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.

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.

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.