bluuebunny/crossref_metadata_2025 huggingface dataset:
2430. Risk Factors for Mortality among Patients who Present from the Community with Central Line-Associated Bloodstream Infections
Authors: Oladapo-Shittu Opeyemi , Ching Patrick R , Hsu Yea-Jen , Saunders Heather , Salinas Alejandra B , Helsel Taylor N , Mayoryk Stephanie , Gadala Avinash , Cosgrove Sara E , Rock Clare , Klein Eili , Maragakis Lisa , Pineles Lisa , Harris Anthony , Mejia-Chew Carlos , Keller Sara C
Published: November 2023

Background

Central line-associated bloodstream infections (CLABSI) lead to significant morbidity and mortality. Surveillance has contributed to reductions in the CLABSI rate in acute care hospitals. Although there are increasing numbers of patients with central venous catheters outside of acute care hospitals, the prevalence of and mortality risk associated with CLABSIs present-on-admission (POA) to acute care hospitals is unknown.

To explore the burden of CLABSI POA and the risk factors associated with an all-cause mortality.

Methods

We identified patients presenting to hospitals with CLABSI (regardless of pre-admission location) in two large health systems based in Maryland, Washington DC, and Missouri between November 2020-October 2021. CLABSI was defined using an adaptation of the acute care CLABSI definition.

Results

Out of 402 patients identified with CLABSI POA, in-hospital mortality was 10.4%. Within six months of hospital presentation, 126 patients died (31.3%) (Figure 1). The median Pitt bacteremia score was 1 (interquartile range: 0-2), with 82 (20.4%) admitted to the adult intensive care unit (ICU), and 9 (2.2%) admitted to the pediatric ICU. The mean hospital length of stay was 8 days (interquartile range: 5-14). Compared with patients < 45 years of age, patients aged 45-64 and >65 had increased mortality within 6 months (OR: 3.49, 95% CI: 1.53-7.96; OR: 5.76, 95% CI: 2.24-14.81, respectively). Compared with patients receiving Medicaid, patients who were self-pay had increased mortality within 6 months (OR: 4.18, 95% CI: 1.13-15.43). Receipt of chemotherapy within the last 6 months and hospital discharge ≤ 30 days before presentation were associated with increased mortality within 6 months (OR: 2.53, 95% CI: 1.12-5.71; OR: 1.19, 95% CI: 1.13-3.23; respectively) (Table 1).

Conclusion

CLABSI POA was associated with a high mortality, with almost one in three patients deceased within 6 months. Patients at risk of higher mortality included those over the age of 44, self-pay insurance, receipt of chemotherapy in the last 6 months, and recent hospital discharge. These results underscore the need for CLABSI prevention initiatives outside acute care settings.

Disclosures

Stephanie Mayoryk, MAS BSN RN CIC, PDI: Honoraria Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Carlos Mejia-Chew, MD, INSMED: Grant/Research Support|RevImmune: Grant/Research Support Sara C. Keller, MD, MPH, MSPH, Pfizer: Advisor/Consultant
132. “Diagnostic and Antibiotic Stewardship based on Urine Culture”
Authors: C Nitheeshwar , Priya Tharsini Mithra , Kumar Dorairajan Suresh
Published: November 2023

Background

Asymptomatic bacteriuria is one of the most common causes of antibiotic use in hospitalised patients. Antibiotic stewardship targeting asymptomatic bacteriuria ( ASB) should focus on diagnostic urine cultures, restricting unnecessary urine cultures, and preventing inappropriate antibiotic use. However, there is limited evidence from developing countries on the impact of the above interventions. This study aimed to assess the appropriateness of urine cultures ordered and also study the antibiotic prescribing pattern for the patient who underwent urine cultures.

Methods

A prospective, observational study was conducted in a tertiary care hospital in south India between February 2023 and April 2023. The medical records of the hospitalised patients who underwent urine culture ( except urological and pregnant women) were reviewed by using the validated audit tool, which contained details of demographic data, indications, results of urine culture, and antibiotics prescribed to the patients. The data was audited by the trained Pharm.D. students to establish the appropriateness of the urine cultures ordered and the antibiotic prescribing pattern for the patients who started antibiotics.

Results

During the study period 329 case records were audited. And the data is given in the table 1.

Table 1: Diagnostic stewardship and antibiotic prescribing practices

Conclusion

Most of the urine cultures ( 90.5%) sent are without any urinary symptoms, and 69.5% of patients with asymptomatic bacteriuria receive antibiotics, which contribute to antibiotic resistance. It is necessary to put effective techniques into practice to increase the appropriateness of ordering urine cultures and the use of antibiotics in hospitals.

Disclosures

All Authors: No reported disclosures
2443. Clinical Characteristics and Outcome of Vascular Access Infections in Patients with hemodialysis : A 12 year study
Authors: LEE E U N J U N G , Yu Shinae , Baek Yae Jee , Jung Jongtak , Kim Tae Hyong , Hong Sunin
Published: November 2023

Background

Infection is the second most common cause of death in ESRD (end-stage renal disease) patients. Although vascular access-related infections are directly related to the prognosis and mortality of ESRD patients, related studies are rare.

Methods

The medical records of adult patients admitted due to hemodialysis vascular access-related infections to a 750-bed tertiary medical institution in Seoul, Korea, were retrospectively analyzed from January 1, 2009 to December 31, 2020. Patients younger than 19 years and history of previous vascular access infections in other sites were excluded.

Results

During the 12-years study period, 372 patients were analyzed. According to the vascular access type, there were 290 (78%) of AV graft infections, 34 (9.1%) of AV fistula infections, and 48(12.9%) of tunneled catheter-related infections. Hemodialysis vascular access-related infection occurred at a median (IQR) of 86 (30-132) days in the tunneled catheter, 357 (105-1283) days in AV graft, and 960 (401-2289) days in AV fistula. Bacteremia was present in 152 (40.8%) patients. Staphylococcus aureus is the most common organism isolated from blood culture (88, 57.8%). Eighteen patients with methicillin-resistant S.aureus (MRSA) bacteremia underwent nasal swabs, and MRSA colonization was confirmed in only 6 of them (6/18, 33.4%). Among the patients without bacteremia, 31 were cultured directly from infected graft tissue or pus.

Metastatic infection was shown in 15 (4%) patients. The most common complication was pneumonia, including septic lung.

Of the 372 patients, 325 (86.7%) underwent surgical treatment. Total excision was performed in 115 (35.3%), partial excision in 178 (54.7%), and incision and drainage in 32 (9.8%). Seventy-nine (24.3%) patients underwent re-operation due to uncontrolled infection.

Three patients died due to vascular access-related infection. Patients who received repeated surgery were at a higher mortality risk (p=0.31).

Conclusion

Tunneled catheter-related infections occurred earliest, while AV fistula infections occurred the latest. S. aureus remained the most common causative organism. Patients who underwent revision surgery were associated with death.

Disclosures

All Authors: No reported disclosures
2459. Prevalence of Nasopharyngeal Carriage of Macrolide and Lincosamide Resistance Genes Among a Household-based cohort of Children and Adults in a Peri-urban Community in Peru
Authors: Charnogusrky Cara , Gil Ana , Ecker Lucie , Cornejo Rubelio , Rios Stefano , Ochoa Mayra Rosana , Peña Peralta Bia M , Flores Omar , Lanata Claudio , Grijalva Carlos G , Howard Leigh M
Published: November 2023

Background

Antibiotic resistant infections commonly occur in healthcare settings, but the prevalence of antibiotic resistant genes (ARGs) in healthy individuals in the community is unknown. We provide an initial assessment of nasopharyngeal carriage of ARGs conferring resistance to macrolides and/or lincosamides, including erm, mph, ABC-F, and lnu genes.

Methods

Nasopharyngeal swabs were systematically obtained at enrollment and weekly thereafter from children and adults enrolled in a household-based prospective cohort study in Lima, Peru. Samples were sequenced using the Illumina Respiratory Pathogen/ID AMR Panel to detect common respiratory bacteria and ARGs. We defined ‘any erm gene’ (erm) as the detection of any specific erm gene class, ‘any mph gene’ as detection of any specific mph gene class, ‘any ABC-F gene’ as any specific ABC-F gene class, and ‘any lnu gene’ as any specific lnu gene detection. We compared the prevalence of erm, mph, ABC-F and lnu gene colonization at enrollment among age groups (ages 0-4, 5-17, 18-44, and 45+ years) using the Fisher's exact test. We then compared the frequency of co-detection of two or more macrolide or lincosamide ARGs between both pediatric age groups (ages 0-17 years) and both adult age groups (18+ years).

Results

114 individuals were included in this analysis (Table 1). At least one macrolide or lincosamide ARG was detected in 61/114 (53.5%) individuals. The prevalence of erm, mph, ABC-F, or lnu gene detection was similar among age groups (Figure 1). Two or more genes were co-detected in 45/114 (39.4%) individuals. Co-detections with two or more erm, mph, ABC-F, or lnu genes were more frequent in children 0-17 years compared to adults 18+ years (p=0.013) (Figure 2).

Conclusion

Conclusions: These preliminary results indicate that macrolide or lincosamide ARGs were commonly detected in healthy community-dwelling children and adults in Lima, Peru. The prevalence of erm, mph, ABC-F, and lnu genes was similar across age groups, and co-detection of ARGs was more common in children. Future studies will assess changes in ARG carriage over time, transmission among household members, and its clinical relevance.  

Disclosures

Claudio Lanata, MD, MPH, CureVAc AG Germany: Grant/Research Support|HilleVac Inc.: Advisor/Consultant|HilleVac Inc.: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support
135. Impact of Clostridioides difficile Toxin Confirmation on Subsequent C. difficile Treatment in a Rural Health System (IT-CDI)
Authors: Crawford Jacquelyn , Cluck David B , Tharp Jennifer , Finniss Mathew , Patel Paras
Published: November 2023

Background

In January 2020, Ballad Health instituted the American College of Gastroenterology recommended algorithm for CDI diagnosis consisting of a reflex toxin confirmation post positive C. difficile PCR result. The study was designed to assess how the addition of the toxin confirmation impacted management of CDI in the inpatient setting.

Methods

IT-CDI was a retrospective, multicenter, observational quasi-experimental study of 200 patients. Patients included in the study were > 17 years old with a positive C. difficile PCR and evaluated in two cohorts, pre-toxin confirmation versus post-toxin confirmation testing. The primary outcome was to determine if adding C. difficile toxin confirmation testing reduced antibiotic prescribing for the treatment of CDI. Secondary outcomes included duration of CDI treatment, impact of infectious diseases consultation, length of stay, accrued costs for C. difficile testing and treatment, and new incidence of vancomycin-resistant Enterococcus infection.

Results

A significant reduction in initiation of treatment was found between cohort 1 (98%) versus cohort 2 (77%) although 54% of toxin-negative patients in cohort 2 still received CDI-targeted therapy. There were also significant reductions in duration of treatment from cohort 1 vs cohort 2 (median 13 vs 12; p=0.002) and hospital length of stay between toxin-positive patients versus toxin-negative patients in cohort 2 (median 13 vs 12; p=0.0027). Infectious disease consultation was not associated with a reduction in treatment and overall incidence of vancomycin-resistant Enterococcus infection was rare. Additionally, results demonstrated that toxin confirmation testing did not significantly reduce the total cost associated with testing and treatment which included the price of each lab test completed and the sum of inpatient CDI-targeted antimicrobial therapy per patient from cohort 1 vs cohort 2 (median $56 vs $57; p=0.3356).

Conclusion

The addition of C. difficile toxin confirmation testing to hospital protocol reduced antibiotic prescribing for the treatment of CDI by 21%. However, over half of toxin-negative patients still received CDI antibiotic treatment. Toxin confirmation did not reduce length of stay nor total costs associated with testing and treatment.

Disclosures

David B. Cluck, PharmD, BCPS, BCIDP, AAHIVP, Astellas: Advisor/Consultant
2464. Implementation of a Candida auris admission surveillance protocol at the NIH Clinical Center
Authors: Forrester LaToya A , Odom Robin T , Michelin Angela V , Scaletta Joseph , Henderson David K , Palmore Tara
Published: November 2023

Background

Candida auris (C. auris) is a highly transmissible and usually multi-drug resistant yeast that causes serious invasive infections, with a high mortality rate, colonizes patients, and persists in the environment, resulting in outbreaks in healthcare settings. In 04/2019, The NIH Clinical Center (CC) identified a sensitive C. auris isolate from a blood culture. In 08/2019, the CC’s first case of resistant C. auris was identified from a patient recently hospitalized abroad. By the end of 2019, a total of 17 cases of C auris were identified in the state in which our institution resides (Maryland), as well as cases in institutions in the District of Columbia and Virginia (DMV). This led the CC to implement a C. auris admission surveillance program.

Methods

From 11/2019 to 03/2023, nares, axilla, throat, and groin swabs (n=1408) were collected on admission from patients hospitalized: 1) abroad, 2) in long-term care facilities (LTAC), or 3) in the DMV within the last 6 months. 467 unique patients were tested, 315 by culture utilizing Sabouraud dulcitol broth containing 10% NaCl, Gentamicin, and Chloramphenicol, incubated at 40 degrees and Candida chrome incubated at 30 degrees. 152 patients were tested by PCR, utilizing E-swabs to collect axilla/ groin specimens and aluminum shafted culturette swabs for the nares. PCR testing was conducted at a reference lab from 10/2021 to 07/2022, while routine culturing was unavailable at our facility.

Results

Of 1408 cultures and PCRs collected on admission, no additional patients were identified with C. auris.

Conclusion

C. auris surveillance is a vital strategy to identify colonized or infected patients. Despite the CC serving a large international patient population and patients hospitalized in facilities from states with a high prevalence of C. auris, our surveillance program has not identified additional positives. With cases steadily increasing across the United States (2022 – 2,377 clinical cases and 5,754 screening cases from 29 states) and because of the vulnerability of our patient population, we will continue screening.

Disclosures

Tara Palmore, MD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Rigel: Grant/Research Support
136. Impact of a Tele-Stewardship and Tele-Infection Prevention Program on Hospital-Onset Clostridioides Difficile Rates in a Community Three-Hospital Health System
Authors: Davis Matthew R , Trzebucki Alex , McCreary Erin K , Gupta Nupur , Suzanne Templer
Published: November 2023

Background

Clostridioides difficile infection (CDI) is a common hospital-acquired infection (HAI) that can be difficult to diagnose accurately given the numerous test modalities with differing performance characteristics. Inaccurate diagnosis of CDI can negatively affect patient care decisions as well as reimbursement rates. Community and rural hospitals (CARH) may lack specialized personnel or knowledge to implement diagnostic best practices, but telehealth solutions like tele-infection prevention (TIP) and tele-antimicrobial stewardship (TASP) can provide specialist support for CARHs to optimize diagnostic pathways, improve accuracy, and reduce unnecessary treatment.

Methods

In June 2021 under the guidance of TIP and TASP recommendations, C. difficile testing was transitioned from a 1-step nucleic acid amplification test (NAAT)-only algorithm to a 2-step algorithm that included NAAT and toxin enzyme immunoassay (EIA) testing. A 6-month pre- and post-implementation assessment was conducted to assess the impacts of this change in hospital-onset CDI (HO-CDI) case rate. Additionally, total C. difficile (community- and hospital-onset CDI) rates per 1000 patient days (PD) and consumption of CDI therapeutics were assessed. For statistical analysis, Wilcoxon ranked-sum test to assess changes in CDI rates. Estimated annualized cost-savings for therapeutics were calculated based on institutional purchasing costs.

Results

Following implementation, a 35.9% reduction in HO-CDI was observed (pre 0.96 cases/1000PD vs. 0.61 cases/1000PD; p = 0.054). A 10.2% reduction was observed in total CDI (pre 3.66 cases/1000PD vs. 3.28 cases/1000PD; p = 0.37). Additionally, a 30.6% reduction was observed in consumption of CDI therapeutics (20.1 doses/1000PD vs. 14.0 doses/1000PD) resulting in an annualized cost-savings of approximately $9200.

Conclusion

Our TIP and TASP advised a community three-hospital health system on optimal diagnostics resulting in a change in their algorithm. Following this, considerable reductions were observed in HO-CDI, total CDI, consumption of CDI therapeutics, and the associated costs of care.

Disclosures

Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria
2481. Interactive Dashboards for Improved Tracking and Communication of CLABSI Prevention Efforts
Authors: Rodriguez-Nava Guillermo , Shepard John , McIntyre Karen , Tompkins Lucy S , Salinas Jorge
Published: November 2023

Background

Central line-associated bloodstream infections (CLABSI) are associated with increased morbidity, mortality, and healthcare costs. Many CLABSIs can be prevented using evidence-based care. To make this information more accessible and actionable, we developed interactive dashboards that translate data on CLABSI-related metrics and prevention efforts into visual formats that can be easily understood by healthcare professionals.

Methods

A multidisciplinary work group of data analysts, infectious diseases physicians, and infection preventionists determined the content and layout of the dashboards. A query was written to extract necessary data elements from the Electronic Medical Record and NHSN. Data was then exported and used to build the dashboards using Tableau® software. The dashboard can be filtered at the facility level or at the unit level.

Results

We present the dashboard of one general ward (Figure 1), one intensive care unit (ICU) (Figure 2), and one cardiovascular ICU (CVICU) (Figure 3). The central line standard utilization ratio (SUR) was higher for the CVICU ( >1.5), followed by the ICU (≈1), and the general ward (< 1). Blood culture intensity (number of blood cultures collected/patient-days) was less for the general ward (< 5%), variable for the ICU (8-14%), and persistently higher for the CVICU (11%). Compliance with daily chlorhexidine bathing was higher for both the CVICU (80%) and the ICU (75%) compared to the general ward (40-60%). The CLABSI rate per 1,000 central line-days has been downtrending for the CVICU and uptrending for the ICU. Besides lower compliance with daily chlorhexidine bathing, the examined ICU has also recently shown a higher proportion of long-term devices (40%), calculated as proportion of central lines ≥ 7 days/all central lines, compared to the CVICU (25%).

Conclusion

Dashboards should contain meaningful outcomes and standardized process metrics that are mapped to strategic goals and be timely to support prompt identification of deviations. Our CLABSI dashboards are effective tools for communicating and tracking performance data. Filtering at the unit level allows us to identify unique unit characteristics, or “fingerprints,” and recognize specific areas for improvement. This enables us to develop targeted interventions for each unit.

Disclosures

All Authors: No reported disclosures
2484. Clinical and genomic comparison of nosocomial-onset and community-onset listeriosis: a nationwide retrospective study in Japan, 2011-2021
Authors: Shinohara Koh , Tsuda Yusuke , Arasawa Soichi , Tsuchido Yasuhiro , Yukawa Satomi , Noguchi Taro , Yamamoto Masaki , Matsumara Yasufumi , Nagao Miki
Published: November 2023

Background

Sporadic, non-clustered, nosocomial-onset (NO) listeriosis has emerged in immunocompromised hosts. However, most previous reports were single-centered and nationwide study is lacked. The genomic investigation of Listeria monocytogenes isolates from NO and community-onset (CO) cases is also scarce.

Methods

We conducted a nationwide retrospective study of consecutive listeriosis cases from 2011 to 2021, in which 24 hospitals participated. Clinical characteristics and outcomes were reviewed. The preserved L. monocytogenes isolates were investigated using whole genome sequencing. NO was defined as onset of listeriosis symptoms after third day of admission for medical conditions other than listeriosis. Fisher’s exact test and Mann-Whitney U test were used to compare categorical and continuous variables, respectively.

Results

A total of 195 cases were included. All 11 perinatal cases were NO. Among 184 non-perinatal cases, 31 cases (17%) were NO cases. Clinical characteristics of the NO and CO cases were summarized in Table. In NO cases, median age was 73 years and male patients accounted for 55%, which were similar to those in CO cases. Median days of admission to onset was 10 (range, 3-127). NO cases significantly associated with immunosuppressive medical conditions, especially patients with solid organ tumor and recipients of cytotoxic chemotherapy. NO cases were less likely to involve central nervous system (CNS). In-hospital mortality was similar among both groups. A total of 95 isolates (NO cases: 19 isolates, CO cases: 76 isolates) were included in genomic analysis. A pair of isolates were suspected as clustered cases. 14 clonal complexes (CC) were identified in NO isolates and 23 CCs were in CO isolates (Figure). CC1, the most prevalent hypervirulent clone, was less likely to be found in NO cases; 1 isolate (5%) in NO cases and 20 isolates (26%) in CO cases.

Conclusion

In a retrospective nationwide surveillance in Japan, 17% of listeriosis was NO and mostly affected patients with immunosuppressive medical conditions. Genomic analysis revealed that NO isolates were less likely to be CC1 and have wider genomic diversity than that in CO isolates.

Disclosures

Yasufumi Matsumara, MD, PhD, Beckman Coulter: Grant/Research Support|Presicion System Science: Grant/Research Support|Toyobo: Grant/Research Support
138. Impact of Emergency Department Rapid Viral Respiratory Multiplex PCR Testing on Antimicrobial Prescribing
Authors: Falk Cassandra , Dumkow Lisa E , Geyer Abigail , Egwuatu Nnaemeka , Langholz Jennifer , Schmidt Kyle , Jameson Andrew
Published: November 2023

Background

Rapid multiplex polymerase chain reaction (mPCR) point-of-care tests detect a variety of viral respiratory pathogens. The impact of mPCR results on antibiotic prescribing in the ED or downstream is not well understood. The purpose of this study was to assess the impact of positive viral mPCR results on antibiotic prescribing for patients presenting with respiratory symptomsin the ED.

Methods

This retrospective cohort study included adult patients presenting to the ED with respiratory symptoms and a positive rapid upper RTI mPCR for a non-SARs-CoV-2 viral pathogen between 11/1/2021 and 10/31/2022. The primary objective was to describe the proportion of patients with appropriate antibiotic management within 24 hours of positive mPCR result. Appropriate management was defined as patients without risk factors for bacterial co-infection who did not receive or continue antibiotic therapy. Those with co-infection risk factors prescribed antibiotic therapy were also considered appropriate. This was determined through independent pharmacist and ID physician review. Secondary objectives compared patient outcomes of those appropriately vs inappropriately managed and admitted vs discharged home from ED. Risk factors for inappropriate antibiotic decisions were also evaluated using logistic regression.

Results

250 patients were included, 206 (82.4%) with appropriate management and 44 (17.6%) with inappropriate management. 164 (65.5%) patients were not prescribed empiric or definitive antibiotics. 39 (15.6%) patients empirically received antibiotics prior to mPCR; 9 (23%) were discontinued following positive viral result. Patients discharged home from the ED were more likely to have appropriate antibiotic management than those admitted (87.5% vs 77.7%, p=0.042). Patients with inappropriate antibiotic management were more likely to be readmitted to the hospital within 30 days (14% vs 3.5%, p=0.005). Purulent sputum (OR 3.61 [95% CI 1.64-8]) and unilobar infiltrate (OR 3.03 [1.22-7.58]) were independent risk factors for inappropriate antibiotic management.

Conclusion

Rapid viral RTI mPCR testing in the ED resulted in a high level of appropriate antibiotic management, with most patients not being prescribed antibiotics.

Disclosures

All Authors: No reported disclosures
2506. Impact of an Innovative Community Based Contracted Pharmacy on HCV Elimination in New Jersey
Authors: Rosmarin-DeStefano Corey L , Slim Jihad , Tempalski Barbara , Leyden Kevin , Levaggi Emily , Duprey Sheena , Torres Juan , Chavez Evelyn
Published: November 2023

Background

North Jersey Community Research Initiative (NJCRI) in Newark, New Jersey has piloted the addition of an innovative community based contracted pharmacy to their mobile hepatitis C clinic to provide seamless care and coordination to the patient.

Methods

A retrospective observational review of patients treated for hepatitis C between October 1st 2020 and Sept 31st 2022 at North Jersey Community Research Initiative (NJCRI), dividing patients in group 1: patients required by their insurance to fill up prescriptions through Managed Medicaid’s Preferred Specialty Pharmacies (PSP), which are corporate mail-order pharmacies and group 2: those who could fill their prescriptions with a local contracted community based pharmacy. We had two primary endpoints comparing those 2 groups: 1- Difference in wait time from the provider’s visit to starting therapy; 2- Difference in percentage of those completing therapy.

Results

NJCRI prescribed hepatitis C treatment to 614 patients during the study period, group 1 had 138 patients (22.4%) and group 2 had 476 patients (78%). The average time to start of therapy was 36 days for group 1 compared to 15 days for group 2. Group 1 on average have a longer wait time to start treatment therapy. Group 2 were more likely to complete therapy utilizing local pharmacies contracted by NJCRI. Patients who started and completion treatment was 81% in-group 1 and 92% for group 2 (p=0.0003). Percentage LTFU after starting therapy was 19% for group 1 and 8% for group 2.

Conclusion

Our study shows that community based pharmacy settings positively affect patient care and adherence because of the convenience and support to the patients as well as the providers. Restrictions of filling medications through corporate mail-order pharmacies.

Disclosures

Jihad Slim, MD, FACP, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support
2525. Identification of lead compounds, belonging to 26-membered thiopeptide antibiotics for new anti-tuberculosis therapeutic agents
Authors: Son Young-Jin , Hwang Hee-Jong , Shyaka Clovis , Kim Dahyun , Lee Jusuk , Eum Seokyong , Lee Sun-Kyung
Published: November 2023

Background

Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). The incidence of TB patients is increasing globally and the wide spread of multi- and extensively drug-resistant TB poses a significant burden to patients. This situation calls for an urgent medical need to develop new anti-TB drugs. Through our proprietary medicinal chemistry platform on D-series 26-membered thiopeptide, we have identified a few lead compounds, such as AJ-099 and AJ-206 that exert potent activity against multi-drug resistant TB strains.

Methods

In vitro minimal inhibitory concentration (MIC) was measured and a Mtb-infected human macrophage model was used to evaluate anti-mycobacterial activity of our compounds in drug-sensitive or multidrug-resistant TB isolates. Cellular toxicity and some in vitro ADME tests were also performed and examined.

Results

We found that our lead compounds exert potent anti-TB activity on H37Rv(MIC: 0.125-0.5 μg/mL) and showed similar MIC levels in multidrug-resistant clinical isolates. In the macrophage infection model, AJ-099 and AJ-206 showed comparable antimycobacterial effects to isoniazid. These compounds showed no cytotoxicity, relatively safe ADME properties, and no hERG inhibition.

In vitro antibacterial activity in multi-drug resistant M. tuberculosis strains

Antibacterial activity in macrophage infection model

In vitro ADMET properties of lead compounds

Conclusion

AJ-099 and AJ-206 may be potential anti-TB therapeutic agents that possess novel modes of action, low cardiac and cellular toxicities.

Disclosures

Young-Jin Son, A&J Science: Employee of A&J Science|A&J Science: Ownership Interest|KHIDI: Grant/Research Support Hee-Jong Hwang, PhD, A&J Science: Stocks/Bonds|KHIDI: Grant/Research Support Clovis Shyaka, n/a, A&J Science: Employee of A&J Science Dahyun Kim, n/a, A&J Science: Employee of A&J Science Jusuk Lee, Ph.D., A&J Science: Employee of A&J Science
2527. Impact of Hypoalbuminemia on Clinical Outcomes Among Patients with Obesity Treated with Ceftriaxone
Authors: Rivera (O'Connor) Christina G , Abu Saleh Omar M , McHugh Jack W , Draper Evan , Mara Kristin , Hannan Kellie Arensman
Published: November 2023

Background

Due to extensive protein binding, use of ceftriaxone in the setting of hypoalbuminemia may result in suboptimal drug exposure via higher concentrations of unbound drug resulting in increased volume of distribution and increased drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone for a bacterial infection.

Methods

This retrospective review included adult inpatients with weight > 100 kg or body mass index (BMI) > 40 who received ceftriaxone 2 grams intravenously every 12 hours for at least 72 hours for one of the following indications: bloodstream infection, pneumonia, urinary tract infection, non-enterococcal endocarditis, skin and soft tissue infection, or bone and joint infection. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Clinical cure was defined as resolution of signs and symptoms compatible with active infection without need to change or extend antibiotic therapy due to inadequate effect of ceftriaxone. Microbiologic cure was defined as negative repeat sterile site cultures, if applicable. Secondary outcomes included length of stay, mortality, and 30-day readmission. Outcomes were analyzed with Mann-Whitney U tests, Pearson’s chi-squared tests, and Fisher’s exact tests (α level = 0.05).

Results

137 patients were included, 34 of whom had a serum albumin ≤ 2.5 g/dL. Patients were predominantly white (94.2%) and male (69.3%) with a median BMI of 48.6 (Table 1). Clinical success, a composite of clinical and microbiologic cure, was achieved in 76.5% and 92.2% (p = 0.013) of those with and without hypoalbuminemia, respectively. Clinical cure was significantly more common among those without hypoalbuminemia (93.2%) as compared to those with hypoalbuminemia (76.5%) (p = 0.007). Death during hospitalization was more common (14.7% vs. 0%, p < 0.001) and median length of stay was longer (14 vs. 9 days, p = 0.009) in the hypoalbuminemia group. No difference was seen in 30-day readmission (23.5% vs. 11.7%, p = 0.089).

Conclusion

Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 grams every 12 hours.

Disclosures

Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria
2535. Physiological-based pharmacokinetic analysis of drug–drug interactions between isavuconazole and vincristine in pediatric subjects
Authors: Choules Mary P , Otsuka Yukio , Kovanda Laura , Bonate Peter , Sinnar Shamim , Desai Amit
Published: November 2023

Background

Invasive fungal diseases (IFD), including invasive aspergillosis (IA) and invasive mucormycosis (IM), occur primarily in immunocompromised and/or hospitalized pediatric patients and are associated with morbidity and mortality. Pediatric patients being treated for leukemia with vincristine frequently experience secondary fungal infections, requiring treatment. Isavuconazole (ISAV) is approved for the treatment of IA/IM in adults; but there is limited data for its use in pediatric patients. Isavuconazonium sulfate is the prodrug of the active triazole ISAV, an antifungal agent that inhibits sterol 14α-demethylase. Isavuconazonium is rapidly converted by plasma esterases to ISAV, which is subsequently metabolized by the liver through CYP3A. ISAV was found in clinical drug–drug interaction (DDI) studies to be a moderate inhibitor of CYP3A, an inducer of CYP2B6, and to have inhibitory potential for P-gp and OCT-2 transporters. Because vincristine is eliminated hepatically via CYP3A and biliary excretion through P-gp, there is a potential for interaction with triazoles. Therefore, a physiological-based pharmacokinetic (PBPK) analysis was conducted to assess the potential for interaction between ISAV and vincristine.

Methods

PBPK models were built for ISAV and vincristine in a pediatric cancer population using Simcyp® simulator software with in vitro and in vivo data. The final verified models were used to predict change in vincristine exposure following coadministration with ISAV.

Results

The predicted geometric mean (GM) area under the curve (AUC) ratio of vincristine co-administered with ISAV ranged from 1.54-fold to 1.69-fold depending on the dosing scheme used for the prediction as detailed in Table 1. Coadministration of vincristine when ISAV was at steady state (14 days) did not result in a significant difference in the magnitude of DDI from other dosing schemes. No effect was predicted on the GM Cmax ratio of vincristine regardless of the ISAV dosing scheme.

Conclusion

ISAV is predicted to be a weak inhibitor of vincristine elimination in pediatric cancer participants, and DDI modelling predicts a slight increase in vincristine exposure when vincristine is co-administered with ISAV.

Disclosures

Mary P. Choules, PharmD, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee Yukio Otsuka, MSc, Astellas Pharma Global Development Inc.: Astellas Employee|Astellas Pharma Global Development Inc.: Stocks/Bonds Laura Kovanda, PhD, Astellas Pharma Global Development Inc.: Astellas Employee Peter Bonate, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee Shamim Sinnar, MD, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee Amit Desai, PhD, Astellas Pharma Global Development, Inc.: Astellas Employee
143. Correlation Between Identification of Gram-positive Resistance Genes and Antimicrobial Susceptibility Profiles in Gram Positive Bacteria
Authors: Ilyas Sahrish , Chasan Rachel , Nowak Michael D , Patel Gopi , Sordillo Emilia Mia , Rana Meenakshi M , Gitman Melissa R
Published: November 2023

Background

GenMark ePlex BCID panels detect common gram-positive resistance genes, allowing for earlier optimization of empiric therapy. Data regarding genotypic and phenotypic concordance of isolates remains limited. Our primary objective was to study the prevalence of mecA and mecC among Staphylococcus aureus isolates and of vanA and vanB among Enterococcus spp. and determine the concordance with phenotypic susceptibility profiles.

Methods

The study was conducted at the clinical microbiology laboratory of Mount Sinai Health System (NY, NY). Samples were collected between March 2019 and April 2021. Presumptive identification and molecular data were obtained from ePlex BCID Panels and compared to phenotypic susceptibility testing performed on Vitek or Microscan systems.

Results

Data were obtained from 1493 isolates tested on the GenMark ePlex BCID gram positive panels. The total prevalence of mecA in Staphylococcus aureus isolates was 460/989 = 46.5%. There was no mecC detected. Of the 460 mecA positive S. aureus isolates, 99% were oxacillin resistant and 1.0% were oxacillin susceptible. Of the 529 mecA negative S. aureus isolates, 98.5% were oxacillin susceptible and 1.5% were oxacillin resistant.

The total prevalence of vanA in enterococcus isolates was 38% (193/504), 81% were detected in E. fecium sp, 17% in E. fecalis sp, 0.5% in E. gallinarium sp and 1.5% in E. raffinosus sp. The total prevalence of vanB was 1.1% (6/504). E. faecium accounted for 83% and E. faecalis for 16% of the isolates. Of the vanA positive isolates, 7/193 (3.6%) were vancomycin susceptible, 2 were e. fecalis and 5 were e. fecium species. None of the isolates in which vanB detected were vancomycin susceptible.

No van gene was detected in 305 of enterococcus isolates. Of these, 250/305 (81%) were E. faecalis sp and 36/305 (11%) were E. faecium sp. 290/305 total isolates were vancomycin susceptible and 15 were vancomycin resistant, of which 12/15 were E. gallinarum and E. avium (which are intrinsically resistant), 1 was E. faecium and 2 were E. faecalis.

Conclusion

Our data shows overall that the susceptibility profile and resistance gene detection by ePlex correlated well with overall minimal discordance. Further studies are needed to determine the optimal management when phenotypic genotypic discordance occurs.

Disclosures

Meenakshi M. Rana, MD, Eli Lilly: advisory board
2546. Administration of Crushed Posaconazole Delayed Release Tablets Failed to Achieve Therapeutic Levels
Authors: Kane Nicholas , Rikard Rachel , McCrory Katie , Marx Ashley H
Published: November 2023

Background

Posaconazole (POS) delayed release tablets (DRTs) are utilized for prophylaxis or treatment of invasive fungal infections. Other POS formulations are limited by impaired absorption, lack of indication for adult patients, and need for intravenous (IV) access. Small retrospective case series have demonstrated success with administration of crushed POS DRTs via enteral feeding tubes (EFTs). In October 2022, UNC Health permitted administration of POS DRTs via EFTs. This study aims to evaluate POS levels in patients that received crushed POS DRTs via EFTs.

Methods

This single-center, retrospective cohort study included patients that received crushed POS DRTs via EFTs with concurrent POS therapeutic drug monitoring (TDM). The primary outcome was achievement of serum POS level per indication of prophylaxis ( > 700 ng/mL) or treatment ( > 1000 ng/mL). The secondary outcome was the proportion of patients whose therapy was altered in response to POS level.

Results

A total of 10 patients were included (Table 1), with both prophylaxis (40%) and treatment (60%) indications. Most were initiated on oral or IV POS (80%). Crushed POS DRTs were administered via nasogastric (70%), post-pyloric (20%), and nasoduodenal (10%) routes. Therapeutic levels with crushed POS DRTs occurred in three patients (30%) and only two patients (20%) maintained therapeutic levels (Figure 1). Of the patients that transitioned from IV or oral POS to crushed POS DRT that maintained the same POS dose, 75% experienced a decrease in their serum POS level. Based on the initial crushed POS DRT level, three patients transitioned to IV or oral POS and 3 had their crushed POS DRT dose modified.

Conclusion

Crushed POS DRTs administered via EFTs failed to achieve therapeutic POS levels in 70% of patients. Caution should be used when implementing crushed POS DRTs and internal data should be reviewed if already implemented. Study limitations include small sample size, single-center design, and limited attempts to titrate crushed POS DRT regimens. Future studies should assess the clinical utility of crushed POS DRTs and explore the impact of standardized nursing administration, drug-drug interactions, and enteral feeding interactions/routes on crushed POS DRT pharmacokinetics.

Disclosures

All Authors: No reported disclosures
2557. Development of Rabbit Models of Ventilator-Associated Carbapenem-Resistant Acinetobacter baumannii Pneumonia
Authors: Petraitis Vidmantas , Petraitiene Ruta , Naing Ethan
Published: November 2023

Background

Carbapenem-resistant (CR) Gram-negative bacteria are emerging worldwide as global public health threats. Mortality rates from these pathogens are especially high in immunocompromised patients. Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of CR Gram-negative bacterial infections. We therefore aimed to develop rabbit animal models of VABP caused by CR strains of Acinetobacter baumannii.

Methods

Persistently neutropenic NZW rabbits were used throughout the study. A novel endotracheal tracheostomy system was developed for intubation. The early-phase intubated model (0-24h) received mechanical ventilation, while the late-phase intubated model (72-96h) was ambulatory. Ventilators were set to FiO2=40% and PEEP=8mmHg. The following outcome variables were assessed: survival, residual tissue bacterial burden (log CFU/g), residual BAL bacterial burden (log CFU/mL), lung weights, pulmonary lesion score, histology, pulse O2 saturation, radiographic imaging, pro-inflammatory cytokines, quantitative tissue and BAL PCR, and histology.

Results

Within the first 12h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, which were established at approximately 106 CFU/g and 105 CFU/mL, persisted through 24h in the early-phase model and were increased in the late-phase model (72-96h) to approximately 107 CFU/g, and 106 CFU/mL. Mean Max SpO2 was ≥99 mmHg and mean nadir SpO2 was ≥74 mmHg. Serial thoracic radiographs over the course of 12-96h demonstrated progressive multilobar pneumonic infiltrates, while lung histology revealed progressive development of focal bronchopneumonia, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, macrophage activation, monocytic infiltration, alveolar septal disruption, and microcolonies of bacteria.

Conclusion

The new rabbit model of VABP produced by CR A. baumannii recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection.

Disclosures

All Authors: No reported disclosures
2567. Clinical Outcomes of Vancomycin Area-Under-the-Curve Monitoring: A Quasi-Experimental Study
Authors: Viteri Alina , Tucker Natalie , Flynn Ryan , Foreman Jena K
Published: November 2023

Background

Previous studies that demonstrated decreased nephrotoxicity with area-under-the-curve (AUC) vancomycin dosing compared to trough monitoring used two levels and a spreadsheet model for calculating AUC. The purpose of this study was to evaluate if the same reduction in acute kidney injury (AKI) was achieved while using a single level Bayesian monitoring program.

Methods

This retrospective quasi-experiment was performed at two sites within the same health system. The primary objective was to assess the rate of AKI between vancomycin dosed by trough monitoring as compared to AUC monitoring using a Bayesian software program. Secondary objectives included mean daily dose of vancomycin, number of vancomycin levels, and severity of AKI. Patients were included in the study if they were 18 years or older with at least one vancomycin concentration drawn. Patients were excluded if they had a baseline serum creatine greater than 2 mg/dL, received renal replacement therapy of any type, or received > 1 dose of vancomycin prior to admission.

Patients were matched 1:1 based on acute physiology and chronic health evaluation II score, body mass index, and vancomycin indication. Multivariable logistic and Cox proportional hazards regression were used to examine the independent association between the monitoring strategy (trough vs AUC) and nephrotoxicity.

Results

Few differences in baseline characteristics were identified between groups. More patients were treated for pneumonia, bacteremia, or urinary tract infection in the trough group, whereas more were treated for skin and soft tissue infection in the AUC group. The AUC group (255 patients) had a 16% incidence of AKI in comparison to the trough group (265 patients) with a 19% incidence of AKI (p = 0.517). Of the secondary outcomes, those in the AUC group received lower daily doses than patients in the trough group (p = 0.015). Multivariable regression analysis identified similar results for each of the study outcomes including the primary outcome (OR 1; 95% CI 0.62 – 1.63).

Conclusion

The use of a single level Bayesian monitoring for vancomycin dosing did not result in a decreased incidence of acute kidney injury when compared to trough monitoring.

Disclosures

All Authors: No reported disclosures
2589. Legionella pneumonia in cancer patients: 12-year experience at MD Anderson Cancer Center 2009-2021
Authors: Matsuo Takahiro , Wurster Sebastian , Jiang Ying , Tarrand Jeffrey , Kontoyiannis Dimitrios P
Published: November 2023

Background

Legionella pneumonia (LP) is an uncommon, yet severe pneumonia in cancer patients, but its clinical features are scarcely studied in contemporary cohorts. Therefore, this study aimed to characterize the clinical manifestations, therapy, and outcomes of LP in contemporary cancer patients.

Methods

We identified cancer patients with LP at MD Anderson Cancer Center in 2009-2021. LP was diagnosed using Legionella urine antigen and/or culture from sputum, tracheal aspirate, or bronchoalveolar lavage. Species identification was achieved by Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry or 16S rRNA. Independent predictors of 30-day mortality after LP diagnosis were determined using multivariable logistic regression analysis.

Results

Table 1.

Conclusion

We identified 64 LP patients; of which 47 (73%) were caused by Legionella pneumophila and 17 (27%) by Legionella non-pneumophila (Figure 1). Most patients (66%) had hematological malignancy, and 31% had a history of hematopoietic stem cell transplantation (HSCT). Lymphopenia (< 1000 cells/µl) was common (75%). Twenty patients (31%) had lung coinfections, especially those with a history of HSCT (9/20, 45%). A total of 30 co-pathogens were isolated, with Gram-negative bacteria, cytomegalovirus, and respiratory viruses (7/30, 23% each) being the most common co-pathogens (Figure 2). Twenty-five patients (39%) had hyponatremia and 17 (27%) had acute kidney injury. Most patients (64%) had bilateral lung involvement. All but one patient received appropriate antibiotics at the onset of LP. Thirty-day mortality of LP was 23% (Table 1). Independent predictors of 30-day mortality were hyponatremia (adjusted odds ratio [aOR], 3.03 [95% CI, 1.21-10.43], P = 0.013), bilateral lung involvement (aOR, 3.78 [95% CI, 1.16-28.98], P = 0.019), and Sequential Organ Failure Assessment (SOFA) score ≥5 (aOR, 2.76 [95% CI, 1.08-9.44], P = 0.029).

Disclosures

Dimitrios P. Kontoyiannis, MD, MS, ScD, PhD, AbbVie: Board Member|Astellas: Grant/Research Support|Cidara: Board Member|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Scynexis/MSGERC: Board Member