bluuebunny/crossref_metadata_2025 huggingface dataset:
872. Voriconazole Therapeutic Drug Monitoring (TDM): How Common is Autoinduction?
Authors: Tyagi Varalika , Lau Cecilia , Doucette Karen , Cervera Carlos , Professor Associate , Kabbani Dima
Published: December 2022

Background

Therapeutic drug monitor (TDM) guided optimized dosing of Voriconazole allows optimal drug exposure in the management of mold infection (MI). In addition to already known nuances in pharmacokinetics such as CYP2C19 genetic polymorphism and the role of drug interactions both necessitating TDM, case reports have suggested that auto-induction may occur after initially achieving a therapeutic level. We assessed whether the levels of Voriconazole can change over time and become subtherapeutic due to auto-induction.

Methods

We prospectively enrolled, adults ≥ 18 y.o of age, on Voriconazole for the treatment of MI at the University Of Alberta Hospital. After achieving an initial therapeutic margin, (1–5.5mg/l), we monitored Voriconazole levels twice a month, using high-performance liquid chromatography, until discontinuation or at 12 weeks of therapy. We calculated the incidence of Voriconazole sub-therapeutic concentrations (auto-induction) defined as drop of Voriconazole level below one, with previous concentrations between the therapeutic margins of 1–5.5 mg/L. Adjustment of Voriconazole dosing in case of auto-induction was at the discretion of the treating physician. The excess Voriconazole dose adjustment was calculated in patients where dosing was increased.

Results

Between January 2021 and April 2022, we enrolled 12 patients. Median age (IQR) was 62 (52–73), and 25 % were female. Patient characteristics are in table 1. Auto-induction was observed in 6/10 (60%) who completed 12 weeks follow up blood work. Median time to auto-induction was of 46 days (39–55). Voriconazole dosing was increased in 4/6 patients with auto-induction. Of the four patients with dose adjustment, the cumulative Voriconazole dose was 13% higher than expected, which correspond to 5,300 mg excess Voriconazole per patient to maintain therapeutic levels.

Conclusion

Auto-induction is common in patients treated with Voriconazole. Future studies are needed to assess if undetected auto-induction affects outcomes.

Funding: AVIR Pharma.

Disclosures

Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant Dima Kabbani, MD, MSc, AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|GSK: Honoraria|Merck: Grant/Research Support.
882. Systematic Underdosing of Oseltamivir in Hospitalized Patients with Influenza
Authors: Bains Ashveen , O'Hara Margaret , Oppenneer Kevin , DeHart Del J
Published: December 2022

Background

Oseltamivir remains the primary treatment for seasonal influenza syndromes and early administration has been shown to increase the clinical benefit of treatment; we studied current practice and describe patient and system variables influencing dosing decisions.

Methods

We reviewed oseltamivir dosing in 135 adult patients in our community hospital admitted with acute influenza over two northern Hemisphere influenza seasons (2016-2017 and 2017-2018) and for whom pharmacy dosing protocols were invoked. We reviewed admitting symptoms for factors suggesting possible dehydration, the timing of treatment in relation to testing for influenza, the estimated creatinine clearance at the time of dose determination for oseltamivir, the initial dose of drug, and dose-adjustment over time.

Results

Patients ranged in age from 27-96 years (mean 74), with 83 males and 52 females among the 135 patients over these two seasons. Testing results were available for 131 patients and 75 (57%) were positive, while 56 (43%) were negative, and therefore treated empirically based on presenting symptoms.

Ninety patients (67%) received an initial dose of 30 mg of oseltamivir, while 45 patients (33%) received an initial dose of 75 mg. Of the 90 patients who were dose-adjusted by the pharmacist to 30 mg for the initial dose, 24 (27%) had a creatinine clearance > 60 mL/min, and it is not clear what factors influenced those decisions. Of the 90 patients with an initial creatinine clearance of < 60 mL/min, 22 (24%) showed a clinically significant improvement to > 60 mL/min within the first 24 hours of hospitalization yet only 8 patients had their dose adjusted. Presenting symptoms did not predict patients who had rapid improvement of creatinine clearance. Of the 45 patients receiving an initial dose of 75 mg of oseltamivir, 19 (42%) had creatinine clearance values of < 60mL/min, and were therefore given a loading dose, followed by dose adjustment.

Conclusion

We found a significant percentage of patients were underdosed initially and dosing was not adjusted for changes in renal function. Reviewing and revising dosing protocols and guidelines may lead to more effective treatment for influenza and may serve as a model for future test-to-treat options for therapies for other acute viral respiratory infections in the future.

Disclosures

All Authors: No reported disclosures.
885. Integrated Blood Culture and Molecular Diagnostic Device Reduces Time-to-Result to a Quarter of Traditional Methods
Authors: Huning Laura , Varma Devika , Jackson Abbey , Bohlen Peter , Ng Rainer , Pamula Vamsee
Published: December 2022

Background

Prolonged antibiotic exposure in infants with negative blood cultures is associated with adverse outcomes, disruption of the developing microbiome, and increased carriage of antibiotic resistance genes. However, early administration of antibiotics significantly reduces risk of infant morbidity and mortality caused by infections, and therefore faster culture-to-identification is highly desirable. We combined blood culture (BC) and PCR-based pathogen identification into a single digital microfluidic (DMF) device to speed up BC results.

Methods

Our DMF BC+PCR device has a custom-built BC bottle incubator, which is connected to a disposable cartridge that performs sample preparation and PCR. Standard BC bottles were inoculated with K. pneumoniae, then incubated in either the DMF BC device or a traditional BC device (BD BACTEC 9050). Samples were drawn from the DMF BC bottle at 3, 4 and 5 hours and loaded in the cartridge for automated sample processing and PCR. Time-to-positivity for the DMF BC+PCR device was determined using cycle threshold and compared with the traditional method, which uses fluorescence from BC bottle followed by PCR on a separate device.

Results

Bacterial presence could be detected as quickly as 3 hours post inoculation (Ct values of 34, 31 and 28 at 3, 4, and 5 hrs) with five replicates of K. pneumoniae samples on the DMF BC+PCR device (growing 10x every hr), compared to > 12 hrs for the traditional method (10.5 hr culture and 2 hr PCR identification). Additionally, for 5 common pathogens that cause neonatal sepsis (K. pneumoniae, E. coli, S. aureus, S. agalactiae, or S. epidermidis), we also demonstrated that the DMF BC bottle incubator and the traditional BC device show similar growth curves using optical methods to determine growth.

Conclusion

The DMF BC system yields bacterial growth rates equivalent to traditional methods, but can drastically reduce time to pathogen identification, from 12 hrs to 3 hrs by leveraging PCR sensitivity to determine growth rather than fluorescence in the BC bottles. To our knowledge, this is the first demonstration of using an integrated microfluidic PCR platform to speed up culture and identification. Further work is ongoing to include antibiotic susceptibility testing and expand the panel of pathogens detected on the same cartridge.

Disclosures

Laura Huning, PhD, Baebies, Inc.: Stocks/Bonds Devika Varma, PhD, Baebies, Inc.: Stocks/Bonds Abbey Jackson, PhD, Baebies, Inc.: Stocks/Bonds Peter Bohlen, n/a, Baebies, Inc.: Stocks/Bonds Rainer Ng, PhD, Baebies, Inc.: Stocks/Bonds Vamsee Pamula, PhD, Baebies, Inc.: Stocks/Bonds.
886. Positive Bacterial Blood Cultures and Time to Positivity in Children: Should Empiric Antibiotics be Reconsidered Sooner?
Authors: Patel Pratik A , Locsin Miguel , Xiang Yijin , Lu Lydia , Fernandez Alfred , Jaggi Preeti
Published: December 2022

Background

Evaluation for bacterial bloodstream infections (BSIs) is often associated with prescribing empiric antibiotics while awaiting blood culture results, typically 48 hours. We examined characteristics associated with positive cultures treated as BSI vs contaminant in children and BSIs associated with prolonged (≥ 24 hours) time-to-positivity (TTP).

Methods

In a retrospective study of children (≤ 21 years) at our pediatric healthcare system, we abstracted demographic, clinical, and blood culture data from the electronic medical record for all initial positive bacterial blood cultures from March 2021 to February 2022. We excluded fungi and cultures collected within 14 days of a previous positive. TTP was calculated from time/date of collection to Gram stain report. Host status was categorized as previously healthy, immunocompromised (IC), and chronic condition/s. A BSI was defined as a positive culture treated for ≥ 3 days. BSI cultures were categorized as Gram-positive definite (GPD) pathogens, other Gram-positive (OGP), Gram-negative (GN), or polymicrobial (PM). Characteristics associated with prolonged TTP for BSIs were identified using mixed-effects logistic regression.

Results

There were 816 positive cultures identified in 697 children, with 582 (71%) treated as BSIs and 536 of those (92%) positive in < 36 hours. Positive cultures drawn with adequate blood volume, in the setting of fever, severe neutropenia, and from IC children were significantly more likely to be treated as BSIs (all p< 0.05, Table 1). The most common BSI was a GN pathogen (34.2%, Figure 1). Characteristics associated with prolonged TTP were absence of fever and cultures drawn peripherally. Early TTP (< 24 hours) was associated with cultures drawn outpatient and growth of high likelihood pathogenic organisms (GPD, GN, PM) compared to OGP (all p< 0.05).

On multivariate analysis, cultures drawn peripherally remained associated with prolonged TTP (p< 0.01), while GPD, GN, and PM cultures remained associated with early TTP (p< 0.01, Table 2).

Conclusion

We found that 92% of clinically significant BSIs in children were identified by 36 hours with BSIs with pathogenic organisms (GPD, GN, PM) associated with TTP < 24 hours. Reassessment of the need for antibiotics after 24–36 hours should be considered.

Disclosures

Pratik A. Patel, MD, Cardinal Health, Inc: Advisor/Consultant.
1542. MR-proADM Biomarker Predicts COVID-19 Clinical Outcomes: a US-based Cohort Study
Authors: Mansour Michael
Published: December 2022

Background

Mid-regional proadrenomedullin (MR-proADM) is a biomarker released following endothelial damage. Our study aimed to investigate baseline MR-proADM as a predictor of a wider range of clinical outcomes of varying severity in patients admitted with COVID-19 from a US-based multicenter trial.

Outcomes Within 28 days Stratified by Binary MR-proADM (Cutoff 0.87 Nmol/L), Number of Events (percentage)

Values expressed as percentages (%) indicate either the proportion of the total population or the respective MR-proADM stratum. Statistical significance between MR-proADM strata was determined by the chi-square test or the Fisher's exact test when applicable. P-Values were not corrected for multiple testing.

Methods

Data from the Boston Area COVID-19 Consortium Bay Tocilizumab Trial (NCT04356937) was used in this study. Patients with biomarker determinations, and not admitted to the intensive care unit (ICU) on admission, were included. MR-proADM cutoff of 0.87 nmol/L was assessed in predicting clinical outcomes.

Results

Out of 182 patients, 11.0% were mechanically ventilated or dead within 28 days. Of patients with MR-proADM >0.87 nmol/L, 21.1% were mechanically ventilated or dead within 28 days, versus 4.5% of those ≤0.87 nmol/L (p< 0.001). The sensitivity, specificity, NPV, and PPV of MR-proADM cut-off of 0.87 nmol/L in predicting mechanical ventilation or death were 75%, 65%, 95%, and 21% respectively, with an AUC of 0.76, outperforming other biomarkers. Specifically, MR-proADM outperformed plasma IL-6 in predicting mechanical ventilation and death.MR-proADM was independently associated with mechanical ventilation or death, ICU admission, prolonged hospitalization beyond day 4, and worsening on the COVID-19 ordinal scale.

Conclusion

MR-proADM functions as a valuable prognostic biomarker in predicting clinical outcomes of patients with COVID-19, outperforming other commonly utilized biomarkers.

Disclosures

Michael Mansour, MD, PhD, ThermoFisher Scientific: Grant/Research Support.
1168. Crimean-Congo Hemorrhagic Fever Virus in Central, Eastern, and South-eastern Asia
Authors: Fereidouni Mohammad , Kuhn Jens H , Apanaskevich Dmitry A , Pecor David , Pshenichnaya Natalia , Keshtkar-Jahromi Maryam
Published: December 2022

Background

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Africa and in areas below the 50th parallel of north (latitude 50°0' N) in Asia and Europe, but the epidemiology of CCHF needs to be better characterized in most regions.

Methods

We comprehensively searched scientific databases for studies on CCHF epidemiology in these regions. We used a One Health approach to describe disease burden through human cases, animal and human serology studies, and Crimean-Congo hemorrhagic fever virus (CCHFV) isolation from ticks. In addition, we leveraged a classification scheme tosort countries into five categories based on the level of evidence and the maturity of their CCHF surveillance systems.

Results

We identified 2,253 CCHF cases that occurred in the region during the period 1944–2021. Central Asian countries reported the majority of cases (1,966). China is the only country in Eastern and South-eastern Asia that reported CCHF cases (287). Six countries (China, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) were assigned to level 1 or level 2, based on the maturity of their surveillance systems. Two countries (Mongolia and Myanmar) were assigned to level 3, due to conclusive evidence of CCHFV circulation in the absence of reported CCHF cases. Subsequently, 13 countries in Eastern and South-eastern Asia were categorized in levels 4 and 5, based on CCHFV vector prevalence.

Conclusion

This paper describes past and present status of the CCHF reporting systems to inform international and local public-health agencies to strengthen or establish CCHF surveillance systems and address shortcomings in the region.

Disclosures

All Authors: No reported disclosures.
1170. Effects of Helminths and Anthelmintic Treatment on Cardiometabolic Diseases and Risk Factors: A Systematic Review
Authors: Pham Khanh , Mertelsmann Anna , Mages Keith C , Kingery Justin , Mazigo Humphrey D , Jaka Hyasinta , Kalokola Fredrick M , Changalucha John , Kapiga Saidi , Peck Robert , Downs Jennifer A
Published: December 2022

Background

Growing evidence suggests a link between helminth infections and cardiometabolic diseases, but their relationships have not been reviewed systematically. Further, the possibility that helminth eradication could increase the risk of cardiometabolic diseases has not been comprehensively investigated.

Methods

We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development or severity of cardiometabolic diseases and risk factors. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and updated on March 1, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently.

Results

Eighty-three studies were included in the final analysis (Figure). Most studies reported on lipids (44), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and cardiomyopathy (4) (Table). Fifteen different helminth infections were represented. Helminth-infected subjects were less frequently reported to have dyslipidemia, metabolic syndrome, diabetes, and atherosclerosis, including coronary artery disease. Only 11 studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment adverse increases in lipids, diabetes or glucose levels, and/or metabolic syndrome. Figure.PRISMA Flow Diagram of Systematic ReviewTable.Trends of Cardiometabolic Diseases and Risk Factors Reported in All Included Studies

Conclusion

Animal and human reports consistently indicate that helminth infection may offer protection against dyslipidemia, metabolic syndrome, diabetes, and cardiovascular disease, and this protection may lessen after anthelmintic treatment. Our findings highlight the need for further cross-disciplinary research, which would have implications for both individual and population health, including mass drug administration, and could point towards ground-breaking new strategies to address the challenges of non-communicable diseases worldwide.

Disclosures

All Authors: No reported disclosures.
1172. Factors Associated With Febrile illnesses in Children in 27 Countries of Sub-Saharan Africa
Authors: Ssentongo Paddy , Chinchilli Vernon M , Shah Khush , Ba Djibril M
Published: December 2022

Background

Evidence on the relative importance of various factors associated with febrile illness in children and their heterogeneity across countries can inform the prevention, identification, and management of communicable diseases in resource-limited countries.

Heatmap of odds ratios.

Country-Specific Odds Ratios for 18 Factors Associated With Febrile illness From Multivariable Adjusted Models.

Methods

This cross-sectional study of 298 327 children aged 0 to 59 months assessed the strengths of associations of 18 factors with childhood fevers, using Demographic and Health Surveys (2010-2018) from 27 sub-Saharan African countries. A total of 7 direct factors (i.e., respiratory illness, diarrhea, breastfeeding initiation; vitamin A supplements; child's age; full vaccination; sex) and 11 indirect factors (household wealth; maternal education; maternal unemployment, water source; indoor pollution, stool disposal; antenatal care; family planning needs; maternal age, rural residence, and maternal marriage status) were assessed. Febrile illness was defined as the presence of fever in 2 weeks preceding the survey.

Results

Among the 298 327 children aged 0 to 59 months included in the analysis, the weighted prevalence of fever was 22.65% (95% CI, 22.31%-22.91%). In the pooled sample, respiratory illness was the strongest factor associated with fever in children (adjusted odds ratio [aOR], 5.46; 95% CI, 5.26-5.67; P < .0001), followed by diarrhea (aOR, 2.96; 95% CI, 2.85-3.08; P < .0001), poorest household wealth (aOR, 1.33; 95% CI,1.23-1.44; P < .0001), lack of maternal education (aOR, 1.25; 95% CI, 1.10-1.41; P < .0001), and delayed breastfeeding (aOR, 1.18; 95% CI, 1.14-1.22; P < .0001. Febrile illnesses were more prevalent in older children >6 months than those 6 months and younger.

Conclusion

In this study, respiratory illness, diarrhea, and socioeconomic conditions were the strongest factors associated with fevers in children of sub-Saharan Africa. Major causes of fevers in sub-Saharan Africa may mostly be attributed to respiratory infections and possibly viral—that may not be treated by antimalarial or antibiotics. Point of care diagnostics are needed to identify the pathogenic causes of respiratory infections to guide the clinical management of fevers in limited-resource countries.

Disclosures

All Authors: No reported disclosures.
1181. Predictive Score for Dengue Infection with Complete Blood Count Parameters, Including the New Monocyte Distribution Width – a Retrospective Single Center Derivation and Validation Study
Authors: Phuttasen Naiyana , Pornprasitsaeng Surapong , Onthong Yupapin , Sinthana Thurdsak , Limvorapitak Wasithep
Published: December 2022

Background

Dengue infection is a differential diagnosis in patients with acute undifferentiated fever. Early detection and management may reduce mortality. Monocyte distribution width (MDW) is a new parameter in complete blood count (CBC). It is recently approved for early detection of sepsis. We have noticed high MDW in Dengue patients. This study aimed to describe MDW changes in Dengue infection and to develop predictive score for early detection of Dengue infected patients.

Methods

We retrospectively retrieved data of adult patients with acute fever who had CBC and Dengue serology (NS1 antigen, IgM and IgG) performed during September 2019 to May 2020 at Thammasat University Hospital. Medical records were reviewed. MDW was compared between groups. Patients were randomly divided into training and validation set. Predictive score was developed from the training set and validated in the validation set with multivariable analysis.

Results

A total of 431 patients, with Dengue infection in 127 patients (29.5%), were included in the analyses. The median (interquartile range) of MDW in Dengue patients were higher than non-Dengue patients [29.7% (26.5 – 34.7) vs. 24.2% (21.1 – 27.8), P < 0.001]. In patients with confirmed Dengue infection, MDW increased with increasing severity (Figure). Training and validation sets included 216 and 215 patients with 64 and 63 Dengue infection, respectively. Independent predictive factors of Dengue infection were white blood cell < 4 x 109 /L (score 1), platelet < 100 x 109 /L (score 1) and MDW > 24% (score 1). No clinical features were independently predictive of Dengue infection. The area under receiver-operating-characteristic curve (95% confidence interval) of the prognostic score in the training and validation set were 0.839 (0.779 – 0.899) and 0.742 (0.674 – 0.811), respectively. With the cut-off score ≥ 1, the sensitivity and specificity of the score were 92.2% and 40.8% in the training set and 88.9% and 44.1% in the validation set.

Monocyte distribution width in Dengue and non-Dengue patients

Box-plot showing monocyte distribution width in patients with Dengue in comparison with non-Dengue (panel A) and compared between each Dengue severity (panel B)

Conclusion

MDW increase in patients with Dengue infection and also increase with Dengue severity. We have developed and internally validated a simple predictive score for Dengue infection based on only results from CBC and MDW. Further large-scale external validation study is required to confirm the utility of our predictive score.

Disclosures

All Authors: No reported disclosures.
1182. Risk factors for colonization with extended-spectrum cephalosporin resistant and carbapenem resistant Enterobacterales among community adults, Bangladesh: An Antibiotic Resistance in Communities and Hospitals (ARCH) study
Authors: Mah-E-Muneer Syeda , Chowdhury Fahmida , Hossain Kamal , Luvsansharav Ulzii-Orshikh , Hassan Md Zakiul , Smith Rachel Mann , Styczynski Ashley R
Published: December 2022

Background

Antimicrobial resistant (AMR) organisms are an increasing global health threat that are spreading within communities. Understanding the risk factors for colonization with AMR organisms is critical for implementing prevention and control strategies, particularly in resource-limited settings such as Bangladesh.

Methods

During 2019, we conducted a population-based observational study in Dhaka (surveillance site of icddr,b). We collected stool samples from randomly selected adults and tested for Enterobacterales with extended-spectrum cephalosporin resistance (ESCrE) and carbapenem resistance (CRE) using selective media followed by VITEK-2 confirmation. Participants completed demographic surveys assessing food consumption, animal contact, sanitation, water sources, and healthcare exposure. We identified factors associated with ESCrE and CRE colonization using bivariable and multivariable logistic regression, adjusting for potential confounders and clustering.

Results

Of 714 enrolled individuals, 557 (78%) were colonized with ESCrE and 66 (9%) with CRE. In bivariable analysis, factors associated with ESCrE colonization included fresh fruit consumption in the past week (OR 1.8, 95% CI 1.2-2.9), public tap as main source of drinking water compared with basic improved source (OR 3.3, 1.0-11.0), and unimproved toilet (pour/flush to open drain, pit latrine without slab) compared with basic improved toilet (OR 11, 2.9-42.0). Only consumption of fresh fruit was significant in the multivariable analysis (aOR 2.0, 1.3-3.2). Factors associated with CRE colonization in bivariable analysis were hospitalization in the last 3 months (OR 3.2, 1.2-8.6), limited sanitation facility (improved toilet shared with other households) (OR 2.0, 1.0-3.8), and limited hygiene (availability of handwashing facility on premises without soap and/or water) (OR 3.3, 1.4-7.7). The only factor that was significant in multivariable analysis was hospitalization in the last 3 months (aOR 3.0, 1.0-8.7).

Conclusion

While ESCrE colonization is common in urban communities, hospitals may be contributing to community spread of CRE. Targeted interventions focused on healthcare facilities may be needed to mitigate the transmission of AMR organisms.

Disclosures

All Authors: No reported disclosures.
1193. Disinfection of the Sink Drains to Reduce a Source of Serratia marcescens During Infection Outbreaks in a Neonatal Intensive Care Unit
Authors: Bourdin Thibault , Benoit Marie-Ève , Charron Dominique , Bédard Emilie , Prévost Michèle , Quach Caroline , Déziel Eric , Constant Philippe
Published: December 2022

Background

Sink drains are known reservoirs of pathogens and have been associated with multiple nosocomial outbreaks. In this study, the distribution of Serratia marcescens was investigated within the sink environment of a NICU and in colonized or infected newborns. The effect of different types of drain disinfection on bacterial concentration and on the detection of Serratia marcescens in sink drains was also investigated.

Methods

Sink drains from a NICU were sampled: 20 drains sampled for 6 weeks in the first year and 28 drains sampled for 5 months in the second year. S. marcescens isolated from positive patients were collected. A high-throughput short sequence typing (HiSST) method was developed to identify S. marcescens and compare strains and environmental DNA from sink drains with 56 clinical strains from 5 nosocomial outbreaks. Five interventions were tested: self-disinfecting drains, hot water disinfection, chlorine disinfection, steam disinfection and hot tap water flushing. Bacterial concentration of samples was measured in culture and flow cytometry and the HiSST method was used to identify S. marcescens.

Results

During the first and second sampling campaigns, 40% and 60% of sink drain samples were positive for S. marcescens with a moderate genotype diversity (1 to 11 different STs). The genotype profile of the 56 clinical strains was heterogeneous (26 STs). Four distinct STs were retrieved in 8 sinks after detection in patients whereas 1 ST was detected in a sink before detection in patient. Some environmental and clinical strains were found in drains for up to a year after the first sampling campaign. Each tested drain intervention reduced culturable bacteria (4-8 log) and viable bacteria (2-3 log), except for chlorine. The self-disinfecting drains, hot water and steam disinfection were able to remove temporarily S. marcescens from the drains.

Conclusion

The high genotypic diversity of the clinical strains suggests diffuse sources of S. marcescens within the NICU likely to cause nosocomial infection outbreaks. The self-disinfecting drains, hot water and steam disinfection seem to be the best methods to reduce bacterial concentration in drains and eliminate S. marcescens in the short term, thus limiting the risk of pathogens spread from the sink environment to patients.

Disclosures

All Authors: No reported disclosures.
1574. Patient, Health System, and Clinical Encounter Characteristics Associated with Use Of Antibiotics Without A Prescription In The United States
Authors: Grigoryan Larissa , Paasche-Orlow Michael K , Alquicira Osvaldo , Barning Kenneth , Mahmood Hamad , Porter Thomas , Khan Fareed , Salinas Juanita , Raphael Jean , Fowler Michele , Street Richard , Trautner Barbara
Published: December 2022

Background

Use of antibiotics without a prescription (purchased in the United States (U.S.), purchased in other countries, or obtained from friends and relatives) is potentially unsafe and may increase the global risk of antimicrobial resistance. We evaluated the effect of patient, health system, and clinical encounter factors on intention to use antibiotics without a prescription.

Methods

Waiting room survey conducted from January 2020 and March 2021 in three continuity and three same-day public primary care clinics and two private emergency departments. Non-prescription use was defined as the consumption of antibiotics not prescribed for the individual’s current condition. Intended use was defined as professed intention to take antibiotics if feeling sick, without contacting a doctor, nurse, or clinic, in any of the following situations: 1) buying antibiotics without a prescription in the U.S., 2) buying antibiotics without a prescription in another country, and 3) getting antibiotics from friends or relatives. The effect of patient, health care system, and clinical encounter factors were studied using multivariate logistic regression.

Results

Of the 564 respondents, 247 (43.8%) reported prior use of non-prescription antibiotics; half of these instances involved penicillins (mostly amoxicillin). Overall, 177 (31.4%) of the respondents intended to use antibiotics without a prescription from one of the three sources (Figure 1). Younger age, lack of health insurance and high cost of doctor visits were predictors of intention to buy antibiotics without a prescription in the U.S. (Table 1). Predictors of intention to buy antibiotics without a prescription from other countries included younger age, being interviewed in Spanish, and reporting that a language barrier is a major problem for medical appointments. Lack of health insurance and high cost of physician visits were associated with the intention to use antibiotics obtained from relatives or friends.

Conclusion

Interventions aimed at reducing non-prescription antibiotic use should focus on addressing language barriers, ensuring health insurance coverage, and reducing financial barriers to primary care visits.

Disclosures

Larissa Grigoryan, MD, PhD, Rebiotix Inc: Grant/Research Support Michael K. Paasche-Orlow, MD, MPH, GlaxoSmithKline: Advisor/Consultant Barbara Trautner, MD, PhD, Genetech: Advisor/Consultant.
1200. Measuring the Contamination of Transport and Emergency Ambulances and Emergency Medical Service (EMS) Providers
Authors: Graves Amanda M , Schaps Diego , Isaacson Julia , Barrett Aaron , King Carly , Warren Bobby G , Anderson Deverick J
Published: December 2022

Background

Contamination of ambulances and EMS providers is poorly understood.

Methods

We conducted a prospective observational study to determine contamination of ambulances and EMS providers at two agencies in central North Carolina. Study ambulances and providers were enrolled and sampled prior to the start of day shift on each sampling day. Ambulances were then disinfected with bleach by a study member. Ambulances and providers were sampled again immediately following shift completion and before final disinfection.

Samples were obtained from ambulances and providers (Table 1). Cellulose sponges and flocked swabs used for sampling were pre-drenched with disinfectant neutralizing buffer. RODAC plates for clothing cultures were filled with disinfectant neutralizing agar. Sponges were processed using the stomacher method, swabs were plated onto media directly, and RODACs were read and worked up using standard microbiology techniques. All samples were plated on general and selective media for study pathogens. We calculated total colony forming units (CFU), total CFU for each sample area and proportions of samples harboring clinically important pathogens (CIPs), defined as MRSA, MSSA, and VRE. The Mann-Whitney U test was used to compare CFUs between samples, ambulances, and providers, and the Z score proportionality test was used to compare proportions of samples with CIPs. P < .05 was considered significant. Table 1.Sampling Methods and Locations of Ambulance and EMS Providers

Results

10 emergency and 10 transport ambulances, and 40 providers were sampled from September 2021 - March 2022 resulting in 980 total samples. Transport and emergency truck CFUs (Table 2) were similar between sample 1 and 2 (p=0.1, 0.9, respectively). EMS providers CFUs were similar at sample 1 and 2 (p=0.2, 0.2, respectively). Before a shift, 100 samples harbored CIPs (19 MRSA, 66 MSSA, 15 VRE). Following the shift, 88 new CIPs were recovered (24 MRSA, 53 MSSA, 11 VRE). At Sample 1, 59 (59%) of CIPs were harbored on EMS uniforms, and 41 in ambulances. At Sample 3, 62 (70%) of CIPs were harbored on EMS uniforms. Other results can be seen in Table 2. Table 2.Median CFUs for Emergency and Transport Ambulances and EMS Providers by Sample, and Number of CIPs Recovered

Conclusion

Our data demonstrate provider uniforms were contaminated upon arrival and ambulances were contaminated when deemed ready for service. Further studies are needed to determine optimal disinfection procedures of ambulances and EMS uniforms.

Disclosures

All Authors: No reported disclosures.
1202. A Multi-Center Validation of the Electronic Health Record ‘Admission Source’ Field Against Clinical Notes for Identifying Hospitalized Patients with Long-term Care Facility Exposure
Authors: Goodman Katherine E , Taneja Monica , Magder Laurence , Resnik Philip , Sutherland Mark , Sorongon Scott , Klein Eili , Tamma Pranita , Harris Anthony
Published: December 2022

Background

A current or recent long-term care facility (LTCF) stay is a strong risk factor for antibiotic-resistant bacterial colonization and infection. However, most electronic health record (EHR) systems do not systematically record LTCF exposure. Absent manual chart review, which is resource-intensive and cannot be incorporated into automated screening algorithms, there is no definitive method for identifying LTCF-exposed inpatients. As a surrogate, researchers often use ‘Admission Source’ to identify LTCF transfers, but this EHR field has not been previously validated, and it may miss the unknown percentage of patients with recent, but not current, LTCF stays. This study evaluated the accuracy of ‘Admission Source’ in identifying LTCF-exposed inpatients.

Methods

This was a retrospective study of adult admissions from 2018 – 2021 across 12 hospitals in the University of Maryland Medical System. We extracted patient and encounter data and classified patients as LTCF-exposed by ‘Admission Source’ if they were LTCF transfers. For 315 randomly sampled admissions, M.T. and K.G. reviewed the admission ‘History & Physical’ note for mention of LTCF exposure (Fig. 1). Assuming an indication of LTCF in either the ‘Admission Source’ field or clinical note represented true exposure, we estimated each method’s sensitivity with 95% confidence intervals.

Results

Across 280,581 admissions, 9,476 (3.4%) had an ‘LTCF transfer’ admission source. In the validation sample, 26 (8.3%) were classified as LTCF-exposed by either ‘Admission Source’ or clinical note, of which 12 were identified in the ‘Admission Source’ field and 25 in the notes (Fig. 2). The sensitivity of ‘Admission Source’ for detecting LTCF exposure was 46% (29% – 65%) and for clinical notes was 96% (81% - 99%). Most (12/14) patients missed by ‘Admission Source’ were current LTCF residents (Fig. 3).

Conclusion

The EHR ‘Admission Source’ field misses the majority of inpatients with recent or current LTCF exposure, risking substantial misclassification in research studies and clinical algorithms that incorporate this variable. Automated techniques for analyzing free-text notes, such as natural language processing, could significantly improve detection of these patients to assist hospital epidemiology and infection control efforts.

Disclosures

All Authors: No reported disclosures.
1219. Outbreak Investigation of Burkholderia cepacia Linked to Contaminated Ultrasound Gel
Authors: Weyhmuller Carol , Lynch Caitlin , Maglio Michael , Milligan Sarah , Otero Sally , Sherman Eileen , Lindao Daniel H , Gilbert Brett , Chaparro-Rojas Fredy
Published: December 2022

Background

This presentation will highlight how a multiuse hospital product was determined to be contaminated with Burkholderia cepacia (BCC) in the summer of 2021. The investigation began when there was a cluster of inpatients at one campus with blood cultures growing BCC. A multidisciplinary team was quickly assembled to investigate these cases. Swift action by the system team identified the source of the contamination, removed the product from use, and implemented evidence-based guidelines for safe ultrasound gel use.

Methods

The investigation began with thorough chart reviews. An epi curve was created to visually display the outbreak. A literature review was conducted to review previous outbreaks of BCC. It was determined that all the patients had undergone ultrasound procedures. The team immediately focused on multiuse bottles of ultrasound gel.

Results

Initial case investigation revealed a cluster of 9 patients growing BCC. The specimen source was primarily blood, but 2 patients had cultures from other sources. Ultrasound was the only commonality found. 37 opened and unopened product samples of 9 different water-based products were sent to the lab for testing. BCC was identified in 8 samples of non-sterile ultrasound gel. Immediate action was taken to rapidly recall the product system wide. Supply Chain quickly purchased and distributed a replacement product at all campuses. The manufacturer was contacted, the Department of Health was notified, and Infection Prevention alerted neighboring health care systems.

Conclusion

Risk assessments were done to assess the use of ultrasound gel and the cleaning of transducers within the health care system. System wide education commenced for the proper use of ultrasound gel and equipment to prevent patient infections. A total of 11 patients were identified with BCC during the outbreak. Whole genome sequencing linked 10 of the patient isolates to a national outbreak associated with contaminated ultrasound gel. This investigation emphasizes both the need for rapid mobilization in the event of an outbreak to prevent additional morbidity and mortality and the importance of assessing appropriate use of non-sterile ultrasound gel and equipment within healthcare facilities.

Disclosures

Brett Gilbert, D.O., F.A.C.O.I., Pfizer: speaker bureau.
1225. The Perfect Storm: A Hardy and Lethal Pathogen and a Unit Filled with Immunocompromised Patients with Large Open Wounds. Troubles with Candida Auris in a Burn Intensive Care Unit
Authors: Moore Riley , Lie Louise , Pua Herminia , Slade David H , Rangel Sharon , Davila Anthony , Carson Joshua S , Parada Jorge Paiva
Published: December 2022

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.
1238. Evaluation of Children Exposed to Perinatal Hepatitis C in the US : A Literature Review
Authors: Saleh Ezzeldin , Rodriguez Marcela , Chaudhary Subhash
Published: December 2022

Background

Incidence of Hepatitis C virus (HCV) infection is rising in the United States (US), largely due to the ongoing opioid epidemic. In children, perinatal transmission is the most common route of HCV infection, which is almost always asymptomatic. Therefore diagnosis is confirmed by HCV antibody testing by ≥18 months due to persistence of maternal antibodies. Identification of HCV-infected infants is critical as up to 80% develop chronic HCV infections with significant morbidity and mortality. In this review, we examine studies evaluating appropriate testing for perinatal HCV.

Methods

We performed a systematic literature review with PubMed and Embase (through April 2022) for studies evaluating optimal testing of children exposed to perinatal HCV in the US. Full text articles in English were included and conference proceedings were excluded.

Results

We analyzed 13 articles; all were published in the last decade with study periods spanning from 1993 to 2018 [Table1]. Most of the studies were retrospective, except for one prospective and two before-and-after intervention. Rates of optimal HCV testing showed vast regional differences and varied widely, with rates as low as 7%. Only 3 studies achieved ≥ 50% complete testing, with the highest rate (61%) achieved in a study that adopted EMR-reminders for testing. The two interventional studies showed over 40% increase of adequate testing. Interventions included early engagement of caregivers at time of birth with consultation, education, and close follow-up, EMR leverage to document HCV-exposure and send reminders for final testing at 18 months of age. Five studies retrospectively evaluated maternal and infant risk factors associated with perinatal HCV testing [Table2].

Conclusion

Overall, rates of perinatal HCV appropriate testing were suboptimal and varied widely. Prospective and EMR-based interventional studies showed higher rates of testing. Innovative testing schemes, public health and social support programs, similar to perinatal HIV model, are strongly needed to substantially improve perinatal HCV management. Further prospective and interventional studies are needed to formulate effective guidelines for perinatal HCV evaluation, and to identify and address barriers and enablers to optimal perinatal HCV care.

Disclosures

All Authors: No reported disclosures.
1248. Relationship Between ALT and New HBV Biomarkers in HBV/HIV Coinfected Persons Started on Antiviral Therapy
Authors: Rouster Susan D , Blackard Jason T , Horn Paul S , Stec Michael E , Sherman Kenneth E , Anderson Mark C , Peters Marion G , Cloherty Gavin
Published: December 2022

Background

While HBV DNA has served as a primary biomarker of HBV infection, newer biomarkers including pre-genomic HBV RNA (pgRNA) and quantitative HBV surface antigen (qHBsAg) may prognosticate treatment responses better. We analyzed the changes in these biomarkers over time following initiation of antiviral therapy in persons living with HIV (PLWH) to determine the relationship to ALT, a key marker of liver injury. FigureBiomarker changes

Methods

NIH AIDS Clinical Trials Group Study 5127 enrolled HBV/HIV PLWH into a Phase 2 treatment trial that randomized them to receive 48 weeks of either tenofovir (TDF) or adefovir (ADV). ALT and HBV DNA were evaluated as measures of treatment response. Stored samples were tested for HBV pgRNA and qHBsAg at baseline, 4, 12, 24, 36, and 48 weeks. HBV pgRNA was isolated using RNA-selective extraction chemistry followed by a multiplex RT-qPCR that targets the HBV X and core targets on the m2000 system (Abbott Molecular, Des Plaines, Illinois). A sensitive second-generation assay with a lower limit of quantification (LLOQ) of 10 copies/mL was utilized. Quantitative HBsAg was determined by Abbott ARCHITECT (List# 6C36) with a LLOQ of 0.05 IU/mL. Data were analyzed using SAS® version 9.4.

Results

Overall, 47 study participants had sufficient samples for biomarker testing. Participants were predominantly male (93.6%) and identified as white, non-Hispanic (55.3%) or black (34%). Groups were evenly randomized to receive either TDF (n=23) or ADV (n=24). Baseline ALT mean was 64.9 U/L, and HBV DNA was 9.1 (+1.6) copies/mL. Pre-treatment pgRNA serum concentration was 7.0 (+1.3) log U/mL, and qHBsAg was 195,574 (+272,190) IU/mL. Over the course of treatment, pgRNA was significantly correlated with the change in serum ALT levels (r=0.48; p=0.0035) but not HBV DNA (r=0.21; p=0.226). ALT was negatively correlated with qHBsAg (r=-0.52; p=0.02). pgRNA was also highly negatively correlated with qHBsAg (r=-0.49l; p=0.03) but not HBV DNA (r=0.13; p=0.59). (Figure).

Conclusion

HBV pgRNA is a better predictor of ALT change – a key measure of hepatocyte injury – than HBV DNA in PLWH who are initiated on nucleotide/nucleoside therapy. Quantitative HBsAg is inversely associated with ALT levels, supporting the hypothesis that HBsAg inhibits immune mediated injury to hepatocytes.

Disclosures

Michael E. Stec, MSc, Abbott Laboratories: Employee of Abbott|Abbott Laboratories: Stocks/Bonds mark C. Anderson, PhD, Abbott Laboratories: Employment|Abbott Laboratories: Stocks/Bonds Marion G. Peters, MD, Aligos: Advisor/Consultant|antios: Advisor/Consultant|Excision Biotherapeutics: DSMB Gavin Cloherty, PhD, Abbott: Employee|Abbott: Stocks/Bonds|Abbott Labs: Employee.