bluuebunny/crossref_metadata_2025 huggingface dataset:
113. Knowledge, Attitudes, and Practices towards HPV vaccination among reproductive-age women in an HIV hotspot in the US
Authors: Paz Aasith Villavicencio , Nogueira Nicholas Fonseca , Kelsey Gray , Zukerberg Julia , Salazar Ana S , Hernandez Lucila , Raccamarich Patricia , Jones Deborah L , Alcaide Maria L L
Published: December 2022

Background

Human papillomavirus (HPV) is the most common STI in the US, responsible for cervical cancer and increased risk of HIV acquisition. Despite an effective HPV vaccine, women’s HPV vaccination coverage and rates remain far below desired levels. This study aimed to evaluate HPV knowledge, screening, and vaccination practices as well as factors associated with HPV vaccination among women of reproductive age living in Miami, Florida, a Southern US city with a high incidence of STIs and low HPV vaccination coverage.

Methods

In April 2022, HIV-negative, cisgender, sexually active women aged 18-45 years were referred from a study evaluating HIV risks. Surveys assessed socio-demographics and sexual behaviors. Validated questionnaires assessed HPV knowledge, screening, and vaccination practices. A cumulative HPV knowledge score was generated. Factors associated with HPV vaccination were analyzed by Chi-square, Fisher’s exact test, studentized t-test, and multivariate logistic regression (MLR).

Results

A total of 67 participants were enrolled, and 54 who knew their vaccination status were included in the analysis: median age was 26 (IQR 22-34.5) years; 50% were White, 26% Black, and 33% were Hispanic. Median age at first sexual encounter was 18 (16-18) years, the mean number of sexual partners in the previous month was 1.45 (±1.44), and 33% had previous pregnancies. Mean HPV score was 13.4 (±8.84) out of 29, 43% reported a history of HPV/Pap smear screening. Barriers to HPV vaccination included: 28% low-risk perception, 24% healthcare barriers, and 41% vaccine hesitancy. In MLR, a one-point increase in HPV knowledge score increased the odds of vaccination by 21.5% (0.8-3.67%; p< 0.01). Age, number of sexual partners, and pregnancy history were not significant predictors of HPV vaccination.

Conclusion

Findings suggest low HPV knowledge among women of reproductive age in a high-risk area, and suggest that increasing knowledge may reduce barriers to HPV vaccination and increase vaccine uptake.

Disclosures

Maria L L. Alcaide, MD, Gilead: Advisor/Consultant.
122. Streptococcus pneumoniae Nasopharyngeal Colonization in a Colombian Cohort of Patients with Comorbid Conditions
Authors: Ibáñez-Prada Elsa D D , Serrano-Mayorga Cristian C , Fuentes Yuli V , Lozada Julian , Bustos Ingrid G G , Mendez Lina , Crispin Ana M , Reyes Luis Felipe F
Published: December 2022

Background

Community-acquired pneumonia (CAP) remains the first cause of infectious death and morbidity worldwide. Nevertheless, its etiological pathogen is only isolated in almost 30% of cases, and its most representative bacteria is S. pneumoniae. Some researchers have proposed that the nasopharyngeal colonization by S. pneumoniae could risk developing CAP. However, the prevalence of nasopharyngeal colonization in patients with chronic comorbid conditions in Latin America is unknown, where vaccination rates are low. This study aims to determine the rate of S. pneumoniae colonization in a Colombian cohort. Figure 1.Pneumococcal vaccination and colonization in the whole cohort.

Methods

This is a prospective cohort study in 3 centers in Colombia carried out between 2020 and 2022. According to the world health organization guidelines, the nasopharyngeal aspirate (NPA) samples from each participant were obtained. Samples were incubated with 5% CO2 in blood agar, and MALDI-TOFF identified the colonies obtained. We compared the number of S. pneumoniae isolated and stratified by anti-pneumococcal vaccination status.

Results

The cohort was composed of 810 patients. The median [IQR] age was 63 [53-62] and the most common comorbidities were 52.2% [423/810] arterial hypertension, 21.7% [176/810] coronary disease, 19.0% [154/810] congestive heart failure, and 17.4% [141/810] chronic kidney disease. Nasopharyngeal colonization by S. pneumonie was only documented in the patients' 2.1% [15/723] (Figure 1). Moreover, 10.7% [87/810] patients from the cohort were vaccinated against S. pneumoniae, and none were colonized.

Conclusion

Nasopharyngeal colonization by S. pneumoniae in our cohort of adults with chronic comorbidities was low. Notably, all the colonized patients were not vaccinated, at higher risk of developing the invasive pneumococcal disease. More robust vaccination policies should be implemented for adults in Colombia.

Disclosures

All Authors: No reported disclosures.
123. The change of meningococcal carriage rate and serogroup among military trainees since the introduction of meningococcal vaccine, and the genetic characterization of the carriage isolates
Authors: Heo Jung Yeon , Oh Hong Sang , Kim Young Rong , Yoo Jin Sae , Kim Eun Jin , Choi Young Hwa , Kim Min Young
Published: December 2022

Background

Monovalent meningococcal conjugate vaccines against serogroups A or C have resulted in significant reduction of pharyngeal carriage rates against the vaccine serogroups. However, the effect of the quadrivalent meningococcal conjugate vaccine on meningococcal carriage has not yet been evaluated.

Methods

We assessed changes in pharyngeal carriage rates of Neisseria meningitidis after introduction of the quadrivalent meningococcal conjugate vaccine in Korean military trainees. Two rounds of oropharyngeal swabs of Korean military trainees were obtained, at the beginning and the end of the army training period. The first oropharyngeal swabs were collected prior to vaccination; the second round was performed 5 weeks later.

Results

In 2013, the overall N. meningitidis carriage rate was higher at the end of the training period (13.8%, 60 of 434 participants) than upon entry into military service (8.9%, 39 of 434 participants). Although the carriage rates of nongroupable and serogroup X isolates increased over the 5-week interval, carriage of the serogroup strains included in the quadrivalent meningococcal vaccine was reduced, from 7 to 2 isolates, after vaccination. However, in 2014, the overall carriage rate of N. meningitidis was significantly lower at the end of the training period (5.2%, 23 of 443 participants) than on entry into military service (12.6%, 56 of 443 participants) (p = 0.028). Carriage of vaccine serogroups isolates was significantly decreased, compared to that of non-vaccine serogroup B over the 5-week interval. Carriage isolates belonging to the ST-178, ST-31 and ST-41/44 were frequently identified clonal complex.

Meningococcal carriage rate before and after Meningococcal vaccination in Korean military trainees

Conclusion

Meningococcal vaccination in Korean military trainees could lead to reduce pharyngeal carriage rates of vaccine serogroup meningococci. Therefore, the quadrivalent meningococcal conjugate vaccine is likely to prevent carriage acquisition of meningococci in closed populations such as military trainees.

Disclosures

All Authors: No reported disclosures.
130. Bacteremia among patients with cancer in a Latinamerican country, clinical and molecular data
Authors: Cruz-Vargas Sergio A , García-Muñoz Laura , Cuervo-Maldonado Sonia I , Cortés Jorge A , Álvarez-Moreno Carlos , Saavedra-Trujillo Carlos , Álvarez-Rodríguez José C , Arango-Gutiérrez Angélica , García-Guzman Katherine , Leal-Castro Aura , Garzón-Herazo Javier , Martínez-Vernaza Samuel , Guevara-Pulido Fredy
Published: December 2022

Background

Infections are common complications in patients with cancer. Data on antimicrobial resistance is important to guide empirical antimicrobial therapy. However, resistance rates varies among different regions and countries and, in general, is higher in Latin America. There are limited data from these patients in this region.

The aim of this work is to determine the frequency and antibiotic susceptibility profiles, as well as to identify the most frequent genes related to resistance, among microorganisms implicated in bacteremia in patients diagnosed with cancer

Methods

A cross-sectional multicenter study conducted in six hospitals in Colombia. An active laboratory search was carried out for adult patients with cancer and bacteremia. Data was obtained from the electronic medical records, and according to the resistance of the microorganisms, molecular tests were performed in a standardized way to identify genes related to methicillin-resistance, extended spectrum beta lactamases and carbapenemases. In addition, an exploratory multivariate analysis was performed using a logistic regression method to predict mortality

Results

195 patients from 6 hospitals were included in the study. The clinical variables of the patients are described in Table 1. Gram-negative bacteria were more common and their resistance rates were high. The genes found in the different resistant bacterial isolates are described in Table 2; The main resistance genes identified were blaCTX-M and blaKPC, generating ESLB-type beta-lactamases and carbapenemases, respectively. 30 day-mortality was 26%, which is similar to other studies. Multivariate analysis showed that adequate antibiotic treatment (OR: 0.26 (95%CI 0.1-0.63)) and higher number of platelets (per 10,000, OR: 0.97 (95%CI 0.94-0.99)) were associated with survival. Mortality was associated with patients in palliative care (OR 3.51 (95%CI 1.05-12.04)).

Conclusion

Gram-negative bacilli are frequently found in patients with cancer and bacteremia. A high level of resistance was identified. The frequency of the genes identified varies from what has been described in other regions of the world. Appropriate and prompt treatment in these patient would improve the outcomes.

Disclosures

Jorge A. Cortés, MD, pfizer: Grant/Research Support Carlos Saavedra-Trujillo, MD, pfizer and merck: Grant/Research Support.
133. Ceftriaxone-resistant Haemophilus influenzae in Korean children
Authors: Lee Sanghoon , Lee Euntaek , Kim Gahee , Kim Jung Hwa , Kim Mina , Lee Ji-Na
Published: December 2022

Background

Haemophilus influenzae is known to develop resistance to β-lactam antibiotics by either producing β-lactamase or modifying structure of penicillin-binding protein 3 (PBP3) by ftsI gene mutation. Since 2017, H. influenzae with ceftriaxone resistance has been continuously appearing in our hospital, and the genotypic characteristics of these strains was analyzed.

Methods

Among a total of 69 H. influenzae isolated from the patients who admitted to Asan Medical Center Children’s Hospital from March 2014 to April 2019, 23 isolates resistant to ceftriaxone by EUCAST disk diffusion method were included. The ceftriaxone MIC was checked again with the E-test and ceftriaxone MIC ≤ 0.125 mg/L were categorized as susceptible. As test for β-lactamase production, the cefinase test and PCR amplification for blaTEM-1 and blaROB-1 were performed. The sequencing of the ftsI encoding PBP3 amplified by PCR was performed, and amino acid sequences were compared with H. influenzae Rd KW20.

Results

Among total 23 ceftriaxone-resistant isolates by disk diffusion method, 21 isolates restored for further molecular characterization were included, and 19% (4/21) were reported as susceptible by E-test. Among the 21 ceftriaxone-resistant isolates, 76.2% (16/21) were non-susceptible to amoxicillin/clavulanate, and one of them were resistant to meropenem. The prevalence of b-lactamase-producers was 57.1% (12/21), all of which were positive for blaTEM-1. For ftsI gene sequencing, either R517H or N526K amino acid substitution was observed, and none had both. The number of isolates having S385T was 17, of which 15 isolates accompanied with both M377I and L389F. The median ceftriaxone MIC of 3 isolates with only N526K was 0.012 ug/ml (range 0.008-0.125 ug/ml), and 12 isolates with N526K, M377I, S385T, and L389F was 0.19 ug/ml (0.19-0.25 ug/ml). Lastly, the three isolates with R517H, M377I, S385T, and L389F showed the highest median ceftriaxone MIC with 0.25 ug/ml (0.19-0.75 ug/ml).

Conclusion

Ceftriaxone-resistant H. influenzae isolates in Korea seems to be related to the combination of R517H, M377I, S385T, and L389F by ftsI gene mutation. Although clinical concerns about treatment failure may be low, continuous monitoring of the emergence of highly resistant strains is necessary.

Disclosures

All Authors: No reported disclosures.
136. Prevalence of Plasmid-Mediated Antibiotics Resistance Genes in Klebsiella pneumoniae in United States
Authors: Hwang Munok , Choi Hosoon , Jinadatha Chetan
Published: December 2022

Background

Multidrug resistant (MDR) bacteria which resist at least three different antibiotic classes are serious threat to public health and patient treatment. Antimicrobial resistant (AMR) genes are often mediated through plasmids due to its horizontal transferability from bacteria to bacteria. Here, we assessed the prevalence of AMR genes in the USA by analyzing longitudinal K. pneumoniae plasmid genome data obtained from PATRIC (Pathosystems Resources Integration Center) database.

Methods

The PATRIC database have 176 K. pneumoniae plasmid genome data collected in 9 states of US from 2004 to 2019. The isolation source are various patient samples including urine, blood, etc. The sequence information was downloaded from GeneBank. The AMR genes on plasmids of K. pneumoniae were identified using open-source AMR database, Resfinder which search AMR genes for 16 types of antibiotic classes.

Results

Multidrug resistance was spread all over the US as most of isolates have AMR genes against more than one antibiotic classes, and some isolates contain against up to 8 antibiotic classes AMR genes. Most common AMR genes are against 9 classes including Aminoglycosides, beta-lactamase (carbapenem), Chloramphenicol, Macrolide, Quinolone, Rifampicin, Sulfonamide, Tetracycline, and Trimethoprim. Aminoglycosides and beta-lactamase including carbapenem resistance genes showed higher frequency than other classes of antibiotics. Carbapenem resistance genes, especially blaKPC showed higher frequency in east region of US including NY, PA, and VA (Fig 1A). While some resistances reduced over time, Aminoglycosides and beta-lactamase resistance genes are sharply increased (Fig 1B). Many isolates contain 3∼4 plasmids and plasmid amplicon types were various by isolates but no co-relation between plasmid types and AMR genes was observed.

Conclusion

Database analysis of K. pneumoniae isolates from different regions and time provides insight of the prevalence of AMR genes. The prevalence of the multidrug resistance obtained from databases analysis showed the abundance of AMR genes regardless of the region or time, especially for Aminoglycoside and beta-lactamase. Bacterial sequence database such as PATRIC is a useful tool for tracking the existence and emergence of AMR genes.

Disclosures

Chetan Jinadatha, MD, MPH, AHRQ R01 Grant-5R01HS025598: Grant/Research Support|EOS Surfaces: Copper Coupons and materials for testing.
138. Description of Repeat Carbapenem-resistant Enterobacterales (CRE) Submitted to a State Laboratory from the Same Individuals, Kentucky - December 2018 - March 2022
Authors: Spicer Kevin B , Elathamna Marwa , Zinner Rachel
Published: December 2022

Background

CRE and carbapenemase-producing CRE (CP-CRE) can be persistently detected during screening in long-term care facilities. Re-identification of these organisms during normal care and movement through healthcare settings is less well described.

Objective: To describe repeated submission of CRE to a state laboratory, including persistence of detection and progression from colonization to infection.

Methods

Submission of CRE isolates was requested from labs in late 2017 and became mandated by legislative regulation in December 2020. Isolates were tested at the Kentucky Division of Laboratory Services (DLS) for CP using the modified carbapenem inactivation method (mCIM), with follow-up testing for specific carbapenemases using the Cepheid Xpert Carba-R assay. Results were maintained in the DLS lab information system. Descriptive statistics were derived for testing results from repeat submissions.

Results

From December 2018 through March 2022, 1,822 isolates were submitted to DLS from 1,498 distinct individuals; 324 repeat submissions were obtained from 214 individuals, with 141 individuals tested > 14 days after the initial result (Figure). Several individuals had > 2 submissions and some cultures had CRE both with and without CP identified. The same CP-CRE (species and mechanism) was identified from 42 individuals (29.8%) when tested > 14 days after initial identification (median 71 days, IQR 40-151, max 857). The same CRE (species) without CP was identified from 66 individuals (44.1%; median 111.5 days, IQR 55-237, max 676). Urine was the most common specimen source among resubmissions (67% of resubmissions). Of 47 individuals with a discrepant result (i.e., different species or mechanism) after > 14 days, only four had the same species identified initially as CP-CRE and then subsequently as non-CP-CRE. Ten individuals (7%) had screening and then clinical specimens with the same CP or species.

Conclusion

Persistence can occur with CP-CRE and with CRE without CP and may continue for >500 days. The in vivo loss of CP by CRE appears to occur infrequently. Clinicians and infection preventionists should remain vigilant for persistent CRE colonization during clinical and infection control decision making.

Disclosures

All Authors: No reported disclosures.
140. Enterococcus faecalis CL Synthases Have Redundant Roles and Play A Major Role in Phospholipid Redistribution Associated with Daptomycin Resistance
Authors: Nguyen April , Polamraju Vinathi , Zhang Rutan , Panesso Diana , Khan Ayesha , Mileykovskaya Eugenia , Cecilia Tran Truc , Xu Libin , Vitrac Heidi , Arias Cesar A
Published: December 2022

Background

Daptomycin (DAP) is a lipopeptide antibiotic targeting membrane anionic phospholipids (APLs) at the division septum. DAP resistance (DAP-R) has been associated with activation of the LiaFSR system resulting in redistribution of APL microdomains (likely containing cardiolipin, CL) away from the septum. E. faecalis (Efs) possess two CL synthase genes, (cls1 and cls2) and changes in Cls1 are associated with DAP-R. However, the roles of each enzyme are unknown. Here, we characterize the roles of cls genes in DAP-R in the context of LiaFSR activation.

Methods

cls1 and/or cls2 were deleted from Efs OG117 and OG117ΔliaX (DAP-R strain with an activated LiaFSR response). qRT-PCR was used to study gene expression of cls1 and cls2 in the cls mutants. Membrane lipid content was analyzed using hydrophilic interaction chromatography-mass spectrometry. Mutants were characterized by DAP minimum inhibitory concentration (MIC) using E-test and localization of APL microdomains with 10-N-nonyl-acridine orange.

Results

cls1 and cls2 are upregulated in exponential phase of DAP-R Efs OG117ΔliaX relative to DAP-S Efs OG117, with only cls1 upregulated in stationary phase. Deletion of cls1 or cls2 resulted in upregulation of the other cls gene, independent of activation of LiaFSR. Lipidomics analysis confirmed that deletion of both cls resulted in complete absence of cell membrane CL content. When comparing CL profiles of Δcls1 relative to Δcls2 in both DAP-S and DAP-R, both strains produced similar levels and species of CL. However, development of DAP-R caused a change in membrane lipid content, namely, an increase in CL with no significant difference in phosphatidylglycerol compared to DAP-S strain. Evaluation of CL species in DAP-R shows a shift towards species containing longer fatty acid chains and higher saturation. Independent deletions of cls1 or cls2 did not revert the DAP phenotype. In contrast, deletion of both cls genes decreased the DAP MIC (2-3 fold) relative to the parent strain and restored septal localization of APL microdomains. DAP MIC was restored upon trans complementation of either cls1 or cls2 into the double deletion mutant.

Conclusion

Our results support a major role of Cls in changes in cell membrane architecture and DAP-R in enterococci, with overlapping roles for Cls1 and Cls2.

Disclosures

Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support.
144. Gram Negative Bacteria with Increased Minimal Inhibitory Concentration for Cefiderocol among Pediatric Patients in a Northern Italy Hospital.
Authors: Russo Chiara , Sette Claudia , Medici Chiara , Losurdo Giuseppe , Palmero Candida , Saffioti Carolina , Mariani Marcello , Ricci Erica , Ugolotti Elisabetta , Bondi Elisabetta , Montalto Shana , Tavella Elisa , Castagnola Elio , Mesini Alessio
Published: December 2022

Background

Cefiderocol is a siderophore cephalosporin active against Gram negative (GN) carbapenem resistant bacteria, approved in Italy in September 2020 for adult patients. In pediatric population off label use is allowed when severe infections from multidrug resistance (MDR) GN bacteria occur. Recently, some authors reported the emergence, among strains of Enterobacterales resistant to ceftazidime avibactam, of cross-resistance with cefiderocol.

The aim of this study is to describe GN strains with increased Minimal Inhibitory Concentration (MIC) for cefiderocol isolated in our hospital.

Methods

This is a retrospective, single-center study conducted in Istituto Giannina Gaslini Pediatric Hospital (Genoa, Italy) from 1st January 2020 to 31st April 2022. We collected all strains of MDR GN bacteria whit increased MIC for cefiderocol isolated in our hospital. Cefiderocol susceptibility testing was performed by disk diffusion assay with the disk of 30 μg (Kirby-Bauer method, KB) according to EUCAST’s recommendations and KB breakpoints. We collected demographical data, previous colonization (if note), carbapenemases production, clinical outcomes (infections from MDR; death at 7 and 30 days; ICU admission).

Results

Overall, 10 GN strains with increased MIC for cefiderocol were collected. 9/10 were Enterobacterales (4 Escherichia coli, 2 Enterobacter cloacae complex, 3 Klebsiella pneumoniae), one was Acinetobacter baumannii. 8/10 patients were admitted to other hospital in the six months before admission in our hospital, data about previous colonization were unknown. All MDR isolated produced metallo-β-lactamase [MBL] (5/10 New Delhi metallo-β-lactamase [NDM], 5/10 Verona integron-encoded metallo β-lactamase [VIM]). Four patients developed infection due to MDR (2 urinary tract infections, 1 bloodstream infection, 1 surgical wound), 2/4 patients died during the hospitalization.

Conclusion

Our study confirms that MDR producing MBL carbapenemases may have reduce susceptibility to cefiderocol, even if never exposed to this siderophore cephalosporin.

Due to the possibility of cross resistance with MDR resistant to ceftazidime/avibactam, cefiderocol should be carefully prescribe in empirical treatment of MBL producers strains.

Disclosures

All Authors: No reported disclosures.
147. Identification of Novel Colistin Resistance Genes in an Extremely Colistin Resistant Pseudomonas aeruginosa Clinical Isolate
Authors: Gatesy Samuel W , Bertucci Hanna , Vessely Madeleine , Vessely Madeleine , Valdes Aliki , Alisoltanidehkordi Arghavan , Ozer Egon A , Marty Francisco M , Mekalanos John , Hauser Alan R , Bachta Kelly E R
Published: December 2022

Background

Pseudomonas aeruginosa (PA) readily acquires genomic mutations and exogenous genetic elements that confer antimicrobial resistance (AMR). With the rise in AMR, there are limited antibiotics available to treat multidrug-resistant (MDR) PA. As such, clinicians have returned to previously used antibiotics. Colistin, sidelined for neurotoxicity and nephrotoxicity, has returned to clinical practice as a viable but suboptimal option for MDR-PA treatment. The most common mechanism of resistance to colistin involves modifications of the lipid A moiety within the bacterial lipopolysaccharide (LPS). Following the identification of a MDR PA isolate, BWH047, we experimentally determined its colistin MIC to be > 1,280 µg/mL and used genomic approaches to identify novel genetic mechanisms of extreme colistin resistance.

Methods

We created a random, saturated transposon (Tn) insertion library in PA BWH047 using the Himar1 mariner system. After exposure of the library to 640 µg/mL colistin for 10 hours, genomic DNA was harvested, and the Tn insertion sites were sequenced. Insertion sequencing (INSeq) analysis was performed. We identified 27 genes conditionally important for BWH047 growth in the presence of colistin. We selected five initial targets arnC, dedA, wapH, speE2, and bchE and tested their impact on colistin resistance using standard microbroth dilution methods.

Results

Of our deletion mutants, three showed loss of resistance to colistin. ArnC was chosen as a positive control as its role in colistin resistance in PA is well described. Colistin MICs of BWH047 ΔarnC, ΔdedA, ΔwapH, ΔspeE2, and ΔbchE were determined to be 0.5, 0.5, 1, > 1,280 and > 1280 μg/mL, respectively.

Conclusion

Here, we used INSeq to identify novel genes involved in extreme colistin resistance. Thus far, we have identified two new candidate genes dedA and wapH, critical for colistin resistance in PA BWH047. Neither gene has been associated with colistin resistance in PA; However, dedA orthologs in Burkholderia thailandenesis and Klebsiella pneumoniae have been shown to be important for colistin resistance. The gene wapH is part of the LPS core oligosaccharide biosynthetic pathway and its discovery hints that additional alterations in the bacterial outer membrane may impact colistin resistance.

Disclosures

All Authors: No reported disclosures.
175. Evaluation of Optimal Urinalysis Criteria for Conditional Urine Culturing
Authors: Li Cecilia , Claeys Kimberly C , Morgan Daniel J , Coffey K C , Tadesse Yeabsera
Published: December 2022

Background

Asymptomatic bacteriuria is a common condition that is often treated unnecessarily with antimicrobials. Conditional urine reflex culturing leverages the negative predictive value of the absence of pyuria, often defined by a minimum urine white blood cell (WBC) count cutoff > 10 cells/hpf. This value has not been extensively validated. This study evaluated parameters from urinalysis (UA), including various WBC cutoffs, and their ability to detect urinary tract infections (UTIs).

Methods

Retrospective cohort study of adult patients with or without urinary catheters with at least one UA between July 2020 to July 2021. Conditional reflex urine culturing with urine WBC cutoff of > 10 cells/hpf was standard practice. Pregnant patients, patients with urologic procedures, and those who were mechanically ventilated at time of UA were excluded. UTIs were defined as definitive, probable, possible, or unlikely (Table 1). Comparisons between definitions and those with definitive/probable versus possible/unlikely UTIs were made using Chi-squared test. Table 1.UTI definitions

Results

368 patients were included in the final analysis. 154 (41.8%) were male and mean age was 56.9 ± 17.9 years. 117 (31.8%) had urinary catheters. 296 (80.4%) of UAs were treated with antibiotics which were administered after UA collection 89.2% of the time. The total incidence of definitive, probable, possible, and unlikely UTIs according to WBC count is listed in Table 2. UA parameters including leukocyte esterase positivity and presence of nitrites did not differ when compared between definitive/probable versus possible/unlikely UTIs (94.3% vs. 97.1% and 23.9% vs 26.4% respectively). Differences in leukocyte esterase positivity and presence of nitrites were not seen for non-catheterized patients when compared between definitive/probable versus possible/unlikely UTIs (92.3% vs. 96.5% and 21.2% and 29.3% respectively). Table 2.Urine WBC categorization stratified by UTI definition

Conclusion

Urine WBC cutoff > 10 cells/hpf identifies many patients with unlikely UTIs. Current UA parameters do not definitively differentiate UTIs from not in catheterized or non-catheterized patients. Most patients with a positive UA were treated.

Disclosures

Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria.
197. The Clinical Impact of Early Detection of ESBL-Producing Enterobacterales with PCR-Based Blood Culture Assays
Authors: Chang Kai-Ming , Haghamad Aya , Saunders-Hao Patricia , Jain Sumeet , Epstein Marcia , Streva Vincent , Juretschko Stefan , Gautam-Goyal Pranisha
Published: December 2022

Background

Bloodstream infections (BSIs) due to extended spectrum beta-lactamase (ESBL) producing Enterobacterales can cause significant morbidity and mortality. The first-line treatment for these is a carbapenem. ESBL-encoding genes such as blactx-m can be detected by ePlex® Blood Culture Identification (BCID) panels by utilizing polymerase chain reaction (PCR)-based techniques. Our primary objective was to assess the impact of BCID on time to appropriate therapy; secondary objectives were to assess the clinical impact on mortality, 30-day readmission, and length of stay (LOS).

Methods

This study was a retrospective multicenter observational study of hospitalized patients with ESBL-producing Enterobacterales positive blood cultures. Patients with ESBLs identified in the final blood culture by conventional methods pre-ePlex® BCID (Jan 1 to Sep 30, 2019) were compared to patients with ESBLs identified by ePlex® BCID (Jan 1 to Sep 30, 2021). Patients who expired or were discharged prior to Gram stain results were excluded. Time to appropriate therapy was defined as the time from Gram stain result to ordering a carbapenem. In-hospital mortality, 30-day readmission rate, and LOS were analyzed for each cohort. T-test and Chi-square test were performed.

Inclusion and exclusion criteria for pre-ePlex BICD (2019) and post-ePlex BCID (2021) groups

Results

ESBL BSIs in 503 patients across 11 hospitals were identified and a total of 281 patients (pre-ePlex® BCID n=130; ePlex® BCID n=151) were included. A significant decrease in the median time to carbapenem order was observed (44.5 hours in the pre-ePlex® BCID group vs. 8 hours in the ePlex® BCID group (p< 0.001)). No significant difference was observed in in-hospital mortality, 30-day readmissions, or LOS. The mortality rates were 6.9% and 6.6%, the 30-day readmission rates were 7.7% and 12.6%, and the LOS were 8 days and 10 days, respectively in the pre- and post-ePlex® BCID groups.

Comparison of outcome measure results between the pre-ePlex BICD (2019) and post-ePlex BCID (2021) groups.

Box and whisker graphs for time from Gram stain result to ordering carbapenems (hours)

Conclusion

Implementing ePlex® BCID to detect ESBL BSIs decreased the median time to escalation to carbapenems by 36 hours. Despite the decrease in time to appropriate therapy, no change in in-hospital mortality, 30-day readmission, and LOS was observed.

Disclosures

All Authors: No reported disclosures.
212. Outcomes of Weekly Fluconazole Antifungal Prophylaxis in Pancreas Transplant Recipients
Authors: Williams Samantha M , Vijayvargiya Prakhar , Rizwan Sohail M , Beam Elena , Garrigos Zerelda Esquer
Published: December 2022

Background

Fungal infections following pancreas transplantation carry significant morbidity and mortality with an estimated incidence of 3 to 28%. The American Society of Transplantation (AST) suggests considering fluconazole prophylaxis in pancreas transplant recipients (PTR) at high-risk of invasive candidiasis (IC). However, optimal dosage and duration of prophylaxis is unclear. Weekly fluconazole for prevention of IC has been previously reported in liver and bone marrow transplant recipients. We analyzed outcomes of once weekly fluconazole prophylaxis in PTR.

Methods

We retrospectively reviewed all pancreas transplants performed at our institution from January 2017 through September 2021. PTR at high-risk for IC were defined per AST criteria as those with enteric drainage, vascular thrombosis, and post-perfusion pancreatitis. Patients received once weekly oral fluconazole 200 mg for 12 weeks post-transplant for IC prophylaxis. We analyzed incidence of breakthrough IC within the first 6 months post-transplant.

Results

We identified a total of 22 PTR, all of whom received simultaneous kidney transplantation from deceased donors. Of these, 12/22 (55%) were male and 11/22 (50%) were African American. Median age at the time of transplantation was 39 years (IQR 34-46). The most common indication for transplantation was type 1 diabetes mellitus (17/22, 21%) with associated nephropathy. No donor organ cultures were positive for fungi and all pancreas transplants were performed using enteric drainage. Notably, one patient developed pancreas allograft thrombosis while another developed pancreatitis. No patients required early discontinuation of fluconazole due to intolerance or side effects and none developed breakthrough IC within 6 months post-transplant (Table 1). Table 1.

Conclusion

Weekly fluconazole prophylaxis has not been previously studied in PTR. In our cohort, this approach was well tolerated, with no cases of IC at 6 months post-transplantation in patients at high-risk. Randomized controlled clinical trials are needed to define the optimal strategy in this population.

Disclosures

M. Rizwan Sohail, MD, Aziyo Biologics: Honoraria|Boston Scientific Corporation: Honoraria|Medtronic: Grant/Research Support|TRYX: Grant/Research Support.
215a. Use of Viracor Cytomegalovirus T-Cell Immunity Panel (TCIP) to Predict the Risk of Recurrent Cytomegalovirus Infection in Solid Transplant Patients and Guide Appropriate Management
Authors: Vysniauskaite Indre , Guo Kexin , Angarone Michael P , Stosor Valentina , Tanna Sajal D , Ison Michael G
Published: December 2022

Background

Cytomegalovirus infection (CMV) is the most common opportunistic infection in solid organ transplant recipients (SOTR). Predicting recurrent disease and appropriate use of secondary antiviral prophylaxis is currently poorly defined. CMV-specific T-cell assays have been shown to be promising tools in determining presence of CMV immunity and helping guide primary and secondary antiviral prophylaxis. The goal of this study was to evaluate the ability of commercially available CMV-TCIP in predicting the risk of CMV relapse.

Methods

After IRB approval, clinical and laboratory data was retrospectively collected from our Enterprise Data Warehouse and primary chart review on 74 SOTR. As part of routine clinical care, the CMV T-Cell Immunity Panel (CMV-TCIP, Viracor Eurofins, Lenexa, KS) were collected by the TID provider managing the infection; generally this was done around the time of first negative test to inform choice of 2° prophylaxis. Analysis was completed for the total patient population and a subgroup of patients with CMV-TCIP tests completed ± 21 days of the first negative CMV VL. Descriptive statistics and Cohen’s Kappa statistics were used to assess association of relapse with assay results.

Results

Patient demographics are shown in Table 1. 2° prophylaxis was given to 60 (81.1%) of total patients for a mean of 86 days (0-614 days) after the first negative CMV VL. 26 (35.1%) SOTRs had relapse – 9 with positive CD4 and 20 with positive CD8 CMV-TCIP values. There was no association between specific test results and risk of relapse in the overall study population (see table 2). Similarly, no significance was found in the subgroup analysis of patients with CMV-TCIP results ± 21 days after first negative CMV VL.

Conclusion

In this study, CMV-TCIP did not predict CMV relapse after initial infection and treatment. While prior studies have shown a potential role for assessment of CMV-specific immunity to guide need for secondary prophylaxis, more studies of the CMV-TCIP are needed to assess the utility of this assay for this indication.

Disclosures

Michael P. Angarone, DO, Abbvie: Advisor/Consultant Valentina Stosor, MD, DiaSorin: Advisor/Consultant|Eli Lilly and Company: Grant/Research Support|Med Learning Group: Honoraria Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant.
215b. Real-World Experience of Letermovir Use at an Academic Transplant Center
Authors: Ryu HaYoung , Bowen Christina , Bubalo Joseph , Yu Diana , Lewis James S
Published: December 2022

Background

Letermovir (LMV) is indicated for cytomegalovirus (CMV) prophylaxis in seropositive adults after allogeneic hematopoietic stem cell transplants (alloSCT). LMV is well tolerated compared to its alternatives. Our institution restricts LMV use to high-risk patient groups to maximize the cost/benefit of LMV. Despite these restrictions, LMV was in our institution’s top 50 drug expenditures, prompting a formal evaluation of its use. We describe a real-world experience with LMV at a 576-bed academic transplant center.

Methods

This was a single center, retrospective, descriptive study of LMV use at a transplant center. Any hospitalized patient who received ≥ 1 dose of LMV between August 2021 and January 2022 was eligible for analysis. Data collection included age, LMV administration data, length of stay, transplant status, Infectious Diseases (ID) consultation, documented rationale for non-criteria uses, and drug cost. The primary outcome was incidence of use not aligning with restriction criteria. The secondary outcome was institutional drug expenditure for non-criteria uses compared to approved uses.

Results

Over 6 months, 388 doses of LMV were administered to 31 unique patients during 41 admissions. LMV use during 12/41 admissions (31.7%) fell outside the institutional criteria. ID consult occurred in 58.3% (7/12) of cases. 27/31 (87%) were alloSCT patients, including 1 pediatric patient. There was also 1 liver and 1 heart transplant recipient. Reasons for non-criteria use were: primary prophylaxis in the heart transplant patient to avoid ganciclovir toxicity and in 2 alloSCT patients without high risk for CMV, pre-emptive therapy due to CMV reactivation (n=2), and step-down therapy for CMV viremia (n=4). LMV was used for extended periods ( > 100 days from transplant) in 2 cases. Non-criteria use of LMV accounted for $20 414 in drug cost over 6 months, 29% of total expenditure.

Conclusion

Our data suggest real world use of LMV often differs from the patient types enrolled in the phase 3 trials. Use of LMV as an alternative to available CMV therapies to avoid drug toxicities appears to drive much of this use. In addition, use outside of criteria was frequent and incurred a nontrivial cost. Modification of our criteria, such as requiring an ID consultation for off-label use, should be considered.

Disclosures

James S. Lewis, PharmD, FIDSA, Cidara: Advisor/Consultant|Merck: Advisor/Consultant|SeLux Diagnostics: Advisor/Consultant.
226. Higher Doses of Adintrevimab, an Extended Half-Life Monoclonal Antibody, for the Treatment and Prevention of COVID-19: Preliminary Results from a Phase 1 Single Ascending-Dose Study
Authors: Pu Xia , Gong Jean , Campanaro Ed , Narayan Kristin , Gupta Deepali , Engler Frank , Copans Amanda , Schmidt Pete
Published: December 2022

Background

Adintrevimab is a fully human IgG1 monoclonal antibody engineered to have potent and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential. Adintrevimab is being assessed in two separate phase 2/3 clinical trials: the EVADE trial for prevention of COVID-19 in both post-exposure and pre-exposure settings and the STAMP trial for treatment of COVID-19. Here we report higher doses being evaluated in a healthy volunteer study given that emerging variants may have varying susceptibilities to adintrevimab. Previous results 300 mg IM, 600 mg IM, and 500 mg IV cohorts have been reported.

Methods

This is an ongoing Phase 1, randomized, placebo (PBO)-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged 18–50 years with no current SARS-CoV-2 infection. Participants were randomized 8:2 in 3 high dose cohorts (N=10/cohort: n=8 adintrevimab, n=2 PBO): adintrevimab 1200 mg IM, 1200 mg IV, and 4500 mg IV. Safety, tolerability, and pharmacokinetics (PK) were assessed up to 21 days post dose.

Results

Overall, 30 participants received adintrevimab (n=24) or PBO (n=6). Blinded safety data for all cohorts and PK for 1200 mg IV are reported. Through 21 days post dose all doses were well-tolerated, with no study drug-related adverse events (AEs), serious AEs, injection site reactions, or hypersensitivity reactions reported. The observed PK profile of the 1200 mg IV dose included Cmax of 423±105 µg/ml. Comparison of 500 mg and 1200 mg IV doses indicate dose proportionality of Cmax and exposure (AUC Day 21).

Conclusion

A single dose of adintrevimab, up to 4500 mg, was well tolerated. These preliminary safety data and PK support potential use of higher doses of adintrevimab as needed to address emerging SARS-CoV-2 variants.

Disclosures

Xia Pu, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Jean Gong, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Ed Campanaro, BSN, MSHS, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Kristin Narayan, PhD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Deepali Gupta, B.Sc, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Frank Engler, PhD, Adagio Therapeutics: Advisor/Consultant Amanda Copans, PharmD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds Pete Schmidt, MD, Adagio Therapeutics: Employee|Adagio Therapeutics: Stocks/Bonds.
227. Impact of Asymptomatic Bacteriuria on Primary Efficacy Analyses in the Evaluation of Novel Antimicrobials for the Treatment of Patients with Urinary Tract Infection
Authors: Aronin Steven I , Dunne Michael , Puttagunta Sailaja
Published: December 2022

Background

Per FDA Guidance, the primary efficacy endpoint for trials evaluating antimicrobials for treatment of uncomplicated urinary tract infection (uUTI) and complicated urinary tract infection (cUTI) is a combined clinical/microbiologic outcome response. Overall success requires both resolution of UTI symptoms and demonstration that the causative uropathogen is reduced to < 103 CFU/mL at a fixed time point after randomization, regardless of whether the patient is symptomatic. In clinical practice, it is not standard of care to routinely screen for or treat asymptomatic bacteriuria (ASB), nor to obtain ‘proof of cure’ cultures. In the clinical trial setting, the impact of post-treatment asymptomatic bladder recolonization on the rates of microbiologic response, re-infection, or emergence of resistance is unknown.

Methods

Study IT001-301 and -302 are double blind, double-dummy, Phase 3 randomized trials comparing sulopenem to comparator for patients with pyuria, bacteriuria, and clinical signs/symptoms of uUTI and cUTI, respectively. In Study 301, 1671 ambulatory female adults with uUTI were randomized to oral sulopenem bid x 5d or oral ciprofloxacin bid x 3d. In Study 302, 1395 hospitalized adults with cUTI were randomized to sulopenem IV once daily x 5d followed by oral sulopenem bid or ertapenem IV once daily x 5d followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on baseline uropathogen susceptibility. The primary endpoint was overall (clinical + microbiologic) response in micro-MITT population at TOC visit (D12 in uUTI study and D21 in cUTI study).

Results

Figure 1

Conclusion

Different classes of antibiotics appear to have a differential effect on the frequency of post-treatment ASB with quinolones having a lower rate relative to beta-lactams. The presence of ASB a week or more after completing UTI therapy was not associated with a higher rate of clinical relapse for UTI patients; treatment with ciprofloxacin was associated with the selection of resistant pathogens in the post-treatment flora. Inclusion of ASB in the primary endpoint for studies of UTI should be reconsidered as it implies that a post-treatment culture should be obtained to document resolution of infection, a practice inconsistent with available treatment recommendations.

Disclosures

Steven I. Aronin, MD, Iterum Therapeutics: Stocks/Bonds Michael Dunne, MD, Iterum Therapeutics: Advisor/Consultant|Iterum Therapeutics: Board Member|Iterum Therapeutics: Stocks/Bonds Sailaja Puttagunta, MD, Iterum Therapeutics: Stocks/Bonds.
245. Can Inflammatory Markers be used as an Early predictor for Mechanical ventilation in COVID-19 patients with Stages IIIb-V Chronic Kidney Disease?
Authors: Geetha Harinivaas Shanmugavel , Gogtay Maya , Prabhu Sushmita , Sekar Abinesh , Singh Yuvaraj , Abraham George M , Martin Suzanne
Published: December 2022

Background

The clinical use of inflammatory markers soared during the COVID-19 pandemic. Though studies have shown C-reactive protein (CRP) to predict mechanical ventilation (MV) in patients with COVID-19, its utility is unknown in patients with chronic kidney disease (CKD), who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance of inflammatory cytokines. Our aim was to assess the association of inflammatory markers like CRP, ferritin, LDH, D dimer, and MV rate in patients with stages IIIb-V CKD and COVID-19.

Methods

We conducted a cross-sectional study on inpatients in a community hospital from 12/1/19 to 1/1/22 with COVID-19 and stages IIIb-V CKD without a previous renal transplant. Primary endpoints were invasive MV (IMV) rates, noninvasive MV (NIMV) rates, and no MV. Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables. Cutoffs for variables were CRP 100 mg/L, ferritin 530ng/ml, D-dimer 0.5mg/L and LDH 590 U/L. Univariate analysis and Area under curve (AUC-ROC) between the covariates and outcomes were computed.

Results

290 patients were screened, and 118 patients met inclusion criteria. CRP, D dimer, and ferritin were significantly different among the three groups. On univariate analysis for IMV, CRP had an OR 5.44; ferritin, OR 2.8; LDH, OR 7.7; D-dimer, OR 3.9, WBC count, OR 4.2 (p< 0.05). Admission CRP level was 0.747 for the IMV group (AUC-ROC, sensitivity 80.8%, specificity 50%) and 0.663 for the NIMV group (AUC-ROC, sensitivity 69.2%, specificity 53%)

Conclusion

Our results illustrate a positive correlation between CRP, ferritin, and D-dimer levels and MV and NIMV rates. The ROC demonstrates a good sensitivity for CRP levels in detecting MV thereby emphasizing the utility of these biomarkers as good predictive markers in COVID-19 patients with CKD. With increasing use of inflammatory markers to prognosticate disease severity in COVID, the applicability of these markers in different populations should be investigated. A similar pattern of elevated inflammatory markers predicting the rate of MV was found in patients with stages IIIb-V CKD. This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation due to CKD alone.

Disclosures

All Authors: No reported disclosures.