Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three-hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from February 1, 2016, to November 30, 2016, were screened. Patients were included in the PK group if consecutive serum concentrations were used to calculate individualized PK and determine a dosing regimen. Patients who were dosed using troughs only were then matched 1-to-1 to the PK group by date of vancomycin initiation and included in the traditional group. Fifty patients were included in each group. Baseline characteristics were similar, except the PK group had more patients under the care of the neuromedical ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine clearance <30 mL/min/1.73 m (22% vs 46%; P = .02). Attainment of goal trough concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours (P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96 hours (P = .1), respectively. Incidence of acute kidney injury between the PK and traditional groups was not statistically significant (8.3% vs 14%; P = .5). Utilization of individualized pharmacokinetic dosing of vancomycin in critically ill patients resulted in faster goal trough attainment without an increase in nephrotoxicity.

This study compares pharmacokinetic parameters and colonic tissue concentrations of cyclosporine administered by olive-oil or water-retention enemas with conventional intravenous (i.v.) and oral dosing. Five medical students were enrolled in a prospective crossover study. All subjects received a single dose of cyclosporine on four separate occasions, once orally, once as an olive-oil enema, once as a water enema, and once i.v. Cyclosporine concentration was measured in blood and in colonic tissue obtained by flexible sigmoidoscopy. Bioavailability was 18 +/- 7% (mean +/- SD) for the oral dose and was unmeasurable for the oil and water enemas. The concentration of cyclosporine in colon tissue was 32,443 +/- 17,251 ng/g (mean +/- SD) for the i.v. dose, 2797 +/- 1812 ng/g for the oral dose, 21,727 +/- 14,090 ng/g for the oil enema, and 25,318 +/- 30,408 ng/g for the water enema. The authors conclude that the bioavailability of cyclosporine, and thus the systemic absorption after administration by a retention enema, is negligible. The colonic tissue concentration of cyclosporine after i.v. or rectal administration via an enema is tenfold higher than that for oral dosing. These findings suggest that cyclosporine-retention enemas produce high distal colonic tissue concentrations with negligible systemic absorption after a single dose in healthy subjects and should be evaluated as treatment for patients with left-sided colitis. Because cyclosporine administered by the i.v. route provided sharply higher colonic tissue concentrations than those seen with oral therapy, pulse i.v. cyclosporine should be tried for patients with severe ileitis and colitis.

Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in patients with unique physiology, who were excluded from published clinical trials. Data are also lacking regarding clinical efficacy of C/A in patients with infections due to multidrug-resistant gram-negative pathogens. To expand knowledge in these areas, we present pharmacokinetic data from two patients with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infections, both of whom had renal impairment, and one of whom was morbidly obese. C/A was initiated in both patients at higher doses than those recommended in the package insert. To assess adequacy of dosing at steady state, a trough was drawn before and consecutive levels were drawn after a C/A dose such that half-life and volume of distribution for ceftazidime and avibactam could be calculated using the Sawchuk-Zaske method. Both patients cleared their bloodstream infection without evidence of toxicity. Patient 1 and patient 2 had prolonged half-lives for ceftazidime (22.8 and 14.5 hours, respectively) and avibactam (19.6 and 11.3 hours, respectively). Both patients had volumes of distribution significantly larger than those listed in the package insert: ceftazidime 47.1 L and 24.7 L and avibactam 50.3 L and 38.7 L for patients 1 and 2, respectively. Considering the larger volumes of distribution and levels observed in our patients, recommended doses and intervals may not be sufficient for obese patients with renal failure, especially for those infected with KPC-producing organisms. Additional efficacy and pharmacokinetic data are still needed for this agent to define optimal dosing strategies in patients commonly encountered in clinical practice.