Impact of time to treatment in first occurrence, non-severe Clostridioides difficile infection for elderly patients: are we waiting too long to treat?

Objective: Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study's purpose was to evaluate the impact of time-to-CDI treatment on disease progression. Methods: A case-control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours. Cases included patients who progressed to severe or fulminant CDI; controls were patients without CDI progression. Time to CDI treatment was evaluated in three ways: a classification and regression tree (CART)-defined threshold, time as a continuous variable, and time as a categorical variable. Results: 272 patients were included; 136 with CDI progression, 136 patients without. The median (IQR) age was 74 (69-81) years, 167 (61%) were women, and 108 (40%) were immunosuppressed. CDI progression patients more commonly were toxin positive (66 [49%] vs 52 [38%], P = .087) with hospital-acquired disease (57 [42%] vs 29 [21%], P < 0.001). A CART-derived breakpoint for optimal time-to-CDI treatment of 64 hours established early (184, 68%) and delayed treatment (88, 32%). When accounting for confounding variables, delayed CDI treatment was associated with disease progression (adjOR, 4.6; 95%CI, 2.6-8.2); this was observed regardless of how time-to-CDI-active therapy was evaluated (continuous adjOR, 1.02; categorical adjOR, 2.11). Conclusion: Delayed CDI treatment was associated with disease progression and could represent an important antimicrobial stewardship measure with future evaluation.

Evaluating the impact of severe sepsis 3-hour bundle compliance on 28-day in-hospital mortality: A propensity adjusted, nested case-control study.

OBJECTIVES: The Centers for Medicare and Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) assesses antibiotic administration, lactate measurement, and blood culture collection within 3 h of severe sepsis onset. The impact of the SEP-1 3-hour bundle among patients with severe sepsis is not extensively described. This investigation aimed to describe the impact of 3-hour bundle compliance on 28-day in-hospital mortality in patients with severe sepsis. STUDY DESIGN: This was a retrospective, propensity adjusted, nested case-control study assessing the impact of compliance with a 3-hour sepsis bundle among patients with severe sepsis. SETTING: This study was conducted at a large, academic, tertiary care medical center in Detroit, Michigan from July 1, 2017 to December 31, 2019. PATIENTS: Cases were defined as those suffering 28-day in-hospital mortality. Controls were defined as those surviving at or discharged by 28 days. Patients were separated based on 3-hour bundle compliance or noncompliance. Nested and overall cohorts were assessed. Severe sepsis time zero was manually validated. Patients with shock, requiring vasopressors within 8 h of time zero, or those not meeting SEP-1 inclusion criteria were excluded. INTERVENTION: The primary outcome was the propensity adjusted odds of 28-day in-hospital mortality among 3-hour bundle compliant versus noncompliant patients. Secondary outcomes included mortality for individual bundle element compliance, progression to septic shock, and predictors of mortality according to logistic regression. RESULTS: A total of 325 compliant and 325 noncompliant patients were included. The median Sequential Organ Failure Assessment (SOFA) score was three in each group. There was no difference in propensity adjusted odds of mortality among those compliant versus noncompliant with the 3-hour bundle (odds-ratio [OR] 1.039; 95% CI: 0.721-1.497; p = 0.838) or with individual bundle elements. SOFA score and female sex were predictors of mortality. CONCLUSIONS: Three-hour bundle compliance did not impact 28-day in-hospital mortality in patients with severe sepsis. Further research is needed to understand the impact of 3-hour bundle compliance on mortality in severe sepsis.

T2 Candida versus beta-D-glucan to facilitate antifungal discontinuation in the intensive care unit.

T2 Magnetic Resonance Candida Panel (T2MR) detects Candida directly in blood. Rapid turnaround time and high negative predictive value make it a useful diagnostic test to support antifungal discontinuation. This retrospective quasi-experiment compared empiric anidulafungin days of therapy (DOTs) in intensive care unit (ICU) patients with suspected candidemia that had negative blood cultures and negative 1,3-ß-D-glucan (BDG) versus negative blood cultures and negative T2MR. In 206 ICU patients, median anidulafungin DOTs were 2 (1, 5) compared to 1 (1, 2), respectively (P < 0.001); T2MR was associated with early discontinuation, AdjOR 3.0 95% CI (1.7-5.6), P < 0.001. Proven candidemia after discontinuation of anidulafungin occurred in 3% of BDG and 2% of T2MR patients at a median of 8 and 21 days, respectively. T2MR testing supports safe, early discontinuation of empiric antifungal therapy in ICU patients with suspected candidemia. Prospective studies to better define the role of T2MR in antifungal stewardship are warranted.

Heavy metal in the intensive care unit: a review of current literature on trace element supplementation in critically ill patients.

Trace elements are essential for many physiologic processes. In recent years, supplementation has been studied for a variety of indications, including glycemic control, wound healing, antioxidant effect, and anemia. Critical illness, especially states such as burns, traumas, and septic shock, is associated with inflammatory and oxidative stress, immune dysfunction, and malnutrition. In these patients, enteral and parenteral nutrition or pharmaceutical supplementation is used to provide essential macronutrients, including trace elements. The purpose of this review is to describe trace element supplementation, including iron, copper, chromium, manganese, selenium, and zinc, and highlight their mechanism, pharmacology, outcome data, and adverse effects.

Racial differences in vasopressor requirements for septic shock.

OBJECTIVE: The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. METHODS: This was a retrospective cohort review conducted over a 2-year period measuring total and mean dosage of various vasopressors used between two racial groups during the treatment of patients admitted with septic shock. The study included patients admitted to the intensive care unit with septic shock at an 805-bed tertiary, academic center. All septic shock patients were managed with vasopressors. Vasopressor selection, dosage, and duration were at the discretion of the treating physician. Total, mean, and duration of vasopressor dosing requirements were obtained for study participants. Comorbidities, prehospitalization antihypertensive medication requirements, intravenous fluids given during the septic shock phase, and source of infection were analyzed. RESULTS: One hundred fifty-nine patients with septic shock were analyzed, of which 96 (60.4%) were AAs (P < 0.059). African Americans had higher rates of end-stage renal disease and hypertension compared with whites, 85.7% vs. 14.3% (P < 0.011; odds ratio [OR], 15.684) and 68.3% vs. 31.7% (P < 0.007; OR, 3.357), respectively. Norepinephrine (NE) was administered to 150 patients, 57.2% of which were AAs (P < 0.509). Thirteen patients received dopamine (5% AAs, P < 0.588), 40 patients received phenylephrine (15.7% AAs, P < 0.451), and five patients received epinephrine (1.9% AAs, P < 0.660). Comparing vasopressors between races, only NE showed statistical significance via logistic regression modeling for the AA race in terms of total dosage (AAs 736.8 [SD, 897.3] µg vs. whites 370 [SD, 554.2] µg, P < 0.003), duration of vasopressor used (AAs 38.38 [SD, 34.75] h vs. whites 29.09 [SD, 27.11] h, P < 0.037), and mean dosage (AAs 21.08 [SD, 22.23] µg/h vs. whites 12.37 [SD, 13.86] µg/h, P < 0.01). Mortality between groups was not significant. Logistic regression identified discrepancy of the mean dose NE in AAs compared with whites, with OR of 1.043 (P = 0.01). CONCLUSIONS: African American patients with septic shock were treated with higher doses of NE and required longer duration of NE administration compared with white patients.

Evaluation of a dedicated pharmacist staffing model in the medical intensive care unit.

PURPOSE: Published studies have shown that pharmacists on medical rounds reduce the incidence of preventable adverse drug events (ADEs). However, the impact of a dedicated pharmacist who provides consistent patient care in a critical care unit remains to be evaluated. OBJECTIVE: To determine the impact of a pharmacist who is permanently assigned to the medical intensive care unit (MICU) on the incidence of preventable ADEs, drug charges, and length of stay (LOS) in the MICU. DESIGN: A randomized, experimental versus historical control group design was used. Preventable ADEs were identified and validated by 2 pharmacists and a critical care physician. Information about MICU drug charges and LOS were obtained from the hospital administrative database. RESULTS: The intervention group had fewer occurrences of ADEs (10 ADEs/1,000 patient days) when compared to the control group (28 ADEs/1,000 patient days) at a significance level of .03. No significant differences were found between the 2 groups in MICU drug charges and LOS. The vast majority of the 596 documented recommended interventions (99%) were accepted by the medical team. Nutrition monitoring, medication indicated but not prescribed, and dosage modification were the top 3 problems identified by the pharmacist. CONCLUSION: The addition of a dedicated critical care pharmacist to the MICU medical team improves the safe use of medication. The services of a dedicated critical care pharmacist should be expanded to include weekend hours to ensure the benefits of improved medication safety.

Resuscitation bundle compliance in severe sepsis and septic shock: improves survival, is better late than never.

UNLABELLED: While clinicians' management of severe sepsis and septic shock has been positively influenced by a number of clinical research studies in the last decade, challenges remain regarding early hemodynamic optimization as envisioned in the Surviving Sepsis Campaign's (SSC) resuscitation bundle (RB). We examined the impact of a hospital-wide continuous quality improvement (CQI) initiative on patients presenting with severe sepsis and septic shock, and the impact of the sepsis RB on patient outcomes when completed beyond the 6-hour recommendation period. The study was an 18-month, prospective cohort study enrolling patients who met the definition of severe sepsis or septic shock. Compliance with the hemodynamic components of the sepsis RB was defined as achieving goal mean arterial pressure (MAP) ≥ 65 mm Hg, central venous pressure (CVP) ≥ 8 mm Hg, and central venous oxygen saturation (ScvO2) ≥ 70%. Compliance was assessed at 6 hours and 18 hours after diagnosis of severe sepsis or septic shock. In all, 498 patients with severe sepsis and/or septic shock were evaluated to determine the upper limit of the range of hours that compliance with the RB would still improve outcomes. Using 18 hours as a marker, Compliers at 18 hrs and Non-Compliers at 18 hrs were compared. There were 202 patients who had the RB completed in less than or equal to 18 hours. There were 296 patients who did not complete the RB at 18 hours. The Compliers at 18 hrs had a significant 10.2% lower hospital mortality 37.1% (22% relative reduction) compared to the Non-Compliers at 18 hrs hospital mortality of 47.3% (P < .03). When the two groups were adjusted for differences in baseline illness severity, the Compliers at 18 hrs had a greater reduction in predicted mortality of 26.8% versus 9.4%, P < 0.01. CONCLUSIONS: Initiating the sepsis RB for patients with severe sepsis and/or septic shock decreased mortality. A CQI initiative that monitored the implementation in real-time allowed for improvement in compliance and efficacy of the bundle on outcomes. Multiple studies have shown that compliance to the RB within 6 hours lowers hospital mortality. This study uniquely shows that when bundle completion is extended to 18 hours, the mortality reduction remains significant.

A tight glycemic control initiative in a surgical intensive care unit and hospitalwide.

BACKGROUND: In 2002, tight glycemic control (TGC) was mandated at Henry Ford Hospital (Detroit) to reduce surgical site infections (SSIs). THE FIVE STEPS FOR IMPROVEMENT: The TGC initiative was developed in terms of the five primary steps of the Institute for Healthcare Improvement (IHI) framework for leadership for improvement to drive practice change and maintain continuous improvement. In terms of Steps 1-3 (set direction, establish the foundation, and build will), in April 2002 the chief executive officer of the Henry Ford Hospital (Detroit) announced a hospitalwide initiative to reduce SSIs. For steps 4 and 5 (generate ideas and execute change), the 40-bed surgical intensive care unit (SICU) was designated the practice-change setting. TGC protocols were implemented in cardiothoracic patients, followed by all SICU patients, with target glucose ranges moving from the initial < 150 mg/dL to 80-110 mg/dL. Results showed decreases in SSIs and mortality. The project's success led initiation of hospitalwide TGC in the next two years. RESPONDING TO A CHANGING EVIDENCE BASE: In 2009, as studies began to show that the recommended glucose target of 80-110 mg/dL was not associated with clinical improvement in ICU patients and perhaps may cause harm (increased mortality), the target ranges were modified. LESSONS LEARNED: Barriers to adoption of new practice change must be integrated into the planning process. Leadership champions are required across multiple levels of the organization to drive change to the bedside for effective and lasting improvement. CONCLUSIONS: A universal TGC protocol continues to be used throughout the hospital, with modifications and next-generation improvements occurring as evidence arises.

An insulin infusion protocol in critically ill cardiothoracic surgery patients.

BACKGROUND: Critically ill cardiothoracic patients are prone to hyperglycemia and an increased risk of surgical site infections postoperatively. Aggressive insulin treatment is required to achieve tight glycemic control (TGC) and improve outcomes. OBJECTIVE: To examine and report on the performance of an insulin infusion protocol to maintain TGC, defined as a blood glucose level of 80-150 mg/dL, in critically ill cardiothoracic surgical patients. METHODS: A nurse-driven insulin infusion protocol was developed and initiated in postoperative cardiothoracic surgical intensive care patients with or without diabetes. In this before-after cohort study, 2 periods of measurement were performed: a 6-month baseline period prior to the initiation of the insulin infusion protocol (control group, n = 174) followed by a 6-month intervention period in which the protocol was used (TGC group, n = 168). RESULTS: Findings showed percent and time of blood glucose measurements within the TGC range (control 47% vs TGC 61%; p = 0.001), AUC of glucose exposure >150 mg/dL versus time for the first 24 hours of the insulin infusion (control 28.4 vs TGC 14.8; p < 0.001), median time to blood glucose <150 mg/dL (control 9.4 h vs TGC 2.1 h; p < 0.001), and percent blood glucose <65 mg/dL as a marker for hypoglycemia (control 9.8% vs TGC 16.7%; NS). CONCLUSIONS: An insulin infusion protocol designed to achieve a goal blood glucose range of 80-150 mg/dL efficiently and significantly improved TGC in critically ill postoperative cardiothoracic surgery patients without significantly increasing the incidence of hypoglycemia.

Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.

BACKGROUND: Previous studies found that medication errors result from lack of sufficient information during the prescribing step. Therefore, it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events (ADEs). The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process. METHODS: A single-blind, standard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving standard care (no pharmacist on rounding team). Patients admitted to and discharged from the same general medicine unit were included in the study. The main outcome measure of this study was preventable ADEs. Patient records were randomly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician. Interventions made by the pharmacists in the treatment group were documented. RESULTS: The rate of preventable ADEs was reduced by 78%, from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days. There were 150 documented interventions recommended during the rounding process, 147 of which were accepted by the team. The most common interventions were (1) dosing-related changes and (2) recommendations to add a drug to therapy. CONCLUSION: Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs.

Magnesium sulfate therapy after aneurysmal subarachnoid hemorrhage.

OBJECT: Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH. METHODS: A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II-IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 +/- 0.68 in the MgSO4 treatment group and 2.3 +/- 0.73 in the control group (mean +/- standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 +/- 27 cm/second in MgSO4-treated patients and 102 +/- 34 cm/second in the control group (mean +/- SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 +/- 1.6 and 3.6 +/- 1.5 (mean +/- SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur. CONCLUSIONS: Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.