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IMPORTANCE:. Sepsis and septic shock are major healthcare problems that need early and appropriate management. OBJECTIVES:. To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement. DESIGN, SETTING, AND PARTICIPANTS:. This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes. MAIN OUTCOMES AND MEASURES:. Change in daily SOFA score and vasopressors requirement. RESULTS:. A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T>MIC) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score. CONCLUSIONS AND RELEVANCE:. Achieving 100% T>MIC was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score.

Beta-lactam antibiotics are often the backbone of treatment for Gram-negative infections in the critically ill. Beta-lactams exhibit time-dependent killing, and their efficacy depends on the percentage of dosing interval that the concentration remains above the minimum inhibitory concentration. The Gram-negative resistance rates of pathogens are increasing in the intensive care unit (ICU), and critically ill patients often possess physiology that makes dosing more challenging. The volume of distribution is usually increased, and drug clearance is variable. Augmented renal clearance and hypermetabolic states increase the clearance of beta-lactams, while acute kidney injury reduces the clearance. To overcome the factors affecting ICU patients and decreasing susceptibilities, dosing strategies involving higher doses, and extended or continuous infusions may be required. In this review, we specifically examined pharmacokinetic models in ICU patients, to determine the desired beta-lactam regimens for clinical breakpoints of Enterobacterales and Pseudomonas aeruginosa, as determined by the European Committee on Antimicrobial Susceptibility Testing. The beta-lactams evaluated included penicillins, cephalosporins, carbapenems, and monobactams. We found that when treating less-susceptible pathogens, especially P. aeruginosa, continuous infusions are frequently needed to achieve the desired pharmacokinetic/pharmacodynamic targets. More studies are needed to determine optimal dosing strategies in the novel beta-lactams.

Background: Although the benefits of improved transitions of care regarding medications are widely known, implementation is variable among inpatient settings and populations and requires an interprofessional effort. This article reviews the body of published research on challenges with medication history taking and reconciliation for inpatients requiring treatment of traumatic injuries or surgical intervention., Review of Evidence: A comprehensive search of PubMed and MEDLINE databases from inception to February 2021, the reference lists of qualifying articles, and PubMed's "similar article" suggestions were used to identify publications based on the following key terms: patient transfer, transitional care, medication reconciliation, general surgery, and surgical procedures. Publications relevant to trauma and surgical patient populations were selected. Only 11 articles met the full criteria., Implementation: The general challenges of accurate medication reconciliation at admission are also often barriers in the trauma and general surgery population. Discerning trends in the literature and evidence-based practice may be helpful., Evaluation: The publications revealed many barriers to medication reconciliation at admission, in the intensive care unit, and at intensive care unit and hospital discharge., Sustainability: Practices that can overcome these challenges include persistence in obtaining accurate information, paying close attention to changes in dosage or dosage forms and resumption of home medications at intensive care unit discharge, and having a follow-up plan for prescribing and deprescribing at hospital discharge., Conclusion: Clear guidelines are needed for performing medication assessments at the bedside, including the role of each health care professional who conducts them and how the process is coordinated., (©2024 American Association of Critical-Care Nurses.)