Evaluation of extended interval dosing aminoglycosides in the morbidly obese population.

Aminoglycoside dosing has been studied in the obese population, typically recommending an adjusted weight utilizing a 40% dosing weight correction factor (IBW + 0.4 × (TBW-IBW)). These studies included limited numbers of morbidly obese patients and were not done in the era of extended interval aminoglycoside dosing. Here, we report a retrospective evaluation of morbidly obese patients receiving gentamicin or tobramycin at our hospital. The objective of this study was to evaluate the accuracy of the commonly recommended adjusted weight for weight-based dosing. There were 31 morbidly obese patients who received gentamicin or tobramycin 5-7 mg/kg every 24 hours using a 40% dosing weight correction factor. Our institution utilizes 16-hour postdose concentrations to monitor extended interval aminoglycosides. Twenty-two of the 31 patients (71%) achieved an appropriate serum drug concentration. Four patients (13%) were found to be supratherapeutic and 5 patients (16%) subtherapeutic. The only variable that correlated with supratherapeutic levels was older age (P = 0.0378). Our study helps to validate the current dosing weight correction factor (40%) in the morbidly obese population. We recommend caution when dosing aminoglycosides in morbidly obese patients who are of older age.

Evaluation of an alternative posaconazole prophylaxis regimen in haematological malignancy patients receiving concomitant stress ulcer prophylaxis.

Posaconazole (PCZ) is approved for fungal prophylaxis in high-risk neutropenic patients. Unfortunately, PCZ oral absorption is affected by nutritional intake and drug interactions with proton pump inhibitors (PPIs) and possibly histamine-2 antagonists (H2As). Cancer patients frequently receive stress ulcer prophylaxis (SUP) with PPIs or H2As. Recommended PCZ steady-state concentrations (C(ss)) are difficult to achieve using the traditional dosing regimen of 200 mg thrice daily. Given the paucity of guidance on PCZ dosing in patients receiving SUP, this study evaluated attainment of targeted PCZ C(ss) (0.5 µg/mL and 0.7 µg/mL) with two different PCZ dosing regimens when SUP was given. Twenty patients received the traditional dosing and 34 patients received 400 mg twice daily. Median PCZ C(ss) levels were 0.37 µg/mL and 0.32 µg/mL with the traditional and 400 mg twice-daily regimens, respectively (P=0.809). When stratified by type of SUP, H2A patients had a median PCZ C(ss) of 0.39 µg/mL, whereas PPI patients had a median PCZ C(ss) of 0.32 µg/mL. Despite having more patients with PCZ C(ss) >0.5 µg/mL in the H2A group, a statistical significance was not found (P=0.368). Multiple logistic regression did show that increasing age [odds ratio (OR)=1.08, 95% confidence interval (CI) 1.03-1.19] and use of H2As over PPIs (OR=6.8, 95% CI 1.22-55.16] was associated with PCZ target attainment. These results suggest that PCZ target attainment is similar with either PCZ regimen but that there may be less of an interaction with H2As compared with PPIs.