Hello, everyone. My name is Lauren Andrews, and I'm happy to present Hitting the Target, Therapeutic Drug Monitoring for Beta-Lactam Antibiotics in the Critically Ill as part of SCCM's 2024 Advanced Pharmacology course. As a speaker, I have nothing to disclose. Our learning objectives for today will include the following, determining the appropriate patient population that may benefit from therapeutic drug monitoring, evaluating the evidence to support the implementation of therapeutic drug monitoring for beta-lactam antibiotics in the critically ill, and discussing the challenges with implementing a TDM service within a medical center. As I'm sure we've witnessed in our own practices, beta-lactams account for at least 70% of the antibiotics utilized in caring for critically ill patients, thus forming the backbone of all major treatment algorithms in this population. Substantial inter- and intrapatient variability in beta-lactam concentrations have been observed in the critically ill, which is thought to contribute to suboptimal effectiveness and safety, as well as the development of antibiotic resistance. In addition, these agents often require administration as extended or continuous infusions to combat their short half-life. All of this to say that our main objective is to provide early and appropriate antibiotic administration because we know that it improves clinical outcomes of our septic patients. Particularly in the presence of septic shock, each hour delay is associated with a measurable increase in mortality and other negative endpoints. The 2021 Surviving Sepsis Guidelines have also summarized numerous studies that have reported a strong association between time to antibiotics and death in patients with septic shock, with some further describing mortality increases after intervals exceeding three to five hours from hospital arrival and or sepsis recognition. In 2017, Seymour and colleagues studied time to treatment and mortality during mandated emergency care for sepsis. In their trial of approximately 49,000 patients, the median time to completion of the three-hour bundle was 1.3 hours, and the median time to antibiotic administration was 0.95 hours. Patients who received antibiotics in hours three through 12 had 14% higher odds of in-hospital death than those who received antibiotics within the three-hour bundle. Of note, these associations appeared to be stronger among patients receiving vasopressors than among those who were not. Shown here are the crude in-hospital mortality and predicted risks of in-hospital death for the completion of the three-hour bundle of sepsis care as seen to the right in panel A, and the administration of broad-spectrum antibiotics as seen to the left in panel B for a typical patient. On average, the completion of the three-hour bundle at six hours was associated with mortality that was approximately 3% higher than the mortality associated with the completion of the bundle within the first hour. Another trial in 2017 by Liu and colleagues also studied the timing of early antibiotics and hospital mortality in sepsis. In their review of 35,000 patients, the median time to antibiotic administration was 2.1 hours. The absolute increase in mortality associated with an hour's delay in antibiotic administration was 0.3% for sepsis, 0.4% for severe sepsis, and 1.8% for shock. As illustrated in the figure, each elapsed hour between presentation and antibiotic administration was associated with a 9% increase in the odds of mortality in patients with sepsis of all severity strata. Although antibiotics given within the first hour of registration were associated with the greatest benefit, antibiotics given between hours two and five were associated with similar odds of mortality. Finally, Pelton and colleagues' 2019 study reviewed emergency department door-to-antibiotic time and long-term mortality in sepsis in approximately 11,000 patients. With a median door-to-antibiotic time of approximately 2.8 hours, they found that each hour delay in time from ED arrival to antibiotic administration was associated with 16% increased odds of in-hospital and 10% increased odds of one-year mortality. Mortality at one year was also statistically higher when door-to-antibiotic times were greater than three hours versus less than or equal to three hours by approximately 27%. However, this was not true when comparing greater than one hour versus less than or equal to one hour administration times. The included figures depict the adjusted association of mortality with door-to-antibiotic time, comparing each hourly interval following the first hour to door-to-antibiotic time for one-year mortality as seen on the left and in-hospital mortality as seen on the right. For in-hospital mortality, results from the current analysis are also compared with historical risk-adjusted associations with hospital mortality, including the previously discussed study by Liu et al. Before moving on, it should be noted that all aforementioned studies up to this point were observational analyses and hence at risk for bias due to insufficient sample size, inadequate risk adjustment, blending together the effects of large delays into antibiotics with short delays, or other study design issues. Now that we've thoroughly discussed the important concept of time-to-antibiotic initiation overall, let's get into our first objective, determining the appropriate patient population that may benefit from beta-lactam therapeutic drug monitoring. I'm sure you all are familiar with this graphic, so we'll just do a quick review focused on beta-lactams only. Beta-lactam TDM is designed to optimize drug level within the therapeutic window to ensure maximal effectiveness and safety. More specifically, achievement of an adequate fraction of time above the minimum inhibitory concentration of the organism is associated with a higher likelihood of clinical success and a decrease in the potential for antimicrobial resistance. Conversely, excessive beta-lactam exposure has been associated with an increased risk of concentration-dependent toxicities, most notably neurotoxicity. Time-over-MIC goals for each subset of beta-lactams can be summarized as 40% for carbapenem, 50% for penicillins, and 60-70% for cephalosporins. Although beta-lactams produce little or no post-antibiotic effect against gram-negative organisms, they generally induce a two-hour post-antibiotic effect against gram-positive organisms. However, as mentioned previously, the overall effect of these drugs can be further manipulated by extended or continuous infusion. Because of the safety profile of beta-lactams, TDM was originally thought to be unnecessary for these drugs. However, in line with pharmacokinetic changes in the critically ill, insufficient pharmacodynamic target attainment with beta-lactams has been reported in this population. Therefore, the challenges in achieving optimal drug concentrations in these patients suggest beta-lactam TDM as a useful strategy to optimize drug exposure. Unfortunately, the use of creatinine clearance as a tool to optimize beta-lactam dosing may not be reliable on its own, despite its significant correlation with the concentration and clearance of broad-spectrum beta-lactams. Thus, the PK-PD targets we introduced on the last slide and seen here in the first table give us much clearer indices and magnitudes of beta-lactam clinical efficacy and toxicity. With known thresholds for toxicity, recommended sampling schemes for beta-lactam TDM include the use of Cmin or trough levels drawn 24-48 hours following the initiation of therapy, or the collection of a steady-state concentration sample drawn at any time point during continuous infusion administration of the drug. While therapeutic drug monitoring can also be helpful in obesity and patients infected with a pathogen having an MIC near or above the susceptibility breakpoint, our target group of critically ill septic patients uniquely exhibit a variety of physiologic perturbations that dramatically alter antimicrobial pharmacokinetics. These include unstable hemodynamics, increased cardiac output, increased extracellular volume, which markedly increases volume distribution, variable kidney and hepatic perfusion that affects drug clearance, and altered drug binding due to reduced serum albumin. Acute kidney injury occurs in 50-65% of critically ill patients and in approximately two-thirds of patients within the first 24 hours after being admitted to the ICU. Critically ill patients are usually supported with one of the forms of continuous renal replacement therapy, complicating antibiotic dosing to a significantly higher extent than standard hemodialysis due to the high number of variables including volume of distribution, flow rate, and filter type. In addition, augmented renal clearance, or ARC, is a recently described phenomenon that may lead to decreased serum antimicrobial levels in the early phase of sepsis. Now, in 2014, Roberts and colleagues performed the DALI study, defining antibiotic levels in intensive care unit patients. Outcomes included completion of the treatment course without change or addition of antibiotic therapy, with no additional antibiotics commenced within 48 hours of cessation. De-escalation to a narrower spectrum antibiotic was permitted, but excluded from the clinical outcome analysis. Ultimately, they found that one-fifth of patients did not achieve the most conservative PK-PD target of 50% time over MIC, and less than 50% of patients achieved what was defined a priori as a preferred PK-PD target of 50% time over 4 times MIC. This study generated interesting hypotheses related to much higher target beta-lactam pharmacokinetic exposures than would have been previously considered for clinical outcome of infection, concluding that the idea of one-dose fits all is problematic. In 2018, Wong and colleagues also studied beta-lactam TDM in the critically ill by looking at direct measurements of unbound drug concentrations to achieve appropriate drug exposures. Despite the fact that a large proportion of the studied population received beta-lactams at a non-standard dose that was adjusted according to their clinical condition, as shown here in table 4, almost half of the cases did not achieve 100% time over MIC, thus echoing the concerns raised in other beta-lactam PK-PD studies in the critically ill where significant numbers of patients did not achieve empirical PK-PD targets. The secondary aim of this study was to describe factors associated with failure to achieve these PK-PD targets. Augmented renal clearance, calculated as greater than 130 mL per minute, was found to be the strongest predicting factor for subtherapeutic beta-lactam exposure in this cohort, despite empiric dosing regimen adjustments that had been put into effect for suspected ARC. In conclusion, this study indicates that optimal exposure of unbound beta-lactams, especially for drugs with lower protein binding, is not achieved in a significant proportion of critically ill patients using conventional or empirically adjusted dosing regimens. Although we know that the duration of infusion influences time over MIC, leading to improved target attainment and mortality benefit, this figure breaks the concept down further by illustrating the concentration time profile of unbound piperacillin. Line A, shown in orange, depicts the administration of piperacillin 4 g over 30 minutes every 8 hours. Line B, shown in green, depicts the administration of piperacillin 4 g over 4 hours given every 8 hours. And line C, shown in blue, depicts the administration of piperacillin continuous infusion. The solid gray areas illustrate the fraction of the dosing interval that the free drug concentration is above 1 and 8 mg per liter, respectively. For low target concentrations of 1 mg per liter, both bolus and infusion produce a plasma-free drug concentration above this level for most of the dosing interval. The advantage of the infusion is much more pronounced for higher target concentrations, such as 8 mg per liter. Here, delivery by infusion dosing produces plasma-free drug concentrations above the target for a significantly higher fraction of the dosing interval. From this example, the time that free drug concentration is above 8 mg per liter is 59% following bolus dosing and 100% with continuous infusion. In accordance with this, Monte Carlo simulations consistently show that the difference in target attainment between bolus administration and infusion is most pronounced when the MIC is raised. In 2016, Abdulaziz and their colleagues from the DALI study performed a post-hoc analysis to determine if prolonged infusion of piperacillin, tazobactam, and miripenem in critically ill patients was associated with improved PKPD and patient outcomes. To the left is a clinical cure rate comparison between prolonged infusion and intermittent bolus dosing for patients who received antibiotics for treatment of infections stratified according to subgroups. An asterisk or orange highlighting indicates a significant difference between prolonged infusion and intermittent bolus dosing. To the right is a comparison of 30-day survival between prolonged infusion and intermittent bolus dosing. However, the clinical cure and 30-day survival rate of both groups was equivalent at 73.1%. Overall, 89% of patients achieved the lower PKPD target of 50% time over MIC. For the higher thresholds of 100% time over MIC and 100% time over 4x MIC, 63.2% and 27.5% of patients respectively achieved these PKPD targets. Although prolonged infusion patients generally demonstrated numerically higher target attainment rates compared with intermittent bolus patients across all PKPD indices, a statistically significant difference was only observed at 100% time over MIC with prolonged infusion at 73.1% versus intermittent bolus dosing at 57.4%. When only patients with actual MIC data were analyzed, those who received beta-lactams via prolonged infusion dosing also demonstrated numerically higher target attainment rates, albeit not statistically significantly higher compared with intermittent bolus dosing patients across all PKPD indices. Since international guidelines and consensus statements like the Surviving Sepsis Campaign are now advocating for the use of novel approaches to personalized beta-lactam therapy through real-time drug-level testing, it's time to discuss our second objective, where we will evaluate evidence to support the implementation of beta-lactam-TDM in the critically ill population. In 2018, Heal and colleagues studied pharmacodynamic target attainment for cefepime, miripenem, and piperacillin-tazobactam using a PKPD-based dosing calculator in critically ill patients. Their goal was to determine if measured beta-lactam concentrations in this population helped to achieve predefined therapeutic concentrations, and to assess the frequency at which a change in recommended dosing compared with that from traditional package labeling occurs. In their study, drug-specific target attainment was achieved in 98% of patients, with only one patient not achieving target attainment in the piperacillin-tazobactam group. Drug concentrations remained above the MIC for the entire dosing interval in approximately 96% of patients. However, both patients in whom drug concentrations dropped below the MIC before the end of the dosing interval were receiving piperacillin-tazobactam. MIC values were relatively low in the cohort, with only two patients with an organism MIC by E-test outside the susceptibility range for the antibiotic they were receiving. This included one patient on cefepime for pseudomonas with an MIC of 16 mics per ml, and another patient on piperacillin-tazobactam for pseudomonas with a MIC of 32 mics per ml. When a goal target attainment of 100% time over four times the MIC was considered, overall probability of target attainment decreased to 65%, with 80% receiving cefepime, 85% miripenem, and 37% piperacillin-tazobactam. Doses recommended based on the antibiotic dosing calculator differed from those based on the package insert in 22% of patients, 30% of which received cefepime, 25% miripenem, and 16% piperacillin-tazobactam. Ultimately, doses predicted by an antibiotic dosing calculator to achieve pharmacodynamic targets of MIC greater than 90% achieved this target in 98% of patients. But had a more aggressive target been utilized, such as 100% time over four times MIC, only 65% of patients would have achieved these target concentrations driven largely by piperacillin-tazobactam. Therefore, they concluded that individualized dosing based on population models represents a feasible alternative until point-of-care TDM for beta-lactams becomes more widely available. More recently, in 2022, Mangalorean colleagues performed a meta-analysis reviewing beta-lactam TDM in the critically ill. The included force plot compares three subgroups, target attainment in table A, clinical cure in table B, and microbiologic cure in table C. The dark blue squares represent the effect estimates from individual studies, and the size of the square is proportional to the weight of the study. The horizontal lines represent the 95% confidence interval of the study estimate, and the black diamond represents the pooled effect size. In conclusion, they found no significant pooled effect of TDM-guided dosing of beta-lactams on all-cause mortality in critically ill patients was suspected or proven sepsis. However, TDM-guided dose adaptation was associated with 85% higher target attainment, 17% improved clinical cure, 14% improved microbiological cure, and a 21% reduction in risk of treatment failure. No associations were observed with the application of TDM for length of stay in the ICU or hospital overall. Another study in 2022 by Ubald and colleagues was a multi-center randomized clinical trial that looked into model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin in critically ill patients, also known as the DOLPHIN trial. The primary outcome was ICU length of stay, with secondary outcomes of ICU, hospital, 28-day, and 6-month mortality, as well as the Delta SOFA score, adverse events, and probability of target attainment. For the primary outcome, median ICU length of stay between the model-informed precision dosing and standard dosing groups was non-significant at 10 and 8 days, respectively. For the secondary outcomes, there was also no significant difference between study groups in all mortality outcomes or Delta SOFA scores. In a similar fashion, differences in target attainment between the study groups at any time point were not significant, 64% for the beta-lactam antibiotics and 40% for ciprofloxacin. There were also no major differences in adverse events between the groups, including none likely to be related to the study intervention. As shown by the figure, differences in probability of target attainment were also non-significantly different at three major time points, 24, 48, and 96 hours post-antibiotic initiation. Of note, the MIC values used for assessing pharmacodynamic targets were based on epidemiological cutoff or e-cough values of the expected pathogens per UCAST. Due to this approach, there is a chance that targets were overestimated in the study. Based on the available data, the authors concluded that there is currently no evidence for a clinical effect of model-informed precision dosing of beta-lactam antibiotics or ciprofloxacin in critically ill patients, despite the more promising data presented by HEAL and Mangalore studies. While the main focus of this presentation has been efficacy, beta-lactam TDM is also important in preventing adverse effects like neurotoxicity. Unfortunately, due to co-medication and or comorbidities, it is often difficult to attribute neurological side effects to antibiotics and diagnose neurotoxicity in the ICU, likely resulting in under-reporting of these side effects. The onset of these clinical manifestations is highly variable according to the beta-lactam considered and the clinical setting, and can range from 24 hours to 30 days. Neurotoxicity has been reported in up to 10 to 15 percent of ICU patients, but while it has been associated with significantly higher beta-lactam trough concentrations, this has not been universally linked. Analyzing different beta-lactams, a standardized Cmin over MIC ratio of greater than 8 has been correlated with an incidence of neurological deterioration up to 60 percent. To avoid potentially toxic effects, dose reduction is arbitrarily recommended when the unbound trough levels exceed eight times the MIC. In addition to the conflicting data available for beta-lactam TDM in regard to both efficacy and safety, our third objective's focus is to discuss the challenges of actually implementing a TDM service within a medical center. Fortunately for us, Barreto and colleagues have published multiple times on this topic. As recently as 2021, they released a protocol for a multi-center mixed method study regarding provider perspectives on beta-lactam TDM programs in the critically ill. Later in 2023, they followed up with a result document discussing why implementation of beta-lactam TDM in this population has been falling short. As early as 2015, only 10 to 20 percent of European practices surveyed used beta-lactam TDM in the ICU, compared to less than 1 percent in the United States. To obtain more data to describe current U.S. practices, the Barreto study proposal sought to identify potential limitations of beta-lactam TDM implementation, including the inability to comprehensively survey all clinicians in the selected ICU settings, and that data obtained may not be generalizable to less acute areas of practice. They also recognized that key considerations for other antibiotic TDM programs have included multi-phase plans for rollout, multidisciplinary buy-in, education and training of clinicians, and robust technical integration within the electronic health record. Within the 2021 study protocol, Barreto and colleagues defined the potential work associated with beta-lactam TDM, which was categorized according to normalization process theory, or MPT, domains that focus on explaining what people actually do, rather than their attitudes or beliefs regarding process innovation. The first core construct has to do with coherence, or the work related to a practice's meaning, use, or utility. This is where physicians and other providers make an effort to distinguish the new approach from their current practice method. They are then able to move into a participation phase that involves the initiation, enrollment, and legitimization, or buy-in, among their colleagues about the new practice. For example, having team pharmacists agree that beta-lactam TDM should be a part of their workflow. This can also include the beginning stages of creating standard selection criteria for beta-lactam TDM use. Next is the operational, or collective action phase, where integration of the new practice occurs in a specific context and availability of necessary resources for and availability of necessary resources to enact the practices determined. This would include having IT adequately integrate beta-lactam TDM into the EHR. Finally is the appraisal, or reflexive monitoring phase, when criticism and data related to the effectiveness and utility of the new practice is provided to team leaders to determine how the results of beta-lactam TDM have impacted clinical outcomes. Pareto and colleagues also define the potential associations between provider responses and the Consolidated Framework for Implementation Research, or CFIR, constructs to help guide deeper systematic assessment of both the barriers and facilitators of this process. These five domains can be broken down into the following. Intervention characteristics, like determining processes for specimen collection and securing access to rapid turnaround time for EHR reporting of validated assay results, are a crucial first step to implementing beta-lactam TDM. This is also the point at which the process of integrating checklists, calculators, and standard documentation schema into the EHR would occur. There also needs to be support from outer settings, like large professional organizations capable of providing economic, political, and social context encouraging beta-lactam TDM as a facet of personalized medicine. Even more importantly, the inner setting must be able to provide its team with structural, political, and cultural context through which successful implementation can occur. This is most easily achieved in academic medical centers, where multiple providers from various disciplines participate in caring for the same patient. The institution should also engage relevant leadership and administrative oversight groups for endorsement and resources, including access to online evidence-based resources about beta-lactam TDM. Within those teams, individuals involved with process implementation must be knowledgeable enough to develop and deliver multifaceted education and training for diverse stakeholders. They are also key in determining a local consensus on appropriate PK-PD targets for beta-lactam TDM, as well as disseminating the choice and justification to end-users for the creation of policies, procedures, and practice guidelines. The final step in the implementation process should promote stakeholder engagement so that team members can debrief following difficult clinical scenarios and provide systematic and regular feedback to clinicians regarding beta-lactam TDM performance metrics. Using their 2021 protocol proposal, Barreto and colleagues' sequential mixed-method study was performed at three academic medical centers in both the United States and Australia and New Zealand, with varying degrees of beta-lactam TDM implementation, including no implementation at Center 1, partial implementation at Center 2, and full implementation at Center 3. As reflected in these two graphs, Center 1 deemed beta-lactam TDM as important in survey responses. However, deeper probing revealed skepticism about evidence sufficiency among interviewees. By contrast, clinicians at Centers 2 and 3, who had access to the same published scientific literature as those at Center 1, gauged the evidence as confirmatory to justify beta-lactam TDM implementation. Several potential reasons exist for this observation, with a major one being that historically, much of the literature for precise dosing of beta-lactam TDM emerged from Europe, China, Australia, and New Zealand. Center 3, the non-U.S. site included in the study, could therefore have had greater access to local research, clinical experts, and practical experience with beta-lactam TDM, which were identified as facilitators of implementation. It is also possible that the differences between healthcare systems in the U.S. and Australia and New Zealand contributed to the findings, a component of the outer setting in the CFIR framework. The fee-for-service payment structure in the United States means that new innovations are scrutinized for cost implications and utility, which may limit or slow the adoption of the system. Comparatively, innovations may be more readily implemented in a universal healthcare system, like Australia or the United Kingdom, where the hospital receives payment from the government irrespective of the number of patients seen or the procedures performed. Ultimately, the study concluded that individual internalization, or the sense-making work clinicians do to rationalize an evidence-based practice, differed across centers and distinguished beta-lactam TDM implementation from the implementation of other antibiotic TDM programs. In the same year, Osmond and colleagues published their how-to guide for pharmacist-led implementation of beta-lactam TDM in the critically ill. In addition to providing a key guidance summary and detailed schematic of the project timeline that we will discuss further on the next slide, the authors also developed and distributed a PK calculator within their institution via web-based resources. Unique to previous studies, this study's TDM steering committee was responsible for identifying and proposing recommendations for how to handle inappropriately timed samples, where to sample from patients on extracorporeal circuits, and how to approach unexpected values in the event of accumulation or sample contamination. Guidance on when to pursue a more aggressive PK PD target, when to repeat TDM, and how to respond to subtherapeutic levels in the setting of clinical improvement, and supertherapeutic levels in the setting of clinical deterioration was also created. Based on this information, pharmacists could be directed to a local antimicrobial dosing guide, and providers were encouraged to use their clinical judgment to select the safest and most effective dose for each patient. Please take a moment to review the included timeline from Osmond and colleagues that provides a visual representation of the study's milestones at each phase of the beta-lactam TDM implementation process. Preparatory implementation activities, including identification of the project lead and key disciplines needed to own the steering committee, securing preliminary approvals by local leadership, and prioritization of assay development by the laboratory, occurred over one year preceding pilot implementation, which occurred over the following six months. Throughout the initial six months of implementation, only approximately 120 samples were assayed from 40 critically ill patients. Although this reflects a relatively small fraction of critically ill patients compared with the total number treated with cefepime, piperacil and tazobactam, and miripenem during the same interval, this was imperative to the study design. The deliberately slow introduction of beta-lactam TDM through staged implementation helped to facilitate clinical pharmacists' adaptation and continuous process improvement, as pharmacists were more likely to perform the determination of patient eligibility during their own clinical evaluation rather than deferring until requested by the provider. With this, the study identified that pharmacists naturally chose to perform beta-lactam TDM surrounding a dose rather than on the elimination curve, leading to modifications of the PK calculator and necessitating additional functionality testing. Since the approaches to adjusting beta-lactam doses based on TDM varied widely, the steering committee also invited guest speakers and developed podcasts and presentations to provide insight into external sources of real-world beta-lactam TDM experiences. In the future, the authors recommended expanding patient eligibility to include other populations at high risk for PK derangements, drug resistance, and toxicity. Despite the availability of study guidance for beta-lactam process implementation from authors like Barreto and Osmond, the limited number of diagnostic laboratories able to perform the necessary assays and absence of clinical laboratory improvement amendments or CLIA-approved assays for on-site testing of beta-lactam concentrations remain the most significant barriers to TDM of this drug class. Additionally, the transportation of samples to and from an outside laboratory is detrimental to turnaround time, which leads one to consider if the results remain clinically applicable days after collection in patients undergoing physiologic and interventional changes that can influence pharmacokinetics. Some of the currently available diagnostic laboratories and their contact information is summarized here for your reference. Despite the limited availability of diagnostic laboratories able to assist with beta-lactam TDM, clinicians also recognize the lack of national guidelines to standardize beta-lactam TDM targets, thus leaving us to question, when dose adjustments are required, to what extent and degree of variability will providers be able or need to optimize the dose? And will providers be accepting of dosing interval and amounts that are not endorsed in the package insert but might be necessary to achieve pharmacodynamic targets? As this presentation comes to a close, I'd like to challenge you all to identify and find solutions to barriers within your own institutions because it's becoming clear that beta-lactam dosing individualization is going to be the next frontier in optimizing antibiotic therapy for the critically ill. Other key takeaways include the current strategy of achieving a PKPD target of at least 50% time over MIC for those undergoing beta-lactam TDM to ensure maximal bacterial killing, improved clinical cure, and improved microbiologic cure. We also know that extended infusion strategies can significantly influence time over MIC, leading to improved target attainment and mortality benefit. Hopefully, moving forward, PKPD-based antibiotic dosing software will be able to provide individualized beta-lactam doses since previous studies have associated them with higher probability of target attainment in critically ill patients, especially in those with MICs approaching or exceeding the susceptibility breakpoint. Thank you again to all of you who joined me today for SECM's 2024 Advanced Pharmacology course on Hitting the Target, Therapeutic Drug Monitoring for Beta-Lactam Antibiotics in the Critically Ill.

Lauren Andrews

Therapeutic Drug Monitoring

Beta-Lactam Antibiotics

Critically Ill

Pharmacology

Clinical Outcomes

Personalized Dosing