Is tighter blood glucose control better for ICU patients?
Hyperglycemia is common in critically ill patients, but randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the ICU, resulting in unclear treatment protocols. In a new study published in NEJM on September 28, 2023, researchers participating in the TGC-Fast trial investigated whether variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia could explain these inconsistent results.
TGC-Fast was an investigator-initiated, prospective, multicenter, randomized, controlled, parallel-group trial, in which patients were randomly assigned on ICU admission to liberal glucose control (insulin initiated only when the blood glucose level was >215 mg/dL) or to tight glucose control (blood glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg/dL). Parenteral nutrition was withheld in both groups for 1 week. The primary outcome was the length of time that ICU care was needed.
Of 9,230 patients who underwent randomization, 4,622 were assigned to liberal glucose control and 4,608 to tight glucose control. The median morning blood-glucose level was 140 mg/dL for patients on liberal glucose control and 107 mg/dL with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group, and the length of time that ICU care was needed was similar in the two groups. In addition, analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were all similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent in patients with tight glucose control.
The authors noted that the primary outcome may have been affected by variable discharge policies related to shortage of ICU beds during the COVID-19 pandemic. They also noted that hyperglycemia was less pronounced in this trial compared with previous trials in which patients received early parenteral nutrition, which suggests that avoiding such nutrition could lead to better outcomes in both treatment groups. ■
Does the risk for CDI vary by type of prior antibiotic use?
Prior antibiotic use is an important risk factor for Clostridioides difficile infection (CDI), but does the antibiotic type and class affect the risk? A recent study in the August 2023 issue of Open Forum Infectious Diseases expanded on previous studies of aggregated antibiotic use to evaluate CDI risk across individual antibiotic types. Researchers from the University of Iowa conducted a matched case–control study using a large database of insurance claims capturing longitudinal health care encounters and medications to identify antibiotics associated with CDI.
More than 150,000 patients with CDI were each matched to five control patients by age, sex, and enrollment period, and antibiotics prescribed within 30 days before CDI diagnosis, along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression. The authors were able to differentiate and order the 27 individual antibiotics studied in terms of their relative level of associated risk for CDI and found wide variation in CDI risk within and between classes of antibiotics. The greatest risk for CDI was associated with clindamycin and later-generation cephalosporins, with the lowest risk associated with minocycline and doxycycline.
They note that future work is needed to further assess the time since exposure and the associated level of risk for CDI. ■
Lactated ringers may improve outcomes for patients with acute pancreatitis
Previous trials have found that use of lactated ringers (LR) may result in decreased risk of acute pancreatitis compared with normal saline, but the small size of these studies limits their strength. Researchers at The Ohio State University, along with colleagues from health systems around the world, conducted a multicenter prospective study to investigate these preliminary results.
Close to 1,000 patients directly admitted to 22 international sites with a diagnosis of acute pancreatitis between 2015 and 2018 were prospectively enrolled in the study. Demographics, fluid administration, and disease severity data were collected and mixed-effects logistic regression analysis was performed to determine their relationship with the type of fluid administered during the first 24 hours.
Results of the study, published ahead of print in the American Journal of Gastroenterology in July 2023, showed that use of LR during the first 24 hours was associated with reduced odds of moderately severe/severe acute pancreatitis compared with normal saline after adjusting for region of enrollment, etiology, BMI, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. The authors note that a large-scale randomized clinical trial is needed to confirm these findings. ■
Ceftobiprole shows potential for treatment of complicated S. aureus bacteremia
Antibiotic treatment options are limited for patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, a serious and frequently lethal infection. Few randomized trials have been conducted to inform treatment of S. aureus bacteremia, including one trial that supported approval of daptomycin for treatment of this indication. A new study published on October 12, 2023, in NEJM, compared the use of ceftobiprole, a cephalosporin that has been shown to have efficacy for patients with pneumonia and acute bacterial skin infections, with daptomycin in patients who had complicated S. aureus bacteremia.
In the Phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned to receive 500 mg ceftobiprole intravenously every 6 hours for 8 days and every 8 hours thereafter, or 6 to 10 mg/kg body weight daptomycin intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome was overall treatment success 70 days after randomization, defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia–related complications, and no receipt of other potentially effective antibiotics, with a noninferiority margin of 15%.
Results of the trial showed that ceftobiprole was noninferior to daptomycin in overall treatment success in patients with S. aureus bacteremia. In the ceftobiprole group, 69.8% of patients had overall treatment success compared with 68.7% of patients in the daptomycin group. Findings also appeared to be consistent between the two groups with regard to secondary outcomes, including mortality and occurrence of microbiologic eradication. Adverse events were reported in 63.4% of patients who received ceftobiprole and 59.1% of patients who received daptomycin. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole. ■