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Many infectious diseases (ID) clinicians join Twitter to follow other ID colleagues or “like” people. While there is great value in engaging with people who have similar interests, there is equal value in engaging with “unlike” or non-ID people. Here, we describe how Twitter connected an ID pharmacist with a pediatric surgeon, a vice chair of surgery, a surgeon chief medical officer from Spain, and a surgical intensive care unit pharmacist. This Twitter collaboration resulted in several scholarly activities related to antibiotic resistance and antibiotic stewardship and served as a conduit for global collaboration.

The primary objective was to evaluate the performance of the Cockcroft-Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC).Multicenter, retrospective cohort.Two ICUs in the United States and four ICUs from a previous international observational analysis.Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion.The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 mThe CG-adjusted BW had the best performance in the non-ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC.

Background: Assessment of kidney function is fundamental to optimize drug dosing. The Cockcroft–Gault (CG) equation is widely used but has questionable validity for females, changing renal function, and the critical ill. Eight-hour urine collections (U8h) offer direct measurement of creatinine clearance (CrCl) but lack the data for drug dosing. The primary objective of this study was to determine if there was a difference in renal drug dosing based on the estimation of CG CrCl (CrClCG) versus 8-h CrCl (CrCl8h). Methods: This was an observational, retrospective cohort study of adult patients admitted between March 2018 and September 2018 with a collection U8h during hospitalization. The primary outcome was discordance of renal drug dosing defined as the percentage of U8h for which at least one different active medication CrCl dosing cutoff would result using the CrClCG versus CrCl8h. The secondary outcomes were correlation between CrClCG and CrCl8h and percentage of CrClCG values outside ± 20% of the CrCl8h. Results: One hundred collections drawn from 85 unique patients (50.6% male, median age 55 [41–70] years, intensive care unit 88%) were included in the analysis. Median serum creatinine was 0.76 (0.52–1.06) mg/dL and blood urea nitrogen was 20 (14–28) mg/dL at time of collection8h. Median CrCl8h was 86.2 (43.5–140.3) mL/min versus 99.7 (56.5–166.9) mL/min CrClCG(P < 0.001) and discordance was 25%. The correlation between CrCl8h and CrClCG was 0.76 (P < 0.001). Only 31% of CrClCG values were within ± 20% of the CrCl8h value. Conclusion: We found 25% discordance for drug dosing between CrCl8h and CrClCG. Further studies are needed to determine the impact on clinical outcomes.

Background Overuse of antibiotics from the inpatient to outpatient setting is an antibiotic stewardship initiative where noninfectious disease (ID) pharmacists can have a large impact. Our purpose was to evaluate antibiotic durations across transitions of care from the inpatient to outpatient setting. Methods This is a single-center, retrospective cohort analysis evaluating antibiotic durations from the inpatient and outpatient setting in adult patients admitted to general surgery and medicine services at an academic medical center between January 1, 2017 and September 20, 2017. The primary outcome was to assess total antibiotic duration for patients with uncomplicated and complicated urinary tract infections (UTI, cUTI), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP). Outpatient electronic discharge prescriptions were used to calculate intended antibiotic duration upon transitions of care. Excessive duration of therapy was defined as >3 days—UTI, >5 days—CAP, and >7 days—cUTI or HAP. Results One hundred and one patients met inclusion criteria. Overall, most of the patients (81%) had antibiotics longer than recommended with only 3% receiving less than the recommended duration. Median total duration of therapy compared with recommended duration specified in national guidelines was UTI: 10 days [ 7 – 10 ], cUTI: 12 days [7.5-12.5], CAP: 7 days [ 7 – 9 ], HAP: 10 days [ 8 – 12 ]. The median antibiotic duration was shorter in patients with no cultures or culture negative results compared with patients with positive cultures for all indications (UTI: 10.3 vs 10.8 days, cUTI: 9 vs 12 days, CAP: 8 vs 9.1 days, HAP: 10.5 vs 19.8 days). Overall, the recommended duration of antibiotics was completed while inpatient in 34.7%, but varied by infection. More patients with UTI or cUTI completed recommended duration of therapy while inpatient vs for CAP or HAP (53.8% vs 28%, P = .03). Eighty percent of those with UTI, 18.2% with cUTI, 25.6% with CAP, and 31.2% with HAP had already received the recommended duration of treatment, or more, on day of hospital discharge. Conclusions The median duration of antibiotic therapy for all indications evaluated was longer than recommended in national guidelines. Opportunities for stewardship by non-ID pharmacists to impact postdischarge antimicrobial use at transitions of care have been identified.

Background: Accurate assessment of renal function is essential in hospitalized elderly patients. Few studies have examined the accuracy of Cockcroft-Gault (C-G) estimates of creatinine clearance (CrCl) compared with measured clearance in these patients. Objective: The objective of this study was to determine the correlation between C-G estimates of CrCl and measured CrCl in hospitalized elderly patients. Methods: This Institutional Review Board–approved, single-center retrospective observational cohort study included all patients who were 65 years and older admitted to our medical center in January to September 2018 with either an 8- or 24-hour urine collected during admission. The primary outcome was correlation, bias, and precision of C-G estimates of CrCl versus measured CrCl using Pearson correlation, Spearman linear regression, and Bland-Altman analysis. Outliers were determined using a cut-off of ±20%. Data are presented as median (interquartile range) or percentages. Results: A total of 108 urine collections from 90 unique patients were included in the study. The patients were 51% female, median age was 71 (68-77) years, and median body mass index was 26.6 (22.8-31) kg/m2. Most collections were over 24 hours (66.7%), and 38% were performed while patients were in an intensive care unit. Median blood urea nitrogen (BUN) was 24.5 (17-36) mg/dL and median serum creatinine was 0.71 (0.55-1.09) mg/dL. The median C-G estimation was 75.4 (48.2-110.6) mL/min, and the median measured CrCl was 79.1 (38.1-99.5) mL/min, r2 = .56 ( P < .001). Bland-Altman analysis showed large limits of agreement (-75.5-57.7 mL/min), with a bias of −8.9 and precision (standard deviation of bias) of 34 mL/min. Outliers were common, with 38% of C-G estimation values >120% of measured CrCl, and 18% of C-G estimates

BackgroundCeftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown.MethodsA retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality.ResultsA total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31–5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03–0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4.ConclusionsThese data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

Background: Clostridioides difficile infection (CDI) accounts for as many as 25% of episodes of antibiotic-associated diarrhea and is the most common cause of healthcare-associated diarrhe...

Background: Necrotizing soft-tissue infection (NSTI) is a devastating disease associated with high rates of morbidity and mortality. Hyperglycemia is associated with poor wound healing; ho...

Introduction Previous literature showed an association between hyperthermia and dexmedetomidine (DEX) use for ongoing sedation in non-obese patients. The purpose of this study is to evaluate DEX’s effect on temperature in obese critically ill patients. Methods This single center, retrospective, cohort study included patients ≥18 years, admitted to a surgical or medical ICU, received DEX for ≥8 hours as a single continuous infusion sedative, and weighed ≥120% of ideal body weight. Patients were excluded if they had a fever (≥38°C) and positive cultures within 48 hours of DEX initiation. The primary endpoint was a fever (Tmax of ≥38°C) within 48 hours of DEX initiation. Results A total of 186 patients were included for evaluation. Forty-two patients (22.5%) had a fever during the first 48 hours of DEX initiation. Median weight was not different between the febrile and afebrile groups (99.4 [90.6-122.4] vs 97.6 [81.6-114.2] kg, P = .6). Median change from baseline temperature for all patients within 48 hours was an increase of .5 (.1-.8) °C, P < .001. In multiple regression analysis, duration of DEX and baseline temperature were the only significant predictors of fever development with an adjusted odds ratio of 1.041 (95% CI 1.009-1.074, P = .012) and 7.058 (95% CI 3.307-15.064, P < .001), respectively. Conclusions This study suggests that there is a significant increase in body temperature from baseline for obese patients on DEX. Duration of DEX and baseline temperature were found to be risk factors for fever development in this population. Further studies are warranted.

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Introduction The recent coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re‐evaluated daily processes and therapies used to treat COVID‐19 patients within our institutions from a cardiovascular perspective and share what we have learned. Objectives To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID‐19 patients by drawing on the experiences of cardiology pharmacists across the country. Methods On March 26, 2020, a conference call was convened composed of 24 cardiology residency‐trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID‐19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. Results The collaborative of pharmacists found for the ST‐elevation myocardial infarction patient, many institutions were diverting COVID‐19 rule‐out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision‐making processes with their preceptors and assist as pharmacist extenders. Conclusion Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID‐19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times. This article is protected by copyright. All rights reserved.

Aim: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and Pseudomonas aeruginosa bacteremia or pneumonia treated with extended infusion cefepime or piperacillin/tazobactam. Materials and Methods: Cefepime (2 g every 8 h) and piperacillin/tazobactam (4.5 g every 8 h) were administered over 4 h after a loading dose infused over 30 min, and minimum inhibitory concentration was determined by E-test. Published population PK evaluations in critically ill patients were used, and PD analyses were conducted using estimated patient-specific PK parameters and known minimum inhibitory concentration values for P. aeruginosa. Concentration–time profiles were generated every 6 min using first-dose drug exposure estimates including a loading infusion, and free concentration above the minimum inhibitory concentration (fT> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to P. aeruginosa infection without need for escalation of antimicrobial. Results: One hundred and two patients were included (36 cefepime and 66 piperacillin/tazobactam). The two groups of patients had similar age, serum creatinine, weight, and creatinine clearance. The majority of patients required intensive care unit care (63.9% vs. 63.6%) and most had pneumonia (61%). The fT>MIC (93.6 [69.9–100] vs. 57.2 [47.6–72.4], P < 0.001) and clinical cure (91.7% vs. 74.2%, P = 0.039) were significantly higher in cefepime group, whereas mortality (8.3% vs. 22.7%, P = 0.1) and infection-related mortality (0% vs. 2%, P = 0.54) were similar. Conclusions: Patients with ARC and P. aeruginosa pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher fT>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.

OBJECTIVE: Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN: Cohort study. SETTING: The medical and surgical intensive care units at an academic medical center. SUBJECTS: We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (SIRS) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS: We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P [SAP], and tissue plasminogen activator [TPA]) at onset of suspected sepsis and 24-, 48-, and 72-hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve (AUROC). MEASUREMENTS AND MAIN RESULTS: 14-day mortality was 12.9%, and total in-hospital mortality was 29.5%. SAP was significantly lower (4 of 4 timepoints) and TPA significantly higher (3 of 4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p

Background: Prevention of ventilator-associated pneumonia is a healthcare goal. Although data is inconsistent, some studies suggest that oral chlorhexidine may decrease rates of pneumonia in mechanically-ventilated patients. We sought to assess the rate of pneumonia in the Surgical Intensive Care Unit (SICU) pre and post implementation of routine chlorhexidine mouthwash prophylaxis. Materials and Methods: A retrospective cohort study was conducted, including patients between 1/1/2009 and 12/31/2009 who did not receive chlorhexidine mouthwash compared to patients that received prophylactic chlorhexidine mouthwash between 3/1/2010 and 2/28/2011. The primary outcome of the study was rate of probable ventilator-associated pneumonia (VAP) for the pre-chlorhexidine implementation cohort compared to post-implementation, using the 2013 Center for Disease Control definitions. Mechanically ventilated patients with respiratory cultures were screened for inclusion in the study. Secondary endpoints included duration of mechanical ventilation, in-hospital mortality, ICU and hospital length of stay. Statistical analysis was conducted by Fisher's exact test for nominal data and Mann-Whitney U test for continuous data. Results: A total of 1780 mechanically ventilated patients in the pre-chlorhexidine group and 1854 in the post-chlorhexidine group were screened for inclusion. Of the 601 mechanically ventilated patients that were further evaluated for inclusion; 158 patients (26.3%) had positive cultures and were included in the study (94 pre-group and 64 post-group). The rate of probable VAP was significantly decreased in the post-group compared to the pre-group (1.85% pre vs 0.81% post, P = 0.0082). Conclusion: Use of chlorhexidine mouthwash prophylaxis may reduce rates of probable VAP. Further study is warranted.

Background: Dexmedetomidine is commonly used for sedation in the Intensive Care Unit (ICU), and its use may be associated with hypotension. We sought to determine predictors of dexmedetomidine-associated hypotension. Methods: Retrospective, single-center study of 283 ICU patients in four adults ICUs over a 12 month period. Univariate analyses were performed to determine factors associated with dexmedetomidine-related hypotension. Risk factors significant at the 0.20 level in the univariate analysis were considered for inclusion into a step-wise multiple logistical regression model. Results: Hypotension occurred in 121 (42.8%) patients with a median mean arterial pressure (MAP) nadir of 54 mmHg. Univariate analyses showed an association between hypotension and age (P = 0.03), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P = 0.02), baseline MAP (

Background: Controlling healthcare costs without compromising patient care is a focus given recent healthcare changes in the United States. The purpose of this study was to assess clinical improvement in surgical intensive care unit (SICU) patients initiated on or transitioned to enteral antibiotics compared to those who solely receive intravenous (IV) antibiotic therapy for treatment of bacterial pneumonia. Materials and Methods: This retrospective cohort study included patients with a positive quantitative respiratory culture being treated for bacterial pneumonia in a SICU from 1/1/09 to 3/31/11. Two distinct patient groups were identified: Those treated with IV antibiotics exclusively (IV) and those either initiated on or transitioned to enteral antibiotics within 4 days of antibiotic initiation (PO). The primary endpoint of clinical improvement was assessed on day of antibiotic discontinuation. Results: A total of 647 patients were evaluated; 124 met inclusion criteria (30 patients PO group and 94 IV group). There was no difference in clinical improvement (86.7 PO vs 72.3% IV, P = 0.14) or recurrence (10 PO vs. 12.8% IV, P > 0.99) between groups. Secondary outcomes of duration of mechanical ventilation, ICU and hospital length of stay, and all-cause mortality were also similar. Antibiotic and infection-related costs were significantly decreased in the PO group ($1,042 vs $697, P = 0.04; $20,776 vs $17,381, P = 0.012, respectively). Conclusions: SICU patients initiated on or transitioned to PO antibiotics for pneumonia had similar clinical outcomes, but significantly less infection-related and antibiotic costs compared to those receiving IV therapy. Further, prospective studies are warranted.

Background: A drug shortage of cisatracurium led to use of atracurium as an alternative neuromuscular blocker (NMB). Cisatracurium may be preferred due to less histamine release and potentially less hypotension. The study purpose is to compare the incidence of hypotension with continuous infusion atracurium to continuous infusion cisatracurium in ICU patients. Materials and Methods: This retrospective cohort analysis reviewed 119 ICU patients who received either continuous infusion atracurium (56) or cisatracurium (63). The primary outcome was the incidence of hypotension (mean arterial pressure 20% from baseline, time to first hypotensive episode, treatment for hypotension during NMB use, hospital mortality, ICU and hospital length of stay (LOS), duration of mechanical ventilation (MV), and NMB duration. Results: Hypotension occurred in 64.3% of atracurium patients and 58.7% of cisatracurium patients (P = 0.58), with 60.7% experiencing >20% drop in blood pressure in atracurium group and 54.0% in cisatracurium (P = 0.58). Median time to first hypotensive episode was 9.4[Interquartile range 1.17-19.7] hours atracurium and 4.4[1.5-13.9] hours cisatracurium (P = 0.36). There were no differences between atracurium and cisatracurium groups respectively for median ICU LOS (10.5 days and 12.4 days, P = 0.34), hospital LOS (14.0 days and 17.7 days, P = 0.37), MV duration (9.3 days and 10.5 days, P = 0.43), infusion duration (34.5 hours and 25 hours P = 0.27), or hospital mortality (62.5% and 53.9%, P = 0.336). Hypotension treatment was similar between groups. Conclusions: The incidence of hypotension was similar between atracurium and cisatracurium. Critical drug shortages may provide an opportunity to study alternative drug therapy.

In the last decade, there has been a dramatic increase in advance practice registered nurses (APRNs) in the acute care setting. In 2017, the Joint Commission issued antimicrobial stewardship (AMS) standards for the acute care setting. The role of the APRNs has not formally been recognized in the guidelines for implementing and operative AMS programs. Regardless, APRNs are increasingly performing essential roles in antibiotic stewardship, and the aim of this review is to describe areas APRNs can impact antibiotics stewardship. Articles that described AMS process were indexed from PubMed. APRNs have expertise in managing and coordinating care for across many clinical conditions and are able to improve the quality of care and improve AMS. The following core competencies are addressed in this article: Medical knowledge, Patient care.

Background: Recent review of older (≥45-years-old) patients admitted to our trauma center showed that more than one-third were using neuro-psychiatric medications (NPMs) prior to their injury-related admission. Previously published data suggests that use of NPMs may increase patients′ risk and severity of injury. We sought to examine the impact of pre-injury NPM use on older trauma patients′ morbidity and mortality. Materials and Methods: Retrospective record review included medication regimen characteristics and NPM use (antidepressants-AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day survival were examined. Comparisons included regimens involving NPMs, further focusing on their interactions with various cardiac medications (beta blocker - BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker - ACE/ARB; calcium channel blocker - CCB). Results: 712 patient records were reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect of NPM monotherapy on hospital mortality. Patients taking ≥3 NPMs had significantly lower 90-day survival compared to patients taking ≤2 NPMs (81% for 3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac medication (CM) combinations were associated with increased mortality compared to monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs 4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). Conclusions: Large proportion of older trauma patients was using pre-injury NPMs. Several regimens involving NPMs and CMs were associated with increased in-hospital mortality. Additionally, use of ≥3 NPMs was associated with lower 90-day survival.

Although chronic hypertension is associated with long-term complications, few studies directly examine the effects of in-hospital acute hypertensive episodes in trauma patients. The aim was to determine whether there is an association between in-hospital acute hypertension and morbidity. We included trauma patients between 45 and 89 years who presented to a level I trauma center between January and September 2008. Patients were classified as either experiencing or not experiencing acute hypertensive episode(s) as defined by systolic blood pressure ≥180, or diastolic blood pressure ≥110 mmHg, or at least two readings of systolic blood pressure ≥160 or diastolic blood pressure ≥100 mmHg. The primary outcome was a composite endpoint of myocardial infarction, stroke, venous thromboembolism, new-onset atrial fibrillation, or acute kidney injury. At least one acute hypertensive episode occurred in 42.6 % (69/162) of patients. A total of 10.5 % patients developed the composite endpoint, 17.4 % in the acute hypertensive episode group compared to 5.4 % in the non-hypertensive group, p = 0.012. Patients in the acute hypertensive group were more likely to require an intensive care unit admission compared to the non-hypertensive group (33.3 versus 14.0 %, p = 0.004). Of the 17 patients who developed an acute hypertensive episode and met the primary endpoint, 10 were on home antihypertensive medications. Of those, four were restarted on all medications initially, three on some, two were started on new medications, and one was not resumed on home medications. Development of acute hypertensive episode(s) in older trauma patients was associated with an increase in the composite endpoint. Prospective studies are needed.

The use of nasoenteric tubes (NETs) is ubiquitous, and clinicians often take their placement, function, and maintenance for granted. NETs are used for gastrointestinal decompression, enteral feeding, medication administration, naso-biliary drainage, and specialized indications such as upper gastrointestinal bleeding. Morbidity associated with NETETs is common, but frequently subtle, mandating high index of suspicion, clinical vigilance, and patient safety protocols. Common complications include sinusitis, sore throat and epistaxis. More serious complications include luminal perforation, pulmonary injury, aspiration, and intracranial placement. Frequent monitoring and continual re-review of the indications for continued use of any NETET is prudent, including consideration of changing goals of care. This manuscript reviews NET-related complications and associated topics.

To determine the association between comorbidity-polypharmacy score (CPS) and clinical outcomes in a large sample of older trauma patients, focusing on outcome prognostication.The CPS combines number of preinjury medications and comorbidities to more objectively quantify the severity of comorbid conditions.An urban tertiary care level 1 trauma center in the Midwest.Trauma patients aged 45 and older.Participants were stratified into four groups according to CPS ranges. Survival analyses were performed using Kaplan-Meier/Mantel-Cox testing. Factors influencing mortality, complications, and survivor discharge destination were evaluated using analysis of covariance and multivariate logistic regression.Records for 469 individuals (mean age 62.1, mean injury severity score 9.3) were reviewed. Higher CPS is associated with greater mortality, complications, longer hospital and intensive care unit stay, and need for discharge to a facility. Higher CPS is associated with lower 90-day survival (Mantel-Cox, P.001). Mortality was independently associated with older age (odds ratio (OR) = 1.06 per year), higher injury severity score (OR = 1.19 per point), and higher CPS (OR = 1.11 per point) in multivariate analysis (all P.01). Complications and need for discharge to a facility were independently associated with older age and higher injury severity score and CPS.CPS can be readily determined in the era of medication reconciliation. Trauma patients with CPS of 15 or greater are at greater risk of poor clinical outcomes. CPS constitutes a useful adjunct to currently available injury severity scoring tools as a predictor of morbidity, mortality, hospital resource utilization, and postdischarge disposition in older trauma patients.

BACKGROUND Publications on the use of the bispectral index for sedation monitoring in the intensive care unit are increasing. However, few studies have involved correlation of bispectral index with serum drug concentrations. OBJECTIVES To assess the degree of correlation between bispectral index values, scores on the Sedation-Agitation Scale, and steady-state serum concentrations of lorazepam. METHODS A prospective open-label study of patients in a surgical intensive care unit who were receiving mechanical ventilation and continuous infusions of lorazepam for more than 24 hours. Bispectral index was measured (BIS-XP, Aspect Medical, Norwood, Massachusetts) to assess patients' sedation. Sensors were applied and values recorded before and after stimulation (endotracheal suctioning). Concomitant plasma samples were obtained to measure lorazepam concentration and scores on the Sedation-Agitation Scale were recorded. RESULTS Sixteen patients were studied. Correlations between plasma concentrations of lorazepam and measurements of bispectral index for 1, 2, and 3 minutes before endotracheal stimulation were poor (0.21, 0.29, and 0.25, respectively). Correlation of peak values for bispectral index (after stimulation) with plasma concentrations of lorazepam was 0.29. Correlations of scores on the Sedation-Agitation Scale with the aforementioned values for bispectral index were similarly poor. Area under the curve for bispectral index values also correlated poorly with plasma concentration of lorazepam (0.19) and score on the Sedation-Agitation Scale (0.10). CONCLUSIONS The correlation between bispectral index and score on the Sedation-Agitation Scale was poor. Correlation between bispectral index and plasma concentration of lorazepam was modestly better, but insufficient for clinical utility.

Aim: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and Pseudomonas aeruginosa bacteremia or pneumonia treated with extended infusion cefepime or piperacillin/tazobactam. Materials and Methods: Cefepime (2 g every 8 h) and piperacillin/tazobactam (4.5 g every 8 h) were administered over 4 h after a loading dose infused over 30 min, and minimum inhibitory concentration was determined by E-test. Published population PK evaluations in critically ill patients were used, and PD analyses were conducted using estimated patient-specific PK parameters and known minimum inhibitory concentration values for P. aeruginosa. Concentration–time profiles were generated every 6 min using first-dose drug exposure estimates including a loading infusion, and free concentration above the minimum inhibitory concentration (f T> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to P. aeruginosa infection without need for escalation of antimicrobial. Results: One hundred and two patients were included (36 cefepime and 66 piperacillin/tazobactam). The two groups of patients had similar age, serum creatinine, weight, and creatinine clearance. The majority of patients required intensive care unit care (63.9% vs. 63.6%) and most had pneumonia (61%). The f T>MIC (93.6 [69.9–100] vs. 57.2 [47.6–72.4], P Conclusions: Patients with ARC and P. aeruginosa pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher f T>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.

Background : Glycemic control is an important aspect of patient care in the surgical intensive care unit (SICU). This is a pilot study of a novel glycemic analysis tool - the glucogram. We hypothesize that the glucogram may be helpful in quantifying the clinical significance of acute hyperglycemic states (AHS) and in describing glycemic variability (GV) in critically ill patients. Materials and Methods: Serial glucose measurements were analyzed in SICU patients with lengths of stay (LOS) >30 days. Glucose data were formatted into 12-hour epochs and graphically analyzed using stochastic and momentum indicators. Recorded clinical events were classified as major or minor (control). Examples of major events include cardiogenic shock, acute respiratory failure, major hemorrhage, infection/sepsis, etc. Examples of minor (control) events include non-emergent bedside procedures, blood transfusion given to a hemodynamically stable patient, etc. Positive/negative indicator status was then correlated with AHS and associated clinical events. The conjunction of positive indicator/major clinical event or negative indicator/minor clinical event was defined as clinical match. GV was determined by averaging glucose fluctuations (maximal - minimal value within each 12-hour epoch) over time. In addition, event-specific glucose excursion (ESGE) associated with each positive indicator/AHS match (final minus initial value for each occurrence) was calculated. Descriptive statistics, sensitivity/specificity determination, and student's t-test were used in data analysis. Results : Glycemic and clinical data were reviewed for 11 patients (mean SICU LOS 74.5 days; 7 men/4 women; mean age 54.9 years; APACHE II of 17.7 ± 6.44; mortality 36%). A total of 4354 glucose data points (1254 epochs) were analyzed. There were 354 major clinical events and 93 minor (control) events. The glucogram identified AHS/indicator/clinical event matches with overall sensitivity of 84% and specificity of 65%. We noted that while the mean GV was greater for non-survivors than for survivors (19.3 mg/dL vs. 10.3 mg/dL, P = 0.02), there was no difference in mean ESGE between survivors (154.7) and non-survivors (160.8, P = 0.67). Conclusions: The glucogram was able to quantify the correlation between AHS and major clinical events with a sensitivity of 84% and a specificity of 65%. In addition, mean GV was nearly two times higher for non-survivors. The glucogram may be useful both clinically (i.e., in the electronic ICU or other early warning systems) and as a research tool (i.e., in model development and standardization). Results of this study provide a foundation for further, larger-scale, multi-parametric, prospective evaluations of the glucogram.

Background The emergence of MDR/XDR P. aeruginosa has led to a reliance on suboptimal agents (Poly/AG) for the management of infections due to this pathogen. C/T is a novel agent with excellent in vitro activity against resistant P. aeruginosa that is indicated for cUTI and cIAI and being reviewed for VABP; however real-world comparative data for invasive infections are lacking. The purpose of this study was to assess comparative rates of clinical cure, mortality, and acute kidney injury (AKI) among patients treated with C/T vs. a Poly/AG based regimen for P. aeruginosa infections Methods This was a retrospective, multi-site cohort of adult inpatients from January 1, 2012 to February 28, 2018 with infections due to MDR or XDR P. aeruginosa. Patients treated for ≥48 hours with C/T or a Poly/AG-based regimen were eligible for inclusion. Patients with a creatinine clearance

Background Ceftolozane/tazobactam (C/T) has potent activity against Pseudomonas aeruginosa (PA). Clinical data describing the use of C/T for PA osteomyelitis are limited. Our purpose is to describe clinical and microbiologic outcomes of adult patients treated with C/T for multidrug-resistant (MDR-PA) osteomyelitis. Methods This was a retrospective study of hospitalized patients who received C/T ≥48 hours for MDR-PA osteomyelitis between June 2015 and July 2017. MDR-PA was defined as resistance to ≥1 antibiotic from ≥3 antibiotic classes. Osteomyelitis was diagnosed by imaging, presence of systemic inflammatory signs and symptoms, elevated C-reactive protein, and positive culture for MDR-PA. Combination antibiotic therapy was defined as systemic antibiotics susceptible to MDR-PA for ≥48 hours with C/T. Clinical cure was defined as complete or partial resolution of signs and symptoms of infection without need for escalation of antimicrobials during inpatient and outpatient therapy. Microbiological success is defined as eradication of MDR-PA in follow-up bone cultures. Descriptive statistics were used and presented at percent or median [Interquartile range]. Results Eighteen patients met inclusion and four patients were lost to follow-up. Demographics were male (81.2%), age 58.5 [53.5–68.5] years, 61.1% admitted to ICU, Charlson Comorbidity Index 5.5 [4–8] and APACHE II score 13.5 [11–21]. Site of osteomyelitis was pelvic in 55.6%, sacral in 22.2% and other sites in 22.2%. Surgical debridement occurred in 22.2%, and osteomyelitis was polymicrobial in 77.8%. Duration of hospitalization was 23.5 [12–37] days and all cause in-patient mortality was 16.7%. The median mean inhibitory concentration of C/T was 2 [2–4] μg/mL. Median total duration of C/T was 42 [27–42] days. Combination antibiotics were used in 27.8% (16.7% polymyxins, 11.1% aminoglycosides, 5.6% ciprofloxacin) and 2 patients on polymyxins developed renal insufficiency. No patient developed hypersensitivity, neurologic events or C. difficile infections. Overall, clinical cure was 64.3% and 4 patients had repeat cultures with 75% achieving a microbiologic cure. Conclusion These preliminary data suggest C/T maybe an option for treating patients with MDR-PA osteomyelitis, but more data are needed. Disclosures A. Gerlach, Merck: Grant Investigator, Grant recipient

Nutrition support in the critically ill patient has shifted from adjunctive toward fundamental therapy with the publication of high-grade evidence. Early enteral nutrition (EN) is recommended because it is associated with decreased infectious complications and use of EN is associated with decreased mortality and infections compared with parenteral nutrition (PN). EN is not without risks, such as diarrhea or aspiration, but use of prokinetic agents, head of bed elevation, and use of feeding protocols can maximize benefits and minimize risks. Although recently high-grade evidence on nutrition support in the critically ill population has been published, many controversies still exist. In obese patients, use of hypocaloric feedings with increased protein has been demonstrated to promote weight loss and improved glucose management. In nonobese patients, small studies have demonstrated that providing more than 70% or less than 30% of goal caloric intake may be associated with worse outcomes, but more studies are needed. Additional research is also needed to conclude whether withholding intravenous fat emulsions for the first 7 to 10 days of PN reduces infectious complications. Finally, more high-quality studies are needed to define the role of immune-enhancing nutrients such as arginine, glutamine, omega-3 fatty acids, zinc, and selenium.

Objective: To report the use of subcutaneous lepirudin in an obese patient with heparin resistance. Case Summary: A 34-year-old morbidly obese male (weight 145 kg) presented with hypoxia on postoperative day 1 following a sigmoid colectomy. A continuous unfractionated heparin infusion was started for a suspected pulmonary embolism. Doses were escalated without therapeutic activated partial thromboplastin time (aPTT) response and an antithrombin (AT) tevei was obtained. The AT level was reported as 78% (reference range 85–120%). Computed tomography angiography ruled out pulmonary embolism and lepirudin 50 mg administered subcutaneously twice daily was started (serum creatinine 1.3 mg/dL) for prevention of venous thromboembolism. The resulting aPTT values were therapeutic (63 and 60 sec, reference range 24–34, therapeutic heparin range 55–85). The dose was adjusted to 25 mg twice daily, aPTT values were 35 and 48 seconds. His serum creatinine increased to 1.6 mg/dL and minor bleeding was noted. The dose was decreased to 25 mg once daily, with resulting aPTT values of 31, 39, and 41 seconds. The patient was discharged to home without development of venous thromboembolism, as confirmed by duplex ultrasonography. Discussion: Commonly administered anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, and fondaparinux, exert their effect by complexing with AT and thrombin (Factor IIa), activating AT and preventing thrombin from exerting coagulation effect. Without AT present, these drugs have little effect on inhibiting the coagulation cascade. Lepirudin is a synthetic irreversible direct thrombin inhibitor and does not rely on AT to exert its anticoagulation action. It can be given subcutaneously and is eliminated primarily by the kidneys, Dosage adjustments for both renal function and obesity need to be considered and aPTT should be monitored. Conclusions: In obese patients or those with heparin resistance, subcutaneous lepirudin can be monitored and the regimen adjusted based on aPTT values. Further studies are warranted to maximize efficacy and define dosing.

The Scientific Studies Committee of the Surgical Infection Society undertook the present study to examine the prevalence of and indications for antimicrobial use in intensive care units where members of the Society practice.Information and data collection sheets were posted on the Internet for download by members interested in participating. All centers were required to obtain approval from their local human subjects research office or equivalent. A one-week time was set during which the center could collect information on any one day, at the center's convenience. Data collection sheets were then sent to the lead author for analysis. Seventeen centers reported data for 371 patients in 22 intensive care units.Trauma and general surgical patients comprised 224 of the patients (60%). The indications for anti-infective agents were prophylactic (22%), empiric (27%), therapeutic with known pathogen (41%), therapeutic without known pathogen (e.g., cellulitis) (4%), insistence of influential practitioner (4%), or non-anti-infective purposes (e.g., erythromycin for gastric motility) (2%). Only 44%, 29%, and 54% of the orders for prophylactic, empiric, and therapeutic antibiotics, respectively, had date-certain stop dates. The antimicrobial drugs most commonly used were vancomycin, piperacillin-tazobactam, and fluconazole.Most patients were receiving antimicrobial agents. Polypharmacy was common. Most patients did not have a date-certain stop date. This study sets the benchmark for future study regarding antibiotic prescribing behavior in surgical intensive care units.

The physiological responses to surgery, critical illness, and subsequent resuscitation can alter both pharmacokinetics (PK) and pharmacodynamics (PD) [1]. As a result of these changes, pharmacotherapy may need to be altered to produce the desired outcomes. A basic understanding of the principles of pharmacokinetics, or the movement of drugs in the body, and pharmacodynamics, the cells responses to drugs, is needed to maximize pharmacotherapy [2]. This chapter will review basic pharmacokinetic and pharmacodynamic principles and some changes in the critically ill surgical patient.

Objective: To review recent literature on the safety and efficacy of dexmedetomidine. Data Sources: Articles were identified through searches of MEDLINE (1966–January 2007). Key words included dexmedetomidine, medetomidine, α2-agonist, and sedation. References from selected articles were reviewed for additional references. Study Selection and Data Extraction: Experimental and observational studies that focused on the safety and efficacy of dexmedetomidine in humans were selected. Data Synthesis: Dexmedetomidine is an α2-agonist for short-term sedation in critically ill patients. In postoperative patients, dexmedetomidine produced similar levels of sedation and times to extubation, with less opioid requirements compared with propofol. Dexmedetomidine has also been studied for sedation in critically ill medical and pediatric patients, as adjunct to anesthesia, and for procedural sedation. Hypotension, hypertension, and bradycardia are common adverse effects. Although dexmedetomidine is labeled only for sedation less than 24 hours, it has been administered for longer than 24 hours without apparent development of rebound hypertension and tachycardia. Conclusions: Dexmedetomidine is a safe and effective agent for sedation in critically ill patients. Further, well designed studies are needed to define its role as a sedative for critically ill medical, neurosurgical, and pediatric patients, as an adjunct to anesthesia, and as a sedative during procedures.

Context: Stress ulcer prophylaxis (SUP) has become the standard of care in the intensive care unit (ICU) but is often continued inappropriately at discharge. Aims: The primary aim was to evaluate the impact of granting clinical privileges to assess appropriate discontinuation of SUP in the ICU. Settings and Design: This study was a single-center, retrospective, observational study. Materials and Methods: Patients admitted to medical or surgical ICUs in January 2015 (pregroup) were compared to January 2016 (postgroup). Statistical Analysis Used: Continuous parametric data were analyzed with Student's t-test, continuous nonparametric data were analyzed with Mann–Whitney U-test, and dichotomous variables were analyzed with Fisher's exact method. Results: One hundred and sixty patients were included (80 per group). Over 50% of patients had documented home acid suppression therapy use (52.5% pregroup vs. 58.8% postgroup, P = 0.53) and approximately 30% had gastroesophageal reflux disease documented as a problem in their medical record (27.5% pregroup vs. 31.3% postgroup, P = 0.73). The rate of inappropriate continuation of acid suppression therapy was not different between groups (15.4% vs. 14.9%, P = 0.999). The major reason for appropriate continuation of acid suppressive therapy was the presence of a chronic condition that provided a reasonable indication for therapy (46.1% vs. 60.0%, P = 0.228). Conclusions: Overall we found no difference in continuation of SUP at ICU discharge, but this was confounded by a high rate of reported home acid suppression. Targets for education and improvement have been identified, especially the need for attention to documentation and medication reconciliation across the spectrum of patient care to allow for acid suppression therapy deprescribing. The following core competencies are addressed in this article: Patient care, Systems-based practice

Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol.Multicenter, retrospective, propensity-matched cohort study.Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists.Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics.Continuous sedation with dexmedetomidine or propofol.A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure60 mm Hg) and bradycardia (heart rate50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts.Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

Study Objective. To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency. Design. Retrospective chart review. Setting. University-based tertiary care center. Patients. One hundred six patients who received two or more doses of enoxaparin. Measurements and Main Results. Total bleeding complications occurred in 22% of patients with normal renal function and 51% with renal insufficiency (p