bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1207. Resurgence of Respiratory Viral Infections Among Children Hospitalized in a Tertiary Care Hospital in Thailand After the COVID-19 Pandemic
Authors: Sudjaritruk Tavitiya , Mueangmo Oramai , Saheng Jutamad , Chaito Tanachot , Manowong Suphara 
Published: January 2025

Abstract

Background
To demonstrate the epidemiological and clinical characteristics of respiratory viral infections among children hospitalized in a tertiary care hospital after COVID-19 pandemic.

Methods
A cross-sectional study was conducted among children aged 1 month to 15 years who were admitted to the Chiang Mai University Hospital, Thailand due to non-COVID-19 respiratory tract infections (RTIs) after COVID-19 pandemic (Oct 2022 to Sep 2023). Nasopharyngeal specimens were tested for 16 respiratory viruses (RV: influenza A [IAV] and B [IBV] viruses; respiratory syncytial virus [RSV]; parainfluenza virus types 1-4; rhinovirus; enterovirus; human metapneumovirus; human coronaviruses 229, NL63, OC43, HKU1; bocavirus; human adenovirus), using multiplex RT-PCR. The prevalence each RV was demonstrated. Clinical parameters, treatments, and outcomes of children were compared by type of RV. In addition, the prevalence of IAV, IBV and RSV were compared across 3 periods: pre (Jan 2016 to Dec 2019), during (Jan 2020 to Sep 2022), and post COVID-19 pandemic.

Results
During the study period, 400 children were enrolled; median age 2.9 (IQR 1.5-4.8) years, 59% male, 46% had underlying diseases. On admission, 80% had pneumonia and 5% were admitted to ICUs. Overall, 341 children (85%) were tested positive for ≥ 1 RV (68% single and 17% multiple infections). The prevalence of each RV after the COVID-19 pandemic was shown in Table 1. Compared with other viruses, children with IAV and IVB (n=21) had the highest proportion of fever (100%) and sore throat (19%), whereas those with RSV (n=65) had the highest proportion of oxygen therapy (97%) and bronchodilator (86%) requirement, and those with enterovirus (n=23) had the highest proportion of tachypnea (44%), ICU admission/transfer (22%), ventilator use (22%), and death (4%) (Table 2). Notably, the prevalence of IAV, IBV and RSV significantly declined during the COVID-19 pandemic, and sharply rebounded after the pandemic, particularly for RSV which the prevalence was significantly higher than pre COVID-19 pandemic phase (Figure 1).

Conclusion
COVID-19 pandemic significantly changed the epidemiology of respiratory viral infections in our setting. Active surveillance is needed to better understand the dynamics and seasonal patterns of RV after the pandemic.

Disclosures
All Authors: No reported disclosures
P-1223. Mechanistic Insights to Combating Enterobacter cloacae in Deep Seated Infections
Authors: Gray Rachel , May Elizabeth , Coyne Ashlan Kunz 
Published: January 2025

Abstract

Background
Enterobacter cloacae is a formidable pathogen in deep-seated infections. Increasing prevalence of carbapenem-resistant Enterobacterales exemplifies the need for optimizing non-carbapenem therapeutics. We aimed to evaluate cefepime (FEP) and meropenem (MEM) regimens against E. cloacae isolates in a pharmacokinetic/pharmacodynamic (PK/PD) ex vivo model.Table 1.CDC Antibiotic Resistance Isolate Bank Enterobacter cloacae Strains Tested in Ex vivo Models

Methods
E. cloacae isolates (CDC# 0032, 0060, Table 1) were evaluated in 96h simulated endocardial vegetation (SEV) high inoculum (109 CFU/g) models against humanized FEP (2g q8h via 30-min and 3h infusions) and MEM (2g q8h via 30-min and 3h infusions) regimens. SEV clot and planktonic samples were removed in duplicate from each model replicate at predefined time points and evaluated for bactericidal activity (defined as a ≥ 3 log10 CFU/g reduction from baseline), antibiotic PK target attainment, treatment-emergent resistance, and β-lactamase induction via RT-PCR. Significant differences between regimens were assessed by ANOVA with Tukey’s post hoc modification (α=0.05).Table 2.Beta-lactam PK/PD Targets and Achieved Concentrations in Ex vivo Models

Results
Against E. cloacae 0060, MEM via 3h infusion demonstrated bactericidal activity (-Δ4.79 log10 CFU/g) in SEV clots and greater killing than MEM via 30-min infusion (-Δ2.6 log10 CFU/g; p&lt; 0.001) (Figure 1). Both MEM 3h and 30-min infusions suppressed bacterial growth at detection limits in planktonic samples through 96h against 0060. Against E. cloacae 0032, neither FEP nor MEM regimens demonstrated bactericidal activity or growth suppression at 96h in SEV clots and planktonic samples, respectively (Figure 2). β-lactam PK/PD targets and achieved concentrations in ex vivo models are displayed in Table 2. Treatment-emergent resistance was identified in 96h samples for FEP against 0060 and MEM against 0032 (3- and 5-fold MIC increase). FEP exposure in 0060 models induced ACT-89 β-lactamase expression while FEP and MEM in 0032 models induced ACT-16, KPC-3, and TEM-1.Figure 1.Efficacy of Beta-lactam Regimens in a SEV PK/PD Ex vivo Model Against E. cloacae Isolate 0060

Conclusion
Against E. cloacae isolates in a PK/PD ex vivo model, MEM demonstrated bactericidal activity against E. cloacae 0060, with greater efficacy via 3h compared to 30-min infusion. However, neither FEP nor MEM showed bactericidal activity against E. cloacae 0032, with the emergence of treatment-resistant strains and induction of β-lactamase expression observed in some cases.Figure 2.Efficacy of Beta-lactam Regimens in a SEV PK/PD Ex vivo Model Against E. cloacae Isolate 0032

Disclosures
All Authors: No reported disclosures
P-1241. Cefepime Pharmacodynamics Against Pseudomonas aeruginosa Evaluated in a Chemostat Infection Model: Do Generalized Cephalosporin Targets Translate?
Authors: Edwards Mitchell , Pevear Daniel C , Yi Fan , Daigle Denis M , Avery Lindsay M 
Published: January 2025

Abstract

Background
Cefepime (FEP) is used widely to treat infections caused by susceptible strains of Pseudomonas aeruginosa. However, nonclinical pharmacokinetic-pharmacodynamic (PK/PD) relationships for this drug-bug combination are not fully characterized. An in vitro chemostat (CS) model was used to assess the translatability of broadly established cephalosporin PK/PD targets to support development of FEP combined with taniborbactam (TAN), a novel serine- and metallo-β-lactamase inhibitor.Table.Antimicrobial susceptibility testing results and summary of cefepime pharmacodynamics against strains evaluated in the chemostat (CS) modelAR, denotes strains sourced from the CDC & FDA Antimicrobial Resistance Isolate Bank; FTB, cefepime-taniborbactam

Methods
Cefepime-taniborbactam (FTB) and FEP minimum inhibitory concentrations (MIC) were determined by reference broth microdilution (BMD) against P. aeruginosa isolates with no known acquired β-lactamases (N=6). Cefepime MICs were also assessed in 125 mL of TAN-supplemented media (4 µg/mL) to simulate CS conditions (CS MIC, Figure). In FEP dose-ranging studies in the dynamic CS model, bioreactors were inoculated with ≥ 5 log10 CFU/mL. FEP was dosed every 8 h for 24 h while media was infused to achieve a 2-h half-life. FEP concentrations were determined by a qualified bioanalytical method and used to calculate the percentage of time concentrations exceeded MIC values (T &gt; MIC). Viable bacteria were quantified by serial dilution and plating at time points from 0 to 24 h. CS qualification was performed with Enterobacterales to confirm that the model recapitulated in vivo PD profiles reported previously by others.Figure.Schematic of the chemostat MIC (CS MIC) assay for an example strain with a CS MIC of 4 µg/mL.

Results
P. aeruginosa strains were FEP-susceptible (n=5) and -nonsusceptible (n=1) and BMD MICs ranged from 2 to 16 µg/mL. CS MICs were equal to (n=2), 2x (n=3), or 8x (n=1) the FTB BMD MIC (Table). All strains grew in the CS model to an average (standard deviation) bacterial burden of 7.3 (0.6) log10 CFU/mL. In composite PD models fit to dose-ranging data, change in bacterial burden from 0 to 24 h was best described by T &gt; CS MIC versus T &gt; BMD MIC. Reductions in bioburden were observed at T &gt; CS MICs of 41-49% (Table).

Conclusion
In a dynamic in vitro model of P. aeruginosa infection, efficacious FEP exposures were similar to those established for Enterobacterales when indexed to CS MIC values. The results also indicate that differences between BMD and CS MIC should be considered when performing in vitro PK/PD profiling of discovery-phase antibacterials to prevent underestimation of therapeutic potential.

Disclosures
All Authors: No reported disclosures
P-1254. Improved Vancomycin Target Attainment Following a Quasi-Experimental Change in Pharmacokinetic Model for Bayesian Precision Dosing
Authors: Hughes Maria-Stephanie , Tong Dominic M H , Hughes Jasmine 
Published: January 2025

Abstract

Background
When using a Bayesian approach for vancomycin dosing, pharmacokinetic (PK) models guide dosing decisions. This study explores the impact of moving from the Goti model to the Thomson model on target attainment, dosing decisions, and acute kidney injury (AKI) rates.

Methods
Adults with BMI &lt; 40 kg/m2 treated with vancomycin using InsightRX Nova Bayesian software, who switched from the Goti to the Thomson models as their default between January 1, 2023, and April 15th, 2024, were included. The switch was prompted by internal analyses suggesting the Thomson model was performing better. AUC24 was calculated for the treatment course and days 1, 2, and 3+. Outcomes included the proportion of patients in the target AUC24 range of 400-600 mg*h/L, time to target attainment, average daily dose, severe AKI rates (KDIGO stage 2 or 3 after 48 hours), and levels per course. An interrupted time series analysis was done for AUC24. The relationship between subtherapeutic AUC24 to minimum inhibitory concentration (MIC) ratio and mortality was extrapolated from a study by Lodise et al. (2014) on patients with MRSA bloodstream infections. MICs were assumed to be 1 mg/L.

Results
The study included 27,604 patients before and 23,359 after the intervention across 16 health systems (Table 1). The average AUC24 for days 1, 2, 3+, and the full treatment course showed statistically significant improvement (see Figure 1). AUC24 target attainment increased from 46.5% to 51.1% (p &lt; 0.001) due to fewer subtherapeutic courses. Median time to target decreased from 47.8 to 28.2 hours (p &lt; 0.001), severe AKI rates rose slightly from 1.75% to 2.03% (p = 0.023, number needed to treat (NNT): 358), and average daily dose and levels slightly increased (see Figure 2). The decreased proportion of subtherapeutic AUC24 on days 1 and 2 before and after intervention corresponded to expected mortality rates of 17-18% and 16-17%, respectively (NNT: 130).

Conclusion
Switching the default PK model used in a Bayesian approach for dosing adult patients on vancomycin resulted in improved AUC24 target attainment, and a 41% decrease in time to target attainment, with only slightly increasing AKI rates.

Disclosures
Maria-Stephanie Hughes, PharmD, InsightRX: Employee of company|InsightRX: Stocks/Bonds (Private Company) Dominic M.H. Tong, PhD, Insight RX, Inc: Employee|Insight RX, Inc: Stocks/Bonds (Private Company) Jasmine Hughes, PhD, InsightRX: Employee|InsightRX: Stocks/Bonds (Private Company)
P-1261. Phamacokinetic Model of Oral Minocycline in Critically Ill Adult Patients with Acinetobacter baumannii Infection
Authors: Koumaki Vasiliki , Athanassa Zoe , Valsami Georgia , Papakyriakopoulou Paraskevi , Saitani Elmina-Marina , Marques Silvia , Manioudaki Sofia , Sakagianni Aikaterini , Dokoumatzidis Aristides , Tsakris Athanasios 
Published: January 2025

Abstract

Background
Minocycline has made a comeback in the drug armamentarium as a treatment option for infections due to Acinetobacter baumannii. Although, it has been launched in the 1960s, scarce pharmacokinetic studies have been published. This open-label, prospective clinical study was conducted in critical ill patients with documented infections, mainly VAP-associated pneumonia, attributed to extensively-drug or pan-drug resistant Acinetobacter baumannii, susceptible-or intermediate susceptible to minocycline strains, treated with oral minocycline as a combination therapy.
PTA of 200mg and 400mg of minocycline for a range of MICs after a Monte Carlo simulation of 10000 AUC values

Methods
The PK study population consisted of 20 patients, hospitalized in the ICU of a tetriary Hospital in Athens, Greece. The minimum inhibitory concentration was determined using broth microdilution and a susceptibility breakpoint of ≤ 4mg/L was applied for interpretation, according to the Clinical and Laboratory Standards Institute (CLSI). All patients were given a loading dose of 200mg of minocycline followed by 100mg every 12 hours. Plasma PK samples were collected predose and at 13,14,18,21.5, 59.5,61, 64,68 and 71.5 hours after commencement of minocycline. Minocycline quantification in patient serum sample was conducted using HPLC-PDA, Shimadzu Prominence system (Shimadzu, Kyoto, Japan). A population pharmacokinetic model was developed in Monolix 2023 R1. Monte Carlo simulations were carried out, assuming protein binding of 76%. The probability of target attainment was calculated for each MIC value to achieve an fAUC/MIC ratio of above 25 for daily doses of 200mg and 400mg.

Results
MInocycline PK parameters in critical ill adult patients were best described using a one-compartment model. The PTA values for various MICs are shown in Figure 1, which indicates that an oral dosage of 200mg and 400mg daily, could cover infections, due to Acinetobacter baumannii strains exhibiting MICs of 0.125mg/L and 0.25 mg/L ,respectively, with a PTA &gt;90%.

Conclusion
These findings suggest that current oral treatment may be suboptimal for treating such infections, at least as a monotherapy. Further research is needed in order to explore possible dose elevations and synergistic combinations that could enhance its efficacy in combatting XDR, and PDR Acinetobacter baumannii infections.

Disclosures
All Authors: No reported disclosures
P-1263. Safety, Pharmacokinetics, and Antiviral Activity of Ainuovirineas 10-Day Monotherapy in Treatment-Naive Adults with HIV-1
Authors: Wu Hao , Xia Wei , Su Bin , Zhang Li , Yun Xinming , Qin Hong 
Published: January 2025

Abstract

Background
Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics, and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.Table 1.Summary statistics of pharmacokinetic parameters of ainuovirine after single-dose and multi-doses in treatment-naïve HIV-infected adults.
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-t,ss, AUC0-t at steady state; AUC0-∞,ss, AUC from time zero to infinity at steady state; AUC0-τ, AUC at steady state; AUC_%Extrap, percentage of extrapolated AUC; Cmax, maximum plasma concentration; Cmax,ss, Cmax at steady state; Cmin,ss, minimum plasma concentration at steady state; Cav,ss, average steady state concentration; CLss/F, apparent clearance at steady state; DF, degree of fluctuation; MRT0-∞, mean retention time from time zero to infinity; Ra, accumulation ratio; Tmax, time to maximum plasma concentration; Tmax,ss, Tmax at steady state; T1/2z, plasma terminal half-life; Vz/F, apparent volume of distribution; λz, elimination rate constant.

Methods
A single-center, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, 75, 150, or 300 mg, once daily, for 10 days.Figure 1.Mean change from baseline in HIV RNA.Data are expressed in median±standard deviation.

Results
Baseline characteristics were similar across dose cohorts (75 mg, n=8; 150 mg, n=10; 300 mg, n=10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. Pharmacokinetic parameters are shown in Table 1. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2-3 h after dosing. The ANV exposure (AUC and Cmax) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated Cmax,ss, AUCmax,ss, and C24h,ss were observed at 150 and 300 mg on day 10 after repeated dosing. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were -1.73 [-1.90, -1.57], -1.72 [-1.87, -1.57], and -1.66 [-1.80, -1.51], respectively, on day 11 (Figure 1).

Conclusion
ANV demonstrated favorable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1.An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial.

Disclosures
Li Zhang, 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-1268. Evaluation of Mpox Coinfections with Hepatitis B, Hepatitis C, HIV, and Sexually Transmitted Infections During the Outbreak Peak In New York City
Authors: Pelliccione Alex J , Johnson Kimberly , McPherson Tristan D , Pathela Preeti , Braunstein Sarah 
Published: January 2025

Abstract

Background
New York City (NYC) was an epicenter of the 2022 global mpox outbreak. Mpox is spread through skin-to-skin contact, including sexual contact, and there is a high prevalence of coinfections with HIV and other sexually transmitted infections (STI). The frequency of mpox and Hepatitis B/C virus (HBV/HCV) coinfections is unknown, though HBV/HCV can be sexually transmitted, and HBV/HCV prevention and treatment are part of syndemic approaches with HIV/STI. We evaluated mpox coinfections in NYC, focusing on HBV/HCV.

Demographic characteristics of people with mpox-only and people with mpox and coinfection, New York City, May 18–August 19, 2022

Methods
We performed descriptive analyses and assessed coinfections using matched NYC Health Department surveillance registries for HBV/HCV, HIV, STI (chlamydia, gonorrhea, early syphilis), and mpox during the outbreak peak (May 18–August 19, 2022). Registries included all patient laboratory reports for each infection and demographics: age at mpox diagnosis, sex at birth, gender identity, race/ethnicity, NYC borough of residence, and area-based poverty level. People with resolved HCV were excluded.

Results
During the analytic period, 2925 people were diagnosed with mpox; 1299 (44.4%) were living with diagnosed HIV, 32 (1.1%) with HBV, and 30 (1.0%) with HCV, with half (1541; 52.7%) diagnosed with STI in the prior 12 months (Table 1). Coinfections of mpox and HBV/HCV were more common for people living in very high poverty areas (HBV-mpox: 37.5%, HCV-mpox: 40%). For non-Hispanic Black and Latino/Hispanic people, mpox coinfections with HIV (40.3% and 44.2%, respectively); HBV (37.5%; 43.8%); HCV (36.7%; 53.3%); and recent STI (30.1%, 37.1%) were more frequent than mpox monoinfection (17.9%; 31.2%). For non-Hispanic white people, coinfections with HIV (12.6%); HBV (12.5%); HCV (10%); and recent STI (22.3%) were less frequent than mpox monoinfection (32.9%).

Conclusion
Among people diagnosed with mpox, coinfection rates with HBV/HCV were low compared with HIV/STI. This might reflect sexual transmission as a less common driver of HBV/HCV infection in communities affected by mpox. There were more coinfections in Black and Latino/Hispanic people and more HBV/HCV coinfections in people living in very high poverty areas. Place-based HBV/HCV screening could be beneficial in future mpox outbreaks, and universal HIV/STI screening at mpox diagnosis should continue.

Disclosures
All Authors: No reported disclosures
P-1271. Occurrence of Avian Pathogenic Escherichia coli (APEC) with potential for human extraintestinal infections in poultry environments of Bangladesh
Authors: Amin Md Badrul , Hoque Kazi Injamamul , Sraboni Ajrin Sultana , Bhuiyan Md Omar , Poroma Rubaiya Jannat , Islam Mohammad Aminul 
Published: January 2025

Abstract

Background
Avian pathogenic E. coli (APEC) causes colibacillosis mainly in poultry industry. Previous reports suggest that APEC strains often harbor virulence factors that are related to E. coli causing extraintestinal infections in humans known as ExPEC, highlighting their zoonotic potential. However, limited information is available on APEC harboring ExPEC specific genes in Bangladesh. This study aimed to isolate and characterize APEC strains carrying ExPEC genes in urban and rural poultry environments.
Prevalence of of Avian pathogenic E. coli in different poultry samples collected from urban poultry markets and rural poultry farms. LBM, urban live bird market; RPF, rural poultry farm; GIT, gastrointestinal tract

Methods
During 2019–21, we collected 330 gastrointestinal tracts (GIT) of freshly slaughtered poultry from urban live bird markets (LBM) (n=55) and rural poultry farms (RPF) (n=55), GIT of dead poultry from LBM (n=55) and RPF (n=55), along with feces from poultry pens of LBM (n=55) and RPF (n=55). We tested these samples for E. coli by direct plating on TBX agar. Biochemically confirmed five E. coli colonies per sample were investigated for both APEC (iroN, ompT, hlyF, iss, iutA) and ExPEC (cvaA/B5/C, etsA/B, kpsMTK1, kpsMTII, sfsS, ompA, ace35) associated genes using PCR. All the APEC isolates were tested for antibiotic sensitivity to 21 antibiotics, phylogrouping and a subgroup of APEC strains carrying ExPEC genes was subjected to whole genome sequencing.
Phylogenetic analysis of APEC strains carrying ExPEC associated virulence genes. MLST, multi locus sequence type.

Results
All 330 samples were E. coli positive with a mean count of 6.4 (SD 1.5) log10 CFU/g of GIT. Around 50% of samples (n=165) were APEC positive with similar trend of prevelance in both LBM (53%, n=88) and RPF (47%, n=77) (Fig. 1). All APEC isolates were multi drug resistant (MDR), with highest resistance to macrolides (100%), penicillins (98%), tetracyclines (96%), fluoroquinolones (93%), folate inhibitors (89%), phenicols (53%), aminoglycosides (33%), cephalosporins (13%) and carbapenems (4%). Predominant phylogroups were B1 (10%) followed by F (7%), E (5%) and A (4%). Around 68% of APEC isolates (n=113) harbored ExPEC associated genes and were genetically diverse in terms of their serotypes, sequence types except ST117 and 1196, and single nucleotide polimorphism (Fig. 2).

Conclusion
The higher prevalence of MDR APEC with ExPEC traits underlines the risk of human infection given the zoonotic transmission of the organisms. Public health measures should be taken to control the potential spillover of the organisms from poultry to humans.

Disclosures
All Authors: No reported disclosures