bluuebunny/crossref_metadata_2025 huggingface dataset:
420. Immunization Impact on Serotype Distribution of Invasive Pneumococcal Disease - Playing the Serotype Whack-A-Mole!
Authors: Nieves Delma J , Osborne Stephanie , Cheung Michele , Zahn Matt , Arrieta Antonio C
Published: January 2025

Background

Implementation of 7-valent pneumococcal vaccine (PCV7) resulted in significant reduction of invasive pneumococcal disease (IPD) followed by a subsequent increase in IPD by non-vaccine (n-Vac) serotypes (ser) (19A, 7F, 3) with increased severity and antimicrobial resistance. Approved following immunogenicity data, 13-valent PCV (PCV13) adoption reduced IPD again. Surveillance was strongly recommended by the CDC. We present 13 years of countywide (Orange County, CA) surveillance of IPD and serotypes.

Serotype distribution of IPD by Year

Methods

Prospective (1/2010 - 12/2023) countywide study of patients < 18 years old with culture proven IPD. Demographic, clinical course and immunization data were collected. Serotyping was by Quelung method. Antibiotic susceptibilities were obtained.

Results

During the study period 261 patients were identified; 42% female, median age 3.7 years, 52% < 5 years old. IPD rate per 10,000 decreased by 70% (0.408 – > 0.123) from 2010 - 2014 and increased steadily from 2015 to 2019 (peaking at 0.403). As COVID19 pandemic social distancing measures were adopted, IPD rate decreased by 86% (0.057 in 2021); it has since rapidly increased again (0.285) after lifting social distancing measures. Ser was known for 86%; 15B and 22F were the most common nVac ser seen (8% and10% respectively). Ser distributions by year are seen in Figure 1. Table 1 shows the distribution of IPD with immunization status and where the pneumonias and meningitis occurred. Pneumonia (102 [39%]) remains the most common IPD (30% with empyema); we saw a rise of meningitis cases after 2018, 1 was ser3, 13 were n-Vac ser and 3 unknown. IPD attributed mortality occurred in 8 (3%) patients; 4 were due to PCV13 ser. Penicillin resistance (meningitis) increased from 21% to 31%; penicillin non-susceptible (MIC >1) remained unchanged. New 15 and 20 valent ser include 12% and 19% of emerging n-Vac serotypes.

Conclusion

Similar to PCV-7, PCV-13 implementation resulted in an initial significant decrease in IPD, mainly due to 5 of the 6 additional ser included in PCV-13, ser 3 was not significantly affected. This was followed by resurgence of IPD, mainly to n-VAC serotypes. Of our IPD since 2010, 65% are from ser now included in 20-valent PCV. IPD attributable mortality remains high. Active surveillance following higher valent PCVs remains important.

Disclosures

All Authors: No reported disclosures
P-1160. Surge of Pediatric Streptococcus pneumoniae Infections at a Tertiary Healthcare Center after Introduction of 15 and 20 Valent Pneumococcal Conjugate Vaccines: Early Evidence of Serotype Replacement?
Authors: Burkhart Kyle , Aluru Ujwal , Abolhassani Ali , Topping Bradley , Giraldez Ediza M , Hampton Laura L , Samra Hasan , Neshangi Srilatha , Camelo Ingrid
Published: January 2025

Background

Routine pneumococcal vaccination has contributed to the overall decrease in pediatric cases of invasive pneumococcal disease (IPD). However, there has been an increase in non-vaccine serotypes (NVT) causing IPD in North America, Europe, and Australia. We describe hospital admissions of Streptococcus pneumoniae-related illness at a tertiary health care center from 2022-2024.

Methods

Retrospective chart review was conducted of IPD and non-IPD cases admitted to the Children’s Hospital of Georgia from April 2022-April 2023 and April 2023-April 2024. We used the Centers for Disease Control and Prevention (CDC) definition of IPD. IPD and non-IPD disease cases were analyzed for site of infection, concomitant viral infections, vaccination status, Pediatric Intensive Care Unit (PICU) admission, and death. 

Results

From 2023-2024, there were 12 cases of IPD, 8 had bacteremia, 3 had meningitis and bacteremia, and 1 had meningitis compared to only 3 IPD cases in 2022-2023, all with bacteremia. 7 of the 12 cases (58%) of IPD cases in 2023-2024 were fully PCV13 vaccinated compared to 1 of the 3 cases (33%) in 2022-2023. Only RSV and rhino/enterovirus were found concomitantly. 7 patients required PICU admission in 2023-2024, 1 on 2022-2023. 1 patient died during 2023-2024. 2 cases had serotyping during 2023-2024; one had serotype 38 and the other had serotype 10A. PCV20 includes serotype 10A. None of the above serotypes are included in the PCV 13 or PCV 15 vaccines.

From 2023-2024, there were 9 cases of non-IPD infection compared to 13 cases in 2022-2023, all of which had pneumonia as the site of infection. Only 5 cases were fully immunized in 2023-2024 while 8 were vaccinated in 2022-2023. Concurrent viruses included parainfluenza, human metapneumovirus, SARS-CoV-2, coronavirus OC43, adenovirus, and rhinovirus. 4 patients required PICU admission in 2023-2024 and 5 in 2022-2023. 1 case died during 2023-2024, and 1 died during 2022-2023.

Conclusion

The recent surge in IPD cases at our institution could be related to early serotype replacement following vaccine-expanded serotypes since more children with IPD were immunized during the 2023-2024 period. Increased surveillance and serotyping will guide decisions about increased IPD infections. Immunization efforts need to be reinforced in our community.

Disclosures

All Authors: No reported disclosures
P-1187. Comparative Evaluation of Clinical Characteristics in Pediatric Patients Hospitalized in Taiwan with RSV and hMPV Infections
Authors: chiu Yu-Ting , Wei Hsiu-Mei , Hsu Yu-Lung , Chang Yu-Chang , Hsiao Chiung-Tzu , Lai Huan-Cheng , Chen Jiun-An , Low Yan-Yi , Lin Hsiao-Chuan , Hwang Kao-Pin
Published: January 2025

Background

Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (hMPV) are prevalent pathogens responsible for respiratory tract infections in infants and young children. This study aims to conduct a comprehensive analysis of the clinical presentations and outcomes among hospitalized infants and young children with RSV and hMPV infections.

Methods

This retrospective observational study was conducted at China Medical University Children's Hospital (CMUCH) from January 2020 to December 2021. The study enrolled patients under 5 years old admitted due to respiratory tract infections, with RSV or hMPV detection confirmed using a commercial respiratory panel employing real-time polymerase chain reaction. Demographic details, clinical manifestations, and outcomes were gathered and analyzed to facilitate comparative assessments.

Results

A total of 145 pediatric patients were included in the study. Among them, 82 patients tested positive for RSV, while 63 patients tested positive for hMPV. There were no significant differences in age and gender distribution between the two groups. Common symptoms such as fever, cough, and rhinorrhea were observed in both groups without notable disparities. No significant differences were found in laboratory parameters between the groups. Pneumonia patches were more frequently observed in the hMPV group and less frequently observed in the RSV group (28.3% vs. 8.3%, p=0.001). Medical interventions did not significantly differ between the two groups. However, the hMPV group exhibited a notably higher rate of antibiotic usage compared to the RSV group (90.5% vs. 57.3%, p<0.001). Moreover, there were no significant discrepancies in the duration of hospitalization (5 vs. 5 days, p=0.110), requirement for oxygen (36.6% vs. 25.4%, p=0.151), and admission to the intensive care unit (ICU) (14.6% vs. 9.5%, p=0.355) between the two groups. Only one RSV patient required intubation, and there were no reported fatalities in either group during the study period.

Conclusion

The findings indicate that RSV and hMPV infections have similar clinical presentations, highlighting diagnostic challenges in the absence of molecular methods. Patients with hMPV are more likely to develop pneumonia patches and receive antibiotic therapy.

Disclosures

All Authors: No reported disclosures
P-1191. Maternal Antibodies Against Parechovirus-A3 Before and During the Coronavirus Disease 2019 Pandemic
Authors: Tachikawa Jun , Aizawa Yuta , Watanabe Kanako , Haino Kazufumi , Nishijima Koji , Saitoh Akihiko
Published: January 2025

Background

Parechovirus-A3 (PeV-A3) is an important emerging virus that causes severe disease in neonates and young infants. The coronavirus disease 2019 (COVID-19) pandemic greatly affected the incidence of infectious diseases, including PeV-A3 infection. Before the pandemic, we reported that maternal neutralizing antibody response against PeV-A3 was important in protecting neonates and young infants from PeV-A3 and that neutralizing antibody titers (NATs) were higher in younger mothers (Emerg Infect Dis. 2015;21:1966-1972). Because the impact of the COVID-19 pandemic on maternal NATs against PeV-A3 is unclear, we investigated NATs against PeV-A3 during the COVID-19 pandemic and compared our findings with previous data.

Methods

Cord blood (CB) samples for healthy newborns born at full-term were collected from June through December 2023 at Niigata University Hospital in Niigata, Japan. Maternal clinical data were collected, and NATs measured using LLC-MK2 cells were compared with the pre-pandemic data, classified by age group, ie, 16–24 years, 25–34 years, and 35–44 years.

Results

In total, 102 CB samples were collected. Median maternal age was 34.5 years (range: 30–37 years), and the geometric mean titer (GMT) of antibodies against PeV-A3 was 98.4 (95% CI: 61.7–156.8). The GMT values for age 25–34 years during the pandemic (184.6, n = 45) and age 16–24 years before the pandemic (336.5, n = 11) did not significantly differ (P = 0.84). Similarly, the GMT for age 35–44 years during the pandemic (56.3, n = 51) did not significantly differ from that for the matching age group, 25–34 years, before the pandemic (31.9, n = 107) (P = 0.14). Notably, the GMT was significantly higher for age 25–34 years during the pandemic than for age 25–34 years and age 35–44 years before the pandemic (P < 0.001), which is consistent with our finding that the pre-pandemic age group 16–24 years had the highest GMT.

Conclusion

Maternal NATs against PeV-A3 in CB before and during the COVID-19 pandemic were similar, which suggests that humoral immunity to PeV-A3 was not substantially altered even after 3 years of limited PeV-A3 infections during the COVID-19 pandemic.

Disclosures

All Authors: No reported disclosures
P-1195. Incidence and Diagnosis of Neonatal Herpes Simplex Virus (HSV) Following Transition to In-House Serum Testing
Authors: Patt Elizabeth , Ribes Julie A , Howard Joel I , Olney Katie B
Published: January 2025

Background

Neonatal Herpes simplex virus (HSV) infection is associated with significant morbidity and mortality, and previously estimated to account for 0.2-0.9% of hospitalizations in infants admitted with sepsis nationally. Recently, our institution transitioned the performance of serum HSV PCR testing in-house to expedite evaluation in neonates admitted with concerns for sepsis. This study was conducted to internally review the impact of in-house testing on neonatal HSV diagnosis and incidence.Table 1:Baseline Characteristics, Diagnosis, and Disease Classification in Infants with Positive Diagnostics

Methods

All infants ≤2 months of age admitted to our institution in the pre-implementation (8/2021-1/2022) or post-implementation (8/2022-5/2023) periods who had at least one HSV PCR obtained were included. Patient demographics and results of HSV testing were collected retrospectively. A complete evaluation was defined as the performance of HSV PCRs from blood, cerebrospinal fluid (CSF), and all surface sites (mouth, both eyes, nasopharynx, and rectum). The diagnosis of neonatal HSV was made by positive diagnostic(s) in conjunction with clinical presentation.

Results

A total of 335 infants (pre-transition=131, post-transition=204) were included. Demographics were similar overall between time periods. Diagnosis of neonatal HSV was made in 2 (1.5%) infants evaluated in the pre-transition and 17 (8.3%) infants evaluated in the post-transition period. Following transition to in-house performance of serum HSV PCR testing, infants were more likely to have a complete evaluation performed (82% vs. 0%; p=0.012). Both patients in the pre-cohort had isolated HSV-2 disease while 4 (23.5%) patients in the post-cohort had co-infection with HSV-1 and HSV-2 (Table 1). Overall, 5 (29%) patients in in the post-transition period had only a serum HSV PCR positive at diagnosis.

Conclusion

Incidence of neonatal HSV within our institution was higher than previous national estimates and incidence increased following transition to in-house serum testing, possibly due in part to improved rates of complete evaluation. The nonspecific clinical presentation and frequency for which only a single PCR was positive reinforces the importance of collecting all surface, blood, and CSF PCRs in neonates undergoing a sepsis evaluation.

Disclosures

All Authors: No reported disclosures
P-1206. Dengue Epidemic Outbreak 2023-2024: is it here for good? Experience in a Tertiary Care Pediatric Hospital in Buenos Aires, Argentina
Authors: Carril Sofia S , Tineo Soledad , Sanz Antonella Antonelli , Denardi Agustina , Marin Andrea , Mistchenko Alicia S , López Eduardo L
Published: January 2025

Background

Between epidemiological weeks (EW) 1 and 13 of 2024, the Region of the Americas reported 4,820,955 suspected dengue cases, triple the count from 2023. Argentina ranked second with 379,341 cases, a fourfold increase from the previous season. Our aim is to describe the behavior of dengue in a pediatric population during 2023 and 2024 and compare the characteristics of the latest two dengue outbreaks in Argentina.

Methods

Two cross-sectional studies were conducted in a children’s hospital in Buenos Aires City. Clinical, epidemiological, laboratory, and follow-up data were recorded for patients < 18 years with confirmed dengue, according to PAHO definitions. The first season period included from March to May 2023 (EW 11 to 20) and the second from January to April 2024 (EW 2 to 15).

Results

A total of 1145 suspected cases were attended. 565 (49%) patients with confirmed dengue were included. Median age: 11 years (IQR 9-14), 308 (54%) being male. Most common symptoms: fever (100%), median duration of 4 days (IQR 3-5); headache/retro-orbital pain (88%); myalgias (75%). 188 patients (33%) exhibited warning signs, the most common: mucosal bleeding, persistent vomiting and severe abdominal pain. 396 patients had leukopenia (71%) and 346 had elevated liver enzymes (62%). Thrombocytopenia (< 100,000/mm3) was found in 131 patients (24%). Significant differences were observed when comparing warning signs: more mucosal bleeding in 2024 (p< 0,001), and more abdominal pain in 2023 (p=0,023). Regarding diagnosis, 495 (88%) patients were confirmed by detectable RT-qPCR, serotype 2 predominated (57%) and was significantly most frequent in 2023 (p< 0,001). 70 (12%) patients had positive NS1 antigen enzyme immunoassay. 86 patients (15%) required hospitalization. 5 cases (0,8%) of severe dengue. No deaths occurred.

Conclusion

Timely and precise diagnosis, along with proper categorization of severity criteria, are crucial during dengue infection. One third of patients had warning signs. Despite serotype 2 being the most common during the 2023 outbreak, which is often linked with severe dengue, the hospitalization rate was the same in both periods. The new quadrivalent vaccine available could be an important tool to decrease the number of patients in our region.

Disclosures

All Authors: No reported disclosures
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

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

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< 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

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 > 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 > CS MIC versus T > BMD MIC. Reductions in bioburden were observed at T > 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

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 < 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 < 0.001) due to fewer subtherapeutic courses. Median time to target decreased from 47.8 to 28.2 hours (p < 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

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 >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

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

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

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
P-1272. Hepatitis A Investigation and Onsite Response in a Retirement Facility, New York City, 2023
Authors: Badenhop Brittan P , Waechter HaeNa , McElroy Roisin , Latash Julia , Gu-Templin Tingting , Chen Judy , Antwi Mike O , Stavinsky Faina , Barnes Rameez , Crouch Bindy , McPherson Tristan D
Published: January 2025

Background

Hepatitis A is a contagious liver infection that can be transmitted by contaminated food consumption. On August 13, 2023, a healthcare provider notified the New York City Health Department of a hepatitis A case in a food handler who worked at a retirement facility while infectious. Medical frailty, mobility, and transportation limitations complicated exposed persons’ access to postexposure prophylaxis (PEP) within the recommended 2-week window. During the COVID-19 pandemic, the Health Department developed capacity to provide onsite SARS-CoV-2 testing and vaccination services within congregate settings to prevent and respond to outbreaks. We used this infrastructure to deliver timely PEP to contacts and prevent an outbreak.

Methods

Using a risk-assessment algorithm, we evaluated the food handler’s hand hygiene, type and quantity of food prepared, and contact with ready-to-eat food. Anyone who ate food the worker prepared while infectious, defined as 2 weeks before symptom onset, was considered exposed. Following Advisory Committee on Immunization Practices guidance, 1 dose of single-antigen hepatitis A vaccine was advised for exposed adults, with coadministration of 0.1 mL/kg human immunoglobulin (IG) for those age > 40 years. Food handlers were required to receive PEP to prevent workplace exclusion. To enable timely PEP receipt, the Health Department worked with facility staff and a vendor to host an onsite clinic on August 23, 2023.

Results

We identified 84 exposed persons, including 42 (50%) residents, 10 (12%) food handlers, and 32 (38%) staff. Median age of those exposed was 74 years (interquartile range [IQR]: 58–88 years); residents’ median age was 89 years (IQR: 84–91 years). Of 84 exposed persons, 39 (46%) received PEP; 30 (77%) received vaccine and IG, 1 (3%) IG only, and 8 (21%) vaccine only. Seven exposed persons who received only vaccine were eligible for IG. All 10 (100%) exposed food handlers, 18 (43%) residents, and 11 (34%) staff received PEP. One secondary case was identified in a resident who declined PEP.

Conclusion

This intervention ensured residents were protected and prevented work exclusions. Providing timely, accessible clinical services within congregate settings, as was commonly done for COVID-19, might effectively prevent the spread of other infections.

Disclosures

All Authors: No reported disclosures
P-1276. Infant Treatment for Congenital Syphilis Among Syphilis-Impacted Pregnancies
Authors: Sancken Christina L , Carlson Jeffrey , Schubert Sara L , O’Callaghan Kevin P , Fountain Alison , Woodworth Kate Russell
Published: January 2025

Background

Congenital syphilis (CS) has been rising in the U.S. since 2013 and is a significant public health challenge1. The Sexually Transmitted Infections (STI) Treatment Guidelines provide treatment recommendations for four different clinical scenarios based on adequacy of treatment during pregnancy, laboratory testing of both the infant and birth parent, and clinical signs2. We used data from the Surveillance for Emerging Threats to Pregnant People and Infants Network3 from five U.S. state and local health departments to describe patterns of treatment among infants born to people with syphilis during pregnancy (Figure 1).

Methods

Infants were classified based on modified STI Treatment Guidelines clinical scenarios2, and included three of the four clinical scenarios: confirmed/highly probable CS, possible CS, and CS less likely. We describe the frequency of prenatal and neonatal characteristics among those who did and did not receive treatment as recommended by the STI Treatment Guidelines (Figure 2).

Results

Of the 1368 liveborn infants with complete medical record abstraction, 13% were classified as confirmed/highly probable CS, 33% as possible CS, and 54% as CS less likely (Figure 3). Frequency of receiving the standard of care was 65% for confirmed/highly probable, 76% for possible, and 34% for CS less likely. The frequency of no reported treatment was 16% for confirmed/highly probable CS, 20% for possible CS, and 45% for CS less likely. The frequency of no reported treatment among confirmed/highly probable CS was highest among infants born to people who were Black non-Hispanic, though numbers were small. Of infants with CS less likely, 18% received more than the recommended one dose (Table).

Conclusion

This report highlights opportunities for improvement in care of infants exposed to syphilis, including racial disparities in recommended care4, that require multipronged approaches to address. Provider education and strong partnerships with well-resourced public health systems can improve coordination of care to ensure infants receive the standard of care. Efforts to improve care of syphilis exposed infants must include efforts to better address larger issues of systematic racism and historical injustices in healthcare and public health to improve equity.Table.Cohort Characteristics by Clinical Scenario and Infant Treatment Status

Disclosures

All Authors: No reported disclosures
P-1288. Changes in Social Contact Patterns Concerning the Respiratory Illness: A Chronological Study in Japan
Authors: Jeong Hwichang , Park Sehyun , Chun June Young , Kim Yongdai , Tsuzuki Shinya
Published: January 2025

Background

Transmission dynamics of respiratory pathogens are largely dependent on social mixing patterns, Besides, individuals who are ill might change their contact behavior according to their symptoms. However, there is a paucity of data on social mixing patterns concerning the respiratory illness.

Methods

Here, we conducted an internet-based periodic survey in Japan since 2022 to characterize the differences in mixing patterns during and after the illness. First, participants who had the respiratory illness were recruited and followed up 2 weeks later.

Contact matrices consisting of the age-specific average number of contacted persons recorded per day were obtained from the survey data, using the bootstrap method. Reciprocity was achieved by using the weighted averages according to the age-specific population sizes [1].

Results

Contact patterns were generally age-assortative, and the average contact numbers had gradually increased from March 2022 to August 2023. Most recently, the median number of contacts per day during respiratory illness was 3 (interquantile range [IQR] = 1-7) and then rose to 5 (IQR = 3-12) in August 2023. The increase ratio was 1.7 (IQR = 0.1-2.3). The baseline frequency of social contacts during illness was identical to the numbers studied in 2021 in Japan (median number of contacts = 3 [IQR = 1-6]) [2]. The number of contacts increased after illness but considering the contact frequency in the 2011 study (median number of contacts = 12), it has not yet reached the pre-COVD-19 status [3].Figure 1.Contact matrices during and after illness within the study period.

Conclusion

In this study, we found that individuals tend to decrease their contacts by up to 50% when they feel unwell. This gap was not found until March 2022 in Japan when social distancing measures against COVID-19 remain. Afterward, the frequency of social contact tends to rise but has not yet reached the pre-COVID-19 era as of August 2023.

Disclosures

All Authors: No reported disclosures
P-1295. Meningococcal Disease in Children in Argentina: A 4-year Active Sentinel Hospital Surveillance Study during the Post-Meningococcal Vaccination Era: A Difficult Impact Analysis
Authors: Gentile Angela , Bakir Julia , Maydana Mara N , Morales Juan C , Ensinck Gabriela , Ernst Adriana , Melonari Pablo A , Cardozo Ana C , Iturres Alejandro Santillan , Santos Mauricio , Efron Adriana
Published: January 2025

Background

In 2017, MenACWY-CRM197 vaccine was introduced in the national immunization program (NIP) in Argentina (2+1 schedule, +1 dose at 11 years). In the pre-vaccination period (preVp, 2012-2015), the meningococcal disease (MD) burden had been assessed.

The objectives of this study were: to evaluate the impact of the intervention on the burden of MD in ≤15 years during a post-vaccination period (postVp, January 2020 to December 2023) and to describe the clinical-epidemiological-bacteriological pattern of all confirmed MD cases of postVp versus preVp.

Methods

Active hospital surveillance in 6 pediatric sentinel units in Argentina. MD discharge rates per 10,000 hospital discharges between preVp and postVp was compared.

Results

In postVp, of 186,257 hospitalized patients, 1047 (0.6 %) had suspected meningitis or MD, of which 9.1 % (95/1047) had acute bacterial meningitis (ABM) and 1.1 % (11/1047) meningococcemia; 79 % (75/95) of ABM cases were confirmed by culture, corresponding 8.0 % (6/75) to Neisseria meningitidis (Nm). In addition, in 2 out of 11 meningococcemia cases a Nm was confirmed by culture. 41.4 % (12/29) of MD culture-negative cases were confirmed by PCR. Thus, there were a total of 20 MD cases, a discharge rate of 1.1 (0.7-1.7) and a reduction of 78.9 % compared to the preVp. Of the 20 MD cases in the postVp, median age was 38 months (IQR 26-95), 13 had MenACWY-CRM197. Microbiological/molecular diagnosis was made in blood/serum (9; 40.9 %) and CSF (13; 59.1 %). Capsular group was identified in 14 samples (B:13; C:1).

Conclusion

After the MenACWY-CRM197 vaccine introduction in the NIP, the burden of MD in ≤15 years was reduced almost 80%. The predominant serogroup was B.

These findings could be interpreted as an effect of the vaccine, but it is necessary to also take into account the biases inherent in vaccine impact studies (COVID-19 pandemic, lockdown measures, natural fluctuations in the incidence of MD, among others).

Disclosures

All Authors: No reported disclosures