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Janelle J Juul, Caitlin F Mullins, William J Peppard, Angela M Huang Department of Pharmacy, Froedtert & the Medical College of Wisconsin, Milwaukee, WI, USA Abstract: Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies. Keywords: acute bacterial skin and skin structure infections, skin and soft tissue infections, dalbavancin, glycopeptide

Introduction: Clinical pharmacists bring unparalleled medication expertise, but quantifying their impact on a health system's bottom line remains unestablished. Objective: To classify interventions by pharmacists with and without board certification and quantify the cost avoidance (CA) from accepted interventions. Methods: This multicenter prospective observational study, conducted between August 2018 and January 2019, included board certified (BPS) and non-board certified (Non-BPS) emergency medicine (EM) and intensive care unit (ICU) clinical pharmacists from 89 U.S. institutions. Primary outcomes included the quantity, type, and acceptance of interventions and the CA generated by BPS pharmacists compared to Non-BPS pharmacists. Results: 287 pharmacists (227 BPS, 60 Non-BPS) at 89 centers provided care throughout 4184 shifts. BPS pharmacist provided more interventions (overall: 63 693 vs 8690; per shift: 18.8 vs 10.9, P  < .001) with higher acceptance (98.2% vs 97.6%, P  < .001). Accepted interventions per shift included adverse drug event prevention (2.0 vs 1.6, P  = .17), resource utilization (3.6 vs 1.7, P  = .007), individualization of patient care (9.7 vs 5.3, P  = .05), prophylaxis (0.4 vs 0.3, P  = .99), hands-on care (1.4 vs 0.9, P  = .99), and administrative/supportive tasks (1.8 vs 1.1, P  = 0.). BPS pharmacists generated greater mean CA per intervention ($873 vs $801), patient day ($961 vs $501), shift ($8112 vs $4828) and annum ($1 946 942 vs $1 158 784) ( P  < .001 for all). The CA to salary ratio was 10.5:1 for BPS and 6.3:1 for Non-BPS pharmacists. Conclusion: BPS pharmacists in the ED and ICU generated greater CA and a higher monetary CA to salary ratio than Non-BPS pharmacists., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Objective: Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs)., Methods: Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25-48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine., Results: Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female ( n  = 13), 92% intubated ( n  = 22), 25% on CI vasopressors ( n  = 6), and 33% on CI paralytics ( n  = 8). Ketamine indications were analgesia/sedation ( n  = 21, 87.5%) and status epilepticus ( n  = 3, 12.5%). Median starting dose was 0.5 (0.48-0.70) mg/kg/hr and continued for a median of 2.4 (1.3-4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0-24H: 85% ± 10%, and 25-48H: 72% ± 20%; p =0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8-195) mg vs. 0-24H: 4 (0-69) mg and p =0.01), but this was not sustained (25-48H: 24 (2-246) mg and p =0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%)., Conclusions: Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 Christine M. Groth et al.)

Study Objective: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients., Design: Multicenter, retrospective review., Data Source: Electronic health records from participating institutions., Patients: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement., Intervention: Dosing strategy used to determine initial prophylactic dose of enoxaparin., Measurements: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL)., Main Results: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant., Conclusions: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients., (© 2023 Pharmacotherapy Publications, Inc.)

Background: The optimal dosing for enoxaparin venous thromboembolism (VTE) prophylaxis in low-weight trauma patients is unknown. Estimated blood volume (EBV) has shown promise as a dose modifier., Objective: To characterize the association of enoxaparin dose per EBV with the prevalence of VTE and bleeding in low-weight trauma patients., Methods: This was a retrospective study of trauma patients admitted over a 4-year period. Included patients were adults weighing <60 kg who received a minimum of 3 consecutive doses of enoxaparin. The primary endpoint was a comparison of enoxaparin dose per EBV in patients experiencing bleeding and VTE. Secondary endpoints included comparisons of dose per body mass index (BMI) and total body weight (TBW) and the ability of dose per EBV to predict clinical endpoints. Subgroup analyses for patients weighing <50 kg were performed for all endpoints., Results: A total of 189 patients were included. Statistical comparisons for VTE were not performed because of low prevalence. The dose of enoxaparin per EBV was not statistically different between patients who did and did not bleed in all analyses. Doses per BMI and TBW were also not statistically different between the groups. In patients weighing <50 kg, numerically higher doses per EBV, BMI, and TBW were noted in patients that bled versus those that did not. Enoxaparin dose per EBV was not a statistically significant predictor of bleeding in logistic regression models., Conclusion and Relevance: No significant associations between enoxaparin dose per EBV, BMI, or TBW and bleeding were noted in the study. Future analyses of EBV and other dose modifiers should consider inclusion of patients weighing <50 kg., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Patients prescribed higher opioid dosages have a higher risk of persistent opioid use, overdose, and death. There is a lack of standardization for opioid prescribing for acute surgical pain in emergency general surgery (EGS) patients. We hypothesized that implementing a guideline to standardize opioid prescribing would be associated with a decrease in prescribing at hospital discharge for EGS patients without increasing additional postdischarge refills., Methods: This was a quasi-experimental study evaluating opioid prescribing by EGS providers before and after the implementation of a prescribing guideline. Patients were assigned to preguideline and postguideline groups based on admission date surrounding the implementation of the guideline. The primary outcome was the proportion of patients receiving an opioid prescription for ≥50 Morphine Milligram Equivalents (MME) per day on hospital discharge., Results: There were 227 patients in the preguideline group and 226 patients in the postguideline group. After guideline implementation, median total MME prescribed decreased from 113 (interquartile range = 75) to 75 (interquartile range = 75, P = 0.03). The proportion of patients receiving a prescription for daily MME ≥50 also decreased from 75% to 25% (P ≤0.01). There were no increases in requested refills (17% versus 16%, P = 0.72) or received refills (14% versus 14%, P = 0.98). Guideline compliance ranged from 75% in ventral hernia repair patients to 94% in laparoscopic cholecystectomy patients., Conclusions: A departmental guideline to standardize postoperative opioid prescriptions was associated with a decrease in the amount of MMEs prescribed to EGS patients without an increase in requested or received refills., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Fixed-dose and body mass index (BMI)-based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)-based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients., Methods: This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti-factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL)., Results: A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups., Conclusion: Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Enoxaparin is administered for venous thromboembolic (VTE) prophylaxis in bariatric surgery patients. There is concern whether body mass index (BMI)-based enoxaparin dosing consistently achieves prophylactic targets in patients with severe obesity., Methods: This retrospective study included patients who underwent bariatric surgery at an academic medical center from Jan 2015-May 2021 and had an anti-Xa level drawn 2.5-6 h after ≥3 doses of BMI-based prophylactic enoxaparin. The primary outcome was the percentage of patients who achieved a target anti-Xa level. Secondary outcomes were prevalence of venous thromboembolic and bleeding events within 30 d post-operatively., Results: Overall, 137 patients were included. Mean BMI was 59.1 ± 10.4 kg/m 2 , mean age was 43.9 ± 13.3 y and 110 patients (80.3%) were female. Target anti-Xa levels were achieved in 116 patients (84.7%); 14 (10.2%) were above target and 7 (5.1%) were below target. Patients with above target anti-Xa levels were significantly shorter in height than those within target range (167.1 versus 159.8 cm, P = 0.003). Five patients (3.6%) had a bleeding event; no thromboembolisms occurred. Anti-Xa levels correlated more strongly with enoxaparin dose per unit estimated blood volume (EBV) than dose per unit BMI (Rho = 0.54 versus Rho = 0.33)., Conclusions: Target range anti-Xa levels were achieved in 85% of patients using BMI-based enoxaparin dosing. Patients with above target anti-Xa levels were significantly shorter by nearly 3 inches, suggesting an increased risk of overdosing enoxaparin in shorter, obese patients. An EBV-based dosing regimen may better account for patient height and is supported by a greater correlation with anti-Xa levels with dosing based on EBV than BMI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Open-access publishing promotes accessibility to scholarly research at no cost to the reader. The emergence of predatory publishers, which exploit the author-pay model by charging substantial publication fees for publication in journals with questionable publishing processes, is on the rise. Authors are solicited through aggressive marketing tactics, though who is targeted is not well described. The purpose of this study was to identify characteristics associated with critical care pharmacists that make them targets of unsolicited invitations to publish. A prospective, observational study of critical care pharmacists was performed. Participants archived emails received by their professional email that were unsolicited invitations to submit their original work for publication in a journal (unsolicited journals). Variables were evaluated to determine which were associated with unsolicited invitations; these were compared to legitimate journals, defined as all PubMed-indexed journals in which the participants were previously published. Twenty-three pharmacist participants were included, all of whom were residency and/or fellowship trained and practicing in an academic medical center. Participants had a median of 7 years of experience since their post-graduate training, 6 years since their last change in professional email address, and 2 years since their first PubMed-indexed publication. From these participants, 136 unsolicited and 59 legitimate journals were included. The average number of invitations increased 1.04 (95% CI, 1.02-1.05) times for every additional PubMed-indexed publication ( P < .001). Most unsolicited journals were considered predatory. Legitimate and unsolicited journals differed significantly. The number of previous PubMed-indexed publications strongly correlates with the likelihood of critical care pharmacists receiving unsolicited publication invitations, often from predatory journal.

Competing Interests: Conflicts of interest were reviewed and adjudicated by the co-chairs and co-vice chairs of the guidelines. In the event an individual disclosed a conflict or potential conflict by submitted form or verbally during the process of guidelines, those individuals abstained from voting on related questions. The taskforce followed all procedures as documented in the American College of Critical Care Medicine/Society of Critical Care Medicine (SCCM) Standard Operating Procedures Manual. Drs. Singbartl, Nanchal, Killian, Olson, Karvellas, Subramanian, and Truwit disclosed authorship on several related articles with potential intellectual conflicts explored and adjudicated. Dr. Dionne described volunteer service for Canadian Association of Gastroenterology, American College of Gastroenterology, American Gastroenterological Association, and European Society of Intensive Care Medicine. Dr. Hyzy described volunteer service for American Thoracic Society, Quality Improvement and Implementation Committee, and the SCCM Finance Committee as well as service as an expert witness in a previous medical case involving this subject matter. Taylor advised of service as an author on the SCCM/American Society for Parenteral and Enteral Nutrition (ASPEN) nutrition guidelines and service on the ASPEN research committee. Dr. Huang disclosed service on the American College of Emergency Physicians sepsis task force. Dr. Karvellas disclosed service on an acute liver failure study group. Dr. Hyzy and Dr. Olson disclosed being expert witnesses. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Objectives: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU., Design: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development., Interventions: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements., Measurements and Main Results: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence., Conclusions: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence., Competing Interests: Conflicts of interest were reviewed and adjudicated by the co-chairs and co-vice chairs of the guidelines. In the event an individual disclosed a conflict or potential conflict by submitted form or verbally during the process of guidelines, those individuals abstained from voting on related questions. The taskforce followed all procedures as documented in the American College of Critical Care Medicine/Society of Critical Care Medicine (SCCM) Standard Operating Procedures Manual. Drs. Singbartl, Nanchal, Killian, Olson, Karvellas, Subramanian, and Truwit disclosed authorship on several related articles with potential intellectual conflicts explored and adjudicated. Dr. Dionne described volunteer service for Canadian Association of Gastroenterology, American College of Gastroenterology, American Gastroenterological Association, and European Society of Intensive Care Medicine. Dr. Hyzy described volunteer service for American Thoracic Society, Quality Improvement and Implementation Committee, and the SCCM Finance Committee as well as service as an expert witness in a previous medical case involving this subject matter. Dr. Taylor advised of service as an author on the SCCM/American Society of Parenteral and Enteral Nutrition (ASPEN) nutrition guidelines and service on the ASPEN research committee. Dr. Huang disclosed service on the American College of Emergency Physicians Sepsis Task Force. Dr. Karvellas disclosed service on an Acute Liver Failure Study Group. Dr. Hollenberg disclosed that he is a member of American College of Chest Physicians, American Heart Association, and American College of Cardiology. Dr. Olson disclosed that she is a member of American Association for the Study of Liver Disease. Dr. Steadman disclosed that he is a co-author on “Management of the Critically Ill Patient with Cirrhosis: A Multidisciplinary Perspective.” J Hepatology 2015 pending publication, and that he is currently writing guidelines for Anesthesiology Transplant fellowship for the International Liver Transplant Society. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine.)

Background: Patients prescribed higher opioid dosages are at increased risk of overdose and death without added pain reduction. Increases in opioid prescribing continue to fuel the epidemic. We hypothesized a comprehensive guideline to standardize opioid prescribing would decrease postdischarge dosages for patients experiencing trauma without requiring additional refills., Methods: This quasiexperimental study compared opioid prescribing by trauma providers before and after the implementation of a departmental guideline on April 1, 2019, aimed at aligning opioid prescription patterns with Centers for Disease Control and Prevention recommendations. Patients prescribed opioids before implementation were the control group, whereas patients prescribed opioids after were the intervention group. The primary outcome was the proportion of patients receiving ≥50 morphine milligram equivalents per day., Results: We identified 293 and 280 patients experiencing trauma in the control and intervention groups, respectively. There were no differences between the groups' Injury Severity Score (P = .69) or the frequency of having a procedure performed (P = .80). Total morphine milligram equivalents and maximum morphine milligram equivalents per day were 16% and 25% lower, respectively, in the intervention group compared with the control group (P < .001). The proportion of trauma patients prescribed ≥50 morphine milligram equivalents per day at discharge decreased from 57% to 18% after implementation (P < .001). The proportion of trauma patients prescribed ≥90 morphine milligram equivalents per day also decreased, from 37% to 14% (P < .001). There was no significant increase in the frequency of refill requests (P = .105) or refill prescriptions (P = .099) after discharge., Conclusion: A departmental guideline aimed at optimizing opioid prescription patterns successfully lowers the amount of morphine milligram equivalents prescribed to trauma patients and improves compliance with Centers for Disease Control and Prevention recommendations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the effectiveness of a body mass index (BMI)-based enoxaparin prophylaxis dosing protocol at achieving target anti-factor Xa (anti-Xa) concentrations in the trauma population., Methods: This retrospective chart review evaluated anti-Xa concentrations in adult trauma patients who received prophylactic enoxaparin over a three-month period. The primary outcome was the percentage of patients that achieved target anti-Xa concentrations after ≥3 doses of enoxaparin. Secondary outcomes included correlations of anti-Xa concentrations with enoxaparin dose per BMI, total body weight (TBW), and estimated blood volume (EBV). The prevalence of clinically relevant bleeding and venous thromboembolism was also recorded. Multivariable logistic regression was used to identify associated variables for target anti-Xa concentration attainment., Results: Ninety-nine consecutive patients were included in the study. Included patients were predominately male (69.7%) and Black (50.5%) with a mean age of 44.1 years. Target anti-Xa concentrations were achieved in 62.6% of patients. Anti-Xa concentrations were moderately correlated with enoxaparin dose per EBV (ρ = 0.57), followed by dose per TBW (ρ = 0.46), and dose per BMI (ρ = 0.20). Multivariable logistic regression demonstrated that categorization of enoxaparin dose per EBV and per TBW were the only statistically significant predictors of reaching target anti-Xa concentrations (p = <0.001)., Conclusions: In adult trauma patients, the rate of achieving target anti-Xa concentrations remains suboptimal and provides room for further improvement. Enoxaparin dose per EBV was more closely correlated with anti-Xa concentrations when compared to TBW and BMI. Dosing per EBV and TBW was the only variables associated with reaching target anti-Xa concentrations within the study. Further investigation is warranted to elucidate optimal EBV- and TBW-based dosing regimens., (© 2022 Pharmacotherapy Publications, Inc.)

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established., Objectives: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium., Design Setting and Participants: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017., Main Outcomes and Measures: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after., Results: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation ( n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study., Conclusions and Relevance: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: To evaluate the impact of postoperative depth of sedation in free flap transfers to the head and neck., Methods: A single center, retrospective cohort of 92 patients were stratified by depth of sedation, light sedation (RASS -1 or greater) or deep sedation (RASS less than -1), and analyzed for postoperative flap and medical complications., Results: Of the 92 patients 45 were included in the light sedation and 47 in the deep sedation group. Flap complication requiring return to the operating room occurred in 8 (22.2%) patients in light sedation compared to 12 (27.7%) (p = 0.450) patients in deep sedation. A composite outcome of flap and medical complications occurred less frequently in the light sedation group 14 (31.8%) compared to deep sedation 32 (69.6%) (p < 0.001)., Conclusion: There was no difference in return to the operating room between the two groups. Light sedation had reduced incidence of medical complications compared to deep., (© 2021 Wiley Periodicals LLC.)

To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions., Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019., Setting: Community hospitals and academic medical centers in the United States., Participants: ICU clinical pharmacists., Interventions: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance., Measurements and Main Results: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions; $5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions; $9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions; $1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was $418 per intervention, $845 per patient day, and $7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between $3.3:1 and $9.6:1., Conclusions: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between $3.3:1 and $9.6:1., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: Despite potential benefits of intravenous (i.v.) administration of acetaminophen (APAP), consistent outcome data are lacking. This, combined with the higher acquisition cost of the drug, has led to variation in i.v. APAP management strategies. This project evaluated the contemporary formulary status and restrictions of i.v. APAP in the perioperative setting. Methods: A survey focusing on i.v. APAP formulary restriction in the perioperative setting was developed by the Vizient Pharmacy Research Committee and distributed to Vizient Pharmacy Program participant listservs for Pharmacy Directors or Drug Information Pharmacists. The four survey domains included hospital characteristics, perioperative i.v. APAP formulary status and prescribing restrictions, perioperative i.v. APAP use, and perioperative i.v. APAP medication use evaluation (MUE) results. Responses were collected and summarized, and primary outcomes were evaluated using Fisher's exact test. Results: A total of 1195 surveys were distributed with a response rate of 19%. Respondents were equally distributed between academic medical centers (AMC) and non-academic medical centers (non-AMC). Two cohorts were examined: those with i.v. APAP on formulary and those without. The non-AMCs showed a larger proportion of hospitals with the medication on formulary ( P  = .041). Regarding formulary decision-making, the AMCs were more considerate of value. Several different practices were employed to limit or restrict i.v. APAP. Conclusion: A survey of directors of pharmacy and drug information specialists revealed that the majority of hospitals have i.v. APAP on formulary for perioperative use, but use is restricted. Differences in i.v. APAP formulary practices between AMCs and non-AMCs warrant further consideration., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions., Design: A multicenter, prospective, observational study was performed between August 2018 and January 2019., Setting: Community and academic hospitals in the United States., Participants: Emergency medicine clinical pharmacists., Interventions: Recommendations classified into one of 38 intervention categories associated with cost avoidance., Measurements and Main Results: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1., Conclusions: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The optimal dose and timing of enteral nutrition (EN) in septic shock are unclear., Methods: We conducted a phase 3 single-center randomized controlled pilot trial comparing early trophic EN with "no EN" in mechanically ventilated adults with septic shock, with the hypothesis that implementing a protocol comparing early trophic EN with "no EN" in patients with septic shock would be feasible. Patients were randomized to early trophic EN or "no EN" until off vasopressor for 3 hours. The primary outcome was feasibility in achieving >75% consent and compliance rate and <10% contamination rate., Results: One hundred thirty-one patients were eligible for enrollment, and 49 were available for consent. Thirty-one (86%) consented and were randomized and 100% of patients in the early EN arm and 94% in the "no EN" arm completed their protocols. While on vasopressors, early EN group received median 384 kcal, and the "no EN" group received median 0 kcal. Contamination rate was 0 in the early trophic EN arm and 6% in the "no EN" arm. The early EN group had median 25 intensive care unit-free days, as compared with 12 in the "no EN" arm (P = .014). The early EN arm had median 27 ventilator-free days, compared with 14 in "no EN" arm (P = .009)., Conclusion: Our protocol comparing early trophic EN with "no EN" in septic shock was feasible. Early trophic EN may be beneficial, but a larger multicenter trial is warranted to confirm the observed clinical benefits seen in this trial., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Background: The appropriate duration of antibiotic therapy for surgical site infection (SSI) prevention in traumatic mandibular fracture repair is unknown, and practices vary significantly. The objective of this study was to characterize antibiotic duration and outcomes after surgical repair of traumatic mandibular fracture., Methods: A single-center, retrospective analysis of all adult patients who underwent surgical fixation of a mandible fracture between January 2014 and December 2016 was performed. Operative service was categorized between otolaryngology (ear, nose, and throat surgery), plastic and reconstructive surgery, and oral and maxillofacial services. Primary outcomes were SSI and operative complications (including osteomyelitis, nonunion, malocclusion, and hardware infections). Differences in antibiotic prescription pattern were analyzed using analysis of variance test and Pearson chi-squared test., Results: A total of 75 patients were included in the study with 33 (44.0%), 26 (34.7%), and 16 (21.3%) managed by plastic and reconstructive surgery, ear, nose, and throat surgery, and oral and maxillofacial services, respectively. Median age was 30.0 y. Median injury severity score was 4.0. There was no significant difference in hospital length of stay (P = 0.44), intensive care unit length of stay (P = 0.53), or postoperative complications (P = 0.15). None of our patients developed an SSI or postantibiotics complications. Although the total inpatient duration of antibiotics was not significantly different among services (P = 0.37), there were significant differences in outpatient duration of antibiotics (P = 0.007) and total duration of antibiotics (P = 0.003)., Conclusions: Duration of antibiotics is not associated with postoperative SSI or antibiotics-related complications. The wide variation in prescribing practices and lack of any clear benefit for prolonged antibiotics provides an opportunity to explore the benefits of a standardized short course of antibiotics., Level of Evidence: Therapeutic study, III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rib fractures are associated with increased mortality, particularly in the elderly. While opiate-based pain regimens remain the cornerstone of rib fracture management, issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine use in lieu of opioids continues to increase but little evidence exists to support its efficacy or safety within the elderly trauma population., Methods: A prospective, randomized, double-blind placebo-controlled trial of elderly patients (age, ≥65 years) with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included Glasgow Coma Scale score less than 14, and chronic opiate use. Groups were randomized to either low-dose ketamine (LDK) at 2 μg·kg·min or an equivalent rate of 0.9% normal saline. The primary outcome was reduction in numeric pain scores (NPS). Secondary outcomes included oral morphine equivalent (OME) utilization, epidural rates, pulmonary complications, and adverse events., Results: Thirty (50.8%) of 59 were randomized to the experimental arm. Groups were similar in makeup. Low-dose ketamine failed to reduce 24-hour NPS or OME totals. Subgroup analysis of 24 patients with Injury Severity Score greater than 15 demonstrated that LDK was associated with a reduction in OME utilization the first 24-hours (25.6 mg vs. 42.6 mg, p = 0.04) but at no other time points. No difference in other secondary outcomes or adverse events was noted., Conclusion: Low-dose ketamine failed to affect NPS or OME within the overall cohort, but a decrease in OME was observed in those with an Injury Severity Score greater than 15. Additional studies are necessary to confirm whether LDK benefits severely injured elderly patients., Level of Evidence: Therapeutic, level I.

Background: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature., Objective: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide., Methods: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described., Results: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%., Conclusion: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Background: Rib fractures occur in up to 40% of trauma patients and are associated with increased mortality. Opiate-based pain regimens remain the cornerstone of rib fracture management; however, concerns around opioids have fostered interest in alternative analgesics. Ketamine is currently being used in lieu of opioids, but little evidence exists supporting its use within the trauma population., Methods: A prospective, randomized, double-blind placebo-controlled trial of adult patients with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included age older than 64 years, Glasgow Coma Scale score less than 13, and chronic opiate use. The experimental arm received low-dose ketamine (LDK) at 2.5 μg·kg·min while the placebo cohort received an equivalent rate of 0.9% normal saline. All infusions were continued for 48 hours. The primary outcome was reduction in numeric pain score (NPS) during the first 24 hours. Secondary outcomes studied included oral morphine equivalent (OME) utilization, length of stay, epidural rates, pulmonary complications, and adverse events., Results: Forty-five (49%) of 91 patients were randomized to the experimental arm. Both groups were similar in makeup. Overall, 74.7% were male, had a median age of 49 years, and an Injury Severity Score (ISS) of 14. Low-dose ketamine was not associated with a significant reduction in 24-hour NPS or OME totals. Subgroup analysis of 45 severely injured patients (ISS, >15) demonstrated that LDK was associated with a significant reduction in OME utilization during the first 24 hours (35.7 vs. 68, p = 0.03), 24 hours to 48 hours (64.2 vs. 96, p = 0.03), and overall (152.1 vs. 198, p = 0.048). No difference in other secondary outcomes or adverse events was noted., Conclusion: Low-dose ketamine failed to decrease NPS or OME within the overall cohort, but a decrease in OME was observed among patients with an ISS greater than 15. Confirmatory studies are necessary to determine if LDK is a useful adjunct among severely injured patients., Level of Evidence: Therapeutic study, level II.

Objective: Demonstrate the safety and efficacy of a standardized intravenous etomidate infusion protocol in normalizing cortisol levels in patients with severe and life-threatening hypercortisolism., Methods: A retrospective case series of seven patients representing nine episodes of severe hypercortisolism at two large academic medical centers was conducted. Patients were included in this series if they received an etomidate infusion for the treatment of severe and life-threatening hypercortisolism. The etomidate infusion was administered via a newly developed protocol designed to safely reduce cortisol levels until more long-term medical or definitive surgical therapy could be instituted., Results: Seven patients representing nine episodes received etomidate treatment. In eight of nine episodes of therapy, rapid control of hypercortisolemia was achieved, generally defined as a serum cortisol level of 10 to 20 µg/dL. Patients with a median baseline cortisol of 105 µg/dL (range, 32 to 245 µg/dL) achieved a median nadir serum cortisol of 15.8 µg/dL (range, 6.9 to 27 µg/dL) after a median of 38 hours (range, 26 to 134 hours)., Conclusions: A standardized continuous intravenous etomidate infusion protocol is a safe and effective means of achieving a serum cortisol level of 10 to 20 µg/dL in patients with severe hypercortisolemia.

Background: A fixed dose of cefazolin results in serum concentrations that decrease as body mass increases. Current national guidelines suggest a pre-operative cefazolin dose of two grams may be insufficient for patients ≥120 kg; thus a three gram dose is recommended. These recommendations, however, are based on pharmacokinetic rather than outcome data. We evaluate the efficacy of pre-operative cefazolin two gram and three gram doses as measured by the rate of surgical site infection (SSI)., Patients and Methods: We conducted a retrospective review of adult patients ≥100 kg who were prescribed cefazolin as surgical prophylaxis between September 1, 2012 and May 31, 2013 at an academic medical center. Patients were excluded if cefazolin was prescribed but not administered, had a known infection at the site of surgery, or inappropriately received cefazolin prophylaxis based on surgical indication. The SSIs were identified by documentation of SSI in the medical record or findings consistent with the standard Centers for Disease Control and Prevention definition. Inpatient and outpatient records up to 90 days post-operative were reviewed for delayed SSI., Results: Four hundred eighty-three surgical cases were identified in which pre-operative cefazolin was prescribed. Forty-seven patients were excluded leaving a total of 436 patients for final analysis: 152 in the cefazolin two gram group and 284 in the three gram group. Baseline demographics were similar between groups with a mean follow-up duration of 77 days for both groups. Unadjusted SSI rates were 7.2% and 7.4% (odds ratio [OR] 0.98, p = 0.95), for the two gram and three gram groups, respectively. When differences in follow-up between groups were considered and logistic regression was adjusted with propensity score, there remained no difference in SSI rates (OR 0.87, 95% confidence interval 0.36-2.06, p = 0.77)., Conclusion: In otherwise similar obese surgical patients weighing ≥100 kg, the administration of a pre-operative cefazolin two gram dose is associated with a similar rate of SSI compared with patients who received a three gram dose.

Purpose: The effect of a pharmacist on a rapid response team (RRT) was investigated., Methods: This study evaluated 234 patients before and 157 patients after pharmacist involvement on an RRT. The primary outcome was time to medication administration, with a goal turnaround time of less than 30 minutes. Secondary outcomes included most frequently used medications, readmissions to the intensive care unit (ICU) within 48 hours, number of rapid responses that resulted in ICU admission, length of hospital stay, and survival to hospital discharge. Additionally, pharmacist interventions were tracked in the postinterventional group., Results: The preinterventional group screened 326 rapid response events, of which 234 were included for analysis; during the postinterventional phase, 256 rapid response events were evaluated, of which 157 were included. The primary outcome, median time to medication administration from central pharmacy, was lower in the postinterventional group compared with the preinterventional group (32.0 minutes versus 64.5 minutes, p = 0.004). ICU admission rates following rapid response were not significantly different between the two groups. Additionally, there were no significant differences between rates of medical emergency and survival to hospital discharge. The most common medications administered were metoprolol and naloxone. Pharmacists provided documentation for 90 of 157 (57%) patient cases. In the 90 cases with documentation, 18 (20% of patients) had documented pharmacist interventions, including dosing assistance for 8 cases (44% of interventions)., Conclusion: The addition of a pharmacist to an RRT reduced time to medication administration, helped improve medication accessibility, and helped optimize medication selection and dosing., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: The polymerase chain reaction (PCR) test has higher sensitivity and a faster turnaround time than the enzyme immunoassay (EIA) for identification of Clostridium difficile, although the clinical implications of these variables are not well described., Methods: Inpatients with a negative EIA (n = 79) or PCR (n = 87) test were retrospectively evaluated. Patients were excluded if they had a positive EIA or PCR test during the same hospitalization or if they were currently receiving treatment for C. difficile infection (CDI) prior to admission. The primary outcome was empiric CDI antibiotic duration of therapy associated with each test method., Results: Empiric CDI antibiotic duration of therapy was 2.31 (95% confidence interval [CI], 1.48-3.15) days for the EIA group and 0.88 (0.45-1.33) days for the PCR group (P = .007). Number of diagnostic laboratory tests performed per patient were 2.73 (2.64-2.83) and 1.16 (1.04-1.28) tests, respectively (P < .001)., Conclusion: Use of the PCR test to rule out CDI was associated with reduced duration of empiric CDI antibiotic therapy and fewer diagnostic laboratory tests performed per patient. When combined with fewer diagnostic laboratory tests performed per patient and shorter duration of contact isolation, the higher acquisition cost of the PCR test was offset, resulting in cost neutrality. These findings provide additional data to support the routine use of the PCR test.

Objective: To describe 2 cases of clinically significant phenytoin removal during continuous venovenous hemofiltration (CVVH) and review the relevant literature regarding phenytoin removal by renal replacement modalities., Case Summary: A 64-year-old female with chronic kidney disease and cirrhosis was admitted to the intensive care unit (ICU) with a traumatic subdural hematoma and seizures. The patient received a loading dose of intravenous phenytoin 1000 mg, followed by maintenance intravenous administration of phenytoin 100 mg and levetiracetam 250 mg every 12 hours. CVVH was initiated for acidosis. A 63-year-old male was admitted to the ICU after cardiac surgery complicated by hypotension. CVVH was initiated for fluid overload, and phenytoin was initiated 3 days later for seizures. A loading dose of intravenous phenytoin 2700 mg was administered, followed by maintenance dosing of intravenous phenytoin 150 mg every 8 hours. Concentrations of unbound phenytoin in serum and CVVH effluent samples were measured during concomitant treatment in each patient. In both patients, serum and effluent concentrations of unbound phenytoin fell steadily while they were on CVVH. Clearance of phenytoin by CVVH was calculated, as was the daily removal of phenytoin, as a percentage of total daily phenytoin dosage during each sampling period. Phenytoin clearance by CVVH ranged from 11 to 13 mL/min in these patients., Discussion: The clearance of phenytoin with CVVH in these 2 patients was much higher than the renal clearance of phenytoin reported in healthy volunteers with normal renal function. Previous case reports have demonstrated that only small, clinically insignificant amounts of phenytoin are removed by hemodialysis, and the only published report of phenytoin removal by continuous renal replacement therapy used hemofiltration rates much lower than those used in the 2 cases described here., Conclusions: These cases demonstrate that a substantial amount-approximately 30%-of total daily phenytoin dose may be removed by CVVH, and patients may require higher than expected empiric doses. Phenytoin concentrations should be closely monitored in critically ill patients receiving CVVH.

This article provides a review of commonly prescribed medications in the surgical ICU, focusing on sedatives, antipsychotics, neuromuscular blocking agents, cardiovascular agents, anticoagulants, and antibiotics. A brief overview of pharmacology is followed by practical considerations to aid prescribers in selecting the best therapy within a given category of drugs to optimize patient outcomes., (Copyright © 2012. Published by Elsevier Inc.)

Skin and skin structure infections (SSSIs) are a common diagnosis encountered by ambulatory and inpatient practitioners across the country. As the SSSIs become more complicated, they require increased health care resources and often involve hospitalization and intravenous antimicrobials. Complicated SSSIs are caused by a variety of pathogens, including Gram-positive, Gram-negative, and anerobic bacteria. Empiric broad-spectrum antibiotic coverage is warranted, taking into account area disease-state epidemiology and antimicrobial susceptibility data. Telavancin is an antimicrobial agent with a broad Gram-positive spectrum of activity which was recently approved for the treatment of SSSIs. It may especially benefit patients with resistant organisms, such as methicillin-resistant Staphylococcus aureus. This article reviews telavancin and its pharmacology, efficacy, and safety data to enhance the practitioner's knowledge base on the appropriateness of telavancin for the treatment of SSSIs.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased dramatically over the last two decades. The types of infections can range from complicated skin and skin structure infections (cSSSI) to pneumonia and endocarditis. Oral antimicrobial therapy, such as trimethoprim-sulfamethoxazole, clindamycin, long-acting tetracyclines, or linezolid may provide enhanced benefit to those with uncomplicated cutaneous lesions when used in conjunction with incision and drainage in an outpatient setting. However, resistance, susceptibilities, patient-specific circumstances, and adverse effects can impact a healthcare professional's choice of antibiotics. In patients with complicated infections requiring hospitalization or parenteral treatment, vancomycin remains the drug of choice, even though increased resistance and decreased efficacy have crept into clinical practice. Linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline are alternative intravenous agents for the treatment of CA-MRSA. Investigational agents such as dalbavancin, telavancin, oritivancin, iclaprim, ceftobiprole, ceftaroline, and others may expand our therapeutic armamentarium for the treatment of infections caused by CA-MRSA in the future.

Multidrug-resistant pathogens have become increasingly common in contemporary healthcare. Specific to Gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is of particular concern, as it has been associated with increased hospital length of stay, higher healthcare expenditures and poorer outcomes. To date, linezolid is the first and only oxazolidinone approved by the US FDA for the treatment of infections caused by Gram-positive pathogens, including MRSA. This article will serve as a comprehensive review of linezolid, including an overview of the current market and its in vitro activity, with an in-depth review of its pharmacokinetic and pharmacodynamic profile. Emphasis will be placed on clinical data for the drug, both on- and off-label. The article will conclude with a brief overview of linezolid's pharmacoeconomic implications and safety profile, followed by a commentary and 5-year prospective analysis remarking on the future of the antimicrobial field as it relates to MRSA.

Infectious disease continues to evolve, presenting new and challenging clinical situations for practitioners. Specific to device-related and neurosurgical-related CNS infections, Gram-positive organisms are of growing concern. Current Infection Disease Society of America guidelines for the treatment of CNS infections offer little direction after conventional therapy, consisting of vancomycin, has failed or the patient has demonstrated intolerance. A review of literature evaluating alternative therapies, specifically linezolid, quinupristin/dalfopristin, daptomycin and tigecycline, will be presented. Interpretations of these data are offered followed by a brief presentation of future therapies, including ortavancin, telavancin, dalbavancin, ceftobiprole and iclaprim, all of which possess potent Gram-positive activity.

Arpida Ltd, under license from Roche AG, is developing the diaminopyrimidine dihydrofolate reductase inhibitor iclaprim for the potential treatment of methicillin-resistant Staphylococcus aureus infections, including complicated skin and skin structure infections and hospital-acquired pneumonia. Phase III cSSSI clinical trials have been completed and an NDA filing process is ongoing. A phase II clinical trial for hospital-acquired pneumonia is ongoing.

Clostridium difficile, the leading cause of hospital-acquired diarrhea, is known to cause severe colitis. C. difficile small bowel enteritis is rare (14 case reports) with mortality rates ranging from 60 to 83%. C. difficile has increased in incidence particularly among patients with inflammatory bowel disease. This case series of six patients from 2004 to 2006 is the largest in the literature. All patients received antibiotics before colectomies for ulcerative colitis and developed severe enteritis that was C. difficile toxin positive. Three patients underwent ileal pouch anal anastomosis and loop ileostomy. Four of the six patients had C. difficile colitis before colectomy. Presenting symptoms were high volume watery ileostomy output followed by ileus in five of six patients. Four of the six patients presented with fever and elevated WBC. Five of the six developed complications requiring further surgery or prolonged hospitalization. Patients were treated with intravenous hydration and metronidazole then converted to oral metronidazole and/or vancomycin. None of the patients died. A high suspicion of C. difficile enteritis in patients with inflammatory bowel disease and history of C. difficile colitis may lead to more rapid diagnosis, aggressive treatment, and improved outcomes for patients with C. difficile enteritis.

Staphylococcus aureus is the most common cause of complicated skin and soft tissue infections (cSSTIs). Antibiotic choices for these infections continue to evolve. History has seen penicillin progress to antistaphylococcal penicillins and cephalosporins, but these drugs are now giving way to drugs that are effective against methicillin-resistant S. aureus (MRSA). While vancomycin has been the gold standard to treat MRSA infections, newer therapeutic options have been developed over the last 5 years. These include quinupristin-dalfopristin, daptomycin, tigecycline and linezolid, which is the focus for this review. Linezolid is efficacious in the treatment of cSSTIs (including diabetic foot infections) caused by Gram-positive organisms (including MRSA), with a well-defined safety profile and straightforward dosing. It is also approved for nosocomial pneumonia, community-acquired pneumonia and uncomplicated skin and skin structure infections. Linezolid has an oral and parenteral formulation, which are equivalent. The oral formulation has the potential to offer economic benefits as compared with other therapies. Currently, there are only a few new antibiotics in development with MRSA activity. The proper use of all antibiotics, including these newer agents, is increasingly important if we are to slow the evolution of microbial resistance.