247 - Cystatin C Outperforms Creatinine in Predicting Cefepime Clearance among Pediatric Bone Marrow Transplant Recipients

Saturday, April 29, 2023

3:30 PM – 6:00 PM ET

Poster Number: 247
Publication Number: 247.25

H. Rhodes Hambrick, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Kathryn Pavia, Cincinnati Children's Hospital, Cincinnati, OH, United States; Jennifer Kaplan, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Tomoyuki Mizuno, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Peter H. Tang, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Min Dong, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Sonya C. Tang Girdwood, Cincinnati Children' Hospital Medical Center, Cincinnati, OH, United States; Stefanie W. Benoit, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Presenting Author(s)

H. Rhodes Hambrick, MD (he/him/his)

Fellow in Nephrology and Hypertension
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States

Background: Pediatric bone marrow transplant (BMT) patients are at risk of sepsis and altered kidney function. Cefepime (FEP) is often used for empiric coverage post-BMT. FEP’s anti-microbial effect is determined by the time free FEP concentrations exceed bacterial minimum inhibitor concentration (MIC). FEP requires dose-adjustment with changing kidney function. Serum creatinine (SCr) is routinely used to estimate glomerular filtration rate (eGFR) but is affected by muscle mass. Cystatin C (CysC) eGFR is independent of muscle mass, though steroid use and adiposity increase CysC.

Objective:

To investigate which eGFR (SCr, CysC, or combined SCr/CysC) best predicts FEP clearance (CL) and how eGFR impacts pharmacokinetic/pharmacodynamic (PK/PD) target attainment in pediatric BMT patients.

Design/Methods: We prospectively enrolled patients admitted to the pediatric BMT unit who received 2 or more FEP doses. We measured SCr, CysC, and total FEP peak/trough concentrations between the 2^nd-4^th FEP doses (Fig 1). eGFRs were calculated with CKiD U25 equations. Bayesian estimates of individual FEP clearance were done using a pediatric FEP PK model (Shoji 2016)and PK software MWPharm++. We used linear regression to compare FEP CL normalized to body surface area (BSA) to BSA-normalized SCr, CysC, and SCr/CysC eGFRs, using steroid exposure within 120h prior to CysC and BMI percentile (BMIp) as covariates. We assessed % of time free FEP concentrations were above 1x MIC (% fT >1x MIC) and 4x MIC (% fT >4x MIC) using an MIC of 8 mg/L for P. aeruginosa.

Results: 52 FEP concentrations among 28 patients (ages 1-28, mean 10) were used; 3 patients had only a trough and 1 had only a peak. SCr eGFR had a weak positive correlation with FEP CL (r²0.16), while CysC eGFR and SCr/CysC eGFR had stronger positive correlations (r²0.34 for CysC, r² 0.30 for combo) (Fig 2-3). When stratifying by steroid exposure, CysC eGFR remained superior (n=17 steroid-exposed, r²0.32 for CysC, 0.14 for SCr) (n=11 steroid non-exposed, r²0.29 for CysC, 0.03 for SCr). CysC eGFR remained a significant (p=0.002) predictor of FEP CL after controlling for BMIp. Increasing CysC eGFR was negatively correlated with % fT >1x MIC (r² 0.46) and % fT >4x MIC (r² 0.28).

Conclusion(s): CysC eGFR and CysC/SCr eGFR predicted FEP clearance better than SCr eGFR. Steroid exposure and BMIp did not impact predictiveness of CysC eGFR. Increasing CysC eGFR correlated with decreased probability of PD target attainment, raising concerns for underdosing at high eGFRs. CysC eGFR should be used for dosing FEP in pediatric BMT patients.