Background In this pilot study, we aimed to determine the efficacy and safety of enteral erythromycin estolate in combination with intravenous metoclopramide compared to intravenous metoclopramide monotherapy in mechanically ventilated patients with enteral feeding intolerance. Methods This randomized, double‐blind, controlled pilot study included 35 mechanically ventilated patients with feeding intolerance who were randomly assigned to receive 10‐mg metoclopramide intravenously every 6–8 hours in combination with 250‐mg enteral erythromycin estolate (study group) or placebo every 6 hours for 7 days. The primary outcome was an administered‐to‐target energy ratio of ≥80% at 48 hours, indicating a successful feeding. Secondary, prespecified outcomes were daily average gastric residual volume (GRV), total energy intake, administered‐to‐target energy ratio, hospital length of stay, in‐hospital mortality, and 28‐day mortality. Results The rate of successful feeding was not significantly different between the study and placebo groups (47.1% and 61.1%, respectively; P = .51). The average daily GRV was significantly lower in the study group than in the placebo group (β = 91.58 [95% Wald CI, −164.35 to −18.8]), determined by generalized estimating equation. Other secondary outcomes were comparable, and the incidence of adverse events was not significantly different between the 2 groups. One common complication was cardiac arrhythmia, which was mostly self‐terminated. Conclusion Although the combination therapy of enteral erythromycin estolate and intravenous metoclopramide reduced GRV, the successful feeding rate and other patient‐specific outcomes did not improve in mechanically ventilated patients with feeding intolerance.

Empiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New nonrace-based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10-year period. A nonlinear mixed-effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty-three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1-compartment linear elimination with zero-order input and proportional error model. A Thai-specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population-specific eGFR equation.

Study Objective The use of race in medicine can contribute to health inequity. Updated equations for estimated glomerular filtration rate (eGFR) without race have been published. Likewise, de‐indexation of eGFR to body surface area (BSA) has been recommended by regulatory guidance for drug dosing in renal impairment. Clinical data justifying these recommendations for drug dosing are sparse. We examined the gain or loss of precision in drug dosing with estimated creatinine clearance (eCLcr) and eGFR using serum creatinine (eGFRcr) with and without race and BSA indexation by evaluating the population pharmacokinetics of the aminoglycosides as a classic drug class to probe kidney function. Design Medical records from adult patients treated with gentamicin or tobramycin over a 13‐year period were queried. Population pharmacokinetic analyses were performed using a 1‐compartment base structural model. Models compared body size descriptors as covariates of the volume of distribution (V). Estimated creatinine clearance and eGFRcr using multiple contemporary equations with and without BSA indexation were tested as covariates of clearance (CL). Main Results The final data set included 2968 patients treated with either gentamicin (20.2%) or tobramycin (79.8%). Patients self‐identified as Caucasian (82%), African‐American (10%), or other. The median [5th, 95th percentile] weight and BSA were 80.5 [49.4, 136] kg and 1.94 [1.48, 2.56] m2, respectively. Models of eCLcr and eGFRcr without indexation to BSA had a better model fit than eGFRcr indexed to BSA for aminoglycoside CL. The 2021 Chronic Kidney Disease Epidemiology collaboration (CKD‐EPI) eGFRcr equation (no race, no BSA indexation) provided a comparable model fit to the 2009 CKD‐EPI eGFRcr equation (with race, no BSA indexation) for aminoglycoside CL. Conclusions Race is not a relevant covariate of aminoglycoside CL. The 2021 CKD‐EPI eGFR equation without race and BSA indexation is a better method for gentamicin and tobramycin CL estimation. Confirmation of these results for other drugs can support the harmonization of dosing by kidney function.

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