Target Attainment Research Articles

Biomedical outcomes and cardiovascular risks in Chinese adults with type 2 diabetes in the metabolic management center program: Alongitudinal comparative study.

To assess the extent to which biomedical outcomes and cardiovascular risk profile were improved in the management of Chinese patients with type 2 diabetes enrolled in the metabolic management center (MMC) program. We performed propensity score matching of diabetic patients in the MMC program for at least 12 months to those with diabetes under usual primary care, based on age, sex, fasting plasma glucose (FPG) level, and diabetes duration. Difference-in-difference analysis was conducted to compare changes in biomedical outcomes, attainment of treatment targets, and cardiovascular disease (CVD) risk reduction. Of 557 pairs of diabetic patients matched 1:1 (n = 1,114), the MMC cohort exhibited greater improvements in FPG (-0.84 mmol/L, 95% confidence interval [CI] -1.22 to -0.46, P < 0.001), diastolic blood pressure [BP] (-2.08 mmHg, 95%CI -3.21 to -0.94, P < 0.001), body mass index [BMI] (-0.29 kg/m2, 95%CI -0.51 to -0.07, P = 0.009), low-density lipoprotein cholesterol (0.13 mmol/L, 95%CI 0.04-0.23, P = 0.008), high-density lipoprotein cholesterol (0.05 mmol/L, 95%CI 0.01-0.08, P = 0.017), and 10-year CVD risk (Framingham CVD risk, -0.94%, 95%CI -1.71 to -0.17, P = 0.017; atherosclerotic CVD risk, -0.77%, 95%CI -1.34 to -0.20, P = 0.009) when compared to the usual primary care cohort after adjustment for confounders. More patients in the MMC cohort achieved treatment targets with lifestyle modifications than their counterparts under primary care. Enrolment in the MMC program appears promising in the management of FPG, BP, BMI, lifestyle, and CVD risk in diabetic patients, suggesting the necessity of incorporating the MMC program into routine primary care.

Implementation of model-informed precision dosing for tamoxifen therapy in patients with breast cancer: A prospective intervention study.

Tamoxifen is an estrogen-receptor (ER) antagonist, used as adjuvant treatment of ER-positive breast cancer. It is converted by CYP2D6 into endoxifen, its most active metabolite. Patients with endoxifen plasma concentrations <16nM face a higher risk of recurrence. The use of a priori model-informed precision dosing (MIPD) may lead to faster target attainment and thus potentially improve patient outcomes. In total, 106 evaluable patients were prospectively included in this single-arm MIPD-intervention study. Patients received a model-predicted tamoxifen dose when starting tamoxifen-treatment (65.1% of patients received 20mg, 16.0% received 30mg and 18.9% received 40mg). Seventy-five percent of the 40mg group was predicted to be unable to reach the threshold of 16nM despite receiving the highest registered dose. After attaining steady-state, 84.0% of patients reached endoxifen levels ≥16nM, which was not significantly higher compared to a historical control cohort (77.9%, p=0.17). The model showed adequate performance and correctly identified patients requiring 40mg tamoxifen. Endoxifen samples that were acquired 4-6 weeks after treatment initiation, are informative of steady-state endoxifen levels and can be used to inform MIPD and adjust tamoxifen dosing prior to steady-state attainment. In this first MIPD implementation study for patients treated with tamoxifen, MIPD did lead to more patients achieving endoxifen levels ≥16nM as compared to the one-dose-fits-all strategy, albeit insignificant. This may partly be explained by a larger proportion of patients who were recommended to switch to an aromatase inhibitor (AI) in the intervention cohort. In conclusion, MIPD seems beneficial compared to one-size-fits-all-dosing, but TDM still remains an important addition.

P-1224. Individual Target Pharmacokinetic/Pharmacodynamic Attainment Rates among Cefepime-treated Patients Admitted to the ICU with Hospital-Acquired Pneumonia with and without ECMO

Abstract Background The impact of extracorporeal membrane oxygenation (EMCO) on cefepime (FEP) pharmacokinetics (PK) in the absence of renal replacement therapy (RRT) is unclear. Figure 1. Observed versus predicted cefepime plasma concentrations in the population (A) and for each individual (B) Methods We evaluated FEP PK in patients with hospital-acquired pneumonia from June 2018 to May 2023, with/without ECMO in the absence of RRT, in a single-center study nested within the Successful Clinical Response In Pneumonia Treatment (SCRIPT) study. Patient data were extracted from electronic health records. FEP dosing was according to institutional protocols based on renal function and indication. Plasma concentrations were quantified by validated LC-MS/MS assay. We used Pmetrics 2.1.1 for R to estimate population model parameter values [e.g., volume (V) and clearance (CL)] and individual target attainment rates, assuming a free (f) fraction of 80%. Targets of 100% fT&amp;gt;1xMIC and 100% fT&amp;gt;4xMIC were evaluated vs. the susceptible breakpoint MICs of Enterobacterales (2 mcg/mL) and P. aeruginosa (8 mcg/mL) and stratified by concurrent ECMO. Figure 2. Pharmacokinetic parameters (CL and V) standardized to body weight (kg) stratified by ECMO status. Results Sixty-two SCRIPT patients (63% male) contributed 95 plasma FEP samples (1-13 per patient). A total of 9 patients (one female) required ECMO. Patients had a mean±SD CRCL of 123±84 mL/min and a mean±SD body weight of 86±24 kg. The median/max first 24-hr FEP dose was 4/8 grams. A two-compartment PK model fitted best (Fig 1). Body weight and creatinine clearance were related to V and CL, respectively (Table 1). ECMO was not significantly associated with FEP CL (P=0.2) but was associated with V (P&amp;lt; 0.005) (Fig 2). ECMO patients had a median 3.5-fold greater Vd vs. non-ECMO patients. For targets of fT &amp;gt;1xMIC and fT &amp;gt;4xMIC, median individual plasma attainment rates were 100% and 100% against Enterobacterales and 100% and 49% against P. aeruginosa, respectively. Attainment rates were lowest in patients requiring ECMO vs. P. aeruginosa at a target of 100% fT &amp;gt;4xMIC, (Fig 3). Figure 3. Individual predicted cefepime PK/PD target attainment stratified by organism breakpoint and concurrent ECMO status for fT&amp;gt;1xMIC and fT&amp;gt;4xMIC. Conclusion We found that ECMO increased FEP V but not CL suggesting that ECMO patients may require loading doses and prolonged infusions to improve target attainment. Protocolized short infusions of FEP in ECMO patients resulted in suboptimal target attainment for a PK/PD goal of 100% fT&amp;gt;4xMIC against P. aeruginosa. More work is needed to identify the impact of FEP target attainment on clinical outcomes in populations such as these. Table 1. Population Median Parameters and 95% Credible Intervals for Cefepime Patients with and without the Requirement of Extracorporeal Membrane Oxygenation Support Disclosures Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Cidara: Advisor/Consultant|DoseMe: Advisor/Consultant|Entasis: Advisor/Consultant|F2G: Advisor/Consultant|GSK: Advisor/Consultant|Lykos: Advisor/Consultant|Roche: Advisor/Consultant|Third Pole Therapeutics: Advisor/Consultant|Xelia: Advisor/Consultant Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant

P-1254. Improved Vancomycin Target Attainment Following a Quasi-Experimental Change in Pharmacokinetic Model for Bayesian Precision Dosing

Abstract Background When using a Bayesian approach for vancomycin dosing, pharmacokinetic (PK) models guide dosing decisions. This study explores the impact of moving from the Goti model to the Thomson model on target attainment, dosing decisions, and acute kidney injury (AKI) rates. Methods Adults with BMI &amp;lt; 40 kg/m2 treated with vancomycin using InsightRX Nova Bayesian software, who switched from the Goti to the Thomson models as their default between January 1, 2023, and April 15th, 2024, were included. The switch was prompted by internal analyses suggesting the Thomson model was performing better. AUC24 was calculated for the treatment course and days 1, 2, and 3+. Outcomes included the proportion of patients in the target AUC24 range of 400-600 mg*h/L, time to target attainment, average daily dose, severe AKI rates (KDIGO stage 2 or 3 after 48 hours), and levels per course. An interrupted time series analysis was done for AUC24. The relationship between subtherapeutic AUC24 to minimum inhibitory concentration (MIC) ratio and mortality was extrapolated from a study by Lodise et al. (2014) on patients with MRSA bloodstream infections. MICs were assumed to be 1 mg/L. Results The study included 27,604 patients before and 23,359 after the intervention across 16 health systems (Table 1). The average AUC24 for days 1, 2, 3+, and the full treatment course showed statistically significant improvement (see Figure 1). AUC24 target attainment increased from 46.5% to 51.1% (p &amp;lt; 0.001) due to fewer subtherapeutic courses. Median time to target decreased from 47.8 to 28.2 hours (p &amp;lt; 0.001), severe AKI rates rose slightly from 1.75% to 2.03% (p = 0.023, number needed to treat (NNT): 358), and average daily dose and levels slightly increased (see Figure 2). The decreased proportion of subtherapeutic AUC24 on days 1 and 2 before and after intervention corresponded to expected mortality rates of 17-18% and 16-17%, respectively (NNT: 130). Conclusion Switching the default PK model used in a Bayesian approach for dosing adult patients on vancomycin resulted in improved AUC24 target attainment, and a 41% decrease in time to target attainment, with only slightly increasing AKI rates. Disclosures Maria-Stephanie Hughes, PharmD, InsightRX: Employee of company|InsightRX: Stocks/Bonds (Private Company) Dominic M.H. Tong, PhD, Insight RX, Inc: Employee|Insight RX, Inc: Stocks/Bonds (Private Company) Jasmine Hughes, PhD, InsightRX: Employee|InsightRX: Stocks/Bonds (Private Company)

P-1257. Cefazolin Dosage Considerations for Methicillin-Susceptible Staphylococcus aureus (MSSA) Central Nervous System Infections: Exploring Optimal Regimens

Abstract Background Historically, cefazolin (CFZ) has not been considered an appropriate agent to treat central nervous system (CNS) infections. Recent studies have shown that standard CFZ dosing achieves concentrations above the epidemiologic cutoff of minimum inhibitory concentration ≤ 2 mg/L for Staphylococcus aureus, but literature describing optimal dosing for CNS infections is lacking. This study aimed to identify CFZ dosing regimens necessary to achieve adequate probability of target attainment (PTA) for treatment of a methicillin-susceptible S. aureus (MSSA) CNS infection. Methods CFZ plasma and cerebral spinal fluid (CSF) pharmacokinetic parameters were obtained from a previous published study. Monte Carlo simulations were performed utilizing PD targets of 40%fT &amp;gt; MIC for intermittent infusions and 100%fT &amp;gt; MIC and 100%fT &amp;gt; 4xMIC for continuous infusions (CI) to determine probability of target attainment (PTA) for seven CFZ dosing regimens at an MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. Adequate target attainment, defined as ≥ 90% PTA, was evaluated for CFZ dosing regimens ranging from 6-12g/day administered intermittently every 4-8 hours over 30 minutes or as a CI over 24 hours (Table 1). Results The standard intermittent regimen of 2g q8h did not achieve ≥ 90% PTA for any MIC evaluated. Furthermore, no CI regimen achieved ≥ 90% PTA when using the PD target of 100%fT &amp;gt; 4xMIC. All continuous and intermittent regimens achieved ≥ 90% PTA when the MIC remained ≤ 0.5 mg/L. Only the 10 g and 12 g CI regimens achieved ≥ 90% PTA for 100%fT &amp;gt; MIC when the MIC was 1 mg/L while no regimen achieved the desired target when the MIC was 2 mg/L. Conclusion These findings underscore the inadequacy of standard intermittent CFZ regimens in achieving desired PD targets for MSSA CNS infections. Higher total daily doses or CI CFZ is necessary to achieve satisfactory PD targets for MSSA CNS infections. When comparing the same total daily dose administered as an intermittent versus continuous infusion, our results suggest that continuous infusions are more likely to achieve PD target attainment for MSSA CNS infections, particularly when the cefazolin MIC exceeds 0.5 mg/L. Further clinical studies are warranted to evaluate the safety and efficacy of CFZ for CNS infections caused by MSSA. Disclosures All Authors: No reported disclosures

P-1256. Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analyses for Aztreonam-Avibactam Dosing Regimens

Abstract Background Aztreonam-avibactam (ATM-AVI) is a fixed-ratio β-lactam/β-lactamase inhibitor recently approved in Europe for adults with serious Gram-negative infections. Prior to commercial availability of ATM-AVI, doses for ceftazidime-avibactam (CAZ-AVI) + ATM have been proposed.1 We evaluated probability of joint PK/PD target attainment (PTA) for ATM-AVI and CAZ-AVI + ATM in adults with complicated intra-abdominal infection (cIAI). Methods A simultaneous population PK model for ATM and AVI was developed using data from the CAZ-AVI and ATM-AVI adult clinical programs, including two ATM-AVI phase 3 trials. The final model was used to simulate exposures and calculate PTA (5000 patients/simulation) for ATM-AVI dose regimens adjusted for renal function, and two proposed CAZ-AVI + ATM dose regimens in cIAI patients with CrCL 80 to ≤150 mL/min. PTA was calculated for the joint PK/PD target of ATM 60% fT &amp;gt; 8 mg/L and AVI 50% fT &amp;gt; 2.5 mg/L. Results The analysis included 4,914 ATM plasma samples (431 subjects) and 18,222 AVI samples (2,635 subjects). The final model was a two-compartment model for ATM and AVI with zero-order infusion and first-order elimination. Standard allometric exponent functions of body weight on clearances (0.75) and volumes (1) were applied; body surface area-normalized CrCL was used to describe clearance changes during treatment. Infection type was a key covariate on clearance and volume for both drugs. Steady-state exposures for ATM-AVI dose regimens were associated with joint PTA 89 to &amp;gt; 99% across renal function groups (Table 1). CAZ-AVI + ATM dose regimens resulted in similar (or higher) geometric mean ATM Cmax,ss and AUC24,ss compared with ATM-AVI, but AVI AUC24,ss was approximately 25% lower, and joint PTA was &amp;lt; 85% (Table 2). Conclusion ATM-AVI dose regimens achieved high joint PTA across renal function groups. In contrast, joint PTA with proposed CAZ-AVI + ATM dose regimens for normal renal function were &amp;lt; 85% because of insufficient AVI exposures, regardless of the ATM dose (2g q6h or q8h). Joint PTA with both combinations is driven by the AVI plasma PK/PD target and is independent of pathogen MIC up to 8 mg/L. 1. Tamma PD et al. Clin Infect Dis 2023: ciad428. Trial registration: NCT03329092; NCT03580044. Study sponsored by Pfizer. Disclosures Susan R. Raber, PharmD, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Rujia Xie, PhD, Pfizer: Former employee|Pfizer: Stocks/Bonds (Public Company) Elena Soto, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Heidi Leister-Tebbe, BSN, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

P-1789. Implementation of Pathogen Independent Model Informed Precision AUC-based Dosing of Vancomycin at University Hospital Wuerzburg (UKW)

Abstract Background The IDSA guideline concerning monitoring vancomycin in MRSA infections, published in March 2020, recommends model informed precision AUC based dosing for vancomycin. The application of pharmacometrics software with Bayesian calculating is recommended. The summary of product characteristics of vancomycin, issued by EMA (European Medicines Agency), includes also details regarding model informed precision dosing for vancomycin therapies, irrespective of targeted or identified pathogens. Due to the low prevalence of MRSA infections at UKW, model informed precision AUC-based dosing has been instituted for all parenteral vancomycin therapies. Methods The target for vancomycin AUC/MIC (minimum inhibitory concentration) is a range of 400 – 600 mg*h/L over 24 hours. Individual patient covariates, personal dosing information and vancomycin concentrations were converted into dosing recommendations with InsightRX. In order to record the effect of the intervention, the target attainment and the occurrence of AKI (acute kidney injury, defined as an increase in serum creatinine of ≥ 0.3 mg/dL within 48 h) is recorded 18 months before and 12 months after the implementation of the new dosing strategy. Results Since October 2022, a workflow for model informed AUC-based dosing has been launched across 12 wards - mainly intensive care units - encompassing 215 beds. In the conventional dosing strategy according to trough dosing, AKI occurred in 60 of 216 therapies, while AKI was detected in 8 out of 57 AUC-guided vancomycin therapies resulting in an odds ratio of 2.32 [CI 95 % 1.08 – 5.59]. Significantly more AUC guided therapies were in the therapeutic range of 400 – 600 mg*h/L after 120 hours than trough-based vancomycin therapies reached the target [55.1 % vs 70.2 %, OR 0.52, CI 95 % 0.27 – 0.97]. Additionally, more trough-based therapies were in a supratherapeutic range than AUC guided therapies [24.5 % vs 8.8 %, OR 3.23, CI 95 % 1.35 – 9.98] Conclusion The unique concept of pathogen independent model-informed AUC-based dosing of vancomycin was successfully integrated into the clinical routine work. Early dose individualization due to AUC-based dosing can contribute to increase drug therapy safety and improved patient safety for vancomycin therapies. Disclosures All Authors: No reported disclosures

209. Population Pharmacokinetics of Meropenem-Vaborbactam in Acutely Ill Hospitalized Patients with Various Degrees of Renal Dysfunction

Abstract Background Pharmacokinetic-pharmacodynamic (PK/PD) target attainment rates for meropenem-vaborbactam (MV) in real-world acutely ill patients are poorly defined. We sought to evaluate target attainment rates for MV in patients with various degrees of renal dysfunction including those requiring continuous renal replacement therapy (CRRT).Figure 1.Observed versus predicted meropenem concentrations from the population (A) and individual (B) model fits Methods Patients treated with MV from December 2017 to July of 2022 were included. MV was dosed according to institutional protocols based on renal function and indication. After informed consent, opportunistic plasma samples were collected. Plasma MEM and VAB were quantified using a validated LC-MS/MS assay. Patients with acute kidney injury, and those requiring CRRT were included. Patients requiring hemodialysis were excluded. Multiple compartmental models and covariate effects [e.g., Cockcroft Gault calculated creatinine clearance (CRCL) per 1.73m2 on clearance (CL) and total body weight (WT) on volume (Vd)] were tested. Analyses were performed using Pmetrics 2.1.1 for R. A free (f) fraction of 98% and 67% were assumed for MEM and VAB, respectively. Targets of 40% fT &amp;gt;MIC and 100% fT &amp;gt;MIC for MEM and fAUC:MIC of 38 for VAB were evaluated vs. the MIC50 and full EUCAST MIC distribution for K. pneumoniae (https://mic.eucast.org/).Figure 2.Observed versus predicted vaborbactam concentrations from the population (A) and individual (B) model fits Results 18 (50% female) patients aged 54±14 years contributed 83 paired MV observations. Baseline CRCL was 114±102 mL/min/1.73m2, and baseline WT was 91±31 kg. Three patients received CRRT. A one-compartment, two-input, two-output, population PK model was fit for purpose (MEM Fig1, VAB Fig2). Non-CRRT MEM CL was higher than VAB CL (median 10.6 vs. 6.8 L/hr). CRRT MEM CL was also higher than VAB CL (median 4.1 vs. 2.7 L/hr). However, MEM Vd was similar to VAB Vd (median 23.9 vs. 21.5 L) (Table1). The simulated PTA vs. the EUCAST MIC50 of 0.75/8 was high for MEM and VAB targets (Table2). The simulated CFR for MEM was &amp;gt;80% with 4g IV every 8 hr at a 40% fT &amp;gt;MIC goal but was reduced at a 100% fT &amp;gt;MIC goal whereas the CFR for VAB approached 80% across renal states (Table2). Conclusion CRRT patients had roughly 40% lower MV CL vs. non-CRRT patients. VAB had lower CL vs. MEM resulting in accumulation. Aggressive (e.g., 100% fT &amp;gt;MIC) MV targets may be challenging to attain vs. contemporary isolates while target attainment vs. susceptible isolates remains high. Disclosures Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Ciadara: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Brandon Smith, MD, PharmD, Melinta Therapeutics: Advisor/Consultant|Shionogi, INC: Advisor/Consultant Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant

210. Implementation of a Pharmacist Driven Beta-lactam Therapeutic Drug Monitoring Program with Daily Result Reporting: Initial Experiences and Challenges Faced

Abstract Background Beta-lactam (BL) antibiotics are a cornerstone of treatment for patients with serious infections. Individualized BL dosing using therapeutic drug monitoring (TDM) is an emerging approach to address variability in BL exposure that adversely impacts PK/PD; however, challenges can emerge when implementing TDM programs in the real-world. We sought to characterize the implementation of a BL TDM program by describing initial successes and challenges. Methods In September 2023, we implemented a front-line pharmacist driven BL TDM clinical protocol (Figure 1) with daily result reporting for the following BLs: cefepime (FEP), meropenem (MEM), and piperacillin-tazobactam (TZP). Patients with FEP, MEM, and TZP plasma TDM data analyzed between September 26th, 2023 and March 31st, 2024 were included. TDM results were interpreted using Bayesian analysis (InsightRX). For each TDM event, we characterized ordering provider specialty, whether or not TDM was performed per protocol, whether or not changes were made in response to TDM results, Bayesian model fitness, treatment indication, culture information, and PK/PD target attainment [including predicted steady state trough concentration (Ctrss) and fT&amp;gt; 1xMIC and fT&amp;gt; 4xMIC]. Results Eighty-two BL TDM levels were obtained in 47 patients. FEP was most frequently monitored (70.7%). Model fit was good or intermediate in &amp;gt; 95% of cases (Table 1). The most common treatment indications were HAP/VAP (n=12, 25.5%), surgical prophylaxis (n=6, 12.8%), bone/joint (n=6, 12.8%), and CNS infection (n=6, 12.8%) (Table 2). Dose adjustments were made in 34% (n=16) of patients. In 57.4% of patients the level order or dose-adjustment deviated from recommended protocols. Targets of 100% fT&amp;gt; MIC and 100% fT&amp;gt; 4xMIC were achieved in 91.5% and 61.7% of patients, respectively (Table 3). Ctrss was above goal in 21% of patients. Conclusion We found that &amp;gt; 90% of patients undergoing BL TDM achieved 100% fT&amp;gt; MIC, whereas nearly 40% failed to achieve 100% fT&amp;gt; 4xMIC at baseline, and &amp;gt; 20% had a Ctrss exceeding safety goals. BL TDM resulted in dose or agent change over 60% of the time, but protocol deviations in dose adjustment were common. The frequency of interventions observed underscores the potential clinical impact of BL TDM on a broader scale when daily reporting is available. Disclosures Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant

207. Ex vivo Assessment of Cefepime (FEP) Clearance during Continuous Renal Replacement Therapy (CRRT) and Clinical Validation of Optimized Dosing Regimens

Abstract Background Optimal antibiotic dosing in critically ill patients receiving CRRT is crucial. Drug clearance (CL) can be affected by multiple factors such as CRRT mode, effluent rate (ER) or filter type. We investigated FEP transmembrane CL (CLTM) in an ex vivo CRRT model to inform optimal dosing regimens and validate these regimens by re-simulation in a clinical cohort of CRRT patients. Methods CLTM was determined ex vivo in hemofiltration and hemodialysis modes with M100 and HF1400 filters. Bovine blood spiked with FEP was sampled from pre-, post-filter and effluent fluids at 10, 30, and 60 minutes in duplicate runs at ER of 1, 2 and 3 L/h. CLTM was calculated via sieving (SC) and saturation coefficients (SA). A multiple linear regression was performed to describe CLTM as a function of ER, filter, and mode. Monte Carlo Simulations (MCS; n=1000) using the equation CL= non-renal CL + CLTM and distribution parameters from a published population pharmacokinetic (popPK) model were executed for ascending ER (1-5 L/h). The resulting FEP regimens were selected by probability of target attainment (PTA) for 70%fT &amp;gt; MIC (MIC = 8mg/L CLSI susceptible breakpoint) and mean AUC within the 25th-75th percentile of a non-CRRT cohort. Selected regimens were validated by re-simulating fT &amp;gt; MIC and AUC using popPK defined Bayesian parameters in Pmetrics for R from 10 CRRT patients receiving FEP in clinical practice. Results Mean (SD) ex vivo SC/SA were 1.01 (0.08). ER was the main predictor (p&amp;lt; 0.001) for CLTM (CLTM= 0.139+0.841*ER) with no effect from mode or filter type. MCS of FEP 1g and 2g q8h provided 100% PTA at 8 mg/L with AUCs similar to the non-CRRT comparator for ER of 1-2.4 and 2.5-5 L/h respectively. Mean (SD) popPK parameter estimates of the validation cohort were CL, 3.8 (1.1); Vc, 17.3 (15.3) L; k12, 5.0 (3.1) h-1; and k21, 6.4 (7.6) h-1. Selected regimens tested in the validation cohort demonstrated good performance with the algorithm (Figure 1). Conclusion These are the first data to translate the findings of ex vivo CRRT CLTM in a dosing algorithm based on CRRT ER to achievable exposure in patients receiving FEP. For CRRT ER of 1-2.4 L/h and 2.5-5 L/h FEP 1g and 2g 8h as 0.5h infusions achieve 70% fT &amp;gt; MIC, respectively, while retaining AUC in range with safe exposures in non-CRRT patients. Disclosures Christina Konig, PhD, Gilead Inc.: Honoraria|Pfizer Inc.: Honoraria|Shionogi Inc.: Honoraria David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support 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-1223. Mechanistic Insights to Combating Enterobacter cloacae in Deep Seated Infections

Abstract Background Enterobacter cloacae is a formidable pathogen in deep-seated infections. Increasing prevalence of carbapenem-resistant Enterobacterales exemplifies the need for optimizing non-carbapenem therapeutics. We aimed to evaluate cefepime (FEP) and meropenem (MEM) regimens against E. cloacae isolates in a pharmacokinetic/pharmacodynamic (PK/PD) ex vivo model.Table 1.CDC Antibiotic Resistance Isolate Bank Enterobacter cloacae Strains Tested in Ex vivo Models Methods E. cloacae isolates (CDC# 0032, 0060, Table 1) were evaluated in 96h simulated endocardial vegetation (SEV) high inoculum (109 CFU/g) models against humanized FEP (2g q8h via 30-min and 3h infusions) and MEM (2g q8h via 30-min and 3h infusions) regimens. SEV clot and planktonic samples were removed in duplicate from each model replicate at predefined time points and evaluated for bactericidal activity (defined as a ≥ 3 log10 CFU/g reduction from baseline), antibiotic PK target attainment, treatment-emergent resistance, and β-lactamase induction via RT-PCR. Significant differences between regimens were assessed by ANOVA with Tukey’s post hoc modification (α=0.05).Table 2.Beta-lactam PK/PD Targets and Achieved Concentrations in Ex vivo Models Results Against E. cloacae 0060, MEM via 3h infusion demonstrated bactericidal activity (-Δ4.79 log10 CFU/g) in SEV clots and greater killing than MEM via 30-min infusion (-Δ2.6 log10 CFU/g; p&amp;lt; 0.001) (Figure 1). Both MEM 3h and 30-min infusions suppressed bacterial growth at detection limits in planktonic samples through 96h against 0060. Against E. cloacae 0032, neither FEP nor MEM regimens demonstrated bactericidal activity or growth suppression at 96h in SEV clots and planktonic samples, respectively (Figure 2). β-lactam PK/PD targets and achieved concentrations in ex vivo models are displayed in Table 2. Treatment-emergent resistance was identified in 96h samples for FEP against 0060 and MEM against 0032 (3- and 5-fold MIC increase). FEP exposure in 0060 models induced ACT-89 β-lactamase expression while FEP and MEM in 0032 models induced ACT-16, KPC-3, and TEM-1.Figure 1.Efficacy of Beta-lactam Regimens in a SEV PK/PD Ex vivo Model Against E. cloacae Isolate 0060 Conclusion Against E. cloacae isolates in a PK/PD ex vivo model, MEM demonstrated bactericidal activity against E. cloacae 0060, with greater efficacy via 3h compared to 30-min infusion. However, neither FEP nor MEM showed bactericidal activity against E. cloacae 0032, with the emergence of treatment-resistant strains and induction of β-lactamase expression observed in some cases.Figure 2.Efficacy of Beta-lactam Regimens in a SEV PK/PD Ex vivo Model Against E. cloacae Isolate 0032 Disclosures All Authors: No reported disclosures

P-1232. PK/PD Analysis and Dose Optimization of Tebipenem and Faropenem against ESBL-Producing Enterobacterales in Patients with UTI Considering Renal Function

Abstract Background Tebipenem (TBPM) and faropenem (FRPM) have been proposed as effective treatments for urinary tract infections caused by ESBL-producing Enterobacterales. However, appropriate dosage according to renal function needs to be considered. This study utilized PK/PD analysis to investigate the optimal dosage. Methods Monte Carlo simulation using the model of Nakashima et al, 2009 for TBPM and Hirooka et al. 2005, for FRPM generated blood concentration profiles for 1000 cases stratified by renal function. The optimal dose metric was defined as the Probability of Target Attainment (PTA) of 90 percent or more for PK/PD parameters at the MIC90. The PK/PD parameters for TBPM and FRPM were defined as 24h free AUC/MIC/dosing interval 34.58 or more, and free time above MIC 20 and 40 percent or more. The MIC90 values were set at 0.03 and 2 mg/L, respectively. Results For TBPM, the dose achieving PTA of 90 percent or more was 150 mg (q12h) for creatinine clearance (Ccr) less than 30 and 300 mg (q8h) for Ccr 30 or more and less than 80 mL/min. For Ccr 80 mL/min or more was not achieved. None of the doses for FRPM achieved PTA of 90 percent or more. Conclusion The dose for TBPM suggested the need for an even higher dose for Ccr 80 mL/min or more. Cases of post-treatment relapse have been reported for FRPM. Therefore, the optimal dosage considering PK/PD analysis with urinary concentrations needs further validation. Disclosures All Authors: No reported disclosures

P-1229. Assessment of Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment for the Anti-Staphylococcal Antibiotic Afabicin

P-1229. Assessment of Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment for the Anti-Staphylococcal Antibiotic Afabicin

P-298. Treatment of Carbapenem-Resistant Gram Negative Bacteremia based on Polymixin MIC

Abstract Background Recent studies from India have noted increasing resistance against ceftazidime- avibactam in enterobacteriacea and non-fermenters and hence, polymixins are mainstay in the treatment of carbapenem-resistant gram negative (CRGN) infections. There is no susceptible breakpoint for polymixins in view of concerns with clinical outcome and therefore, guidelines recommend combination therapy. However, studies have failed to show the superiority of polymixin combination therapy over monotherapy. Invitro data shows ≥ 90% PK-PD target attainment for isolates with colistin MIC ≤ 0.5 mg/L, but lower success rates in isolates with higher MICs. Aim of the study is to evaluate if the choice of treatment of CRGN infections can be guided by polymixin MIC. Methods We retrospectively evaluated critically-ill patient with CRGN bacteremia with intermediate in vitro susceptibility to colistin (MIC ≤ 2 mg/L; as per CLSI) at a tertiary care hospital in India from January 2022- June 2023. Patients who received treatment for the CRGN bacteremia for &amp;lt;48 h were excluded. Based on polymixin MIC, patients were grouped into two study groups: those that received polymixin monotherapy and those that received polymixin in combination with another agent susceptible in vitro. Chi-square test was used for categorical data and student’s t-test for continuous data. Analysis was performed using SPSS v28 and statistical significance was defined as p &amp;lt; 0.05. Results Of the 114 patients with CRGN bacteremia, 64 (56%) had an MIC of ≤ 0.5 and 50 (44%) had MIC ≥ 1. There was no statistically significant difference in the ICU mortality between monotherapy and combination therapy arms (16% vs 15%; P = 0.9778) for polymixin MIC ≤ 0.5. However, when the MIC was ≥ 1, a higher mortality was observed in the polymixin monotherapy arm (82% vs 39%; P = 0.0029). Conclusion Isolates with MIC ≤ 0.5 can be treated with polymixin monotherapy alone while isolates with MIC ≥ 1 require a combination therapy of polymixin with another antibiotic suseptible invitro. However, this is a single centre retrospective study and further clinical trials are required to ascertain the feasibility of polymixin MIC guided treatment of CRGN infections. Disclosures All Authors: No reported disclosures

P-1255. Dosing of Piperacillin in Altered Renal Function with and without Renal Replacement Therapy for Required Increased Exposition

Abstract Background Piperacillin/ Tazobactam [TZP] is a commonly used antibiotic in critically ill and non-critically ill patients, but not lot is known about TZP pharmacokinetics in non-critically ill patients needing dose reduction due to renal impairment. While Summary of Product Characteristics [SoPC] suggests 16 g Piperacillin daily for severe infections, patients with renal impairment (CrCl &amp;lt; 40 ml/min) are advised by the SoPC to only 8-12 g Piperacillin per day. The aim of this study was to determine the probability of target attainment (PTA), with the PK/PD target being set to unbound concentrations ≥60% of the time above 16 mg/L (MIC of increased exposure pathogen) in patients with decreased renal function especially in consideration of changed definitions on the susceptibility testing by EUCAST advising higher treatment dosing regimens for infections with Pseudomonas aeruginosa. Methods In this prospective two center study we measured 135 piperacillin serum concentration from 49 patients with decreased renal function to determine peak, trough and concentrations between peak and trough. Specific designed software (Monolix 2023R1) was used to develop a population pharmacokinetic model. The PTA was calculated for four groups (eGFR 40, 30 and 20 ml/min and 10 ml/min with intermitted hemodialysis) with different dosing strategies using Monte Carlo simulation (1000 patients per eGFR group). Covariates like age, sex, height, weight, eGFR, body mass index and body surface area (BSA) were evaluated. Results Patients with eGFR 40 and 30 ml/min reached a PTA of over 90% when following the SoPC (eGFR 20-40 ml/min: q8h, 30 min infusions) and increased their PTA to almost 100% when switching to prolonged (over 3h infusions). Patients with eGFR 20 ml/min reached a PTA of almost 90% with a q12h/ 30 min infusion dosage regimen recommended by SoPC for patients with eGFR &amp;lt; 20 ml/min and increased their PTA by about 5% when receiving prolonged infusions (3h). Patients with eGFR of 10 ml/min and intermitted hemodialysis reached a PTA of about 93% (q12h, 30 min infusions) and would reach a PTA of almost 100 % when switching to 3h infusions. Conclusion Prolonged infusions increased the PTA in all groups. The results indicate adjustments for Piperacillin infusions in renal impairment. Disclosures All Authors: No reported disclosures

P-1261. Phamacokinetic Model of Oral Minocycline in Critically Ill Adult Patients with Acinetobacter baumannii Infection

Abstract Background Minocycline has made a comeback in the drug armamentarium as a treatment option for infections due to Acinetobacter baumannii. Although, it has been launched in the 1960s, scarce pharmacokinetic studies have been published. This open-label, prospective clinical study was conducted in critical ill patients with documented infections, mainly VAP-associated pneumonia, attributed to extensively-drug or pan-drug resistant Acinetobacter baumannii, susceptible-or intermediate susceptible to minocycline strains, treated with oral minocycline as a combination therapy. PTA of 200mg and 400mg of minocycline for a range of MICs after a Monte Carlo simulation of 10000 AUC values Methods The PK study population consisted of 20 patients, hospitalized in the ICU of a tetriary Hospital in Athens, Greece. The minimum inhibitory concentration was determined using broth microdilution and a susceptibility breakpoint of ≤ 4mg/L was applied for interpretation, according to the Clinical and Laboratory Standards Institute (CLSI). All patients were given a loading dose of 200mg of minocycline followed by 100mg every 12 hours. Plasma PK samples were collected predose and at 13,14,18,21.5, 59.5,61, 64,68 and 71.5 hours after commencement of minocycline. Minocycline quantification in patient serum sample was conducted using HPLC-PDA, Shimadzu Prominence system (Shimadzu, Kyoto, Japan). A population pharmacokinetic model was developed in Monolix 2023 R1. Monte Carlo simulations were carried out, assuming protein binding of 76%. The probability of target attainment was calculated for each MIC value to achieve an fAUC/MIC ratio of above 25 for daily doses of 200mg and 400mg. Results MInocycline PK parameters in critical ill adult patients were best described using a one-compartment model. The PTA values for various MICs are shown in Figure 1, which indicates that an oral dosage of 200mg and 400mg daily, could cover infections, due to Acinetobacter baumannii strains exhibiting MICs of 0.125mg/L and 0.25 mg/L ,respectively, with a PTA &amp;gt;90%. Conclusion These findings suggest that current oral treatment may be suboptimal for treating such infections, at least as a monotherapy. Further research is needed in order to explore possible dose elevations and synergistic combinations that could enhance its efficacy in combatting XDR, and PDR Acinetobacter baumannii infections. Disclosures All Authors: No reported disclosures

P-1264. Explore The Pharmacokinetic/pharmacodynamics Target Attainment (PTA) of cefoperazone/sulbactam

Abstract Background Cefoperazone/sulbactam (CPZ/SUL) are broad-spectrum antibiotics. Current dosage guidelines consider the renal elimination characteristics of SUL. However, with the risk of antimicrobial resistance, whether current dosage recommendation of CPZ/SUL achieves the desired probability of target attainment (PTA) is unclear. The purpose of this study is to compare the PTA between adjusted-dose (AD) CPZ/SUL and standard-dose (SD) CPZ/SUL therapy. Methods This observational study was conducted in a tertiary hospital in Taiwan during November 2023 to March 2024. Patients using CPZ/SUL (1:1 ratio) were prospectively enrolled. Two blood samples were collected during the dosing interval to measure CPZ and SUL concentrations by using ultra-high performance liquid-chromatography. Concentrations at the middle of the dosing interval (Cm) and before dosing (Ct) were calculated based on measured concentration. PTA was represented by the fraction of time the free concentration was above the minimum inhibitory concentration (fT &amp;gt;MIC). 50% fT &amp;gt;MIC was defined as Cm &amp;gt;MIC, and 100% fT &amp;gt;MIC was defined as Ct &amp;gt;MIC. AD group was defined as reduced CPZ/SUL doses according to the labeling, while SD group had no dose adjustment despite renal impairments. Results A total of 37 patients were enrolled (59.5% male, mean age, 75.4±16.0 years). The most common indication of CPZ/SUL was pneumonia (83.8%). There were 26 patients (70.3%) in the AD group and 11 patients (29.7%) in the SD group. The proportion of patients with 100% fT &amp;gt;MIC was lower in the AD group, as compared to the SD group (CPZ: 15.4% versus 54.5%, P&amp;lt; 0.01; SUL: 11.5% versus 72.7%, P&amp;lt; 0.01). Additionally, 7.7% of patients in the AD group compared to 45.5% of patients in the SD group achieved 100% fT &amp;gt;MIC for both CPZ and SUL (P&amp;lt; 0.01). Thirty patients (81.1%) received weekly vitamin K to prevent CPZ-related coagulopathy, and none had an international normalized ratio above 2. Conclusion PTA was inadequate in patients receiving CPZ/SUL based on current dosage adjustment recommendations. Future investigation is needed to determine if inadequate PTA is linked to worse clinical outcomes, especially in resistant pathogens. Disclosures All Authors: No reported disclosures

P-1247. Cerebrospinal Fluid Penetration of Multiple Antibiotics in Patients With Intracranial Hemorrhage: A Prospective, Observational, Clinical Study

Abstract Background External ventricular drains (EVD) are used for acute hydrocephalus in intracranial hemorrhage(ICH), potentially causing ventriculostomy-associated cerebrospinal fluid infection (VAI). Variable meningeal inflammation in VAI can result in unpredictable antibiotic penetration in cerebrospinal fluid (CSF). This observational study aimed to assess CSF penetration of intravenous antibiotics for suspected VAI treatment in neurosurgical patients. Time to concentrations in CSF and plasma among the patients. The figure presented the concentrations of blood and cerebrospinal fluid (CSF) measured at different time points for each patient. REVD right-sided external ventricular drain. LEVD left-sided external ventricular drain. Methods Adults with EVD for ICH who were receiving antibiotics, including vancomycin, ceftazidime, cefepime and meropenem, for VAI from January 2023 to April 2024 in two north Taiwan medical centers were enrolled in this study. The primary outcome was the area under the concentration (AUC) ratio between CSF and plasma (AUCCSF/plasma). Factors influencing CSF concentration was also investigated. In addition, the probability of target attainment (PTA) of anti-Pseudomonal antibiotics were calculated. A summary of the permeability of vancomycin into the cerebrospinal fluid in this study. ARC augmentation renal clearance. L Left-side external ventricular drain R Right-side external ventricular drain. a. AUC was calculated from the first observation point to the last observation point. b. It was resistant to vancomycin. Results A total of 9 patients (6 male) with VAI were enrolled, and contributed 7 vancomycin, 3 ceftazidime, 2 cefepime and 2 meropenem treatment courses. One patient provided two courses. The ranges of AUCCSF/plasma for vancomycin, ceftazidime, cefepime, or meropenem were as follows 0.85-15.61%, 6.74-15.61%, 0.16-128.73%, and 0.09-13.24%, respectively. The CSF to plasma concentration ratio at the end of vancomycin infusion and at the middle of dosing interval showed good correlation with AUCCSF/plasma (Spearman's coefficient 0.8 and 0.783, p-value ≦0.01) For ceftazidime, both CSF and plasma achieved at least 98% fT &amp;gt;MIC=8 under 2 gram every 8 hours regimen. For meropenem, the fT &amp;gt;MIC=2 for CSF and plasma were 0-100 % and 95.7-99.8% under 2 gram every 8 hours regimen, respectively. For cefepime, the fT &amp;gt;MIC=16 for CSF and plasma were 0-100% and &amp;gt;97%, respectively. Conclusion This is the first study to report real-world data of antibiotic CSF penetration in neurosurgical population in Taiwan. Ceftazidime showed adequate penetration and achieved sufficient PTA in the CSF. Additionally, the single-point ratio of vancomycin at the end of infusion and during the mid-dosing interval may serve as a surrogate for AUCCSF/plasma. Disclosures All Authors: No reported disclosures

P-1226. Dose Optimization of β-lactams against Carbapenem-Resistant Pseudomonas from Turkiye Defined as Susceptible to Ceftazidime, Cefepime or Piperacillin/Tazobactam

Abstract Background Due to the increasing prevalence of carbapenem-Resistant Pseudomonas aeruginosa (CRPA), effective agents are needed to treat these serious infections. Although CRPA may test susceptible to other β-lactams such as ceftazidime (CAZ), cefepime (FEP), and piperacillin/tazobactam (TZP), reduced potency has been observed amongst CRPA. In this study, we used PKPD analysis to assess the adequacy of the EUCAST Susceptible (S) or Susceptible Increased Exposure (SIE)/(I) doses for CAZ, FEP, and TZP against CRPA clinical isolates.Figure 1.Probability of target attainment (PTA) of various ceftazidime different dosing regimens and the MIC distribution of carbapenem-resistant Pseudomonas aeruginosa (CR-PA). Methods CRPA isolates were collected from patients at three Turkish hospitals between January 2017-December 2021. CAZ, FEP, and TZP MICs were determined using broth microdilution according to CLSI methodology. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for a free time above the MIC (fT &amp;gt;MIC) targets for various doses of each agent against isolates defined as susceptible. fT &amp;gt;MIC targets were 70% for CAZ or FEP and 50% for TZP. Cumulative fraction of response (CFR) was calculated by integrating PTA with the MIC distribution of the isolates. Optimal PTA and CFR were defined as 90% target achievement.Figure 2.Probability of target attainment (PTA) of various cefepime different dosing regimens and the MIC distribution of carbapenem-resistant Pseudomonas aeruginosa (CR-PA). Results In the setting of CR-PA, the percentages of isolates susceptible to CAZ, FEP, and TZP were 49,8%, 47%, and 31,8%, respectively. Reduced potency was noted with 54,1% of CAZ-S isolates had MICs of 4 or 8 mg/L. Of the FEP and TZP-S isolates, MICs at the breakpoint (8 and 16 mg/L, respectively) were the mode with 45,2 and 53,9% of isolates for each, respectively. At an MIC of 8 mg/L for CAZ, the EUCAST standard dose was found to be insufficient with a CFR of 85%. 3-hour infusions of EUCAST SIE doses were required for 90% PTA at MIC of 8 mg/L and an optimized CFR of 100% (Figure 1). For FEP, the SIE dose of 2 g q8h 0.5 h infusion of was effective (CFR 96%), utilization of an extended 3h infusion further optimized the PTA at 8 mg/L (CFR 99%) (Figure 2). For TZP, the standard dose of 4.5 q6h administered as a 0.5h infusion was inadequate (CFR 86%). A standard TZP dose with an extended infusion (4.5 g IV q8h over 4 h) and the SIE dose 4.5 g IV q6h 3 h inf resulted in CFRs &amp;gt;95% (Figure 3).Figure 3.Probability of target attainment (PTA) of various piperacillin/tazobactam different dosing regimens and the MIC distribution of carbapenem-resistant Pseudomonas aeruginosa (CR-PA). Conclusion These data support the EUCAST SIE breakpoints for FEP and TZP. To optimize PTA at the SIE breakpoint for CAZ, prolonged infusion is required. Disclosures Christian M. Gill, PharmD, Cepheid: Grant/Research Support|Entasis: Grant/Research Support|Everest Medicines: Grant/Research Support|Shionogi: Grant/Research Support David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support

Clinical and Biochemical Factors Associated with Infliximab Pharmacokinetics in Paediatric Patients with Inflammatory Bowel Disease

Monitoring infliximab (IFX) concentrations is crucial for optimizing IFX therapy in children with inflammatory bowel diseases (IBDs) who show low response rates due to inadequate drug exposure. Substantial variation occurs in IFX trough concentrations in paediatric patients. Objectives: This study aimed to investigate IFX pharmacokinetics (PK) in children with IBD during both the induction phase and maintenance phases and to identify covariates associated with IFX PK. Methods: This single-centre retrospective cohort study was conducted at an academic children’s hospital. Data was extracted from paediatric IBD patients receiving IFX between January 2018 and October 2023 and included demographic-, clinical- and laboratory parameters collected from electronic health records. Linear mixed model analysis was performed to investigate associations between these parameters and IFX trough concentrations. Target attainment [≥15 μg/mL in induction or 5–10 μg/mL in maintenance phase] of the IFX dosing regimens was evaluated. Results and Conclusions: A total of 115 children (417 unique IFX concentrations) were included. Multivariate analysis revealed significant positive associations between IFX and albumin concentrations (β = 0.388, p = 0.010) and IFX concentrations with dose (β = 6.534, p &lt; 0.001), and an inversion association between IFX concentrations and treatment phase (β = −4.922, p &lt; 0.001). During the induction and maintenance phases, 57.2% and 30.6% of IFX concentrations were subtherapeutic, respectively. A systematic search of studies investigating factors influencing IFX concentrations was concurrently performed. Our findings were critically compared against existing literature to assess relevant clinical and biochemical determinants of IFX PK in children with IBD. Our findings highlight the need for personalized dosing strategies in pediatric IBD patients, particularly during the induction phase. By implementing therapeutic drug monitoring (TDM) and considering clinical and biochemical factors, clinicians can implement more personalized strategies, potentially improving treatment efficacy and reducing the risk of treatment failure or adverse effects. This approach could lead to better target attainment, potentially enhancing clinical outcomes and minimizing premature switching to other therapies.