Thank you so much for that introduction. Thank you for attending this session. I'm Jenny Schultheis. I'm a critical care clinical pharmacist in the Medical Intensive Care Unit at Duke University Hospital and today I'll be presenting our research project entitled Incidents of Detectable Drug Levels with Inhaled Amino Glycoside Therapy in Critically Ill Adults. And I would like to thank our co-investigators that were involved in this research project. Both myself and my co-investigators have nothing to disclose in regards to this presentation. Inhaled aminoglycosides serve as an attractive mode of delivery for pulmonary infection treatment and prevention. Inhaled compared to intravenous administration of aminoglycosides achieve high concentrations in the lung parenchyma while minimizing or potentially minimizing adverse effects and systemic exposure such as acute kidney injury and potentially ototoxicity. However, systemic accumulation is poorly understood and data is currently limited to case reports and case series which do suggest some systemic accumulation. Inhaled aminoglycosides are utilized for chronic suppressive therapy. So, for patients with cystic fibrosis, their use has been associated with decreased frequency of pulmonary exacerbations, decreased hospitalizations, and improved pulmonary and function tests. They've also been used for patients with non-cystic fibrosis bronchiectasis as well or for adjunctive treatment for patients with non-tuberculosis mycobacterial infections or as an adjunct for ventilator-associated pneumonia. And in this setting, I know results are inconsistent but may be associated with higher rates of clinical cure. And clinical practice guidelines do suggest their potential use for treatment of multidrug-resistant gram-negative infections or for patients with a slow response for clinical progression. So this was a subset setting and our primary objective was to determine the incidence of detectable drug levels with inhaled aminoglycoside therapy in critically ill patients. This was a retrospective cohort analysis at Duke University Hospital. We included adult patients 18 years of age or older who received at least one dose of inhaled amikacin or tobramycin with a drug level during their ICU stay between June of 2013 and July of 2020. We excluded patients who received intravenous aminoglycoside within seven days prior to the drug level or who had a drug level that was not drawn within four hours prior to the next dose. So ideally, these drug levels would be drawn as a trough. We defined a detectable drug level as a tobramycin level greater than 0.5 micrograms per mil or an amikacin level greater than 1.5 micrograms per mil. Our standard doses are tobramycin 300 milligrams inhaled twice daily or amikacin 500 milligrams inhaled twice daily. And over the course of the study period, levels were drawn at provider or pharmacist discretion. We do have institutional guidelines that do suggest potentially weekly monitoring or more frequent monitoring in the cases where toxicity would be suspected such as an acute kidney injury or ototoxicity as well. We identified initially 819 levels, however, a majority of the levels were excluded since they were not drawn within four hours prior to the next dose. There were also a significant number of drug levels that were excluded because patients received intravenous aminoglycosides. And then, of course, we only looked at patients who were in the intensive care unit for this subset study. So we included 93 levels across 54 critically ill patients. Looking at our patient population, the median age was 44 years with 43 percent females. BMI was within average size of 20. There were a significant number of patients who were lung transplant recipients at 79.5 percent. There was also significantly or I'm sorry, a high percentage of patients with mechanical who received mechanical ventilation at 83.8 percent. Around 35 percent had cystic fibrosis. Around 37.6 received continuous renal replacement therapy. The median intensive care unit length of stay was around 27 days. And levels were primarily drawn in the cardiothoracic and medical intensive care units. So surprisingly, 39 levels of the 93 or 41.9 percent of levels that were drawn in the intensive care unit were detectable. So 29 levels for patients who received tobramycin and 10 for patients who received amikacin. The median detectable drug level for tobramycin was 0.9 micrograms per mil. And for amikacin, it was 3.7. And then there were a large number of patients who had a therapy modification. So 76.9 percent of detectable drug levels did receive a therapy modification, with the highest number being a frequency reduction, which was around 60 percent. Therapy was discontinued for 20 percent of patients. And then there were some dose and frequency reductions as well. So this was a small single-center retrospective study, and it was a subset study. The larger study was published in November. So unfortunately, we were only able to utilize descriptive statistics, and I think that this is interesting for research studies in the future. Also there was a lack of criticalized therapeutic drug monitoring, so this could introduce bias as well. But in conclusion, for critically ill adults receiving inhaled aminoglycosides, approximately 40 percent of drug levels evaluated were detectable. Therefore, I think periodic trough concentration should be considered, or of course, whenever toxicity is suspected. So I think future trials are really prudent with protocolized therapeutic drug monitoring, with also outcomes looking at clinical efficacy outcomes, as well as safety endpoints as well. I think we also need additional data regarding dose adjustments, recognizing that a large number of our patients did receive therapy adjustments. So thank you, and I will take any questions.

inhaled aminoglycosides

critically ill adults

pulmonary infection treatment

systemic accumulation

drug levels