P<0.001). Learning and disseminating effective CAABU-avoidance strategies from top-performers throughout the nursing teams could improve quality of care in ICUs.

Abstract Background Urinary tract infections (UTIs) account for 34% of all healthcare-associated infections (HAI). Urinary catheters (UC) are placed in 15–25% of hospitalized patients and >75% of HAI UTIs are UC-related. Bacteria introduced via UC can colonize the bladder within 3 days. So, the greatest risk factor for acquiring a catheter-associated urinary tract infection (CAUTI) is prolonged use of indwelling UC. Nursing (RN) staff noted inconsistency with appropriate use of UC and commonly UC remained in place well after their original indication had expired. Methods As part of a multi-faceted approach for quality improvement and patient safety, we rolled out an Agency for Healthcare Research and Quality (AHRQ)-based initiative to reduce UC days/Standardized Utilization Ratio (SUR). Daily critical reviews of the indication for UC were conducted by two groups. First, frontline night shift RN staff identified patients who no longer had a valid justification for continued UC. They handed-off the information to day-shift RNs, who recommend removal of UC during daily rounds with the physician teams. A second review was performed by Clinical Quality Improvement Specialists (CQIS) based on defined criteria from our nursing decatheterization protocol. Their discontinue UC recommendations were also sent to the care teams. The critical reviews of UC for CAUTI reduction started with 4 ICUs in August 2018, with additional ICUs added in December, January and March. Monthly UC SURs were tracked Results Figure 1 shows the number of UCs recommended for removal by RNs vs. CQIS (bars), as well as the percent discordance between RNs and CQIS (line). CQIS identified many more removable UCs than the RNs (888 vs. 256). 211 UC were removed after RN recommendations, and an additional 386 UCs were removed as a result of the CQIS audits. Figure 2 shows the marked corresponding decline in our SUR over this intervention. Conclusion As more units participated in the initiative, we saw increasing numbers of “discontinue UC” recommendations. Over time there was also a moderate decrease in the discordance between RN and CQIS recommendations for UC removal. CQIS routinely identified many more UCs to be removed compared with RNs, and more than doubled the number of discontinued UC. Notably, the UC SUR markedly improved, decreasing from 0.98 to 0.78. Disclosures All authors: No reported disclosures.

Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting.

Abstract Background It is essential to recognize the true burden of community-onset (CO) Clostridium difficile infection (CDI) in hospital, not only because it prevents late recognition of CO CDI as being classified as a hospital-onset (HO) event, but also to assure appropriate contact precautions and therapeutic measures are deployed in a timely fashion. We recognized that our timely diagnosis of CO-CDI was suboptimal and sought to improve early recognition of CO-CDI. Methods We developed an automated daily report for all patients during their first 3 days of hospitalization who had loose stools documented in the nursing flow sheets and no stool sample sent to the lab. This report was automatically pushed out to the unit nurse managers, as well as reviewed by the infection preventionists (IP). Nurse managers alerted staff to acquire a stool sample to send to the lab. If stool testing still was not sent at the time of IP review of these symptomatic cases, then the IP called the nurse caring for the patient to encourage that a stool sample be sent ASAP and before the third hospital day was completed. Results We increased early appropriate stool testing for patients with documented loose stools during the first 3 days of hospitalization. Improved early diagnosis and better lab stewardship was associated with a marked increase in CO-CDI (15.6/month in 2015 vs 58.7/month in the last year), as well as a decrease in HO-CDI (22.8/month in 2015 vs 7.4/month last year) (Figure 1). In turn, we saw a remarkable drop in our CDI SIR (2 year pre-intervention SIR = 1.49 vs post-intervention SIR for the last 1.5 years = 0.41) (Figure 2). Conclusion After several years of our CDI SIR remaining stubbornly around 1.5, we developed a system of enhanced recognition of patients who had loose stools early in their hospitalization. This aided in better recognition of CDI present on admission, substantially increasing our detection of CO-CDI. We also noted decreases in HO-CDI, presumably secondary to no longer diagnosing patients later in their hospitalization as HO-CDI cases who actually had been admitted with CO-CDI. Better early recognition and isolation of patients with CDI also helped to decrease inadvertent C. difficile transmission in hospital, contributing to decreases in HO-CDI. In turn, we noted a remarkable decrease in our CDI SIR. Disclosures All authors: No reported disclosures.

Background: Central line associated blood stream infections (CLABSI) endanger patient safety and increase morbidity, mortality, length of stay and the cost of medical care. The most common causes of CLABSIs are related to imperfect maintenance of the line and associated tubing. Examples include contamination at the catheter exit site secondary to poor dressing care, or contamination of the extraluminal surface of the catheter access port (which can lead to contamination of the intraluminal portion of the catheter).