Background: Ventilator associated pneumonia (VAP) is associated with significant rates of morbidity and all-cause mortality. Active VAP surveillance can identify risk factors for which targeted preventive measures can be implemented. However, surveillance efforts are complicated by challenges associated with accurate VAP diagnosis. We aimed to improve the accuracy and automation of existing VAP diagnostic algorithms to better identify patients at risk. Methods: The study was conducted at NYU Langone Health from June 2022 through December 2023. We created a semi-automated VAP surveillance system using the Centers for Disease Control & Prevention (CDC) ventilator associated event (VAE) definition as a base framework (Figure 1). We modified this definition to include additional elements, such as having a sputum culture ordered within 48 hours of worsening oxygen status, regardless of culture result. Using this algorithm—followed by manual clinician reviews—we retrospectively assessed possible VAP cases to determine the ability of our surveillance system to correctly identify VAP. Results: Of the 123 possible VAP cases identified through our automated system, 75 (61%) were correctly diagnosed as VAP after clinical review. This reflects a rate of 1.5 infections per 1000 ventilation days across the system and 1.85 infections per 100 patients ventilated for greater than 2 days. Of the 48 remaining patients without VAP after clinical review, 25% (n=12) were characterized as having hospital-acquired pneumonia, 21% (n=10) as acute respiratory distress syndrome or infection at another site and 10% (n=5) as pulmonary embolism/infarction. Among all patients identified through this automated system (VAP and non-VAP), 53% experienced in-hospital death. Discussion: Our automated VAP surveillance algorithm identified 123 cases of potential VAP, 61% of which were consistent with a clinical diagnosis of VAP upon manual chart review. Our VAP rate of 1.5 infections per 1000 ventilation days was similar to published rates at other North American hospital systems. The high in-hospital mortality rate among these patients highlights the need for improved surveillance systems and earlier interventions to reduce the risk of VAP. There are several limitations to the CDC’s VAE definition, including its requirement of a positive microbiologic culture and focus on sputum quality. This potentially misses cases of culture-negative VAP in patients receiving antibiotics prior to sputum collection. Our goal is to continue to validate and improve our algorithm’s ability to correctly identify patients with clinical VAP, so that targeted prevention efforts can be focused upon the patients with the highest risk for poor outcomes.

Background Volatile organic compounds (VOCs) are produced systemically due to varied physiological states such as oxidative stress and are excreted through the lungs. Benchtop and preliminary clinical data suggest that breath testing may be a useful diagnostic modality for viral respiratory tract infections. Methods Patients with influenza-like illness (ILI) presenting to a single clinic in San Antonio, Texas, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for respiratory pathogens. VOCs were assayed with gas chromatography-mass spectrometry (GC-MS), and data were analyzed to identify breath VOC biomarkers that discriminated between ILI patients with and without a polymerase chain reaction (PCR) assay that was positive for influenza. Results Demographic, clinical, PCR, and breath data were available for 237 episodes of ILI, among which 32 episodes (13.5%) were PCR positive for influenza. Twenty candidate VOCs identified patients with influenza with greater than random accuracy. A predictive algorithm using 4 candidate biomarkers identified this group with 78% accuracy (74% sensitivity, 70% specificity). Based on their mass spectra, most of these biomarkers were n-alkane derivatives, consistent with products of oxidative stress. Conclusions A breath test for VOC biomarkers accurately identified ILI patients with PCR-proven influenza. These findings bolster those of others that a rapid, accurate, universal point-of-care influenza diagnostic test based on assay of exhaled-breath VOCs may be feasible. The next step will be a study of patients with ILI using a simplified method of breath collection that would facilitate translation for use in clinical practice.

Background: Although definitions from the CDC were developed to increase the reliability of surveillance data, reduce the burden of surveillance in healthcare facilities, and enhance the utility of surveillance data for improving patient safety, the algorithm is still laborious for manual use. We implemented an automated surveillance system that combines 2 CDC pneumonia surveillance definitions to identify pneumonia infection in inpatients. Methods: The program was implemented at an academic health center with >40,000 inpatient admission per year. We used Window Task Scheduler with a batch file daily to run a validated pneumonia surveillance algorithm program written with SAS version 9.4 software (SAS Institute, Cary, NC) and a natural language processing tool that queries variables (Table 1) and text found in the electronic medical records (EMR) to identify pneumonia cases (Fig. 1). We uploaded all computer-identified positive cases into a Microsoft Access database daily to be reviewed by a hospital epidemiologist. Every week, we also validated 5 computer-identified negative cases from the prior 2 weeks to ensure accuracy of the computer algorithm. We defined negative cases as pneumonia present on admission or chest x-ray indicative of pneumonia but without CDC-defined surveillance symptoms. We also wrote a program to automatically send e-mails to key stakeholders and to prepare summary reports. Results: Since November 2019, we have successfully implemented the automated computer algorithm or program to notify, via e-mail, infection prevention staff and respiratory therapy providers of CDC-defined pneumonia cases on a daily basis. This automated program has reduced the number of manual hours spent reviewing each admission case for pneumonia. A summary report is created each week and month for distribution to hospital staff and the Department of Health, respectively. Conclusions: The implementation of an automated pneumonia surveillance system proves to be a timelier, more cost-effective approach compared to manual pneumonia surveillance. By allowing an automated algorithm to review pneumonia, timely reports can be sent to infection prevention control staff, respiratory therapy providers, and unit staff about individual cases. Hospitals should leverage current technology to automate surveillance definitions because automated programs allow near real-time identification and critical review for infection and prevention activities.Funding: NoneDisclosures: None

Abstract Background Annual influenza epidemics cause significant morbidity and mortality. New, emerging strains threaten to cause catastrophic pandemics. Assay of exhaled breath for volatile organic compounds (VOCs) via gas chromatography-mass spectroscopy (GC-MS) is an emerging diagnostic modality ideally suited to fill the gap in influenza diagnostics. Methods Patients with influenza like illness (ILI) presenting to the Troop Medical Clinic on JBSA Fort Sam Houston, TX, from 3/2017 to 3/2019 submitted a 2-minute breath sample in addition to a nasopharyngeal swab collected for polymerase chain reaction (PCR) assay for influenza virus. ILI was defined as temperature > 100.40F AND respiratory symptoms like cough, sputum production, chest pain and/or sore throat. Breath VOCs were assayed with GC-MS and data were analyzed in order to identify the significant breath VOC biomarkers that discriminated between ILI patients with and without a PCR assay positive for influenza with greater than random accuracy. Results Demographic, clinical, PCR and breath data were available for 237 episodes of ILI. PCR was positive for influenza for 32 episodes (30 influenza A and 2 B). The median age of participants was 21 (IQR 19, 23) and 69% were male. There were no differences in age, gender, education, race, or smoking, between the influenza positive and negative groups. Likewise, there was no difference in days of limited activity or missed work, or symptoms at presentation between the groups. The algorithm achieved near maximal predictive accuracy of 78% with four biomarkers (74% sensitivity and 70% specificity). Based on their mass spectra, these biomarker VOCs were tentatively identified as 2-amino-1-propanol, 2-butanamine, n-nitro, 3-methyl-hexanal, and heptane, which are consistent with products of oxidative stress. Figure. Accuracy, Sensitivity, and Specificity of Influenza Breath Test. Receiver operating characteristic (ROC) of the breath test (sensitivity versus 1-specificity). The accuracy of the breath test was 78%. With a cutoff point at the “shoulder” of the ROC curve, the test had 74% sensitivity and 70% specificity. Conclusion Our findings bolster available benchtop and clinical data suggesting that breath testing may be a useful diagnostic modality for influenza infection. The next step will be to study the predictive algorithm developed in this protocol in a blinded validation cohort. If the predictive algorithm performs well in a validation study, adaptation for its use in a portable, tabletop GC would be warranted to allow for a rapid, accurate, universal point-of-care influenza diagnostic test. Disclosures Michael Phillips, MD, Menssana Research, Inc (Grant/Research Support)

Objective: To quantify the effect of a long-stay patient in a hospital unit on the likelihood of colonization of that patient and other patients in the unit. Prolonged hospital and intensive care unit (ICU) stays have been found to be risk factors for colonization and infection with bacteria such as carbapenem-resistant Enterobacteriaceae (CRE) for which there are limited treatment options and high mortality rates, making prevention of transmission and infection important public health objectives. Many studies have shown that long-stay patients (such as inpatient rehabilitation or skilled nursing facility patients) are at higher risk for hospital-acquired infections than short-stay patients, but the impact of long-stay patients on other patients in the same hospital unit has not received as much attention. Here, we consider a mathematical model of pathogen transmission within a hospital unit and assess the impact at different patient-patient transmission rates of a single long-stay patient on the probability that any other patient leaves the unit colonized with a pathogen. We estimated the increased risk caused by a colonized long-stay patient on colonization of other patients using an ordinary differential equation Markov model with three mechanisms of colonization (pre-existing colonization, environmental transmission, and patient-patient transmission) with parameters previously estimated from a 13-bed hospital rehabilitation unit to evaluate the probability of exiting colonized. A single colonized long-stay patient increases the probability of each other patient exiting the unit colonized from 10.4% to 17.3%, a relative increase in risk of 1.4, and increases the expected number of colonized patients within the unit from 1.37 to 2.07 (not including the long-stay colonized patient). Probability of exiting colonized from a unit with a long-stay, initially colonized patient versus the probability of exiting colonized from a unit with no long-stay patient. The solid black line indicates a unit with regular turnover, whereas the dashed black line indicates a unit with a single long-stay, initially colonized patient. The vertical line shows the value of γ = 0.002 inferred from data from a 13-bed rehabilitation unit, and the shaded regime indicates the uncertainty in this estimate (0.000329, 0.003729). Colonized long-stay patients pose a risk to other uncolonized patients in the unit, especially at higher patient-patient transmission rates. Potential long-stay patients should be screened for CRE at entry and periodically during their stay because they are both at higher risk of colonization and also of transmitting bacteria to other patients. Consider increased surveillance, isolation, and/or decolonization of long-stay patients. All Authors: No reported disclosures

Abstract Background Clostridioides difficile is the most common hospital-acquired pathogen with an unchanged infection prevalence between 2011–2015. The data regarding the effectiveness of chemical prophylaxis to prevent recurrent C. difficile infection (CDI) are conflicting. Methods We conducted a retrospective study of hospitalized patients with CDI history in 2 New York academic hospitals over a 4.5-year period to determine the effectiveness of vancomycin prophylaxis for CDI prevention. The participating hospitals implemented an automated alert to providers recommending oral vancomycin 125 mg twice daily in patients with a history of CDI scheduled to receive any systemic antimicrobials for the duration of therapy and 5 days thereafter. Measured outcomes included the rate of breakthrough and recurrent CDI, defined as CDI during and in the one-month following prophylaxis, respectively. A self-controlled, before and after study design was employed to examine whether the use of oral vancomycin was associated with an increase in the prevalence of vancomycin-resistant Enterococcus species (VRE) both in absolute numbers and in comparison to vancomycin-sensitive Enterococcus species (VSE) in the period following vancomycin prophylaxis. Results 264 patients were included in the final analysis. Breakthrough CDI was identified in 17 (6.4%; 95% CIs 3.8%–10.1%) and recurrent CDI in 22 (8.3%; 95% CIs 5.3%–12.3%) patients. Of the 102 patients with a history of CDI within the 3 months preceding the administration of prophylaxis 4 (3.9%, 95% CIs 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.3%, 95% CIs 5.3%–12.3%). In the 3 months following vancomycin prophylaxis there was an increase in both the absolute number of VRE and the ratio of VRE to VSE isolates compared with the combined period of 1.5 months preceding and the 3–4.5 months following the administration of prophylaxis. The increase in the absolute number of VRE colonized patients remained in the extended period of 6 months following prophylaxis. Conclusion Prophylactic vancomycin is an effective strategy to prevent CDI recurrence, but is associated with an increase in VRE colonization in the immediate period after administration. The risk of VRE infection should lead to careful selection of patients at the highest risk for CDI recurrence. Disclosures All authors: No reported disclosures.

Abstract Background Pneumonia (PNU) is the second most common nosocomial infection in the United States and is associated with substantial morbidity and mortality. While definitions from CDC were developed to increase the reliability of surveillance data, reduce the burden of surveillance in healthcare facilities, and enhance the utility of surveillance data for improving patient safety - the algorithm is still laborious. We propose an implementation of a refined algorithm script which combines two CDC definitions with the use of natural language processing (NLP), a tool which relies on pattern matching to determine whether a condition of interest is reported as present or absent in a report, to automate PNU surveillance. Methods Using SAS v9.4 to write a query, we used a combination of National Healthcare Safety Network’s (NHSN) PNU and ventilator-associated event (VAE) definitions that use discrete fields found in electronic medical records (EMR) and trained an NLP tool to determine whether chest x-ray report was indicative of PNU (Fig1). To validate, we assessed sensitivity/specificity of NLP tool results compared with clinicians’ interpretations. Results The NLP tool was highly accurate in classifying the presence of PNU in chest x-rays. After training the NLP tool, there were only 4% discrepancies between NLP tool and clinicians interpretations of 223 x-ray reports - sensitivity 92.2% (81.1–97.8), specificity 97.1% (93.4–99.1), PPV 90.4% (79.0–96.8), NPV 97.7% (94.1–99.4). Combining the automated use of discrete EMR fields with NLP tool significantly reduces the time spent manually reviewing EMRs. A manual review for PNU without automation requires approximately 10 minutes each day per admission. With a monthly average of 2,350 adult admissions at our hospital and 16,170 patient-days for admissions with at least 2 days, the algorithm saves approximately 2,695 review hours. Conclusion The use of discrete EMR fields with an NLP tool proves to be a timelier, cost-effective yet accurate alternative to manual PNU surveillance review. By allowing an automated algorithm to review PNU, timely reports can be sent to units about individual cases. Compared with traditional CDC surveillance definitions, an automated tool allows real-time critical review for infection and prevention activities. Disclosures All authors: No reported disclosures.

Abstract Background It is common practice among microbiology laboratories in the United States to blind the BioFire FilmArray GI Panel results for Clostridioides (Clostridium) difficile (C. difficile) in fear of over-diagnosis of C. difficile infection (CDI). Methods We conducted a retrospective cohort study in 2 tertiary academic centers in New York to examine the rate of missed CDI diagnosis and the associated adverse outcomes from blinding the BioFire FilmArray GI Panel results for C. difficile. Of note, in one of the two included hospitals the list of daily positives is reviewed by an Infectious Diseases attending to determine whether cases have been tested for CDI and if not if they meet criteria for CDI. Adult patients with FilmArray GI Panel positive for C. difficile on admission to the hospital who lacked dedicated testing for C. difficile were included in the analysis and were stratified as possible, probable and definite cases of missed CDI diagnosis. Results Among the 144 adult patients with a FilmArray GI Panel test positive for C. difficile within 48 hours of hospital admission, 18 did not have a concurrent dedicated C. difficile testing. Eight patients were categorized as possible cases of missed CDI diagnosis, 5 as probable and 4 as definite, for a total of 17 cases of at least possibly missed CDI diagnosis. One case was considered to represent C. difficile colonization rather than infection for a rate of 6.9% of CDI over-diagnosis based on the FilmArray GI Panel results. Missed CDI diagnoses were associated with a delay in initiation of appropriate therapy, admission to the intensive care unit, hospital re-admission, colorectal surgery and death/discharge to hospice. Five out of 17 cases of missed CDI diagnosis (29.4%) lacked traditional risk factors for CDI. Conclusion In conclusion, the practice of concealing FilmArray GI Panel results for C. difficile may lead to a higher rate of missed CDI diagnosis than over-diagnosis and might need to be re-considered at least in patients with community-onset colitis of unknown etiology on presentation to the hospital. Disclosures All authors: No reported disclosures.

Abstract Background Methicillin-resistant staphylococcus aureus (MRSA) colonization of hospitalized patients is associated with higher readmission rates and increased morbidity. Depending on the mechanisms of transmission, numerous potential control interventions exist to reduce the burden of disease. However, given the preponderance of asymptomatic colonization, it is challenging to quantify the relative importance of different transmission mechanisms and assess control efficacy. By identifying clusters of transmission, whole-genome sequencing (WGS) provides an opportunity to overcome these challenges. Methods We sought to apply cluster analysis techniques to WGS data for MRSA, in order to assess MRSA prevalence, transmissibility, the degree of transmission heterogeneity and the potential effectiveness of control. Our model builds upon previous work that showed a direct relationship between the size distribution of infection clusters, the effective reproduction number (R) and the dispersion parameter (k). To demonstrate its functionality, our model was applied to existing WGS data for MRSA isolates collected during a 12 month period in the East of England (DOI: 10.1126/scitranslmed.aak9745) Results The effective reproduction number for the East of England data is 0.29 (95% CI: 0.24–0.36). The dispersion parameter is 0.09 (0.03–0.33) reflecting a high degree of transmission heterogeneity. This implies all transmission is caused by just 12% of the cases. Targeted control of these cases could have decreased overall burden of MRSA colonization by 29% during the time period of the study. Conclusion The high degree of transmission heterogeneity seen in MRSA transmission suggests that the risk for infection is variable.This observation motivates the need for more detailed mechanistic modeling of hospital-based MRSA transmission that integrates patients-specific factors, movement data and genome sequencing. Such models could be used to forecast which patients are at greatest risk for either acquiring or transmitting MRSA, thereby improving targeted control. Disclosures All authors: No reported disclosures.

Abstract Background Staphylococcus aureus infection confers high mortality. S. aureus-colonized hospitalized patients are more likely to develop invasive infection and can transmit S. aureus to other patients in the absence of symptoms. Our health system has a baseline S. aureus colonization rate of 21% (MSSA and MRSA combined). To reduce risk of invasive S. aureus infection in our patients, we implemented an inpatient S. aureus screening and decolonization program. Methods Interventions include universal S. aureus screening and targeted decolonization for all patients on the Medicine and Pediatrics inpatient services. Adult patients are screened at admission and change in the level of care; pediatric patients are screened weekly. S. aureus screening began incrementally by unit between 2016 and 2017, and extended to transplant units in 2018. All cultures are processed in the hospital microbiology lab for identification of MRSA and MSSA. S. aureus decolonization (mupirocin ointment in nares twice daily, chlorhexidine 2% wipes below the chin daily for 5 days) began in 2017 for patients with a central venous catheter, in intensive care unit or multibedded room. Decolonization was extended to all S. aureus-colonized patients beginning in June 2018, with involvement of a dedicated clinical nurse specialist. We compared compliance with screening and decolonization and the secondary outcome of MRSA bacteremia in the 6 month period before and after the addition of the clinical nurse specialist. Results 21.5% of screened patients were colonized with S. aureus (82.4% MSSA, 17.6% MRSA). Screening compliance improved from 39.4% of eligible patients (N = 1805) to 52.1% (N = 2024) and decolonization increased from 18.6% of colonized patients to 41.2% comparing January-June 2018 with July-December 2018. The MRSA bacteremia rate fell from 0.2/1,000 patient-days in the first half of 2018 to 0.1/1,000 patient-days in the second half of 2018. Conclusion A system-wide program that includes S. aureus screening and decolonization of hospitalized patients found that 21% of patients had S. aureus colonization. Screening and decolonization compliance increased with the introduction of a dedicated clinical nurse specialist, and the MRSA bloodstream infection rate fell. Disclosures All authors: No reported disclosures.

SESSION TITLE: Cardiovascular Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Acute rheumatic fever and subsequently rheumatic heart disease (RHD) has been significantly reduced in developed countries during the 20th century. Although uncommon, RHD remains present in undeveloped countries and immigrant populations. Knowledge of common presentations of this once ubiquitous disease thus remains clinically useful. CASE PRESENTATION: A 32-year-old African-American male presented for 7 days of progressive dyspnea, diaphoresis with exertion, and pleuritic chest pain. Prior evaluation was concerning for community acquired pneumonia treated with azithromycin and doxycycline without improvement. On admission, the patient reported subjective fever without recent travel or known sick contacts. He is a naturalized citizen who lived in Sierra Leone until age 16 and currently works with a predominantly immigrant population as a pig butcher. The patient’s past medical history was grossly unremarkable. Physical exam was significant for right lung crackles on inspiration and grade 3 holosystolic murmur with normal respiratory rate and oxygen saturation on room air. Chest x-ray at the time of presentation was notable for progressive worsening of a right upper lobe (RUL) infiltrate. Patient was started on Levaquin and admitted to the hospital for pneumonia versus tuberculosis. CT of the chest was completed for concern of non-resolving pulmonary symptoms and noted for RUL infiltrate and left ventricular hypertrophy (LVH). ECG also suggested LVH and transthoracic echocardiogram showed a dilated cardiomyopathy with severely reduced ejection fraction (20-25%), severe mitral regurgitation and severe aortic regurgitation. This presentation was highly suggestive of RHD with pulmonary infiltrate secondary to retrograde flow secondary to significant valvular disease, confirmed with transesophageal echocardiogram. The patient was transferred to a tertiary surgical center on hospital day 6 for valve replacement. DISCUSSION: This case represents classic findings of RHD with secondary mitral valve regurgitation and RUL pulmonary infiltrates. Per the REMEDY trial, the patient’s presentation of chronic rheumatic valvular disease leading to acute heart failure is the most common presentation of RHD. This exemplifies the need to suspect this disease in patients with the appropriate clinical history and in patients from countries where rheumatic fever and RHD are still common. CONCLUSIONS: RHD continues to be clinically relevant despite significant decrease in incidence among the US population. Presentation with signs of pulmonary infiltrate due to retrograde flow via the pulmonary veins is more than a theoretic presentation and supports maintenance of a broad differential especially in patients tied to the developing world. Reference #1: Essop MR, Nkomo VT. Rheumatic and nonrheumatic valvular heart disease: epidemiology, management, and prevention in Africa. Circ. 2005;112(23),3584-3591. Reference #2: Watkins DA., Johnson CO, Colquhoun SM, et al. Global, regional, and national burden of rheumatic heart disease, 1990-2015. N Engl J Med. 2017;377:713-722. Reference #3: Zuhlke L, Engel ME, Karthikeyan G, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J. 2015; 36(18),1115-1122. DISCLOSURES: no disclosure on file for Travis Bentz; No relevant relationships by Nathan Boyer, source=Web Response No relevant relationships by Aaron Farmer, source=Web Response No relevant relationships by Samone Franzese, source=Web Response No relevant relationships by John Lammie, source=Web Response No relevant relationships by Michael Phillips, source=Web Response

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6. Veber B, Gachot B, Bedos JP, Wolff M. Severe sepsis after intravenous injection of contaminated propofol. Anesthesiology 1994;80:712–713. 7. Bennet SN, McNeil MM, Bland LA, et al. Postoperative infections traced to contamination of an intravenous anaesthetic, propofol. N Engl J Med 1995;333:147–154. 8. Wachowski I, Jolly DT, Hrazdil J, Galbraith JC, Greacen M, Clanachan AS. The growth of microorganisms in propofol and mixtures of propofol and lidocaine. Anesth Analg 1999;88:209– 212. 9. O’Donnell NG, McSharry CP, Wilkinson PC, Asbury AJ. Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro in the presence or absence of human serum albumin. Br J Anaesth 1992;69:70– 74. 10. El-Ebiary M, Torres A, Ramirez J, Xaubet A, Rodriguez-Roisin R. Lipid deposition during the long-term infusion of propofol. Crit Care Med 1995;23:1928–1930.

 Due to broad spectrum of activity and high potential to cause collateral damage, meropenem is restricted to:  Antimicrobial Stewardship Program (ASP), Infectious Diseases (ID), and Critical Care (CC) Disclosure: The authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities. Contact Information: Yanina Dubrovskaya, PharmD, AQ-ID NYU Langone Medical Center 550 First Avenue New York, NY 10016 Email: yanina.dubrovskaya@nyumc.org

In May 2001, The New York City Department of Health and Mental Hygiene was informed of a cluster of 4 patients treated at an outpatient gastroenterology center who developed acute hepatitis C virus infection. An investigation identified a total of 12 clinic-associated hepatitis C virus transmissions and the outbreak and was traced to unsafe handling of multidose anesthetic vials and possible re-use of contaminated needles. This report typifies the types of outbreaks that continue to occur despite safe injection guidelines. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

174 Background: The primary aim of this exploratory trial was to determine the feasibility and safety of chemoradiotherapy (CRT) with combinatorial immunotherapy in LA or BR PC. Methods: 10 patients (pts) with untreated, LA (n=6) or BR (n=4) biopsy-proven PC received gemcitabine (GEM) in combination with telomerase peptide vaccine (GV1001) and sargramostim (GM-CSF) both by intradermal injection. Tadalafil was taken once daily throughout the course of therapy for myeloid derived suppressor cell inhibition. The 2 nd month of treatment included external beam radiation therapy (50.4 Gy, 28 fractions) and concurrent twice-weekly GEM 50 mg/m2. Disease response was assessed at 12 weeks. Following recovery from either concurrent CRT or resection, 8 weeks of GV1001 + GM-CSF, tadalafil and GEM completed treatment. Peripheral blood was analyzed by quantitative multiparameter whole blood flow cytometry of immune cell subtypes. Samples were also cryo-preserved for future analysis of peripheral blood mononuclear cell (PBMC) populations and ELISPOT analysis of antigen-specific T cell numbers. Tumor resection specimens were sectioned for immunohistological analysis of macrophage and T cell infiltration. Results: 9 of 10 pts completed therapy to assess response. Grade (Gr) 3-4 hematologic adverse events (AE) were observed during CRT. Immune-related AE were infrequent and mild. 3 of 4 pts with BR disease and 1 with initial LA (unresectable) disease achieved R0 resection. No unanticipated surgical complications were observed. Changes in monocytes and granulocytes occurred throughout treatment and may correlate with clinical benefit. At least 50% reduction in serum CA19-9 was observed in 8 pts. Partial response (n=2) or stable disease (n=7) was achieved in 9 pts. Conclusions: Combinatorial immunotherapy concurrent with GEM-based CRT is feasible and appears safe in LA or BR PC. Initial biochemical responses as well as disease control were observed in the majority of pts. Preliminary immune correlative data suggest a relationship between hematopoietic populations and clinical response.

There is a great deal of interest in the establishment of a standardized animal model for the acute radiation syndrome to allow development of diagnostic approaches and countermeasure treatments following radiological terrorist events. Due to physiological, anatomical, and biochemical similarities to humans, the minipig is an attractive large animal model for evaluating countermeasure efficacy. This study was conducted in order to aid in the establishment of the minipig, and the Gottingen minipig in particular, as an animal model for the hematopoietic acute radiation syndrome. Animals were exposed whole-body to Co-60 at doses of 0 (sham control), 0.25, 0.5, 0.75, 1.0, and 2.0 Gy, and hematological parameters followed in time from pre-irradiation to post-irradiation Day 7. Following irradiation, a dose-dependent decrease in total white blood cells was observed, which was determined to be statistically different as compared to control animals at all dose levels above 0.25 Gy at 24 h post-irradiation. Similarly, a dose-dependent reduction in both absolute lymphocyte count and absolute neutrophil count occurred by the earliest time point measured for all exposed animals. A significant decrease in platelets was observed at postirradiation Day 7 in animals exposed only at the highest (2.0 Gy) level. The platelet-to-lymphocyte ratio generated for exposures ranging from 0.25-2.0 Gy was able to differentiate response between high and low exposure levels even at 7 d post exposure. In conclusion, the present study supports the development of the Gottingen minipig as a suitable large animal model to study radiation-induced hematopoietic syndrome.

Background and Objective Chlorhexidine is recommended by several anesthesiology societies for antisepsis before regional anesthesia, but there is concern it may be neurotoxic. We evaluated the cytotoxicity of chlorhexidine and povidone-iodine in human neuronal and rat Schwann cells. Methods Human SH-SY5Y neuroblastoma and rat RSC96 Schwann cells were incubated with serial dilutions of 2% chlorhexidine gluconate and 10% povidone-iodine for 10 minutes, and viability was assessed with the MTT colorimetry assay and a fluorescent assay using calcein and ethidium. Cell morphology during antiseptic incubation was observed under light microscopy. To estimate the amount of antiseptic a needle carries through tissues, tritium radioactivity was measured in an animal injection model. Results Chlorhexidine at all tested concentrations significantly decreased viability compared with controls in both SH-SY5Y and RSC96 cells (P < 0.001). Povidone-iodine significantly decreased viability for both cells at concentrations of 0.2% or higher (P < 0.001). At the same dilutions of 1:200, 1:150, and 1:100, chlorhexidine was more cytotoxic than povidone-iodine for both cells (P< 0.001). During chlorhexidine treatment, both cell types became rounded and shriveled. Less dramatic changes were observed with povidone-iodine. In the injection model, 1.75% ± 1.29% of the maximum amount of radioactive contamination was carried through tissues. Conclusions Chlorhexidine gluconate and povidone-iodine were cytotoxic to SH-SY5Y (neuronal) and RSC96 (Schwann) cells. Chlorhexidine was more potent than povidone-iodine at more dilute concentrations. However, the toxicity of the two was not different at concentrations used clinically. When using either of these agents for antisepsis before regional anesthesia, it is prudent to allow adequate drying time after application.