bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1149. Short versus Long Duration of Antibiotic Therapy in Pediatric Intensive Care Unit Patients with Uncomplicated Community Acquired Pneumonia: Impact of an Institutional Guideline Update
Authors: Jan Irza , Nagel Jerod , Tribble Alison C , Riggsbee Daniel , Davidge Karen N
Published: January 2025

Background

Community acquired pneumonia (CAP) is a significant cause of morbidity and antibiotic overutilization among pediatric patients. The 2011 Infectious Diseases Society of America (IDSA) guidelines recommend a treatment duration of 10 days for pediatric CAP but recognize that shorter courses may be appropriate in certain settings. In February 2022, based on newer literature and extrapolations from the adult population, Michigan Medicine updated its institutional guidelines to recommend an antibiotic duration of 5 days to treat uncomplicated CAP in hospitalized pediatric patients. However, there remains limited evidence to support a shorter duration of therapy for patients admitted to the pediatric intensive care unit (PICU).

Baseline characteristics of patients treated for uncomplicated CAP in the PICU at Michigan Medicine from November 2020 to December 2023

Methods

This was a single-center, retrospective cohort study of patients aged 6 months to 17 years old with CAP who were admitted to the PICU at Michigan Medicine from November 2020 to December 2023. Patients with complicated CAP, hospital acquired or ventilator associated pneumonia, cystic fibrosis, severe neutropenia, solid organ or stem cell transplant, tracheostomy dependence, sickle cell disease, or suspicion for fungal infection were excluded from the study. The primary outcome was treatment failure, defined as a composite of readmission, emergency department or outpatient visit, need for antibiotic retreatment, or death attributable to CAP within 30 days of completing antibiotic therapy.

Clinical outcomes of patients treated for uncomplicated CAP in the PICU at Michigan Medicine before and after the institutional guideline update

Results

A total of 128 patients met eligibility criteria; 59 (46%) patients were treated before the guideline update and 69 (54%) were treated after the guideline update. The median antibiotic treatment duration was 7.71 days in the pre-guideline update group and 5.58 days in the post-guideline update group (P < 0.001). Three patients in the pre-guideline update group and five patients in the post-guideline update group experienced 30-day treatment failure, which was not a statistically significant difference (P = 0.615). There was no difference in the median hospital length of stay between groups.

Conclusion

This study demonstrated that a shorter course of antibiotic therapy did not increase the rate of treatment failure compared to a standard course of therapy for patients admitted to the PICU with uncomplicated CAP.

Disclosures

All Authors: No reported disclosures
P-1164. Prevalence of invasive Candidiasis and antifungal resistance in neonates: a multicenter three-year retrospective analysis from two large Mexican NICUs
Authors: Garza-Castro Abraham P , Ballesteros-Suarez Ana , Concha-Mora Lindsay A , Prieto-Baca Ericka Paulina , Tamez-Rivera Oscar
Published: January 2025

Background

Candida infections are increasingly recognized as clinically relevant pathogens in NICUs, particularly among preterm and low birth-weight infants (LBWI). Due to the emergence of Fluconazole-resistant Candida spp, current treatment guidelines of neonatal invasive Candidiasis (IC) suggest Amphotericin B as first line therapy, leaving Fluconazole as an alternative agent. Microbiological surveillance focused on fungal etiologies in Mexican NICUs is scarce, which may lead to inappropriate antifungal use.

Methods

Retrospective multicenter study conducted in the NICUs of the two pediatric reference hospitals in NL, Mexico. Clinical and microbiological data of all newborns ≤28 days diagnosed with blood culture-proven invasive Candidiasis from 2021-2023 were collected. LBWIs were defined as newborns < 2500 g at birth, and very LBWI (VLBWI) as < 1500 g. Descriptive statistical analyses were performed to determine the frequency of Candida spp and frequency of antifungal resistance.

Results

During the studied period, 928 positive blood cultures were included. Only 38 blood cultures (4%) were positive for Candida spp. No outbreaks occurred during the studied period. Twenty one patients (75%) were preterm. Mean gestational age was 29 weeks. Most patients (55%) were VLBWI (Table 1). All episodes were classified as late-onset sepsis. The most common isolated species were C. albicans (45%), followed by C. glabrata (29%), and C. parapsilosis (16%). No Fluconazole resistance was observed (Table 2). Caspofungin resistance was found in 5 C. glabrata isolates and 1 C. albicans. No cases of endophthalmitis or endocarditis were documented.

Conclusion

We report a low prevalence of blood culture-proven neonatal IC (4%) in two large Mexican NICUs during the studied period. Most patients were LBWI. This is consistent with international data. C. albicans was the most common isolated species. Based on the local epidemiology in two large NICUs of NL Mx, Fluconazole may be considered as a first line antifungal agent instead of Amphotericin B. Local microbial epidemiology and antifungal susceptibility patterns should be considered for the empirical treatment.

Disclosures

All Authors: No reported disclosures
P-1168. Activity of Isavuconazole and Comparator Agents against Pediatric Fungal Isolates Collected from 2017–2023 in a Global Surveillance Program
Authors: Winkler Marisa , Rhomberg Paul , Fedler Kelley A , Klauer Abigail , Castanheira Mariana
Published: January 2025

Background

Isavuconazole (ISA) is an azole antifungal agent with desirable properties, often making it the treatment of choice for invasive fungal infections. In December 2023, ISA became the sole FDA-approved azole antifungal for the treatment of invasive aspergillosis and mucormycosis in pediatric patients as young as 1 year old. Here, we compare the in vitro activity of ISA and comparator agents against pediatric fungal isolates collected from 2017–2023 in the SENTRY Antimicrobial Surveillance Program.

In vitro Activity of Isavuconazole and select comparator agents against pediatric isolates from the SENTRY database in 2017–2023

Methods

A total of 851 isolates from invasive fungal infections were collected from patients ≤ 17 years old, including 284 patients ≤ 1 year old (yo), 186 2–5 yo, 204 6–12 yo, and 177 13–17 yo. The majority of isolates were from bloodstream infections (515/851, 60.5%). The second most common infection source was pneumonia in hospitalized patients (129/851, 15.2%). Antifungal susceptibility testing was performed by broth microdilution according to CLSI guidelines. Results were interpreted using epidemiological cutoff values (ECV) where applicable.

Results

Isolates were from 28 different countries, with 25 hospitals in North America, 25 in Europe, 13 in Asia-Pacific, and 7 in Latin America. There were 684 Candida spp., 19 other yeasts, 123 Aspergillus spp., and 25 other moulds. For ISA tested against Candida spp., the MIC50 was ≤ 0.008 mg/L and the MIC90 was 0.06 mg/L (Table 1). This result was comparable to MIC50/90 for voriconazole (VRC) against Candida spp. The fluconazole (FLC) MIC50/90 was higher at 0.25/2 mg/L. For Aspergillus spp., the MIC50/90 for ISA was 0.5/2 mg/L and 89.2% of isolates were wildtype (WT) by ECV. The VRC MIC50/90 was 0.5/1 mg/L and 95% of isolates were WT. For Mucorales, MICs were 1–8 mg/L for ISA and 4– > 8 mg/L for VRC. For all other moulds, MICs ranged from 0.25– > 8 mg/L for ISA and 0.12– > 8 mg/L for VRC.

Conclusion

ISA has good activity against pediatric fungal isolates from diverse geographical locations and infection sources. MICs were low for Candida spp. and Aspergillus spp., lower than FLC, and comparable to VRC. All agents had high MICs to non-Aspergillus moulds, highlighting the continued need for novel antifungal agents targeting these organisms.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support Kelley A. Fedler, BS, Paratek Pharmaceuticals: Grant/Research Support
P-1188. Mortality among U.S. Children Aged < 18 Years Hospitalized with Laboratory-confirmed Respiratory Syncytial Virus (RSV) Infection, 12 States, 2018–2019, 2021–2022, 2022–2023
Authors: Toth Eszter , Whitaker Michael , Milucky Jennifer , Pham Huong , Kirley Pam Daily , Kent LeAnna , Kim Daewi , Openo Kyle P , Brooks Alicia , Leegwater Lauren , Como-Sabetti Kathryn , Smelser Chad , Rowe Adam , Popham Kevin , Sutton Melissa , Talbot Keipp , Chatelain Ryan , Havers Fiona P , Patton Monica E
Published: January 2025

Background

Pediatric RSV-associated hospitalizations are well-described but mortality data are limited.

Methods

RSV Hospitalization Surveillance Network (RSV-NET), a 12-state population-based surveillance system, captured laboratory-confirmed RSV hospitalizations among catchment-area residents during October–April in 2018–19 and October–September in 2021–22 (excluding May–June) and 2022–23. Medical charts were reviewed for children who died in-hospital and for those who died ≤30 days post-discharge in 2018–19 via matching case and death certificate data. We described in-hospital and 2018–19 post-discharge mortality among RSV-NET children aged < 18 years. 2019–21 and 2020–21 data were excluded due to COVID-19.

Results

During 2018–19, 2021–22, and 2022–23, 18,511 pediatric RSV hospitalizations were reported with 32 (0.2%) in-hospital deaths among 10, 17, and 5 children aged < 1, 1–4, and 5–17 years, respectively (Table 1). Among 28 children with race and ethnicity data, 9 were non-Hispanic (NH) Black, 8 were NH White, 4 were NH Asian, 5 were Hispanic, and 2 were another race or ethnicity. Almost all (83%) children with medical chart review had ≥ 1 underlying medical condition (UMC); 72% had ≥ 2 UMCs. UMCs included chronic lung disease (CLD) (53%), neurologic disorders (37%), and cardiovascular disease (23%). In all, 33% of children had CLD of prematurity; prematurity, only collected for those < 2 years (n=18 deaths), was noted for 5 (28%) children. Co-detections, including 9 bacterial from respiratory or sterile sites and 11 respiratory viral detections, were noted for 16 (55%) children who died (Table 2).

In 2018–19, 8 in-hospital and 4 post-discharge deaths occurred; the median age at death was 1.5 and 6.5 years, respectively, and the median length of stay was 5.5 and 11.5 days, respectively. All (100%) children had ≥ 1 UMC; ≥ 2 UMCs were noted among 50% and 100% of children with in-hospital and post-discharge deaths, respectively. An RSV-specific cause of death was listed on 4 (33%) of 12 death certificates from 2018–19.

Conclusion

Almost all RSV-NET children who died had ≥ 1 UMC; bacterial or viral co-detections were common. RSV-attributable pediatric deaths are likely underestimated if limited to in-hospital deaths or death certificates with RSV-specific causes.

Disclosures

All Authors: No reported disclosures
P-1192. Association between adeno-associated virus 2 and pediatric acute hepatitis of unknown etiology in Japanese children
Authors: Kawada Jun-ichi , Iwada Ken-ichi , Torii Yuka , Sakai Aiko , Fukuda Yuto , Haruta Kazunori , Yamaguchi Makoto , Suzuki Takako , Etani Yuri , Takahashi Yoshiyuki , Umetsu Shuichiro , Inui Ayano , Sumazaki Ryo
Published: January 2025

Background

Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that the adeno-associated virus 2 (AAV2) and other viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), were frequently detected in patients with AHUE. As HAdV and HHV-6 are known as “helper viruses” that facilitate AAV2 replication, co-infection with AAV2 and helper viruses has been postulated as a potential trigger of AHUE. However, whether hepatitis associated with AAV2 existed prior to the AHUE outbreaks in 2022 has not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children as well as the incidence of AAV2-related hepatitis before 2022.

Visual abstract

Methods

Preserved blood samples from 49 pediatric patients (median age: 3 years) with acute hepatitis of unknown etiology between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses, such as infectious diseases and 50 children with chronic conditions were used as controls. Viral DNA loads were quantified using real-time PCR.

Results

AAV2 DNA was detected in 12% (6/49) of acute hepatitis cases (median age: 2.5 years), but in only one acute illness case and none of the chronic condition control cases. The concentration of AAV2 DNA (range: 2.5×103 to 5.0×108 copies/mL) in the six patients in the acute hepatitis group was higher than that in the patient in the acute-illness control case (7.8×102 copies/mL). Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein–Barr virus, was observed in five of six AAV2-positive acute hepatitis cases.

Conclusion

Our results indicate the sporadic occurrence of severe pediatric hepatitis associated with AAV2 infection in Japan prior to AHUE outbreaks in Western countries in 2022. Conversely, the detection rate of AAV2 in this study was much lower than that of AHUE in Western countries, suggesting that the outbreak of AHUE related with AAV2 is an exceptional phenomenon associated with mitigation measures against COVID-19. Our findings suggest that coinfection with AAV2 and helper viruses plays a role in the development of severe hepatitis.

Disclosures

All Authors: No reported disclosures
P-1202. Human Bocavirus detection among children presenting to tertiary care with acute respiratory infections in Oman: clinical characteristics, seasonality and comparison with common viruses
Authors: Al Fahdi Ahmed S , Al Qanobi Abdulrahman S , Al Maani Mohammed , Al Maani Bushra , Al Khatri Mariya , Al Khatri Hanan , Al Hinai Abdulaziz , Alhinai Zaid
Published: January 2025

Background

Human Bocavirus (HBoV) was first identified in 2005 among children suffering from acute respiratory symptoms. It is frequently detected as a co-infecting virus, and the degree to which it causes to symptoms is unclear. Little is known about its epidemiology in the Middle East.

Methods

Children who presented to Sultan Qaboos University Hospital, Muscat, Oman between January, 2018 and December, 2019, with acute respiratory symptoms and were tested for respiratory viruses were reviewed. Respiratory specimens were tested using the FTD Respiratory Pathogens 21 Assay (Siemens Healthineers). Patients with HBoV detection were included. A subset of patients with sole detection of RSV or Rhinovirus was included for comparison. Clinical presentation, laboratory results, and outcomes were analyzed and compared.

Results

A total of 3789 patients were tested for respiratory viruses, of whom 2714 (72%) had positive results, and 163 (5%) were positive for HBoV. HBoV was detected as the only pathogen in 34 cases (21%), while 129 (79%) represented co-infection. For comparison, 252 cases of Rhinovirus and 80 cases of RSV were included. HBoV detection occurred year-round with no clear seasonal variation (Figure 1). HBoV detection was most common in children under 2 years of age, and uncommon after 5. RSV was only detected under 2 years of age, and Rhinovirus was commonly detected in all age groups (Figure 2). Patients with HBoV without co-infection were more likely to be immunocompromised (29% vs 8%, P 0.002) or suffer from other chronic disease (68% vs 35%, P 0.001) compared to those with co-infection (Table 1). They were also more likely to suffer from diarrhea (35% vs 14%, P 0.009) and tachycardia (77% vs 54%, P 0.032). Patients with HBoV without co-infection did not significantly differ otherwise from those with co-infection. Compared with RSV, patients with HBoV had a higher median age (1.95 vs 0.2 years, P < 0.001) and were more likely to be immunocompromised (29% vs 1%, P < 0.001) (Table 2). Patients with RSV were more likely to require respiratory support (67% vs 29%, P < 0.001).

Conclusion

HBoV had year-round circulation with no seasonal pattern. HBoV likely contributed significantly to acute respiratory disease in children under 5 years of age, especially those with chronic underlying conditions.

Disclosures

All Authors: No reported disclosures
P-1208. Multi-year Analysis of Respiratory Viral Dynamics at a Los Angeles County Academic Health System Reveals Significance of Rhinovirus in Young Children with Severe Respiratory Illness
Authors: Caldera J R , Saleh Tawny , Fuller Trevon , Yang Shangxin , Nielsen-Saines Karin
Published: January 2025

Background

Respiratory infections in children are highly dynamic requiring frequent assessments of epidemiological trends to mitigate their impact on the population. We aimed to analyze the landscape of viral respiratory illnesses (VRIs) in a large metropolitan area in Southern California with a focus on the COVID-19 pandemic.

Methods

We conducted a retrospective cohort study within the UCLA Health System, which evaluated children aged 0-5 years who received comprehensive respiratory viral panel (cRVP) testing during August to February of 2018 to 2023. Patient demographics, disease severity, and clinical course were specifically compared during the pandemic. Predictors of moderate-to-severe VRI were determined by multivariate logistic regression.

Results

In total, 1,321 children with a median age of 2 years (44% female) underwent cRVP testing. A total of 753 positive subjects were identified during the study period. Rhinovirus (RV) was by far the most frequent virus identified in children across 5 years, even during the COVID-19 pandemic period, followed by respiratory syncytial virus (RSV). Along with RSV and human metapneumovirus, rhinovirus (RV) was associated with the highest disease severity across the years, particularly in the Hispanic/Latino ethnic group. Importantly, RV-driven respiratory disease occurred independently of co-infection with other viruses.

Conclusion

RV was the most common viral pathogen in young children even during the height of the COVID-19 pandemic and was an independent driver of moderate-to-severe disease particularly in children with co-morbidities. Ethnic disparities were observed in disease severity, underscoring the need for targeted interventions, and heightened clinical vigilance in pediatric populations.

Disclosures

All Authors: No reported disclosures
P-1218. Assessment of Cefepime-Taniborbactam (FEP-TAN) Transmembrane Clearance (CLTM) in an Ex vivo Continuous Renal Replacement Therapy (CRRT) Model
Authors: Fouad Aliaa , McGrath Cole , Buyukyanbolu Ecem , Kuti Joseph L
Published: January 2025

Background

Optimal antibiotic dosing in patients undergoing CRRT is influenced by many factors that affect drug adsorption and clearance. These factors include filter type, CRRT mode, effluent rate (ER), and drug characteristics. FEP-TAN is an investigational β-lactam/β-lactamase inhibitor combination having broad-spectrum activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. Both FEP and TAN are primarily eliminated through glomerular filtration. Hence, we conducted an ex vivo CRRT model to characterize the adsorption and CLTM when co-administered.

Methods

CLTM was characterized in hemofiltration (CVVH) and hemodialysis (CVVHD) modes using the Prismaflex ST150 and HF1400 hemofilter sets. One liter of heparinized bovine blood was allowed to circulate in the CRRT system for 10 minutes. FEP and TAN were then added simultaneously to attain plasma concentrations of 70 and 20 mg/L, respectively, the average Cmax achieved in humans following FEP-TAN 2g/0.5g q8h as a 4h infusion. Pre-filter blood, post-filter blood, and effluent samples were collected over 60 minutes to determine FEP and TAN concentrations. Combinations of filters, modes, and points of fluid replacement were tested at ERs of 2, 3, and 4 L/h. The sieving coefficient (SC) for CVVH and the saturation coefficient (SA) for CVVHD were calculated to determine CLTM. Protein binding (PB) was assessed by ultrafiltration. Adsorption was determined using a closed circuit bypassing effluent elimination.

Results

Adsorption and degradation in the ex vivo CRRT model were negligible for both drugs. Mean ± SD initial FEP and TAN concentrations were 66.9 ± 5.3 and 18.7 ± 1.7 mg/L, respectively. PB was 0% for FEP and 5.4 ± 3.7% for TAN in bovine plasma. The overall mean ± SD SC/SA across different modes, filters, and ERs were 1.1 ± 0.06 for FEP and 1.0 ± 0.05 for TAN. The CLTM at ERs of 2, 3, and 4 L/h were 2.1 ± 0.2, 2.9 ± 0.3, and 3.8 ± 0.5 for FEP and 1.9 ± 0.2, 2.7 ± 0.2, and 3.4 ± 0.3 L/h for TAN, respectively.

Conclusion

FEP and TAN were efficiently cleared by both CVVH and CVVHD CRRT modes through ST150 and HF1400 filters. When incorporated into an established population pharmacokinetic models, these data can be used to develop dosing recommendations for FEP-TAN in patients undergoing CRRT.

Disclosures

Joseph L. Kuti, PharmD, Abbvie: Advisor/Consultant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria|Venatorx: Grant/Research Support
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

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 >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 > 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

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

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

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

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 > MIC for intermittent infusions and 100%fT > MIC and 100%fT > 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 > 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 > 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

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

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

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 > 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

Background

Early antiviral treatment (< 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 < 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 < 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
P-1333. Influence of Allocation Proportion of Intervention and Control on Results Analyzed Using the Cox Proportional Hazard Model: A Pilot Meta-Analysis Using Actual Clinical Trials
Authors: Takeishi Soichi , Inoue Tatsuo , Miyamura Koichi
Published: January 2025

Background

In reports assessing the effect of an intervention (I) on COVID-19–related endpoints using the Cox proportional hazard model, “allocation proportions of I and control (C)” vary. The effect of these allocation proportion on results analyzed using Cox regression in actual clinical trials is unknown. Therefore, we conducted a pilot meta-analysis of clinical trials to investigate this effect.

The correlations between metrics

Methods

Articles published in The New England Journal of Medicine were included as part of a pilot meta-analysis if the following conditions were satisfied: 1. assessing endpoints related to COVID-19, and 2. using Cox regression. We referred to “upper limit of 95% confidence interval (CI) of hazard ratio (HR) (U95%CI) − lower limit of 95%CI of HR (L95%CI)” as the 95%CI range. Partial regression coefficients (β) were calculated as Loge(HR), and the standard error of β was estimated using ((Loge(U95%CI) – Loge(HR)) ÷ 1.96 + (Loge(HR) − Loge(L95%CI)) ÷ 1.96) ÷ 2, denoted as eSE. We calculated eSE ÷ an absolute value of β (eSE/|β|). The number of subjects (n) in an intervention group (nI) ÷ (nI + n in a control group (nC)) × 100 was termed “intervention proportion % (IP)”, and nC ÷ (nI + nC) × 100 was termed “control proportion % (CP)”. We calculated the absolute value of 40 − CP (|40 − CP|) and 40 – IP (|40 – IP|). For HR< 1, “HR< 1 adjusted group” (HR< 1aG) retained the original metrics, while the “HR >1 adjusted group” (HR >1aG) used metrics calculated with the reciprocal of HR and its 95%CI (e.g. 0.50 (0.20-0.80) → 2.00 (1.25-5.00)). For HR >1, HR< 1aG used metrics calculated with the reciprocal of HR and its 95%CI, while HR >1aG retained the original metrics.

Results

We included 50 outcomes from 22 studies. The figure shows the correlations between metrics. In HR< 1aG, |40 − CP| correlated with the 95%CI range (r=0.62, p< 0.001), whereas |40 – IP| did not correlate with the 95% CI range (r=0.01, p=0.93) in HR >1aG. In HR< 1aG, |40 − CP| correlated with the eSE/|β|, and |40 − IP| correlated with the eSE/|β| in HR >1aG (both r=0.63, p< 0.001).

Conclusion

The present study results may indicate that extremely biased allocation proportions of I and C diminish the credibility of HR. Replacing eSE/|β| with 95%CI range may not accurately assess this diminished credibility.

Disclosures

All Authors: No reported disclosures