»» All right. Thank you guys for joining. As previously mentioned, my name is Sydney Wilson and myself as well as my co-authors perform research on the evaluation of achieving targeted vancomycin levels and augmented renal clearance. So I am currently the PGY2 Critical Care Pharmacy resident at St. Luke's Hospital of Kansas City. I don't want to go back. So go Chiefs. And I also completed my PGY1 residency there during which time we completed this research. So myself as well as the other study investigators do not have anything to disclose in terms of conflicts of interest. So our objectives today are to review augmented renal clearance and St. Luke's Health System's current collaborative drug therapy management agreement and then to analyze the results of research evaluating the use of vancomycin in patients with augmented renal clearance. So augmented renal clearance, or ARC, is defined as a creatinine clearance greater than 130 milliliters per minute per meter squared. And then super augmented renal clearance is defined as a creatinine clearance greater than 180 milliliters per minute per meter squared. The ARC is usually calculated from an 8- or 24-hour urine collection. And then it can be observed in 30-65% of patients in the intensive care unit. And then rates can be as high as 50-85% in the setting of sepsis or trauma. So most of us are familiar with vancomycin. We use it on a daily basis. Just some reminders in terms of things we need to consider. So achieving targeted vancomycin trough levels is important for treatment success and can be impacted by renal function. Some potential impacts of augmented renal clearance on vancomycin therapy would include decreased ability to achieve targeted vancomycin levels, an increased risk of treatment failure, and then delayed clinical improvement or resolution of infection. So at St. Luke's, we currently have a protocol. And our vancomycin collaborative drug therapy management agreement does not provide specific initial dosing for augmented renal clearance. And by CDTM, it is just our protocol for pharmacists to dose. We just dose essentially all vancomycin within our health system. And our current CDTM recommends targeting vancomycin trough levels of 10-20 for severe complicated infections. Of note, our CDTM was based on an average age or demographic of patients who were 65-year-old white males. And it does provide a clause with which pharmacists can use clinical judgment to deviate from the protocol. And then at the top here, I do have an AHRQ scoring system, which has been a validated scoring system for predictors of augmented renal clearance. So it takes into consideration the patient's age, if they were admitted for trauma, and then their modified SOFA score upon admission. And if patients have an AHRQ score of at least 7, it indicates they're at high risk for augmented renal clearance. So I've included our current St. Luke's Health System vancomycin dosing protocol. So as you can see, all patients with a creatinine clearance greater than 80 milliliters per minute are dosed purely on their weight. So any patient with a creatinine clearance greater than 80, so 80 up to 170, 200, whatever it may be, will be dosed based on weight. And if they weigh less than 90 kilograms, they'll receive every 12-hour dosing. And if they weigh 90 kilograms or greater, they'll be dosed based on every 8-hour dosing. At the bottom, we did include for our CNS or meningitis, we do have a slightly higher tropical of 15-20, and we do use more aggressive empiric therapy. But as we can see here, it's not really built for patients with augmented renal clearance and they're not taken into consideration at this time. The current protocol is dose in mg per kg. And it's rounded to the nearest 250-milligram dose. So roughly 10 mg per kg every 8 hours or 15 mg per kg every 12 hours. So the purpose of our study was to evaluate St. Luke's Health System's current vancomycin CDTM and achievement of targeted vancomycin trough levels in our patients with augmented renal clearance. We also evaluated predictors of an initial therapeutic trough to try to build a clinical model for achieving early therapeutic levels and to make necessary adjustments to our current protocol. So we conducted a multi-site single health system retrospective cohort study looking at patients who were treated within our health system between January 2018 and May of 2021. Patients were included in our study if they were at least 18 years of age, if they had one accurately drawn vancomycin trough level, which we defined as a trough drawn before the fourth, fifth, or sixth dose within a 1-hour time window. So it could be 30 minutes before the dose should have been drawn or 30 minutes after. And then they had to have had a creatinine clearance greater than 130 mL per minute squared, which was calculated based on the Cockcroft-Galt equation and adjusted for body surface area. Patients were excluded from our study if they had renal impairment requiring continuous renal replacement therapy or hemodialysis at the initiation of vancomycin. And they were also excluded if they transferred from an outside hospital already on vancomycin therapy. So in terms of our study outcomes, our primary outcome was the rate of achieving an initial therapeutic vancomycin trough level. We looked at multiple secondary endpoints, including an association between the ARC score and achieving an initial therapeutic vancomycin level. Use or need for alternative gram-positive antibiotics, nephrotoxicity, as well as use of concomitant nephrotoxic agents, and then identifying prediction variables associated with achieving an initial therapeutic vancomycin level, and then assessment of trough appropriateness based on our current CDTM. So descriptive statistics were used for our primary outcome and our secondary outcomes of alternative gram-positive antibiotics in hospital mortality, ICU length of stay, nephrotoxicity, and concomitant use of nephrotoxic agents. A univariate logistic regression analysis was performed to test for the association with ARC score and achieving an initial therapeutic trough level. For this we used a P-value of less than 0.05 to determine statistical significance. And then the Pearson's Chi-square test was used to perform a subgroup analysis. So in terms of our patients, we had 300 patients that were included in our study. The median age was 50 years. We had 72% of our patients who were male. The median weight was 107 kilograms. And the median creatinine clearance was 178 mLs per minute. And then 48.3% of our patients met the definition of super augmented renal clearance. So for our primary outcome, the rate of achieving an initial therapeutic trough, 57% of our patients did achieve an initial therapeutic trough, while 43% of patients had a subtherapeutic initial trough level. For our secondary outcomes, we identified an ARC score association that was actually an inverse relationship. So the higher the ARC score, the higher ARC scores were associated with lower odds of achieving an initial therapeutic trough level. 10.7% of our patients were switched to daptomyosin. And then in terms of nephrotoxicity, 8.7% of our patients experienced nephrotoxicity as defined by the Acute Kidney Injury Network. While I know this is a highly debated topic, when we looked at concomitant use of nephrotoxic agents, the use of zosyn with vancomycin occurred in 43% of our patients. That being said, we did not do any further investigation of nephrotoxicity aside from just incidence. So in terms of vancomycin therapy and trying to evaluate was our CDTM used to dose these As you can see here, the loading dose, maintenance dose, and dosing frequency were dosed in accordance with our CDTM demonstrating high compliance and minimal deviations from the protocol. We then performed a multivariate regression analysis to identify predictors of an initial therapeutic trough. So our statistician ran this regression analysis looking for predictors of an initial therapeutic trough, but we were not trying to create a new ARC score. Age, weight, and body mass index, as well as serum creatinine were directly correlated with achieving an initial therapeutic vancomycin trough level. So as our patients weighed more or were older, they were more likely to achieve that initial therapeutic trough. However, ARC score and creatinine clearance, which is a composite of serum creatinine weight and age, were inversely related to achieving an initial therapeutic trough level. So as creatinine clearance and ARC score increased, patients were less likely to be therapeutic on that first trough. So we then performed a subgroup analysis. And this was to evaluate predictors of an initial therapeutic trough to try to build a clinical model assessing initial therapeutic trough levels and to adjust our current CDTM. So from the regression analysis that I previously mentioned, our statistician was able to develop breakpoints with regard to age, weight, and creatinine clearance. So patients who were less than 50 years of age and had a creatinine clearance of at least 140 milliliters per minute achieved an initial therapeutic trough 40% of the time. Whereas patients who were at least 50 years of age or had a creatinine clearance less than 140 milliliters per minute achieved an initial therapeutic trough level 64.3% of the time. So we did identify a statistical difference there. So then when we looked at patients who were less than 50 years of age or had a creatinine clearance of at least 140 milliliters per minute, 51% of them achieved an initial therapeutic trough. While patients who were at least 50 years old and had a creatinine clearance less than 140 milliliters per minute achieved an initial therapeutic trough 67.9% of the time, again identifying another statistically significant difference. From this we were able to create an ARC risk group for patients who were likely to have a subtherapeutic initial trough. So patients who were less than 50 years of age and had a creatinine clearance of at least 140 milliliters per minute met the criteria for our ARC risk group. So with this we then looked at weight. So as I mentioned in our protocol, patients weighing up to 89 kilograms with augmented renal clearance or dose every 12 hours and those weighing 90 kilograms or higher are dosed every 8 hours. So when we looked at patients who weighed less than 90 kilograms and met that ARC risk group definition, so were less than 50 years of age and had a creatinine clearance of at least 140 milliliters per minute, 35.1% of them achieved an initial therapeutic trough level. And then we looked at patients who weighed less than 90 kilograms and did not meet that ARC risk group definition and only 43% of them achieved an initial therapeutic trough level. So we didn't identify a statistically significant difference. Rather patients who weighed less than 90 kilograms had poor initial therapeutic trough achievement rates regardless of whether or not they met the ARC risk group definition. So then we also looked at patients who weighed at least 90 kilograms. And those who met the ARC risk group definition, 43% of them achieved an initial therapeutic trough. Whereas patients who weighed at least 90 kilograms but did not meet our ARC risk group definition, 71% of them achieved an initial therapeutic trough. So we again identified another statistically significant difference between these two groups. From this, patients who weighed at least 90 kilograms and met that ARC risk group were more likely to benefit from a dose increase. However, patients who weighed at least 90 kilograms but did not meet our ARC risk group definition would actually run the risk of being supratherapeutic if we implemented an empiric dose increase. So from our results, we saw that higher ARC scores were associated with an increased likelihood of an initial therapeutic trough level, sorry, subtherapeutic trough level. And then age, serum crottening, crottening clearance and weight were major predictors of achieving an initial therapeutic trough. The difference in a patient's ability to achieve an initial therapeutic trough level was due to the dosing outlined in our current protocol rather than pharmacist clinical judgment and deviation from our CDTM. And patients who weighed less than 90 kilograms who are currently being dosed at every 12 hours with our current CDTM would benefit from a dose frequency adjustment to being dosed every 8 hours. So some limitations from our study. It is retrospective in nature. We do not routinely perform 8- or 24-hour urine collections at our institutions. That was not used to calculate crottening clearance. Pregnancy, traumatic brain injury and trauma were not represented in our study due to low numbers. And then the average weight of our patients was 107 kilograms, which is quite a bit higher than the national average of 80 kilograms. And then the ARC risk factors that we identified were specific to our protocol and our patient population. So we are currently working on a draft proposal for updates to our CDTM to reflect certain changes. So implementing a new row at the top of the protocol for patients with a crottening clearance greater than 130 milliliters per minute. And then for patients who weigh 70 to 89 kilograms, we're recommending every 8-hour dosing. And then for patients who weigh greater than 90 kilograms, we're recommending a dose increase or one step up as we call it in our current protocol if they do meet the definition of an ARC risk group. But for patients who weigh 90 kilograms and are not within the parameters of our ARC risk group, we're not going to recommend an empiric dose increase. So with that, thank you guys. And I'm happy to answer any questions.

ARC

vancomycin levels

dosing protocol

therapeutic trough level

creatinine clearance