Browsing by Author "Rule, Andrew D."

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    318. Beta-lactam Therapeutic Drug Monitoring Improves Attainment of Target Drug Levels in Critically Ill Patients
    (Oxford University Press, 2023-11-27) Ausman, Sara; Braga, Shienna; Hagy, Natalie T.; Rivera, Christina G.; Moreland-Head, Lindsay; Wessel, Rebecca; Abu Saleh, Omar M.; Rule, Andrew D.; Gajic, Ognjen; Barreto, Erin F.; Pharmacology and Toxicology, School of Medicine
    Background: Critically ill patients, particularly those treated with extracorporeal devices or at extremes of weight, experience pharmacokinetic variability which can compromise beta-lactam (BL) antibiotic target attainment and treatment response. Therapeutic drug monitoring (TDM) for BL antibiotics can improve precision pharmacotherapy but has had limited implementation. The objective of this study was to evaluate the frequency of BL target attainment among adult intensive care unit (ICU) patients who underwent TDM. Methods: This observational study evaluated adults treated with cefepime, piperacillin/tazobactam or meropenem in ICUs at the Mayo Clinic in Rochester, Minnesota who underwent TDM from June-September 2022. During the study timeframe, multidisciplinary teams were encouraged to perform BL TDM on patients requiring extracorporeal membrane oxygenation, continuous kidney replacement therapy, or at an extreme of body weight (weight < 40 kg or >120 kg or BMI < 18 kg/m2 or > 40 kg/m2). Percentage of patients with initial serum trough concentrations within the therapeutic range was calculated. Results: During the study timeframe, 59 trough concentrations were performed on critically ill patients, of which 5 were excluded due to uninterpretable results. Of the remaining 54 BL trough concentrations analyzed, 49 (91%) were initial troughs during the antibiotic course, and 5 (9%) were repeat troughs. Thirty-six (73%) of the initial trough concentrations were within the therapeutic range. Among the trough concentrations outside the therapeutic range, 10 (77%) were too high, and 3 (23%) were too low (Table 2). Dose adjustment occurred in 19 (39%) of initial trough evaluations, including 6 which were adjusted despite a level within the therapeutic range. All of the repeat trough concentrations drawn during the same antibiotic course were within the therapeutic range (n = 5/5; 100%). Conclusion: One-fourth of initial BL trough concentrations were outside of the therapeutic range. BL levels outside the therapeutic range prompted dose adjustment to improve the potential for effectiveness or limit the potential for toxicity. BL TDM appears to be a promising strategy to enhance precision pharmacotherapy in the critically ill.
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    Phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intra-renal calcification
    (Elsevier, 2013) Linnes, Michael P.; Krambeck, Amy E.; Cornell, Lynn; Williams, James C., Jr.; Korinek, Mark; Bergstralh, Eric J.; Li, Xujian; Rule, Andrew D.; McCollough, Cynthia M.; Vrtiska, Terri J.; Lieske, John; Anatomy, Cell Biology and Physiology, School of Medicine
    Interstitial Randall's plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. The 24-h urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall's plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall's plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.