bluuebunny/crossref_metadata_2025 huggingface dataset:
107. Identification of state-level variables associated with changes in vaccination coverage rates in adults aged 18 to 64 in the United States
Authors: Eiden Amanda , Hunter Shannon , Garbinsky Diana , Price Mark A , Russo Jon N , Hartley Louise C , Nyaku Mawuli , Bhatti Alexandra
Published: December 2022

Background

Despite the recognized value of life-course vaccination, adult vaccine uptake remains low. State-level vaccination coverage disparities may be associate with state-level variables (e.g., policies, programs, practices, and population characteristics). The objective of this study was to identify state-level variables associated with increased adult vaccination coverage rates (VCR) in the US for influenza, tetanus, herpes zoster (HZ), and pneumococcal vaccines over time.

Methods

Retrospective, exploratory database analysis of 2011-2019 Behavioral Risk Factor Surveillance System (BRFSS) data was used to calculate state-level VCRs for adults 18-64 years old. Using publicly available data, state-level variables associated with increases in VCRs were identified via a systematic variable selection. The multivariable regression models included variables meeting the criteria: correlations > 0.4 or < -0.4 (continuous) or Kruskal-Wallis Test p-value < 0.2 (categorical).

Results

Final multivariable regression models included 5 variables: Medicaid expansion status, accountable care organizations in place, health homes program, percentage of adults who report not seeing a doctor in past 12 months because of cost, and percentage of adults who report participating in any physical activity.

In the multivariable models, the following state-level variables were significantly associated with changes in VCR: Influenza: percentage of adults who report participating in any physical activity (p = .01)Pneumococcal: percentage of adults who report not seeing a doctor in the past 12 months because of cost (p = .02)HZ: health homes (p = .04); percentage of adults who report participating in any physical activity or exercise (p = .01); percentage of adults who report not seeing a doctor in past 12 months because of cost (marginally significant, p = .056)Tetanus: none

Conclusion

Few state-level variables demonstrated an association with changes in VCR but some significant findings were observed in final models. Associated variables may not have a direct relationship but may be associated with public health infrastructure supporting vaccination ecosystems. Further research is underway to better understand the factors affecting adult vaccination.

Disclosures

Amanda Eiden, PhD, MBA, MPH, Merck & Co., Inc.: Stocks/Bonds Mark A. Price, MA, MEd, Merck: Advisor/Consultant|Merck: I am an employee of RTI Health Solutions. Merck has contracted with my company to conduct the study described in the abstract. Alexandra Bhatti, JD, MPH, Merck & Co. Inc.: Grant/Research Support|Merck & Co. Inc.: Stocks/Bonds.
2235. Discordance of Clinical and Microbiological Endpoints in Clinical Trials for Complicated Urinary Tract Infection (cUTI)
Authors: Kadry Nadia A , Natarajan Mukil , Bein Edward , Kim Peter , Farley John
Published: December 2022

Background

Complicated urinary tract infections (cUTI) are a clinical syndrome characterized by pyuria and a documented microbial pathogen on urine or blood culture, accompanied by local and systemic signs and symptoms, in the presence of urinary tract abnormalities or acute pyelonephritis. Current FDA guidance recommends that the primary endpoint for cUTI clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed time after therapy. In recent trials, it has been noted that while some patients have clinical resolution of symptoms, they are considered failures due to positive urine cultures. These discordant outcomes have raised questions about the utility of the microbiological endpoint.

Methods

We analyzed patient data from 13 phase 3 clinical trials submitted to the FDA. We focused on the microbiological modified intent-to-treat (m-MITT) population, including patients who have at least 1 bacterial pathogen known to cause cUTI and received at least one dose of study drug (N=4842). Outcomes were determined at the Test of Cure (TOC) visit 7-10 days after therapy, and the Late Follow Up (LFU) visit 3-4 weeks after therapy. Clinical and microbiological success were defined as the resolution of cUTI symptoms present at entry, with no new symptoms (clinical cure), and reduction of the pathogen at entry to ≤ 103 CFU/mL on urine culture (microbiological eradication).

Results

Among all included patients, 70.7% were overall successes at the TOC, exhibiting clinical and microbiological success. 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). In a multivariate logistic regression model, discordance was associated with obesity, lithiasis, use of analgesics, and receipt of carbapenem antibiotics. Discordant patients were at an increased risk for clinical failure at the LFU visit, and the risk of late clinical failure increased with longer time between the TOC and LFU visits.

Conclusion

Microbiological persistence at the TOC visit despite resolution of symptoms was associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component in the composite endpoint.

Disclosures

All Authors: No reported disclosures.
2242. Nitrofurantoin Use and Resistance in Urinary Tract Infections Across a Large, Integrated Health System
Authors: Voyer Kira , Shihadeh Katherine C , Jenkins Timothy C
Published: December 2022

Background

Nitrofurantoin is a preferred empiric antibiotic for the treatment of acute cystitis; however, there are limited data on nitrofurantoin utilization patterns and bacterial resistance in the outpatient setting. The objectives of this study were to describe nitrofurantoin use in an integrated health system and evaluate nitrofurantoin resistance.

Methods

A retrospective review of patients prescribed nitrofurantoin at Denver Health from January 1, 2017 to December 31, 2021 in 9 community health centers, 2 urgent cares, and the emergency department was completed. Patients were included if they received nitrofurantoin within 72 hours of a positive urine culture, defined as > 100,000 cfu/mL of a single organism (Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, or Klebsiella oxytoca) and excluded if they were less than 18 years old.

Results

A total of 634 unique patients were included. Of 934 positive urine cultures, the organism was resistant to nitrofurantoin in 16 (1.7%). Mean patient age was 42.7 years, 99% were women, and nearly 75% were of Hispanic, Latinx, or Spanish ethnicity. The most common comorbid conditions were pregnancy (40.5%) and diabetes (24.6%). Over 90% of organisms identified were Escherichia coli. Despite institutional guidance for 5-day nitrofurantoin courses, prescribed durations were discordant in 46% of cases. Of the 16 cases associated with a nitrofurantoin-resistant pathogen, 9 (56.3%) had recent exposure to nitrofurantoin: 3 were taking nitrofurantoin suppressive therapy for recurrent UTIs and 6 received a treatment course within the last 90 days. Nitrofurantoin-resistant pathogens included E. coli (12), Klebsiella pneumoniae (3), and Enterobacter cloacae (1). A new antibiotic was prescribed for 15 of the 16 patients. 3 patients presented to an outpatient location within 30 days of the index nitrofurantoin prescription for ongoing urinary symptoms.

Conclusion

Increasing guideline-concordant durations of nitrofurantoin is an important antibiotic stewardship opportunity. Despite widespread use, resistance among urinary pathogens remains uncommon and may be associated with recent nitrofurantoin exposure.

Disclosures

All Authors: No reported disclosures.
16. Evaluation of a Monkeypox virus PCR assay and suggestions for future improvement
Authors: Zhang Fan , Murnane Courtney , Joseph Ansamma , Duong Scott , Lemon Jamie , Juretschko Stefan , Streva Vincent
Published: December 2022

Background

Monkeypox virus is an Orthopoxvirus in the Poxviridae family currently responsible for an ongoing global epidemic including active transmission in all 50 US states. To date, nearly 12,000 US cases have been confirmed, with the largest case count in New York State, where over 2,500 cases have been confirmed. Of these, the vast majority (greater than 90%) of cases are residents of New York City (NYC). Nearly all described cases have been identified in men, predominantly in men who have sex with men. Until recently, laboratory testing for Monkeypox virus was limited to state and local public health laboratories or the US Centers for Disease Control (CDC). Northwell Health is the largest healthcare provider in the NYC region and is responsible for molecular PCR testing for over 25 hospitals in the area.

Methods

We describe the evaluation of two real-time PCR assays developed by the CDC: one specific for Monkeypox virus and the other a generic Orthopoxvirus assay. We describe performance characteristics in a high-prevalence patient population, identify room for improvement in future assay iterations, and discuss potential scalability of the assay and portability to an ultra high-throughput platform.

Results

We evaluated the CDC Orthopoxvirus and Monkeypox virus PCR assays using 50 clinical specimens collected from patients presenting with lesions. We determined the limit of detection for both assays is 250 copies/mL. Additionally the assays are highly specific with no cross-reactivity with other viruses tested, including HSV-1, HSV-2, and VZV. One significant limitation is the high rate of indeterminate results due to the use of an RNase P specimen control. Indeterminate results were not the result of assay inhibition and may be from inadequate specimen collection. However, since RNase P signal was often absent in positive specimens, the clinical impact of the RNase P result is questionable.

Conclusion

The CDC Orthopoxvirus and Monkeypox virus PCR assays were useful tools for clinical laboratories to launch rapid testing capacity for these viruses early in the course of the outbreak. However, limitations of the assays prevent them from being expanded to more high-throughput testing platforms. Moving forward, additional work is needed to optimize these PCR assays for more widespread clinical use.

Disclosures

All Authors: No reported disclosures.
LB1534. Cord blood and maternal cytokine levels following SARS-CoV-2 infection during pregnancy
Authors: Sunderraj Ashwin , Otero Sebastian , Miller Emily , Shanes Elisheva D , Goldstein Jeffery A , Mithal Leena B
Published: December 2022

Background

Pregnant people and fetuses are uniquely vulnerable to SARS-CoV-2, a driver of inflammation and immune dysregulation. Prior investigations have shown that pregnant people with SARS-CoV-2 are at higher risk of severe illness, mortality, and obstetric complications. We investigated the impact of SARS-CoV-2 infection severity and latency on maternal and infant cytokine levels.

Methods

We collected maternal blood and cord blood at delivery from mother-infant dyads (Chicago, IL; 3/2020-1/2022). A multiplex cytokine panel (IsoPlexis) was run on plasma from 93 SARS-CoV-2 infected dyads and 32 matched controls. Clinical data was abstracted by chart review, including latency (acute being ≤14 days and distant >14 days from SARS-CoV-2 infection to delivery) and severity (NIH criteria: asymptomatic, mild, moderate, severe/critical). Kruskal-Wallis tests with post-hoc pairwise Dunn Tests were used (α=0.05).

Results

SARS-CoV-2 exposed infants had lower levels of MIP-1b (p=0.037) and PDGF (p=0.008) than controls [Fig 1]. There were no differences in maternal blood cytokines at time of delivery following SARS-CoV-2 infection during pregnancy (pooled analysis of all SARS-CoV-2).

Stratifying by latency, acutely exposed infants showed higher levels of MCP-1 than controls or those with distant maternal SARS-CoV-2 (p=0.016). There were no significant differences in maternal cytokines between control, acute, and distant SARS-CoV-2.

In mothers with acute SARS-CoV-2, differences in levels of IL-1B (p=0.011) and IL-10 (p=0.046) were observed across severity groups, with a significant linear trend for each among severity groups (p for trend < 0.001, respectively). Severe/critical acute infection resulted in higher maternal granzyme and IL-8 than mild infection (p=0.037 and 0.047) [Fig 2]. There were no differences across severity groups in 1) mothers with distant infection, 2) infants with acute maternal infection, or 3) infants with distant maternal infection.

Maternal and infant cytokine levels in acute SARS-CoV-2 infection across severity

Conclusion

Cytokine levels in SARS-CoV-2 positive dyads were altered only in the setting of acute or more severe infection and demonstrated anti-inflammatory, anti-viral, and anti-angiogenic responses. In acute infection, greater severity drives higher levels of both a pro- and anti-inflammatory cytokine in pregnant people.

Disclosures

All Authors: No reported disclosures.
LB1579. A single and a two-dose regimen of MVA-BN elicit similar memory responses to a boost vaccination two years after the initial regimen, indicating potential flexibility for a delayed second dose of MVA-BN in the ongoing monkeypox emergency
Authors: Weidenthaler Heinz , Lienert Florian , Reichhardt Daniela , Schmidt Darja , Silbernagl Günter , Meyer Thomas , Chaplin Paul
Published: December 2022

Background

The ongoing monkeypox outbreak, a WHO-declared PHEIC, requires fast and broad rollout of MVA-BN vaccinations among risk groups. An initial single-dose strategy, followed by a delayed second dose beyond the approved 4-week interval, could help managing tight vaccine resources.

Methods

Bavarian Nordic has run a study in vaccinia-naïve participants, randomized to receive either 1 MVA-BN vaccination (N = 181) or 2 MVA-BN vaccinations 4 weeks apart (N = 183). Of note, this study also evaluated participants with prior smallpox vaccination, who received 1 MVA-BN boost (N = 200). Subsets of approximately 75 participants of the vaccinia-naïve subjects having received either 1 or 2 doses of the vaccine were administered an MVA-BN boost 2 years later. Neutralizing antibodies (nAb) were measured using Vaccinia PRNT.

Results

The 1xMVA-BN and 2xMVA-BN groups responded as expected to the primary regimen, with modest increases in nAb GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination (at Week 6) (2xMVA-BN) nAb GMTs peaked (45.6) before stabilizing at Week 8 (34.0). In both the 1x and 2xMVA-BN groups, the nAb levels were near baseline 2 years after primary vaccination. After the MVA-BN boost at 2 years, both groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-boost (80.7 and 125.3), at higher levels than those observed at any timepoint following primary vaccination, remaining elevated at 6 months post-boost (25.6 and 49.3). These anamnestic responses support the presence of durable immunological memory in both groups. No safety concerns were identified and the most common adverse event following a 2-year MVA-BN boost was injection site erythema in 82.2% of participants.

Conclusion

A single dose of MVA-BN elicits a durable memory immune response for at least 2 years. Similarly, high nAb responses following a boost dose among subjects in the initial 1xMVA-BN or 2xMVA-BN groups indicate that the approved 4-week interval of the two-dose regimen could optionally be extended up to at least 2 years.

NCT00316524 and NCT00686582

Disclosures

Heinz Weidenthaler, MD, Bavarian Nordic GmbH: Employee and received warrants Florian Lienert, PhD, Bavarian Nordic GmbH: employee Employee and received warrants Daniela Reichhardt, PhD, Bavarian Nordic A/S: employee Employee and received warrants Darja Schmidt, Dr, Bavarian Nordic GmbH: Employee and received warrants Günter Silbernagl, MSc, Bavarian Nordic: Employed|Bavarian Nordic GmbH: employee Employee and received warrants Paul Chaplin, PhD, Bavarian Nordic A/S: employee (CEO)|Bavarian Nordic A/S: Stocks/Bonds.
LB1581. Exhalation Delivery System with Fluticasone (EDS-FLU) Significantly Reduces Acute Exacerbations and Associated Antibiotic Use in Chronic Rhinosinusitis
Authors: Mahmoud Ramy
Published: December 2022

Background

Data suggest chronic rhinosinusitis (CRS) may be the top reason for adult outpatient antibiotic use; of ≈10 million office visits per year for CRS, ≈70% result in antibiotic use. Acute exacerbations of CRS (AECRS) are common, possibly due to persistently impaired mucociliary clearance, and drive use of antibiotics. No drugs have been shown effective for reducing AECRS. ReOpen1 and 2 are randomized controlled trials that evaluated prevention of AECRS with the exhalation delivery system with fluticasone (EDS-FLU; XHANCE®), a novel device delivering topical steroid into chronically inflamed sinonasal regions not typically accessible with standard nasal sprays (eg, past the nasal valve and above the inferior turbinate).

Methods

CRS patients were randomized to EDS-FLU one or two sprays per nostril or placebo twice daily (BID) for 24 weeks. Frequency of AECRS, defined as worsening of at least 1 cardinal symptom of CRS (nasal congestion/obstruction, rhinorrhea, facial pain/pressure, hyposmia/anosmia) for ≥ 3 days requiring escalation of medical care (eg, doctor visit, antibiotic or steroid prescription), was analyzed using pooled data from both trials.

Results

Among 555 patients enrolled, 39.4% were using standard nasal steroids at study entry and 38.8% reported prior sinus surgery. There were 76 AECRS over 24 weeks, almost all (71) resulting in antibiotic use. Patients receiving EDS-FLU had a large reduction in AECRS versus placebo (incidence rate ratio [IRR]=0.39, P=0.001, vs placebo). Reduction was greater at the higher dose (2 sprays/nostril BID) than the lower dose (1 spray/nostril BID): IRR=0.34, P=0.002; IRR=0.44, P=0.012, respectively. 9.9% of low-dose patients and 7.8% of high-dose patients had ≥ 1 AECRS (20 and 15 events, respectively) vs 15.7% receiving placebo (41 events; P=0.012 and P=0.002 vs placebo, respectively). Treatment was well tolerated: adverse events in ≥ 3% of patients and more common in one active group than placebo were epistaxis, COVID-19, headache, and nasopharyngitis.

Conclusion

EDS-FLU is the first and only medication shown in randomized controlled trials to significantly reduce acute exacerbations of CRS, offering potential to improve antibiotic stewardship by substantially reducing one of the most common drivers of outpatient antibiotic use.

Disclosures

Ramy Mahmoud, MD, MPH, OptiNose Inc.: Employee of OptiNose Inc.
121. Safety, Tolerability, and Pertussis Immunogenicity Findings From a Randomized, Participant-Blinded, Active-Controlled, Dose-Escalating, Phase 1 Trial of a Tetanus/Diphtheria/Pertussis Booster Vaccine (Tdap-1018 CpG Adjuvanted) Compared With Boostrix in Healthy Adults Aged 18 to 22 Years
Authors: Janssen Robert , McGirr Anthony , Napier-Flood Fiona , Leah Amber , Nolan Terry , Richmond Peter , Boyce Tammy , Xie Fang , Godeaux Olivier
Published: December 2022

Background

Bordetella pertussis is a gram-negative bacterium causing the highly contagious respiratory infection pertussis in over 151 000 individuals annually worldwide. A tetanus/diphtheria/pertussis (Tdap) vaccine combined with CpG 1018 adjuvant (Tdap-1018) may induce higher antibody titers than existing aluminum-adjuvanted Tdap vaccines used as a booster in adults.

Methods

In this randomized, active-controlled, participant-blinded, phase 1 trial, healthy adults aged 18 to 22 years received 1 booster injection of Tdap-1018 (with same Tdap composition as in Boostrix and escalating CpG 1018 dose of 1500 µg and 3000 µg) or Boostrix on Day 1. Pertussis immunogenicity evaluations assessed booster response rates (BRRs) for anti-pertussis toxin (anti-PT), anti-filamentous hemagglutinin (anti-FHA), and anti-pertactin (anti-PRN) antibodies, and systems serology at Week 4 post-vaccination. Safety and tolerability were assessed for solicited local and systemic post-injection reactions for 7 days and unsolicited adverse events for 12 weeks after vaccination.

Results

Of the 87 enrolled adult participants, 84 had post-vaccination immunogenicity results. The median age was 19.0 years, 35% were men, and 83% were white. At Week 4, BRRs in the Tdap-1018 3000 µg group were statistically significantly higher (based on lower 95% confidence interval [CI] >0%) than the Boostrix group for anti-PT (difference in BRRs 22.2% [95% CI: 1.5%–42.8%]) and anti-PRN (22.2% [95% CI: 8.2%–40.9%]) antibodies, and similar for anti-FHA (14.8% [95% CI: -2.6%–33.9%]) antibodies (Table). Tdap-1018 1500 µg, Tdap-1018 3000 µg, and Boostrix were generally well tolerated with no observed safety concerns.

Conclusion

In this phase 1 trial, both dose levels of Tdap-1018 were generally well tolerated. Tdap-1018 3000 µg induced statistically significantly higher BRRs than Boostrix for anti-PT and anti-PRN, and a similar response for anti-FHA antibodies.

Disclosures

Robert Janssen, MD, Dynavax Technologies Corporation: employee|Dynavax Technologies Corporation: Stocks/Bonds Tammy Boyce, MEd, Dynavax Technologies Corporation: Employee|Dynavax Technologies Corporation: Stocks/Bonds Fang Xie, PhD, Dynavax Technologies Corporation: Employee|Dynavax Technologies Corporation: Stocks/Bonds Olivier Godeaux, MD, MPH, Dynavax: Advisor/Consultant.
143. Genomics analysis of Carbapenem resistance in BCC Identify PenR E151V substitution and novel Burkholderia cepacia complex specific OXA-1043 subgroup
Authors: Liao Ya-Chun , University Chung Shan Medical , Liu Po-Yu , Huang Yao-Ting
Published: December 2022

Background

Treatment options for Burkholderia cepacia complex (Bcc) remain limited, and previous study revealed 26% of strains was susceptible to meropenem.

In B. cenocepacia and many Bcc species, ampC and its regulator, ampR, named penR in Burkholderia genomes are not associated, sharing a divergent promoter, as in other previously studied species. Recently, Josselin Bodilis et el (2018) found that there was no different in genetic organization between imipenem-sensitive and imipenem-resistant strains.

Our study is to provide an answer to the different of genetic expression pattern between imipenem resistance and imipenem sensitive Burkholderia cepacia complex species.

Methods

The Bcc species genome was deeply sequenced using Nanopore technology. Protein-coding genes, and coding and non-coding RNAs in the chromosomes and plasmids were annotated via the NCBI PGAP pipeline. Antibiotic-resistant genes (ARGs) were predicted by aligning protein-coding genes against the Comprehensive Antibiotic Resistance Database (CARD) using Diamond.

Results

In our study, drug susceptibility test of different antibiotic showed only Burkholderia cenocepacia strain MC0-3 revealed sensitive to imipenem (Table 1). Further genetic organization between imipenem-resistance and imipenem-sensitive strains showed similar β-lactamase-encoding genes (Figure 1). In the multiple sequence alignment of PenR, nine imipenem-resistance Bcc stains, which amino acid sequence at position 151 is glutamic acid, however, in imipenem-sensitive strain amino acid substitute glutamic acid with valine (Figure 2b). PROVEAN also showed amino acid substitutions at position E151 in PenR is deleterious (Table 2). We also analyzed 95 strains of Burkholderia, and drew the phylogenetic tree which showed PenR E151V subsititution consisted in other imipenem-sensitive strains of Burkholderia. In addition, a novel Burkholderia cepacia complex specific OXA-1043 subgroup is found in stain toggle 2, toggle 3 and toggle 4 (Figure 3). Figure 1.Genetic organization of imipenem resistance and imipenem sensitive in different strain of Burkholderia cepacia complex.

Conclusion

The results of this study indicate that antibiotic resistance related to the amino acid substitutions, which may explain the imipenem-sensitive strain of Burkholderia cenocepacia. Bedsides, a new OXA family is found in Burkholderia cenocepacia strain, and is named OXA 1403. Figure 2.Multiple sequence alignment PenR in different strains of Burkholderia cepacia complex and phylogenetic tree of Burkholderia spp.

Disclosures

All Authors: No reported disclosures.
159. Antibiotic and diagnostic stewardship surrounding pre-operative testing in patients undergoing cardiac surgery
Authors: Winkler Marisa , Huang Joanne , Starr Jessica , Paras Molly L , Letourneau Alyssa R , Hooper David , Shenoy Erica S
Published: December 2022

Background

Despite national guidelines from the US Preventative Services Task Force and the Infectious Diseases Society of America that recommend against screening for asymptomatic bacteriuria (ASB, defined as > 105 CFU of an organism) in most circumstances, pre-operative screening urine culture (UCx) continues. Detection and treatment of ASB leads to antibiotic exposure and risk of antibiotic-associated adverse events like drug reactions, Clostridioides difficile infection (CDI), and colonization by drug-resistant organisms. We describe the implementation of eliminating pre-operative screening for ASB in patients undergoing cardiac surgery. Figure 1Pre-operative checklist for cardiac surgery prior to intervention

Methods

This was a pre-post study of practice change involving removing ASB screening as part of the pre-cardiac surgery checklist (Figure 1). The pre-intervention period was 08/18/21 – 11/17/21, the post intervention period was 12/1/21 – 3/1/22. We identified all patients who underwent a cardiac arterial bypass graft procedure with or without vein harvesting. We reviewed pre-operative UCx, test indication, antibiotic administration pre-operatively due to culture growth, and post-operative CDI and CAUTI within 30 days post procedure identified through routine infection prevention and control surveillance.

Results

Pre-intervention, 117/128 (91.4%) patients undergoing cardiac surgery had a UCx collected. Of the UCx, 100% were ordered as part of the pre-operative checklist and not for symptoms. Five patients pre-intervention had ASB detected. Four patients received antibiotics to treat ASB. A fifth patient received antibiotics for bacteriuria which did not meet ASB count threshold. Post-intervention, 15/123 had a UCx (12.3%). Of these, 12/15 were ordered as part of the pre-operative checklist (80%), and the remaining three had symptoms documented. Post-intervention, one patient had ASB detected and did not receive antibiotics. Pre- and post-intervention there were 2 cases of CDI (2/128, 1.6% and 2/123, 1.6%, respectively). There were no CAUTIs either pre- or post-intervention.

Conclusion

Standard pre-operative UCx is known to be a low-value test and is not recommended by national guidelines. In this single-center diagnostic stewardship intervention, screening was reduced by 87.2%. There was no change in infectious outcomes.

Disclosures

All Authors: No reported disclosures.
184. Impact of the BioFire® FilmArray® Blood Culture Identification 2 Panel on Antimicrobial Treatment of Enterobacterales Blood Stream Infections
Authors: Logan Ashley , Beardsley James , Taylor Alex D , Williamson John C , Palavecino Elizabeth , Luther Vera , Ohl Christopher , Stone Tyler
Published: December 2022

Background

The BioFire® FilmArray® Blood Culture Identification 2 (BCID2) panel is a rapid diagnostic tool that uses multiplex polymerase chain reaction technology to identify 43 different genetic targets. BCID2 detects 13 additional targets, including 7 resistance markers, not detected by the original BCID panel. For this reason, our institution changed panels from BCID to BCID2 in August 2020. The purpose of this study was to assess the time to antibiotic change for Enterobacterales bloodstream infections before and after switch to BCID2.

Methods

This was a retrospective, observational, before-and-after study conducted at an 885-bed academic medical center. Adult patients with blood cultures positive for E. coli or K. pneumoniae (EC/KP) who received broad spectrum beta-lactam therapy were included. Patients with a polymicrobial or concurrent infection, hemodynamic instability, lack of source control by day 5, or death within 72 hours (hrs) of cultures being collected were excluded. The primary outcome was time to antibiotic change in the BCID group compared to the BCID2 group. Secondary outcomes included time to de-escalation or escalation and the number of opportunities for de-escalation or escalation.

Results

88 patients were included, 55 in the BCID-group and 33 in the BCID2-group. Baseline characteristics are reported in Table 1. Median time to first antibiotic change was 65.3 hrs in the BCID-group vs 69.6 hrs in the BCID2-group (p=0.53). Times to first de-escalation and escalation and number of opportunities for de-escalation and escalation are presented in Table 2. Proportion of missed de-escalation opportunities based on panel results was greater in the BCID2 group (63.6% vs 0%, p< 0.05).

Conclusion

Opportunities to make timely antibiotic modifications with the use of the BCID2 panel exist for EC/KP blood stream infections. While no difference in time to first antibiotic change was present between groups, this highlights the importance of having an active stewardship team member available to respond to rapid diagnostic test results.

Disclosures

All Authors: No reported disclosures.
210. Neutropenia and Associated Infectious Complications Among Kidney Transplant Recipients Receiving Valganciclovir Prophylaxis in the United States: An Administrative Claims Database Study
Authors: Turzhitsky Vladimir , Raval Amit D , Moise Pamela , Merchant Sanjay
Published: December 2022

Background

Valganciclovir (VGCV) prophylaxis is commonly utilized to prevent cytomegalovirus (CMV) infection among high (D+/R-) and intermediate (R+) risk kidney transplant recipients (KTRs). Due to the myelosuppressive effects of VGCV, KTRs may be at an increased risk of opportunistic infections (OIs) resulting in interruptions to VGCV therapy. Therefore, we aimed to quantify the clinical burden of neutropenia among adult KTRs receiving VGCV prophylaxis.

Methods

A retrospective cohort design was utilized to identify adult KTRs who received VGCV prophylaxis using the IBM MarketScan Commercial and Medicare Supplemental claims databases. First-time KTRs between 1/1/2012 - 12/31/2018 with 1 year of continuous pharmacy and medical coverage before (baseline period) and after (follow-up period) were included. KTRs with a History of other solid organ transplantation were excluded. Fills of ≥ 1 prescription of VGCV (either 450 mg or 900 mg/day) within 30 days of the kidney transplant (KT). Neutropenia events were identified as either ≥ 1 inpatient, or ≥ 2 outpatient ICD-9/ICD-10 diagnoses codes within 14 days.

Results

Of the 4,965 adults KTRs with baseline and follow-up enrollment, 3,258 (66%) used VGCV prophylaxis. 311/3256 (9.5%) developed neutropenia within 1-year post KT. Baseline characteristics were similar between those with and without neutropenia (table 1). The majority received the following pre-transplant immunosuppression: tacrolimus (78.9%), mycophenolate mofetil (62.8%) and steroids (prednisone, 79.3%, methylprednisolone 10.6%). KTRs with neutropenia had a nearly two-fold increase in the development of CMV infection compared to those without neutropenia. In addition, KTRs with neutropenia had significantly higher rate of bacterial or fungal infections compared to those without neutropenia (Table 2). Interruptions in VGCV prophylaxis (gap >15 days) were more common in KTRs with neutropenia (P< 0.001).

Conclusion

Our findings showed that neutropenia was associated viral, bacterial, and fungal OIs among adults KT receiving VGCV prophylaxis. The findings highlight the needs for interventions to reduce neutropenia and its associated OIs. These results suggest that clinical management steps to reduce rates of neutropenia among KT recipients may warrant further study.

Disclosures

Vladimir Turzhitsky, PhD, Merck & Co., Inc.,: Employee|Merck & Co., Inc.,: Stocks/Bonds Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Pamela Moise, PharmD, Merck & Co., Inc: Employee & Shareholder Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds.
217. A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of the Lipopeptide QPX9003 in Healthy Adult Subjects
Authors: Griffith David , Carmeli Yehuda , Gehrke Shawnee , Morgan Elizabeth , Dudley Michael , Loutit Jeff
Published: December 2022

Background

QPX9003 is a fully synthetic lipopeptide with potent activity against MDR Pseudomonas and Acinetobacter spp. This report describes the safety and pharmacokinetics of QPX9003 following single and multiple doses.

Methods

Twelve healthy subjects were enrolled in 2 cohorts of up to 8 subjects (each cohort randomized to have up to 6 active and 2 placebo) each in the multiple ascending dose phase (100 or 200 mg every 6 hrs). Subjects received a single dose of QPX9003 followed by 48 hours of washout, then were administered QPX9003 q6h for 7 days. All infusions were administered over 1 hour. Intensive plasma sampling was obtained after dosing and assayed for QPX9003 content using validated HPLC/MS methods.

Results

Single and multiple dose QPX9003 pharmacokinetic parameters (mean +/- SD) are shown below:

No subjects discontinued due to AEs and no SAEs were observed. There was no evidence of increasing numbers or severity of AEs with increasing dose, and all AEs were mild or moderate in severity.

Conclusion

QPX9003 was safe and well tolerated at all doses tested. QPX9003 plasma AUC and Cmax increased with increasing dose. QPX9003 plasma exposure accumulated ∼ 1.5 fold over 7 days of q6h dosing consistent with its plasma half-life. Based on the PK and safety profile, QPX9003 produces plasma exposures that exceed the PK-PD target safely and warrants further clinical development.

Disclosures

David Griffith, n/a, Qpex Biopharma: Employee Yehuda Carmeli, MD, Allecra Therapeutics: Advisor/Consultant|MSD: Advisor/Consultant|Nabriva: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex Pharmaceuticals: Advisor/Consultant|Roche: Advisor/Consultant|Shinogi: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant Shawnee Gehrke, n/a, Qpex Biopharma: Employee Elizabeth Morgan, n/a, Qpex Biopharma: Employee Michael Dudley, n/a, ArrePath: Board Member|Qpex Biopharma: Board Member|Qpex Biopharma: Employee Jeff Loutit, MBChB, Qpex Biopharma: Employee.
219. A Randomized, Double-Masked, Placebo-Controlled Phase IIB Trial of Azithromycin and Trimethoprim-Sulfamethoxazole as Bacterial STI Prophylaxis in Pregnant Women with HIV
Authors: Dionne Jodie , Pol Barbara Van Der , Long Dustin , Tih Pius , Mbah Rahel , Ngah Edward , Pekwarake Seraphine , Kifem Mirabelle , Fondzeyuf Anthony , Bruxvoort Katia J , Tita Alan , Marrazzo Jeanne
Published: December 2022

Background

This phase IIB randomized clinical trial was designed to test the efficacy of a novel regimen to prevent bacterial sexually transmitted infections and malaria in pregnant women with HIV in Cameroon, where HIV prevalence in pregnancy is 5.7%. Here we present the analysis of STI rates.

Methods

Pregnant women in prenatal care with confirmed HIV, gestational age < 28 weeks and singleton pregnancies were randomized to monthly azithromycin (AZ) 1 gram daily for 3 days and daily trimethoprim-sulfamethoxazole (TMPS) or the standard regimen of daily TMPS with monthly placebo AZ.

The main outcome of interest was the proportion of women with a composite STI measure: chlamydia, gonorrhea and/or incident syphilis at delivery. Nucleic acid amplification testing (NAAT) for CT/NG was performed on provider-collected vaginal swabs. Incident syphilis was defined serologically as a newly positive treponemal test or 4 fold increase in RPR/VDRL titer since baseline. The proportion was compared by relative risk with 95% confidence intervals and a significant p value set at < 0.05.

Results

A total of 308 women were enrolled at three hospital facilities between March 2018 and August 2020. In all, 155 women were randomized to the AZ/TMPS arm and 153 women to the TMPS arm. A total of 260 women (84%) had delivery samples collected. Both groups were similar with median age 32 years, maternal education (71% secondary school or university), HIV diagnosis 3 years prior, and 94% reported excellent adherence to antiretroviral therapy (ART). Median CD4 count was 473 cells/mm3 (IQR 326-663). At baseline, prevalence of chlamydia was 1.4%, gonorrhea 1.0% and syphilis 1.9%. There was no difference in the proportion of women with the composite STI measure (3.2% in the AZ/TMPS arm and 3.3% in the TMPS arm; RR 0.78 (95% CI 0.21 – 2.84); p=0.70). Adverse birth outcomes were lower in the AZ/TMPS arm, but not significantly (preterm delivery 5% vs 10.3% [p=0.1], low birthweight 2.8% vs 5.1% [p=0.34], composite adverse birth outcome 8.4% vs 13.1% [p=0.19]. Table 1:Baseline Characteristics of Study Participants (n=308)Table 2:Efficacy Outcomes at Delivery by Arm - Intention to Treat Analysis (n= 278)

Conclusion

The addition of monthly azithromycin to standard daily TMPS prophylaxis in pregnant women living with HIV in Cameroon did not reduce the rate of bacterial STI at delivery. Women reported excellent ART adherence and rates of STI, malaria, and adverse birth outcome were low.

Disclosures

Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support.
241. Antibiotic Prescription in COVID Intensive Care Unit (ICU): Empiric Treatment vs. FilmArray Pneumonia (FAP) Panel Guided Treatment
Authors: Jimenez Maria F , Garcia Bayron , Ordonez Karen M , Moreno German A
Published: December 2022

Background

The empiric prescription of antibiotics in COVID 19 ICU patients is frequent due to the severity of disease and presentation of patients with septic shock. In this study we compared two approaches of antimicrobial prescription: empiric use vs. FilmArray pneumonia (FAP) panel guided treatment. We evaluated costs of intervention, clinical outcomes as development of hospital acquired infections (HAI), length of stay and mortality.

Methods

Retrospective study. Patients with severe COVID-19 infection hospitalized in ICU of two institutions in Pereira were included. The prescription of antibiotic without FAP panel was defined as empiric. The prescription according to FAP panel results was defined as guided. Data analysis was performed in Epiinfo version 7.5.2.0. The study protocol was approved by the ethics committee of Universidad Tecnologica de Pereira.

Results

252 patients were included, 180 received empiric therapy and 72 were FAP panel guided. The median age was 65 years (IQR 53-73), the PaO2/FiO2 ratio mean was 108 (IQR 64-130). In the group of empiric treatment, 21 (11.67%) patients presented confirmed bacterial infection. Patients on guided antimicrobial therapy presented less HAI (RR 0,54 (IC 95% 0.30-0.95) p 0.02). The median length of stay in ICU was 16 days for both groups. Klebsiella pneumoniae was the most frequent bacteria identified during the first episode of infection followed of Pseudomonas aeruginosa. Mortality on guided group was 54% Vs. 42% on empiric group (p< 0,3). Meropenem was the main antibiotic prescribed (DDD empiric 3.17 Vs. 1.8 DDD guided) followed of cefepime (DDD empiric 0.9 Vs. DDD guided 0.12). The median cost of antimicrobial treatment in the empiric group was US$530 (US$30-US$1579) per patient compared to the median cost of guided prescription that was US$292 (US$16-US$8767). When including the cost of FAP panel, the median cost per patient treatment course was US$429 (US$153-US$8904) p< 0.7.

Conclusion

Implementation of a guided antimicrobial therapy using FAP panel could be useful and cost effective in COVID-19 ICU patients to reduce antimicrobial consumption and adverse outcomes related to the inappropriate use of antibiotics without significant impact on mortality or length of stay.

Disclosures

Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony.
254. Clinical significance of antineutrophil cytoplasmic antibody positivity in patients infected with SARS-CoV-2
Authors: Lee Lucy Eunju , Jeong Wooyong , Park Yong-Beom , Jeong Su Jin , Lee Sang-Won
Published: December 2022

Background

The Coronavirus Disease 2019 (COVID-19) is well-known for its broad spectrum of immune-related phenotypes similar to those seen in autoimmune or inflammatory diseases. Furthermore, evidence has gradually accumulated that COVID-19 may induce systemic inflammatory manifestations such as multisystem inflammatory syndrome, haemophagocytic syndromes, and systemic vasculitis. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis characterised by necrotising vasculitis. So far, there have been several case reports regarding AAV occurrence after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which have indicated a triggering potential of SARS-CoV-2 infection for AAV occurrence. This study investigated the rate of ANCA positivity and its clinical significance in COVID-19 patients.

Methods

This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort of a single center. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA from the stored blood sera were measured using the immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as poor outcomes. Severe infection was defined as a medical condition that required a high-flow nasal cannula and/or mechanical ventilator care. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among the study subjects

Results

The detection rate of ANCA positivity was 18.5%: MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients. Patients with ANCA positivity exhibited a lower cumulative survival rate than those without, but the difference was not statistically significant (P = 0.057). However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) FIGURE 1.Comparison of the cumulative survival rate

Neither ANCA positivity nor ANCA subtype (MPO-ANCA and PR3-ANCA) positivity had a significant influence on poor outcomes of SARS-CoV-2.

ANCA: antineutrophil cytoplasmic antibody; MPO: myeloperoxidase; PR3: proteinase 3; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Conclusion

SARS-CoV-2 infection may increase the rate of ANCA positivity, which may not affect poor outcomes but contribute to the classification of GPA and MPA despite uncertain clinical significance

Disclosures

All Authors: No reported disclosures.
266. Cumulative Steroid Dose in Hospitalized Patients and COVID-19 Associated Pulmonary Aspergillosis
Authors: Ramonfaur Diego , Salto-Quintana Jack , Hernández-Mata Nadia , Aguirre-García Gloria Mayela , Villanueva-Lozano Hiram , Martínez-Reséndez Michel
Published: December 2022

Background

Severe COVID-19 elicits a hyperimmune response frequently amenable by high-dose steroids, although treatment may increase the risk for opportunistic infections. Invasive pulmonary aspergillosis (IPA) is a known complication of COVID-19, termed COVID-19 associated pulmonary aspergillosis (CAPA). While steroid use is a known risk factor for CAPA, the role of cumulative steroid dose in the development of CAPA is unclear. This study evaluates the relationship between cumulative steroid dose in hospitalized individuals and the risk for CAPA.

Methods

This retrospective cohort study includes 130 hospitalized patients with RT-PCR-confirmed COVID-19 pneumonia at a specialized center in north Mexico. Patients who developed CAPA were matched by age and gender to two patients who did not develop CAPA. CAPA was defined according to 2020 ECMM/ISHAM criteria. Patients with either possible, probable, or proven CAPA were considered positive cases. Steroid dose was converted to dexamethasone equivalents according to potency and duration. Cumulative dose was obtained in every patient from admission until discharge or diagnosis of CAPA. We assessed the risk of CAPA by the continuous cumulative steroid dose using a logistic regression model.

Results

A total of 42 patients were diagnosed with possible, probable, or confirmed CAPA and were matched to 88 controls. Mean age was 61 ± 14 years, 94 (72%) were male, 11 (12%) were smokers, and 55 (50%) were obese. Mean cumulative steroid dose was 66 ± 75 in patients without CAPA vs 195 ± 226 in patients with CAPA (P< 0.001) (Figure Panel A). The risk for CAPA was higher as the cumulative dose of steroids increased, in a near-linear relationship (OR 1.008; 95% CI 1.003, 1.013, P< 0.001) (Figure Panel B).

Conclusion

Patients who develop CAPA have a history of higher cumulative steroid dose during hospitalization. The risk for CAPA increases in a near-linear fashion as the cumulative steroid dose during hospitalization increases. While causality cannot be drawn by this study, caution while prescribing high-dose steroids is warranted among individuals hospitalized with COVID-19 pneumonia. Clinical suspicion of CAPA should increase in individuals with a high cumulative dose of steroids and clinical decline.

Disclosures

All Authors: No reported disclosures.
267. Delayed Pulmonary Tuberculosis (PTB) Diagnosis During the COVID-19 Pandemic: A Case Series
Authors: Khaitov Mikhail , Salomon Nadim , Perlman David , Humphreys Sarah
Published: December 2022

Background

The COVID-19 pandemic has been associated with underreporting of pulmonary tuberculosis (PTB). Overlapping risk factors, clinical features, and chronicity of post COVID-19 sequelae can lead to attribution of respiratory disease solely to COVID-19 and result in delayed recognition of PTB.

Methods

Identification of inpatients with both sputum (spu) culture (clt) positive TB and SARS-CoV-2 + PCR was achieved using data extraction tool Slicer Dicer Epic system during 3/2020-1/2022 followed by a retrospective review of electronic medical records. We defined COVID-PTB as a patient (pt) who had positive spu clt for TB ≤ 12 months (mos) following a COVID-19 diagnosis.

Results

8 pts had both PTB and COVID-19. Two had PTB > 5 mos prior to, and one had PTB > 12 mos after COVID-19. 3/8 were promptly suspected to have PTB [1 with right upper lobe (RUL) infiltrate; 1 RUL cavitary infiltrate; 1 with miliary nodules and cavities]; in these 3, spu was tested for MTB ≤ 48 hours (h) (hrs) of presentation. 5/8 had COVID-PTB. All 5 had fever and/or respiratory symptoms and ≥ 1 risk factors for TB identified at the time of presentation with COVID-19. Spu was tested for MTB in 48 hs in 1 with RUL cavitary infiltrate, and 5 days after chest CT findings of apical densities and scattered nodules in another. In the remaining 3, spu testing was delayed a median of 36 days (range, 8-133) after initial TB consistent CT findings (LUL opacity and nodular densities in 1; RLL cavitary infiltrate in 1; and clustered RML nodules in 1) and despite immigration from high burden TB countries in all 3; known LTBI in 2; diabetes in 1, and immunosuppressive therapies in 2.

Conclusion

We observed a delay in sputum collection after COVID-19 diagnosis in the presence of epidemiological risk factors for TB disease and clinical features consistent with PTB. Lack of familiarity with the range radiological TB features, a diagnostic bias towards more typical radiographic (e.g., cavities, miliary patterns) and COVID-19 anchoring bias may have contributed to delayed PTB diagnosis. PTB should be considered, when clinically appropriate, in the setting of COVID-19 or apparent post COVID-19 sequelae.

Disclosures

All Authors: No reported disclosures.