bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1234. Evaluation of Empirically Dosed Parenteral Vancomycin Using Weight-Based Versus Bayesian-Based Modeling
Authors: Mei Julie , Deyab Sheren , Pereira Luis , Faour Rita , Budovich Aliaksandr 
Published: January 2025

Abstract

Background
Vancomycin is an efficacious antibiotic in treating infections caused by Staphylococcus Aureus (including MRSA), streptococci, and enterococci. Intravenous administration of vancomycin requires close monitoring to optimize safety and efficacy. As per ASHP/IDSA/SIDP guidelines, an empiric maintenance dose of 15-20 mg/kg (based on actual body weight) administered every 8-12 hours (based on normal renal function) with a target AUC of 400-600 is recommended for most adults. Given the lack of data comparing empiric Bayesian modeling to weight-based dosing of vancomycin, our study aims to evaluate the relationship between these two regimens.

Methods
This is an IRB approved retrospective cohort study conducted at One Brooklyn Health Brookdale. A random sample of non-critically ill hospitalized patients aged 18 or older who have been treated with empirically dosed vancomycin (15-20 mg/kg) administered at the recommended frequency for suspected or documented infections between January 1, 2023 and December 31, 2023 will be included. Patients will be excluded if they have acute kidney injury (AKI), are on hemodialysis, or have a BMI &gt;30 kg/m2. Pertinent patient data will be collected such as patient demographics, laboratory values and etc. Statistical analysis will be conducted using SAS statistical software.

Results
A total of 97 patients met inclusion criteria. Primary outcome was defined as the difference in numbers of patients achieving AUC 400-600 using empiric weight-based versus Bayesian modeling dosing. Patients were about 26% more likely to have a therapeutic AUC when being dosed on a weight-based regimen. Secondary outcomes looked at the correlation between weight and weight-based dosing and Bayesian modeling dosing in terms of subtherapeutic or supratherapeutic AUC and found that there was no association. Safety outcome was defined as the difference in number of patients at an increased risk of AKI (AUC &gt; 650) using empiric weight-based versus Bayesian modeling dosing. Patients were 50% less likely to be at an increased risk of AKI when being dosed on the weight-based regimen.

Conclusion
Bayesian-based modeling for empiric dosing was associated with higher rates of supra-therapeutic AUC and individuals were at a higher risk of getting AKI.

Disclosures
All Authors: No reported disclosures
P-1237. Comparison of Non-trapezoidal and Trapezoidal Pharmacokinetic Equations to Calculate Vancomycin Area Under the Curve within 24 Hours of Therapy in Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Msdi Abdulwhab Shremo , Tan Karen K , Abdul-Mutakabbir Jacinda C 
Published: January 2025

Abstract

Background
Achieving target vancomycin (VAN) area under the curve within 24 hours of therapy (AUC0-24) is associated with better clinical outcomes for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Two first-order pharmacokinetic (PK) equations, e.g. the trapezoidal and non-trapezoidal methods, can be used to estimate AUC. The 2020 vancomycin monitoring guidelines do not address which PK equation to estimate AUC0-24. Furthermore, there is limited data directly comparing these methods on day 1 of therapy, especially in patients with confirmed MRSA infection. This study aims to compare the calculated VAN AUC0-24 using the two PK equations in patients with persistent MRSA bacteremia. Then, compare the first-order PK computed values to a Bayesian-calculated AUC0-24.

Methods
This was a retrospective cohort study of adult patients with persistent MRSA bacteremia (MRSAB) for ≥ 3 days between December 1st 2020, to December 31st 2023. Patients treated with intravenous vancomycin for ≥ 48 hours and had two consecutive serum VAN concentrations collected within 48 hours of therapy were screened for study inclusion. AUC0-24 was calculated using first-order PK equations (e.g. non-trapezoidal, trapezoidal), and Bayesian software (DoseMeRx). Spearman correlation coefficient (rs) was used to assess correlations between linear PK equations and Bayesian software.

Results
A total of 79 patients with MRSAB were screened, 12 of whom had a persistent MRSAB. The median duration of bacteremia was 7 days (4, 11). The median AUC0-24 estimated by non-trapezoidal and trapezoidal methods were 605 mg*h/l (IQR 403, 484) and 453 mg*h/L (IQR 356, 707), respectively. A stronger correlation was observed between AUC0-24 estimated by the non-trapezoidal method and Bayesian (rs = 0.82; P 0.001), compared to the trapezoidal method and Bayesian (rs = 0.61; P 0.035).

Conclusion
Both first-order PK equations correlated with Bayesian-estimated AUC0-24, with a stronger trend towards non-trapezoidal method. Further research is needed to corroborate this finding.

Disclosures
Jacinda C. Abdul-Mutakabbir, PharmD, MPH, CSL Sequiris: Advisor/Consultant|CSL Sequiris: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria
P-1248. The Effect of Pantoprazole on Doravirine/Islatravir Pharmacokinetics
Authors: Matthews Randolph P , Kim Nancy , Liu Yang , Rudd Deanne Jackson , Garrett Graig , Gilmartin Jocelyn , Kraft Walter , Vargo Ryan , Aubrey Stoch S , Iwamoto Marian 
Published: January 2025

Abstract

Background
Doravirine/islatravir (DOR/ISL 100/0.25 mg) is a daily, oral, fixed-dose combination being developed for the treatment of HIV infection. As people living with HIV are commonly prescribed antacids or acid-reducing agents, we investigated the effects of pantoprazole, a proton pump inhibitor (PPI), on DOR/ISL pharmacokinetics (PK).

Methods
This was a randomized, open-label substudy in participants without HIV. Single-dose DOR/ISL (100/0.75 mg) was administered, followed by a DOR/ISL washout interval of at least 7 days. During the washout period, pantoprazole 40 mg daily was initiated and administered for 5 days, with DOR/ISL coadministered on day 5. Blood was collected to evaluate ISL and DOR PK. Safety and tolerability were assessed throughout the study.

Results
Twenty-one participants were randomized to receive DOR/ISL; 6 participants completed the DOR/ISL + pantoprazole substudy. Pantoprazole had no clinically meaningful effect on DOR PK after coadministration with DOR/ISL. ISL PK were similar after coadministration of pantoprazole compared with PK after administration of DOR/ISL alone. The geometric least-square mean ratio (GMR) (90% CI) (DOR/ISL + pantoprazole over DOR/ISL) for DOR AUC0-24 and Cmax were 0.93 (0.78-1.11) and 0.98 (0.80-1.20), respectively. The GMR (90% CI) for ISL AUC0-24 and Cmax were 1.05 (0.94-1.16) and 0.99 (0.72-1.35), respectively. DOR/ISL administered alone or in combination with pantoprazole was generally well tolerated. Of participants who received DOR/ISL alone or with pantoprazole, 24% (5/21) had ≥ 1 adverse event (AE). No AE was reported more than once. There were no serious AEs, and one participant discontinued due to an AE (abdominal pain thought to be secondary to pantoprazole).

Conclusion
Pantoprazole had no clinically meaningful effect on the PK of DOR, and ISL PK was similar after coadministration with pantoprazole, supporting the use of DOR/ISL with acid-reducing agents. The combination was generally well tolerated.

Disclosures
Randolph P. Matthews, MD, PhD, Merck & Co., Inc.: Employee Nancy Kim, MD, Merck & Co., Inc.: Employee Yang Liu, PhD, Merck & Co., Inc.: Employee Deanne Jackson Rudd, PhD, Merck & Co., Inc.: Employee Graig Garrett, BS, Merck & Co., Inc.: Employee Jocelyn Gilmartin, BS, Merck & Co., Inc.: Employee Ryan Vargo, PhD, Merck & Co., Inc.: Employee S. Aubrey Stoch, MD, Merck & Co., Inc.: Employee Marian Iwamoto, MD, PhD, Merck & Co., Inc.: Former employee
P-1250. Pharmacokinetic Evaluation of Colistin Methanesulfonate in Critically Ill Patients: Implications for Clinical Management
Authors: Jose Riya Mary 
Published: January 2025

Abstract

Background
The study aims to assess the pharmacokinetics of colistin methanesulfonate (CMS) and colistin, and its impact on clinical outcomes, particularly clinical cure (CC), and the development of acute kidney injury (AKI) in critically ill patients with normal baseline renal function.

Methods
This prospective observational study focuses on adult critically ill patients with MDR/XDR infections treated with intravenous CMS. Patients receive a loading dose (LD) of 9 MU followed by a maintenance dose (MD) of 3 MU every 8 hours. Pharmacokinetic (PK) sampling occurs pre- and post-LD, and during MD. Colistin plasma levels are quantified using liquid chromatography–mass spectrometry (LC–MS). Clinical outcomes, including clinical cure, impact on renal failure and mortality, are assessed.

Results
A total of 144 serum samples were analyzed from the 12 patients, with 60% having pneumonia. Predominant pathogens were Klebsiella pneumoniae (7) and Acinetobacter spp. (5). The mean estimated creatinine clearance (CrCl) was 120 ± 22 mL/minute (range: 75.4–215.2). All patients received combination therapy, with 80% receiving meropenem and 40% receiving tigecycline. The clinical cure rate was 50% (6/12), with a mortality rate of 25% (3/12). The mean LD colistin Cmax was 3.1 ± 1.2 mg/L (range: 1.6–5.5) and 2.4 ± 1.3 mg/L (range: 1.4–5.8) among the CC and CF groups, respectively (P = 0.14). MD colistin Css avg was 2.3 ± 1.4 mg/L and 1.8 ± 1.2 mg/L in CC and CF groups, respectively. The mean AUC0–24/MIC ratio of MD colistin was 94.3 ± 68.2 and 78.1 ± 53.6 for CC and CF groups, respectively (P = 0.28). In pneumonia, AUC0–24/MIC for Acinetobacter spp. was higher in the CC (72.1 ± 11.3) than in the CF group (41.5 ± 15.8) (P = 0.06). Renal injury was observed in 40% (5/12) of patients at the end of therapy, with acute kidney injury (AKI) being the most common complication. Additionally, a subset of patients (n = 3) demonstrated evidence of chronic kidney disease (CKD) progression, highlighting the nephrotoxic potential of colistin therapy.

Conclusion
The findings underscore the importance of therapeutic drug monitoring in optimizing colistin therapy and the necessity for vigilant monitoring of renal function to mitigate the risk of AKI and CKD progression.

Disclosures
All Authors: No reported disclosures
P-1257. Cefazolin Dosage Considerations for Methicillin-Susceptible Staphylococcus aureus (MSSA) Central Nervous System Infections: Exploring Optimal Regimens
Authors: Tyler Pitcock C , Burgess David S , Olney Katie B 
Published: January 2025

Abstract

Background
Historically, cefazolin (CFZ) has not been considered an appropriate agent to treat central nervous system (CNS) infections. Recent studies have shown that standard CFZ dosing achieves concentrations above the epidemiologic cutoff of minimum inhibitory concentration ≤ 2 mg/L for Staphylococcus aureus, but literature describing optimal dosing for CNS infections is lacking. This study aimed to identify CFZ dosing regimens necessary to achieve adequate probability of target attainment (PTA) for treatment of a methicillin-susceptible S. aureus (MSSA) CNS infection.

Methods
CFZ plasma and cerebral spinal fluid (CSF) pharmacokinetic parameters were obtained from a previous published study. Monte Carlo simulations were performed utilizing PD targets of 40%fT &gt; MIC for intermittent infusions and 100%fT &gt; MIC and 100%fT &gt; 4xMIC for continuous infusions (CI) to determine probability of target attainment (PTA) for seven CFZ dosing regimens at an MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. Adequate target attainment, defined as ≥ 90% PTA, was evaluated for CFZ dosing regimens ranging from 6-12g/day administered intermittently every 4-8 hours over 30 minutes or as a CI over 24 hours (Table 1).

Results
The standard intermittent regimen of 2g q8h did not achieve ≥ 90% PTA for any MIC evaluated. Furthermore, no CI regimen achieved ≥ 90% PTA when using the PD target of 100%fT &gt; 4xMIC. All continuous and intermittent regimens achieved ≥ 90% PTA when the MIC remained ≤ 0.5 mg/L. Only the 10 g and 12 g CI regimens achieved ≥ 90% PTA for 100%fT &gt; MIC when the MIC was 1 mg/L while no regimen achieved the desired target when the MIC was 2 mg/L.

Conclusion
These findings underscore the inadequacy of standard intermittent CFZ regimens in achieving desired PD targets for MSSA CNS infections. Higher total daily doses or CI CFZ is necessary to achieve satisfactory PD targets for MSSA CNS infections. When comparing the same total daily dose administered as an intermittent versus continuous infusion, our results suggest that continuous infusions are more likely to achieve PD target attainment for MSSA CNS infections, particularly when the cefazolin MIC exceeds 0.5 mg/L. Further clinical studies are warranted to evaluate the safety and efficacy of CFZ for CNS infections caused by MSSA.

Disclosures
All Authors: No reported disclosures
P-1262. Safety and Pharmacokinetics of Ainuovirine, a Novel Non-NucleosideReverse Transcriptase Inhibitor, in Healthy Chinese Adults
Authors: Wu Hao , Wang Meixia , Su Bin , Yang Juan , Yun Xinming , Qin Hong 
Published: January 2025

Abstract

Background
Ainuovirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of human immunodeficiency virus type 1 (HIV-1) infection. The safety profile and pharmacokinetics of ainuovirine was characterized in healthy adults administered with single ascending dose.Table 1.Summary statistics of pharmacokinetic parameters of ainuovirine after single oral doses in healthy participants.
Data are expressed in median ± standard deviation (min, max); AUC0–t, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration; AUC0–∞, AUC from time zero to infinity; AUC_%Extrap, percentage of extrapolated AUC; Cmax, maximum plasma concentration; C24h, concentrations at 24 hours postdose; CLz/F, apparent clearance; MRT0-t, mean retention time from time zero to time of the last quantifiable concentration; MRT0-∞, MRT from time zero to infinity; Vz/F, apparent volume of distribution; T1/2z, plasma terminal half-life; Tmax, time to maximum plasma concentration; λz, elimination rate constant.

Methods
A single-center, open-label, single-dose escalation study was conducted among healthy Chinese adults. Thirty participants, aged from 18 to 45 years, were randomly allocated to each cohort given a single-dose ainuovirine 75, 150 or 300 mg (10 participants per cohort), respectively. Inhibitory quotient (IQ) was defined as the ratio of the clinical trough concentration (C24h) to the protein-binding adjusted 50% effective concentration (pa-EC50).

Results
Across all dosage groups, most adverse events were rated as mild in severity. Major reported adverse events were abnormal serum lipids and elevated liver transaminase. No rash was reported and only one participant experienced central nervous system events (150 mg dose group). Pharmacokinetic parameters are shown in Table 1 for single-dose ainuovirine. Ainuovirine was readily absorbed, with a median Tmax of approximately 3 hours. Ainuovirine exposure (Cmax and AUC) increased to a lesser extent than the dose proportionality. Median apparent terminal half-life (T1/2z) remained similar across three dose cohorts, slightly longer than 24 hours. The IQs for wild type (pa-EC50=4.78 ng/mL) were 16.8, 23.8, and 28.1 folds, respectively. Those were 2.0, 2.9, and 3.4 folds for K103N (pa-EC50=39.17 ng/mL), respectively, and 1.1, 1.5, and 1.8 folds for Y181C (pa-EC50=232.2 ng/mL), respectively. All the IQs were above 1 fold.

Conclusion
Ainuovirine was well tolerated and showed a dose-dependent,nonlinear pharmacokinetics. The pharmacikinetics supported once daily oral dosing regimen of ainuovirine, with candidate doses of 75 to 300 mg in subsequent dose-ranging, proof-of-concept study.

Disclosures
Juan Yang, M.S., Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Xinming Yun, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Hong Qin, MD, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd: Honoraria
P-1274. Mpox: Characterization and Clinical Outcomes of Patients Attended in Health Service Providing Institutions in Colombia
Authors: Alvarez-Moreno Carlos A , Mesa Rubio María Lucia , Mora Leonardo Arévalo , Porras Villamil Julián Felipe , Reveiz Ludovic , Alzate Juan Carlos , Chaillon Antoine , de la Hoz Ilich , Firdavs Kurbonov , Rylance Jamie , Valderrama Sandra , Aristizabal Claudia , Sussmann Otto A , Andrade Javier , Murillo Carolina , Galindo Ximena , Martínez Daniela , Arango Lisandra , Buitrago Ernesto Martínez , Reyes Karyna , Suárez Mónica Mantilla , Gutierrez Juana , Garay Alexandra , Pinzón Wendy , Crispin Ana 
Published: January 2025

Abstract

Background
The monkeypox virus, part of the Orthopoxvirus genus, triggered a worldwide outbreak in 2022. While this outbreak had widespread effects, there's limited information on mpox's specific impact in Colombia, particularly in terms of how it is managed, its burden, and its epidemiology. This research seeks to examine the medical context, clinical variations, and health consequences in individuals diagnosed with mpox, especially those with HIV in Colombian health institutions

Methods
This retrospective study was conducted in health institutions in Colombia based on clinical records from Jan 2022 to Dec 2023. . Participants in the study were diagnosed through molecular methods and their clinical evolution was tracked through medical records. CD4 groups, BMI groups, viral suppression status, and HIV status were used to analyse the results.

Results
One thousand four hundred thirteen (1,413, 97.2% male) individuals, including 2.6% identified as healthcare workers were included in this study. Concomitant sexually transmitted diseases were common, affecting 30.1%, mainly syphilis (80%) and Neisseria gonorrhoeae (16.4%). 54% of the population (764/1413 individuals, 99.3% male) were persons living with HIV (PWH), and almost one-third (31%, n=284) of participants had concomitant sexually transmitted diseases and HIV
PWH also had a higher proportion of gastrointestinal symptoms and genital symptoms. An important difference between HIV-positive and negative patients is that the former had a higher proportion of syphilis (p-value 0.5909) and other STIs (p-value 0.0026). Although PWH were younger (34.3±7.7 vs. 37.7±7.5), the difference in mean age was not statistically significant, although the differences in proportion were (15 to 44 years group, p-value 0.0097).

Conclusion
The evidence presented shows that half of the population were people living with HIV, and the presence of mpox was not statistically significant in people with unsuppressed viral load or with low CD4 levels. The evidence provided by this study, whose results were standardized by the CRFs, and emphasizes the importance of interdisciplinary attention for patients suffering from mpox. Special emphasis should be placed on individuals support and follow-up, focusing on detecting concomitant STIs.

Disclosures
All Authors: No reported disclosures
P-1284. Impact of Timing of Measles Vaccine Doses on IgG Levels
Authors: Pérès Évrard , Laghdir Zineb , Boissonneault Sophie , St-Pierre Annie , Vallières Émilie , Quach Caroline 
Published: January 2025

Abstract

Background
Although measles was eliminated from Canada, recent outbreaks worldwide are increasing the risk of importation with local transmission. Healthcare workers (HCWs) are known to be at higher risk of measles, compared to the general population. Recent measles breakthrough infection in immune individuals have raised several questions about levels of immunity. We examined the proportion of HCWs who were considered seropositive for measles and evaluated factors associated with lower IgG levels.

Methods
Measles IgG were measured in a convenient sample of HCWs from the Centre hospitalier universitaire Sainte-Justine (CHUSJ), a tertiary-care hospital, located in Montreal, Canada, in the context of an outbreak and the need to rapidly assess our workforce protection. Data from the Occupational Health clinic was used (age, vaccination history, sex). Sera were tested using LIAISON® Measles IgG (Diasorin) for quantitative measurement of measles-specific IgG. IgG levels &gt; 16.5 IU/L were considered protective. Data were compared using the Welch’s t-test on Microsoft Excel.

Results
A total of 114 HCWs were tested. Of the 42 individuals born before 1970 without vaccination, 92.9% were considered protected with a mean IgG level of 239.07 IU/L (SD - 103). A total of 45 HCWs were born in 1970 or thereafter; of those 32 received two doses of vaccine, with a first dose received between 12 and 15 months of age. HCWs (n = 8) who received their second dose between 17 and up to 21 months of age had mean IgG titers of 71.38 IU/L (SD - 104). In comparison, the 24 HCWs who received their second dose after 21 months of age, at a mean age of 142.43 months (range [28,393]), had a mean IgG level of 177.12 IU/L (p = 0.03).

Conclusion
These results suggest that the second dose of measles vaccine administered at a later age is associated with a higher IgG level. The clinical impact of these higher IgG levels remains to be explored.

Disclosures
All Authors: No reported disclosures
P-1316. Influenza Antiviral Prescribing Practices for Outpatients with an Acute Respiratory Illness and at Increased Risk for Influenza-Associated Complications pre- and post-COVID-19 pandemic — United States, 2016–2022
Authors: Chung Jessie R , Ellington Sascha , Price Ashley 
Published: January 2025

Abstract

Background
Early antiviral treatment (&lt; 2 days after illness onset) can reduce the risk of influenza-associated complications and is recommended for outpatients at increased risk. However, in previous influenza seasons, antivirals have been underprescribed. We describe influenza antiviral prescribing practices for outpatients from 2016-2022.

Methods
We analyzed influenza antiviral prescription data from 5 US Influenza Vaccine Effectiveness Network sites pre-pandemic, 2016-2017 through 2019-2020, and post-pandemic, 2021–2022 (2020-2021 season not included due to low influenza circulation). Patients enrolled were aged ≥6 months presenting with an acute respiratory illness with a new or worsening cough ≤7 days duration. All had respiratory specimens collected for influenza RT-PCR testing. Patients at increased risk for severe outcome included those aged &lt; 2 years, ≥ 65 years, and those with at least one underlying medical condition. Electronic medical records were examined to determine whether antivirals were prescribed within 7 days after enrollment.

Results
Among 21,483 patients at increased risk enrolled in the US Flu VE Network between 2016-2017 and 2021-2022, 8% (1,852) were prescribed antivirals within 7 days. In pre-pandemic seasons, the average proportion of those prescribed antivirals was 9.5% overall and lowest during the 2019-2020 season (6%); post-pandemic, this proportion decreased to 1%. Among confirmed influenza cases, 40% (874/2210) of those at increased risk who presented for care &lt; 2 days after illness onset were prescribed antivirals across all 5 seasons. Similarly, during the pre-pandemic seasons the average proportion of patients prescribed antivirals was 40% with the lowest percentage observed during the 2019-2020 season (26%). This proportion continued to trend downward post-pandemic (21%).

Conclusion
Over the last several seasons, influenza antiviral medications have been infrequently prescribed, including among those at increased risk for severe illness who present early in their illness. Efforts to increase appropriate antiviral prescribing may reduce influenza-associated complications among outpatients presenting early for care.

Disclosures
All Authors: No reported disclosures