bluuebunny/crossref_metadata_2025 huggingface dataset:
195. Reducing Time to Optimal Antimicrobial Therapy (OAT) for Bloodstream Infections (BSI) due to Gram Positive Cocci (GPC) in Chains Using Rapid Diagnostics Paired with Antimicrobial Stewardship (ASP) Efforts
Authors: Ma Justin K , McSweeney Terrence D , McManus Dayna , Davis Matthew W , Merwede Jacob , Peaper David , Topal Jeffrey E
Published: December 2022

Background

Rapid microbiology diagnostic results paired with immediate ASP intervention have been shown to decrease time to OAT and improve patient outcomes. For Gram positive (GP) BSI, studies have primarily focused on Staphylococci. However, the value of using rapid diagnostics for GPC in chains is not well studied. With the use of BioFire® FilmArray® Blood Culture Identification 2 (BCID2) to identify GPC in chains, we aimed to compare the time to OAT between pre- and post- implementation.

Methods

In May 2021, our institution implemented the use of BCID2 for GPC in chains, which detects 5 types of GPC in chains to the species level and the van A/B gene. Positive results were communicated in real time 24/7 to ASP who provided recommendations on OAT to the treatment team.

A retrospective chart review compared the pre-implementation cohort (Jan - Sept 2019) to the post-implementation cohort (May 2021 - Jan 2022). The following patients were excluded from analysis: < 18 years of age, presence of polymicrobial infection or Streptococci with unidentified species by BCID2, discharged or deceased before rapid diagnostic result, on comfort measures or left against medical advice within 72 hours of result.

The primary study endpoint was time to OAT which was defined as time from positive Gram stain to OAT. Secondary outcomes included percentage of ASP recommendations accepted, length of stay (LOS), and 30-day mortality.

Results

A total of 199 patients met inclusion criteria, 117 pre-cohort vs. 82 post-cohort. Baseline demographics were similar in both groups with the exception of the post-cohort having a numerically higher Charlson Comorbidity Index (Table 1). The most common sources of the bacteremias were intra-abdominal, skin and soft tissue, and endovascular (Table 2).

The primary endpoint, average time to OAT, was 35 hours in the pre-cohort and 18 hours in the post-cohort with a difference of 16.8 hours (95% CI 9.8 – 23.8; p < 0.0001) (Table 3). ASP recommendations were accepted 91% of the time. The median LOS was 9 days (IQR 6 - 21) in the pre-cohort vs. 13 days (IQR 7-32) in the post-cohort (p = 0.07). The 30-day mortality rate was numerically lower in the pre-cohort (6.1% vs. 10.3%; p = 0.79).

Conclusion

For BSI due to GPC in chains, rapid diagnostics via BCID2 paired with 24/7 ASP led to markedly decreased time to OAT.

Disclosures

David Peaper, MD, Tangen Biosciences: Stocks/Bonds.
196. Repeat Tracheal Aspirates in Pediatric Intensive Care Patients: Frequency, Resistance and Antimicrobial Use
Authors: Lyon Edward , Goldman Jennifer , Lee Brian R , Selvarangan Rangaraj , Monsees Elizabeth
Published: December 2022

Background

Tracheal aspirates (TA) are frequently obtained in the pediatric intensive care unit (PICU); however, no data exists on the frequency or clinical management of multiple TA cultures on the same PICU patient. In this study, we describe the frequency of repeat TAs in PICU patients, the emergence of multidrug resistant organisms (MDRO), frequently cultured pathogens of TAs, and associated antibiotic prescribing patterns.

Methods

We identified 70 PICU patients between 2018-2019 who met our criteria for retrospective chart review with ≥ 2 TAs obtained during their hospitalization. The following information was collected: patient demographics, number of TAs per patient, microbiology with susceptibilities, antibiotic use, and clinical data summarizing patient condition. Descriptive statistics established the frequency and time between initial and repeat TAs, reason for collection, antibiotic exposure, and frequency of MDRO development.

Results

Preliminary data on 15 patients showed 90 total TA cultures, with a median of 4 [IQR 2.5, 8] cultures per patient during their PICU stay (Figure 1). The median days between cultures was 10 [IQR 4, 26]. Most patients were < 5 years of age (n=14; 94%), male (n=13; 87%), and were admitted to the medical ICU service (n=8, 53%). Fever (46%) was the most common reason for TA collection followed by vital sign changes and secretion burden (34% and 32% respectively). A total of 133 organisms were isolated, with Pseudomonas aeruginosa (n=32), Methicillin-susceptible Staphylococcus aureus (n=16), and Klebsiella oxytoca (n=11) comprising the top pathogens (Figure 2). Eleven of the 15 patients (73.3%) had the same organism detected on ≥ 2 separate cultures. A total of 616 antibiotic days were prescribed with 149 (24%) antibiotic days prescribed for the TA result specifically. Six (40%) patients developed a MDRO after a median of 14.5 antibiotic days [IQR 11.75, 37.5]. Figure 1Number of tracheal aspirate cultures per patient

Figure 2 Frequency of identified pathogens

Conclusion

Repeat TAs are performed in the PICU, often identifying the same pathogen repeatedly, likely representing colonization. Development of resistance is common and only one-fourth of TAs are directly treated with antibiotics. These data provide an opportunity to further explore clinical criteria to maximize the impact of TA cultures in the PICU.

Disclosures

Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
200. The Utility of a Rapid Multiplex PCR Assay in the Management of Staphylococcus Aureus Bacteremia at a Tertiary Care Center
Authors: Gholami Sherry , Chundi Vahini , Fan Katherine , Duong Lan , Kumar Princy N , Timpone Joseph G
Published: December 2022

Background

Staphylococcus aureus bacteremia (SAB) is a major cause of community and healthcare-acquired bacteremia and is associated with a high burden of morbidity and mortality. Appropriately tailoring management based on methicillin sensitivity can help minimize unnecessary administration of broad-spectrum antibiotics and ensure adequate treatment of MSSA/MRSA. The Verigene® (Luminex Corporation) is a multiplex PCR assay that provides rapid identification of bloodstream pathogens. We performed a QI project to determine the utility of this assay in managing patients with SAB.

Methods

We performed a single-center retrospective cohort study of positive SAB cultures from May 2020 to May 2021. Electronic health record review was conducted to abstract patient demographics, clinical characteristics, outcomes, blood culture data, and antibiotic management. Statistical analysis was done with the unpaired t-test and fishers exact test to identify associations of statistical significance.

Results

We identified 97 cases of SAB: 66% MSSA (n = 64), 34% MRSA (n = 33). Patient characteristics included: mean age 61 years, 58.8% male, 42% immunocompromised, 83.5% with ID consult, 38.1% with ICU admission, mean length of stay 20.3d, and 24.7% mortality. Using the Verigene® assay, we noted 2.6% discordance with standard microbiological technique (n = 2). The timing of Verigene® results and provider response were as follows:

The mean duration of SAB was 3.1d (MSSA = 2.8d, MRSA = 3.6d, p = 0.2477). There was a statistically significant difference in patient mortality with respect to methicillin sensitivity status: MSSA 15.6%, MRSA 42.4%, p = 0.0075, as well as mortality with ID consult 19.8% versus no ID consult 50%, p = 0.0223.

Conclusion

Despite the incorporation of a rapid multiplex PCR assay to detect bloodstream infections, the time to de-escalation for MSSA was sub-optimal (2.7 days). ID consultation continues to be an important component of SAB management as it improves patient outcomes and contributes to education of healthcare providers.

Disclosures

Lan Duong, PharmD, Johnson & Johnson: Stocks/Bonds|Lilly USA: Stocks/Bonds|Novavax: Stocks/Bonds Princy N. Kumar, MD, American Gene Technologies: Grant/Research Support|BioHaven: Grant/Research Support|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Stocks/Bonds|GSK: Grant/Research Support|GSK: Stocks/Bonds|Johnson&Johnson: Advisor/Consultant|Johnson&Johnson: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Stocks/Bonds|Moderna: Stocks/Bonds|Pfizer: Stocks/Bonds|Regeneron: Grant/Research Support|TheraTechnologies: Grant/Research Support|ViiV: Advisor/Consultant Joseph G. Timpone, Jr., MD, Gilead: Stocks/Bonds|Merck: Stocks/Bonds.
202. Vintage or Vogue? The Utility of Procalcitonin for Identifying Secondary Infections in Patients With Influenza or Covid-19 Receiving Extracorporeal Membrane Oxygenation
Authors: Patel Kajal D , Sobieszczyk Michal J , Marcus Joseph E , Aden James
Published: December 2022

Background

Secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) are difficult to identify as many signs traditionally associated with infection, such as temperature, are partially controlled by the ECMO circuit. This study analyzes the utility of procalcitonin (PCT) as a diagnostic marker in identifying secondary infections in patients receiving ECMO with influenza or COVID-19.

Methods

A single center retrospective study was performed on patients receiving ECMO with underlying influenza or COVID-19 from November 2017 to October 2021. Patient demographics, time receiving ECMO, culture data, and PCT levels were extracted. The first PCT within three days of an infection designated positive was compared to negative values, PCT extracted from patients without an identified infection or any PCT 10 days after the most recent infection. Furthermore, PCT levels were compared by type of pathogen as well as site of infection via Mann-Whitney U tests.

Results

84 patients (77% males) met inclusion criteria with median age of 43 (interquartile range (IQR): 35-51). Median ECMO time was 416 hours (IQR: 232-824), with 64 (76%) of the patients admitted for COVID-19. A total of 276 (3.3 per patient) PCT were ordered during the study period. Of the 92 infections identified, 33 (36%) had an associated PCT value with 19 (58%) PCT collected on the day of positive culture, 10 (32%) within one day, and 4 (12%) collected two to three days after positive culture. There was no significant difference between median PCT value among the infection group (1.0 IQR: 0.40-1.19) compared to the non-infectious group (1.27 IQR: 0.47-4.26, p= 0.19), between Gram-positive and Gram-negative infections (1.09 IQR: 0.43-2.70 vs. 0.95 IQR: 0.4-1.29 p= 0.35) or between bloodstream infections and respiratory infections (1.3 IQR 0.45-2.70 vs. 0.55 IQR: 0.4-1.38, p=0.35). PCT does not decline after infection is identified (Figure 1).

Procalcitonin Trends Figure 1.Procalcitonin levels do not statistically decline over the course of an infection.

Conclusion

While PCT has been proposed as a potential diagnostic marker for secondary infections in patients receiving ECMO, this single center study did not demonstrate utility of PCT in identifying secondary infections. Furthermore, there was no association of PCT levels with either the site of infection or type of infectious organism.

Disclosures

All Authors: No reported disclosures.
204. Genomic comparison of blood and colonizing nasal isolates in patients hospitalized with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia
Authors: Nadkarni Devika , Nadkarni Devika , Alburquerque Bremy , Chung Marilyn , van de Guchte Adriana , Caban Ana Berbel , Schwarz Erika Reategui , Sullivan Mitchell , van Bakel Harm , Altman Deena
Published: December 2022

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health-care associated infections, particularly bloodstream infections (BSI). Concomitant colonization of the anterior nares has been shown to have implications on persistence, recurrence, and transmission events. We performed genomic comparisons between paired nasal and blood MRSA isolates obtained from the same patient to elucidate the genetic differences that may contribute to within-host invasion and virulence.

Methods

Patients hospitalized with MRSA bloodstream infection were swabbed in the bilateral nares. Paired blood and nasal isolates underwent DNA extraction and spa typing. Nasal and blood isolates from the same patients with matching spa types were sequenced by Illumina and PacBio respectively. For genomic analysis, PathoSPOT and Snippy were used to compare genomes of nasal and blood isolate pairs to evaluate single nucleotide polymorphisms, insertions and deletions.

Results

Of 121 patients with MRSA BSI, 87 patients (72%) had concomitant colonization of the anterior nares with MRSA. Spa type of t002 predominated in both blood and nasal isolates. From the 76 pairs that underwent genomic analysis, several mutated genes were identified across all pairwise comparisons, 8 of which recurred in more than one patient pair. These included genes involved in conferring antibiotic resistance, increased mutability, immune evasion, and adaptive metabolism.

Conclusion

In patients with MRSA BSI and concomitant MRSA nasal colonization, mutations identified by genomic analysis in blood-nasal pairs are implicated in contributing to invasion and within-host adaptability.

Disclosures

All Authors: No reported disclosures.
206. Using Genome-Wide Association Analysis of Pneumococcal Isolates to Identify Novel Gene Variants in Central Nervous System Infection
Authors: Sanchez John Michael , Pershing Nicole L , Nielsen Shannon , Kapusta Aurelie , Crandall Hillary , Blaschke Anne J
Published: December 2022

Background

Streptococcus pneumoniae is the leading cause of meningitis in children and is associated with significant morbidity and mortality. Despite conjugate pneumococcal vaccines that have otherwise been successful in reducing invasive disease caused by vaccine serotypes, the incidence of pneumococcal meningitis remains relatively unchanged. Using genome-wide association, we identified sequence elements associated with pneumococcal central nervous system (CNS) infection.

Methods

From 1996 to 2018, 366 clinical pneumococcal isolates were collected from pediatric patients and paired with clinical metadata. All isolates underwent whole-genome sequencing and in silico serotyping. Fifty-four clinical isolates were from children with CNS infection. Sequence element enrichment analysis was performed using elastic net and linear mixed modeling statistical methods to find genetic variants associated with CNS infection. We identified associated genes by mapping statistically associated variants to a serotype 19F reference S. pneumoniae genome.

Results

CNS isolates spanned 22 unique serotypes; the most common were 22F (n = 6), 7F (n = 5), 18C (n = 4), and 35B (n = 4). We identified two intergenic sequence variants and one intragenic sequence variant significantly associated with CNS infection (p < 1.48 × 10-7). The top intragenic candidate in our analysis was located within cpsC, a gene involved in regulation of capsule synthesis. The CNS infection-associated cpsC variant was found in serotypes 22F (n = 1), 18C (n = 4), and 14 (n = 2).

Conclusion

The diversity of pneumococcal isolates associated with CNS infection suggests the importance of genetic determinants beyond capsular serotype. We identified a number of novel microbial genetic variants significantly associated with pneumococcal CNS infection across serotypes, including a coding mutation in cpsC. Functional characterization of cpsC variants is needed to inform mechanisms contributing to pneumococcal CNS virulence.

Disclosures

Anne J. Blaschke, MD, PhD, BioFire Diagnostics/Biomerieux: Advisor/Consultant|BioFire Diagnostics/Biomerieux: Grant/Research Support|BioFire Diagnostics/Biomerieux: IP licensed to BioFire Diagnostics through the University of Utah and royalties received through the University of Utah related to the FilmArray|Merck: Advisor/Consultant.
211. Outcomes Following a Protocol Change to decrease Perioperative Antibiotic Duration Among Liver Transplant Recipients
Authors: Brandon Hutton , Truax Crystal M , Zarate Eduardo Rodriguez , Tritle Brandon , Odrobina Robert , Imlay Hannah
Published: December 2022

Background

Liver transplant recipients (LTRs) are at high risk for infections. The optimal duration of perioperative antibacterial prophylaxis remains unclear, particularly in patients hospitalized prior to transplant. Our study examines the impact of a change in our institutional perioperative antibiotic protocol in LTRs on post-transplant infection and antibiotic-associated toxicity.

Methods

We conducted a retrospective cohort study of all adult LTRs at our center who underwent transplant from 1/1/2018 until 9/1/2021. Patients were categorized as low risk if they are hospitalized < 24 hours prior to transplant and high risk if they were hospitalized ≥ 24 hours prior to transplant. We investigated patient outcomes after a change to our perioperative antibiotic guideline on 1/19/21, which reduced the duration of post-operative antibiotics for low risk patients from 48 to 24 hours and for high risk patients from 5 days or duration of post-operative ICU stay to 72 hours. Outcomes included post-transplant infection within 30 days (composite outcome of bacteremia and surgical site infection), C. difficile infection (CDI), and isolation of multi-drug resistant organisms (MDROs) from any site. Chi-squared and Fisher’s exact test were performed with p < 0.05 considered significant.

Results

There were 154 LTRs who underwent transplantation during the study period, including 63 high risk patients (43 before and 20 after the protocol change). The median duration of prophylactic antibiotics in the high risk group decreased from 6 (IQR 5-8) to 4.5 (IQR 4-5) days after the protocol change (p = 0.04), and in the low risk group decreased from 2.5 (IQR 2-5) to 1 (IQR 1-2) day (p = 0.04). Prophylactic antibiotics consisted of piperacillin-tazobactam in 145 (94%) and vancomycin in 104 (68%) of cases. In the high risk group, infection occurred in 4 (9%) patients before and 0 patients after the protocol change (p=0.3). CDI occurred in 4 (9%) patients before and 1 (5%) patient after the protocol change (p=1). Resistant organisms were isolated in 10 (23%) patients before and 1 (5%) patient after the protocol change (p=0.15). Figure 1.Antibiotic duration as a percentage of each cohortTable 1.Clinical outcomes before and after protocol change among low and high risk patientsTable 2.Antibiotic-associated outcomes before and after protocol change among low and high risk patients

Conclusion

The policy change reduced the median duration of perioperative antibiotic prophylaxis but was not accompanied by an observed increase in postoperative infection.

Disclosures

All Authors: No reported disclosures.
214. The impact of preservation fluid culture on graft site arteritis: a systematic review and metanalysis.
Authors: Rinaldi Matteo , Bonazzetti Cecilia , Gatti Milo , Caroccia Natascia , Comai Giorgia , Ravaioli Matteo , Morelli Maria Cristina , Viale Pierluigi , Giannella Maddalena
Published: December 2022

Background

The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear.

Methods

Systematic literature search retrieving all-languages observational studies comparing SOT recipients with culture positive PF versus culture negative PF. Graft site arteritis within 180 days from transplant was selected as primary outcome. Data were independently extracted using a pre-specified form, and quality of included studies was independently assessed according to ROBINS-I tool for observational studies. Meta-analysis was performed using Mantel-Haenszel random-effect models.

Results

2,492 articles were screened, and twenty-one observational studies (N=2,208 positive PF vs. 4,458 negative) were included in the meta-analyses. Among positive PF, 857 (38.8%) were classified as high-risk group pathogens (fungi, Gram negative, Enterococcus spp., beta-hemolytic streptococci and Staphylococcus aureus) and 1,351 (61.2%) as low-risk (mostly coagulase negative Staphylococci) pathogens. A significant higher risk of graft arteritis was found in SOT recipients with a PF yielding a high-risk pathogen (odds ratio [OR] 18.43, 95%CI 7.83-43.40), with low heterogeneity (I²=2.24%). Similar results were found considering separately high-risk bacteria (OR 12.02, 95%CI 4.88-29.60) and fungi (OR 71.00, 95%CI 28.07–179.56), with no heterogeneity (I²=0%), and in the subgroup analyses of liver (OR 16.78, 95%CI 2.95–95.47) and kidney (OR 19.90, 95%CI 4.78–82.79) recipients. However, data about diagnostic features of graft arteritis were very limited, indeed for only 11 of the 93 events histological or microbiological results were reported.

Conclusion

Our results may support the performance of PF culturing and a preemptive diagnostic or therapeutic management upon isolation of high-risk pathogen. Further studies based on reliable diagnosis of graft arteritis are needed to confirm our findings.

Disclosures

All Authors: No reported disclosures.
220. Acute kidney injury incidence comparison of vancomycin trough-based vs AUC/MIC monitoring at a tertiary care hospital
Authors: Ruiz Gaviria Rafael E , Ramdeen Sheena , Chou Jiling , Norman Sarah J , Elgendi Sarah H , Llama Adrian , Kitana Farah I
Published: December 2022

Background

Therapeutic drug monitoring (TDM) of vancomycin is a fundamental part of optimizing efficacy and adverse effects. The Infectious Diseases Society of America (IDSA) consensus guidelines recently recommended a change in vancomycin monitoring from trough-based levels to area under the curve/minimum inhibitory concentration (AUC/MIC). The objective of this study was to compare the incidence of acute kidney injury (AKI) utilizing trough vs AUC/MIC vancomycin monitoring.

Methods

This retrospective cohort study included patients ≥18 years old that had received vancomycin for >48 hours. Patients who developed an AKI within 48 hours of vancomycin were excluded. One cohort included patients monitored by vancomycin trough levels from January to June 2019, and the second cohort included patients monitored by AUC/MIC from July to December 2021. The primary outcome was incidence of AKI per Kidney Disease Improving Global Outcomes (KDIGO) definition. Data were analyzed using a multivariate logistic regression model with covariates that are described to be associated with AKI.

Results

A total of 371 patients were included; 229 patients from the trough-based cohort and 142 patients from the AUC/MIC cohort. The incidence of AKI was 20.1% in the trough-based cohort and 13.5% in the AUC/MIC cohort (p=0.153). Around 39% and 30% patients were admitted to the intensive care unit from the trough based cohort and the AUC/MIC respectively. A multivariate logistic regression analysis identified higher odds of AKI among patients with supratherapeutic vancomycin levels regardless of dosing method, OR=5.89 (95% CI 3.03-11.54) ,and the OR comparing trough based dosing with AUC/MIC dosing was OR=1.1 (95% CI 0.58-2.12).

Conclusion

The incidence of AKI was higher in the vancomycin trough-based cohort vs AUC/MIC cohort. The difference was not statistically significant, but these findings are clinically relevant to practice. These findings align with the IDSA guidelines and suggest that vancomycin AUC/MIC monitoring may cause less nephrotoxicity.

Disclosures

All Authors: No reported disclosures.
230. Multicenter Assessment of the Accuracy of MIC Results for Colistin with MicroScan Dried Gram Negative MIC Panels using CLSI Breakpoints
Authors: Riedel Stefan , Traczewski Maria , Beasley Denise , Brookman Regina , Diaz Jose , Lockett Zabrina , Chau Jennifer
Published: December 2022

Background

A multicenter study was performed to evaluate the accuracy of MIC results for colistin on a MicroScan Dried Gram Negative MIC (MSDGN) Panel when compared to results obtained with frozen broth microdilution panels prepared according to CLSI/EUCAST methodology. Note: Colistin is not available in all countries.

Methods

MSDGN panels were evaluated at three clinical sites (including Beckman Coulter) by comparing MIC values obtained using the MSDGN panels to MICs obtained utilizing a CLSI/EUCAST broth microdilution reference panel. The study included 407 clinical isolates tested using the turbidity and Prompt® methods of inoculation. MSDGN panels were incubated in the WalkAway System (35 ± 1°C) and read on the WalkAway System, the autoSCAN-4 instrument, and read visually at 16-20 hours. Frozen reference panels were prepared and inoculated according to CLSI/EUCAST Joint Working Group Recommendations for MIC determination of Colistin (Polymyxin E) and incubated for 16-20 hours and read visually. CLSI M100 ED32 breakpoints (µg/mL) used for interpretation of MIC results were: Enterobacterales ≤ 2 I, ≥ 4 R; P. aeruginosa ≤ 2 I, ≥ 4 R.

Results

Essential, categorical agreement, and categorical errors were calculated using MIC results from WalkAway reads for MSDGN panels in Table 1. All other read methods yielded similar results. Categorical agreement was not calculated for Acinetobacter spp. as MIC only is reported. Table 1- Results

Conclusion

This multicenter study showed that colistin MIC results for Gram Negative bacteria obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels with CLSI interpretive criteria.

© 2022 Beckman Coulter. All rights reserved. All other trademarks are the property of their respective owners.

Beckman Coulter, the stylized logo, and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the U.S. and other countries.

Disclosures

Stefan Riedel, M.D., PhD., D(ABMM), FCAP, Beckman Coulter, Inc.: Clinical trial data collection funded by Beckman Coulter, Inc. Maria Traczewski, BS, Beckman Coulter, Inc.: Clinical trial data collection funded by Beckman Coulter, Inc. Denise Beasley, BS, Beckman Coulter, Inc.: Clinical trial data collection funded by Beckman Coulter, Inc. Regina Brookman, BS, Beckman Coulter, Inc.: Employee of Beckman Coulter Jose Diaz, BS, Beckman Coulter, Inc.: Employee of Beckman Coulter Zabrina Lockett, PhD, Beckman Coulter, Inc.: Employee of Beckman Coulter Jennifer Chau, PhD, Beckman Coulter, Inc.: Employee of Beckman Coulter.
238. Acalculous Cholecystitis: A Novel and Lethal Unrecognized Complication in Severe CoVID 19
Authors: Pedraza Reyes Carlos A , Zambrano Luisa Rivero , Sosa Garcia Jesus Ojino , Gonzalez Abril Azeneth Sifuentes , Mendez Erick Lopez , Mendez Jorge Oscar Garcia
Published: December 2022

Background

SARS-COV-2 infection is known to cause tissue damage in several organs outside of the respiratory tract. The pathogenesis of tissue damage is hypothesized to be caused by direct viral damage, endothelial injury, and ischemic or thrombotic events. Gastrointestinal symptoms were first characterized mainly as diarrhea and diffuse abdominal pain and discomfort, which can be hard to interpret in the setting of a generalized inflammatory response; gallbladder injury and inflammation causing acute acalculous cholecystitis has been scarcely reported

Methods

Here we discuss five cases of patients presenting with symptoms of cholecystitis. All five patients underwent multiple imaging studies, and all of them were compatible with acute cholecystitis; some of them had an imaging report of lithiasic cholecystitis, while the rest were reported with microlithiasis or biliary sludge. Four out of the five patients underwent laparoscopic cholecystectomy; biopsies were taken, consistently those reported with acalculous cholecystitis. The remaining patient died of CoVID 19 complications prior to surgery, but after a percutaneous cholecystostomy tube was placed.

Results

All these patients have in common the prolonged fasting, because they all required invasive mechanical ventilation, consequently, they all developed multiple focal pneumonia and respiratory distress syndrome. This fast is related to the development of gangrenous ischemia in the gallbladder, which manifests as a late complication due to SARS-CoV-2 infection, in addition to being related to angiotensin-2 converting receptors and virus replication proteins, as well as the pro-inflammatory and hypoxia state that in itself causes the infection (9).

All showed a cholestatic pattern, highlighting that this complication developed in an average time of 3 weeks after the onset of SARS-CoV2 symptoms, in addition to the fact that in most cases a negative test was already shown at the time of the complication.

Conclusion

Acalculous cholecystitis is one of the extrapulmonary complications that has been seen in patients with this infection, not being the most common, but one of those that has generated a higher mortality rate in patients due to its late diagnosis and non-specific clinical picture in certain occasions (9).

Disclosures

All Authors: No reported disclosures.
243. Association Between SARS-CoV-2 Viral Load and Patient Symptoms and Clinical Outcomes Using Droplet Digital PCR
Authors: Hastie Elizabeth , Amogan Harold , Looney David , Mehta Sanjay R
Published: December 2022

Background

Droplet digital PCR (ddPCR) has been shown to be more sensitive and precise in the quantification of SARS-CoV-2 when compared to traditional quantitative RT-PCR. Multiple studies have explored associations between SARS-CoV-2 viral load and patient outcomes; however, few have used ddPCR technology. Here we investigated the associations between viral load measured using ddPCR and clinical presentation and outcomes.

Methods

We performed a retrospective observational study of individuals who tested positive for COVID-19 at the VA San Diego between August 2020 and December 2021. SARS-CoV-2 viral load from nasopharyngeal swabs was determined using ddPCR. Baseline demographics, past medical history, clinical course, and laboratory data were abstracted from the chart.

Results

A total of 696 individuals were included, 86% (n=603) of whom were male. The average age was 50-years-old [range: 19-98]. Three-quarters of individuals (76%, n=528) were unvaccinated at diagnosis. Frequency of comorbidities are shown in Table 1. The majority of individuals developed symptoms with 75% (n=516) reporting respiratory symptoms, 47% (n=317) fever, 34% (n=230) GI symptoms, and 23% (n=161) loss of taste and/or smell. A total of 24% of veterans were evaluated only in the emergency department, 21% (n=149) were admitted to the hospital; 9% (n=60) required ICU level of care, 33% of these (n=20) required intubation, and 16 individuals died during hospitalization.

SARS-CoV-2 log10 viral load was not associated with age, and only a weak correlation was seen with time from onset of symptoms (r2=-0.1, p=0.04). No association was observed between viral load and peak CRP, ferritin, d-dimer, or nadir absolute lymphocyte count. Mean viral load was significantly higher in veterans reporting fever (5.0 vs 5.4, p=0.02) and respiratory symptoms (4.7 vs 5.3, p=0.01). Interestingly, vaccinated veterans also had higher viral loads(5.8 vs 5.0, p< 0.0001).

Baseline characteristics of individuals with COVID-19

Histogram of COVID-19 RNA viral load

Conclusion

Fever and respiratory symptoms were associated with higher viral loads as expected. The association of vaccination with higher viral load may reflect selection bias for infections in the delta wave. Future work will include multivariate analyses to adjust for medical history and timing of sampling.

Disclosures

Sanjay R. Mehta, MD, Zibdy Health: Advisor/Consultant.
248. Change in Incidence of Multisystem Inflammatory Syndrome in Children Across the COVID-19 Pandemic in Chicago — March 2020 – March 2022
Authors: Spencer Hillary , Seo Jennifer , Pacilli Massimo , Robinson Candice L , Matzke Hannah , Joseph Maria , Gretsch Stephanie
Published: December 2022

Background

Peak counts of multisystem inflammatory syndrome in children (MIS-C) have followed each COVID-19 peak by 2–5 weeks. Fewer cases of MIS-C occurred after the Delta-predominant period compared to early waves of the pandemic. The Chicago Department of Public Health analyzed the ratio of MIS-C to pediatric COVID-19 hospitalization by period of variant predominance from March 2020 – mid-March 2022 to evaluate differences by variant.

Methods

MIS-C in Chicago residents was reported using the standard CDC MIS-C case report form. Four periods of COVID-19 infection were identified with dates defined by variant predominance (≥50%); date ranges for corresponding MIS-C periods were defined as starting 21 days after the COVID-19 period (Table 1). MIS-C cases were compared to hospitalizations as a measure of COVID-19 disease activity in children (rather than case counts which are more subject biases inherent in disease testing) among confirmed and probable COVID-19 cases in children ≤21 years reported to CDPH. Ratios of MIS-C cases per 100 corresponding pediatric hospitalizations for each variant period were calculated. Proportions of MIS-C hospitalizations with intensive care unit (ICU) admission, mechanical ventilation (MV), and receipt of vasopressors (VP) were calculated as markers of disease severity in MIS-C for each wave.

Results

90 cases of MIS-C and 1,597 pediatric COVID-19 hospitalizations were reported (Table 2). The overall ratio was 5.6 MIS-C cases/100 pediatric COVID-19 hospitalizations. The first period with predominance of the original lineage had a ratio of 10.2; subsequent periods with variant predominance all had lower ratios. The Delta period had the second highest ratio which was 68% of the first period. Across waves, 74% of MIS-C patients were admitted to ICU (range, 67–82%); 11% underwent MV (range, 0–14%); and 52% received VP (range, 45–71%).

Conclusion

The ratio of MIS-C to pediatric COVID-19 hospitalizations varied by period of SARS-CoV-2 variant predominance. The ratio was highest in the early pandemic. There was no consistent change in MIS-C severity. Further study is needed to determine if the change in ratio is due to increased immunologic exposure (vaccination or previous infection) or if it is variant dependent.

Disclosures

All Authors: No reported disclosures.
249. Characteristics and outcomes of cryptococcosis among patients with COVID-19 compared to non-COVID-19 controls
Authors: Chastain Daniel B , Kung Vanessa , Golpayegany Sahand , Jackson Brittany T , Franco-Paredes Carlos , Thompson George R , Henao-Martínez Andrés F
Published: December 2022

Background

It remains unclear if there is an association between COVID-19 and cryptococcosis. The purpose of this study was to compare demographic characteristics and outcomes of cryptococcosis between patients with COVID-19 to non-COVID-19 controls.

Methods

Patients 18 years and older with cryptococcosis were identified from TriNetX, a global federated research network, and separated into two cohorts based on a diagnosis of COVID-19 within 3 months prior to the index diagnosis of cryptococcosis. The primary outcome was the percent mortality in each group. The secondary outcomes included the proportion of patients in each group who had underlying comorbidities, received immunosuppressive medications, or required hospitalization or ICU admission. Propensity score matching was performed to control for differences between groups based on demographics and comorbidities. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for outcomes, with p < 0.05 as the cut off for statistical significance.

Results

A total of 6252 patients with cryptococcosis were included, of which 4.5% (n=283) had COVID-19 prior to diagnosis of cryptococcosis. Mortality was similar between patients with and without COVID-19 (13% vs 10%, p=0.075). Patients with cryptococcosis and previous COVID-19 were older (55.2 ± 14.5 years vs 52 ± 15.2 years, p=0.0005) and more likely to be non-Hispanic (73% vs 65%, p=0.0049). More patients with COVID-19 had a history of transplant (30% vs 13%, p < 0.0001), malignancy (37% vs 21%, p < 0.0001), and diabetes (35% vs 19%, p < 0.0001), but not HIV (29% vs 31%, p=0.5482). Prednisone and dexamethasone use were higher among patients with previous COVID-19 (32% vs 15%, p < 0.0001 and 17% vs 7%, p < 0.0001, respectively). Hospitalization rates were similar (54% vs 57%, p=0.278), but more patients with COVID-19 required ICU admission (19% vs 11%, p < 0.0001). In propensity score-matched analysis, patients with COVID-19 remained at higher odds of ICU admission (OR 1.85, 95% CI 1.15-2.97, p=0.010), but lower odds of hospitalization (OR 0.57, 95% CI 0.41-0.81, p=0.001).

Conclusion

Patients with COVID-19 who developed cryptococcosis had higher rates of comorbidities, corticosteroid use, and ICU admission but did not experience higher mortality compared to non-COVID-19 controls.

Disclosures

George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support.
257. Coinfection Characteristics among Children with COVID-19
Authors: García Itzel Villanueva , Gómez Nancy Evelyn Aguilar , Atri Aarón Espinosa , Márquez Angela Patricia Vedia , Marin Juan Antonio Gallegos , Tepach Ana Ruth Hernández
Published: December 2022

Background

Coinfection in patients with SARS-CoV-2 has been associated with greater complications. We describe the clinical characteristics and outcomes of 126 pediatric patients with COVID-19 and viral, bacterial, or fungal coinfection.

Methods

We retrospectively reviewed and analyzed electronic data of all pediatric patients who tested positive for SARS-CoV-2 from April 16, 2020, to April 15, 2022, in our center. Confirmation of COVID-19 was based on positive RT-PCR. Viral coinfections (VC) were identified using a multiplex RT-PCR respiratory viral panel, bacterial coinfection (BC) was determined by positive bacterial culture (blood, bronchoalveolar lavage, sputum, urine) or clinical/radiological manifestations and antimicrobial assessment by a pediatric Infectious Diseases expert and fungal coinfection (FC) diagnosis based on Consensus definitions of invasive fungal disease.

Results

During the study period, among 400 pediatric patients with COVID-19, 126 children had coinfection. Children >10 years were the most affected age group. Underlying disease was present in 69%, hematological malignancies were the most common (17.5%). BC was detected in 76.9% (n=97), bacterial pneumonia (54.6%) was the main diagnosis, followed by oncologic patients with initial febrile neutropenia and posterior SARS-CoV-2 detection (14,4%). Unusual BC as congenital syphilis w detected; acute appendicitis was the initial presentation of COVID-19 in 8 patients. VC was identified in 15.87% (n=20), prevailing rhinovirus (9.5%) and adenovirus (3.96%), One FC presented as proven pulmonary aspergillosis (0.8%). B-V and B-F coinfection were detected in 2 patients. Fever and cough were the most common symptoms, higher fever >40°C was mostly observed in the BC group (3%). Twenty-seven patients with BC (27.8%) were admitted to intensive care, with the OR 0.7 IR 95% (0.611–1.008), 4.1% died. One ICU admission was observed in the VC group (5%) and all VC cases resolved without complications.

Conclusion

Pediatric patients with COVID-19 coinfection, especially BC were common in our center representing nearly one-third of the infected children, including unusual coinfections. BC was identified as a risk factor for ICU admission OR 0.7 IR 95% (0.611–1.008). Favorable outcomes were observed in most cases.

Disclosures

All Authors: No reported disclosures.
264. COVID-19 Associated Pulmonary Aspergillosis in Intensive Care Patients Based on Duration of Corticosteroid Administration
Authors: Shah Meera D , Christina Gutierrez G , Moote Rebecca , Reveles Kelly R , Hand Elizabeth O
Published: December 2022

Background

Coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. Corticosteroids are standard of care for COVID-19 patients. Prolonged corticosteroids have been associated with an increased risk of CAPA, but duration of use associated with this risk remains unknown. The objective of this study was to evaluate if the duration of corticosteroid therapy ≤ 10 days vs > 10 days affects the risk of developing CAPA.

Methods

This single-center, retrospective, cohort study included patients ≥ 18 years old admitted to University Hospital between March 2020 and December 2021, diagnosed with severe COVID-19 pneumonia requiring mechanical ventilation, and who received at least 3 days of corticosteroid treatment. CAPA was defined according to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus guideline. Baseline characteristics, CAPA, and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor of CAPA in a logistic regression model.

Results

Final analysis included 278 patients (n=169 ≤ 10 days steroid duration; n=109 > 10 day steroid duration). Baseline characteristics were similar between groups, with the exception of acute kidney injury and solid organ transplantation. Median duration of steroids was 6 days in the ≤ 10 day group vs 18 days in the > 10 day group. In total, 20/278 (7.2%) patients developed CAPA. Patients treated with > 10 days of corticosteroid therapy had significantly higher incidence of CAPA (12% vs 4.1%; p = 0.0156) and duration was independently associated with CAPA (OR 3.25, 95% CI 1.03-10.24). Secondary outcomes including inpatient mortality (43.2% vs 77.1%; p < 0.0001), mechanical ventilation free days at 28 (1.5 vs 0; p < 0.0001) and secondary infections (28.4% vs 44.9% p = 0.0220) were all significantly worse for > 10 day corticosteroid cohort.

Conclusion

Duration of corticosteroid treatment > 10 days in critically ill patients is associated with an increased risk of CAPA. Though patients may require corticosteroids for non-COVID-19 indications, clinicians should attempt to limit prolonged courses of corticosteroids in COVID-19 patients.

Disclosures

All Authors: No reported disclosures.
269. Outcomes comparison of hospitalized patients with COVID-19 during the first three pandemic waves. Experience in Colombia, South America.
Authors: Rosso Fernando , Rodriguez Sarita , Beltrán Estefanía , Valencia Alvaro Martinez , Zarama Virginia , Tafur Eric , Guzmán Tania
Published: December 2022

Background

Differences in access to specialized medical care services and their overcrowding due to the pandemic could impact clinical outcomes. Availability of newer treatments, vaccination, and emergence of newer SARS-CoV-2 variants could also explain these differences.

Methods

We performed a single-centered, observational study comparing clinical outcomes of COVID-19 admitted to the emergency department among the first three waves of the pandemic defined as June to August 2020, November 2020 to January 2021, and May to July 2021, respectively. The primary outcomes included intensive care unit admission, invasive mechanical ventilation requirement, hospital length of stay, and hospital mortality categorized by age groups. Effective COVID 19 antiviral therapy and monoclonal antibodies are not available in Colombia. Vaccination was available after March 2021.

Results

Out of a total of 2264 patients were admitted. Fifty-six percent were male, with a median age of 58 years [IQR, 45-70]. A significant increase of patients was seen after each wave: 530 in the first, 568 in the second, and 1166 in the third-wave worsening hospital overcrowding. Patients from the third wave were significantly younger (59 vs. 62 vs. 56 years, p < 0.01). Patients from the first wave had higher proportion of intensive care unit admission (62.83% vs. 51.23% vs. 52.23%, p< 0.01), invasive mechanical ventilation (39.25% vs. 32.22% vs. 31.22%, p< 0.01), and length of hospital stay (9 vs 7 vs 7 days, p< 0.01). Overall, no difference was found in mortality among waves (18.4% vs 19% 18.8%, p = 0.974). However, patients of 70-79 and ≥ 80 had a lower mortality during the third wave (24.4% vs 33.3% vs 19%, p=0.018), (30.6% vs 29.6% vs 23.6%, p=0.018). Vaccination was very low in all the age groups but was higher in elderly patients. Figure 1

Conclusion

Overall mortality did not increase between infection waves, although there was an increase in cases during the third wave. We found a significant decrease in mortality among the elderly. Major efforts of medical teams succeed in containing COVID 19 mortality. Figure 4

Disclosures

All Authors: No reported disclosures.
276. Factors Predicting Bacterial Coinfection in Hospitalized COVID-19 Patients
Authors: Guo Yi , Cowman Kelsie , Bao Hongkai , Chen Victor , Kim Mimi , Xie Xianhong , Chang Mei H , Bartash Rachel , Azeem Meena , Nori Priya
Published: December 2022

Background

Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes.

Methods

A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection.

Results

A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03).

Conclusion

As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges.

Disclosures

Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.