Trending Topics in Health-System Pharmacy

Are anaerobic antibiotics needed for treating aspiration pneumonia?

Although antibiotic therapy is essential for patients with aspiration pneumonia, the most appropriate type of antibiotic to use has been debated for years. A recent study, published on February 20, 2024, in CHEST, seeks to answer the question of whether antibiotic therapy with limited anaerobic coverage (LAC) or with extended anaerobic coverage (EAC) is most effective in terms of in-hospital mortality and risk of Clostridioides difficile colitis.

Researchers conducted a multicenter retrospective cohort study across 18 hospitals in Ontario, Canada, from January 1, 2015, to January 1, 2022, and included patients who were diagnosed with aspiration pneumonia and prescribed guideline-concordant first-line community-acquired pneumonia parenteral antibiotic therapy within 48 hours of admission. Patients were categorized into the LAC group if they received ceftriaxone, cefotaxime, or levofloxacin and into the EAC group if they received amoxicillin-clavulanate; moxifloxacin; or ceftriaxone, cefotaxime, or levofloxacin in combination with clindamycin or metronidazole. The primary outcome was all-cause in-hospital mortality, with a secondary outcome of incident C. difficile colitis occurring after hospitalization.

In the hospital, 30.3% of patients in the LAC group died, compared with 32.1% of patients in the EAC group. C. difficile colitis occurred in less than or equal to 0.2% of the LAC patients and approximately 1.0% of the patients in the EAC group, indicating that extended anaerobic antibiotic therapy carries an elevated risk for C. difficile colitis. The authors concluded that extended anaerobic antibiotic coverage is likely unnecessary in treatment of aspiration pneumonia because it is associated with no additional mortality benefit, and an increased risk of C. difficile colitis. ■

Low-dose colchicine reduces CV events in patients with T2D

The 2019 COLCOT trial demonstrated that a dose of 0.5 mg colchicine, an orally administered anti-inflammatory medication used for the treatment of gout and pericarditis, led to a significantly lower risk of ischemic CV events among patients with a recent myocardial infarction. In a study published in the March 2024 issue of Diabetes Care, researchers examined the trial data to determine the effect of low-dose colchicine on patients with T2D.

Among the patients enrolled in the COLCOT trial, almost 1,000 also suffered from T2D. After a median monitoring time of 22.6 months, a primary end point (CV death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization) occurred in 8.7% of patients in the colchicine group and in 13.1% of patients in the placebo group. Nausea was reported in 2.7% of patients in the colchicine group compared with 0.8% in the placebo group, while pneumonia occurred in 2.4% of patients in the colchicine group and 0.4% in the placebo group.

Researchers concluded that this low-dose treatment with colchicine leads to a large reduction in CV events for patients with comorbid T2D and supports results of the COLCOT trial in primary prevention of CV events. ■

Oral iptacopan monotherapy shows promise in treating patients with PNH

Patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disease characterized by hemolysis, thrombosis, and bone marrow failure, are primarily treated with anti-C5 monoclonal antibodies. Anemia often persists, however, because of ongoing activation of extravascular hemolysis. A recent study published on March 13, 2024, in NEJM, investigated the efficacy and safety of iptacopan, an oral complement factor B inhibitor, in treating PNH.

Researchers conducted two phase 3 trials to assess iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g/dL. In the first trial (APPLY-PNH), patients who were receiving anti-C5 monoclonal antibodies were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second trial (APPOINT-PNH), patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g/dL from baseline and a hemoglobin level of at least 12 g/dL, each without red-cell transfusion. The primary end point for the second trial was an increase in hemoglobin level of at least 2 g/dL from baseline without red-cell transfusion.

In the APPLY-PNH trial, iptacopan treatment was superior to anti-C5 treatment for both hemoglobin endpoints. In the APPOINT-PNH trial, treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Mild to moderate headache was the most frequently reported adverse event in both trials. ■

RSI intubation with rocuronium could lead to risk of awareness while paralyzed

Rapid sequence intubation (RSI) typically includes administration of induction agents to provide temporary deep sedation and prevent patient awareness of paralysis, followed by paralytic agents, including short-acting succinylcholine and longer-acting neuromuscular blocking agents such as rocuronium and vecuronium. When rocuronium is used for paralysis in the emergency department (ED), delays in sedation have been observed, but timeliness of post-RSI sedation in ICU patients has not been described. Researchers at the University of New Mexico Hospital in Albuquerque conducted a retrospective review at a single academic tertiary care center of patients intubated using rocuronium in an ICU between July 2019 and August 2020 to determine if ICU patients who receive a long-acting paralytic for intubation are likely to experience delays in sedative administration time.

The primary objective of the study, published online in JAPhA Pharmacotherapy on April 7, 2024, was to determine the proportion of patients in the ICU who received sedation within 15 minutes following intubation using rocuronium. Secondary objectives included determining the time to sedation (minutes) and the time to sedation between provider specialties.

Of the 192 patient intubations using rocuronium included in the study, 77 (40.1%) received sedation within 15 minutes of induction agent administration. The mean time to sedation was 25.1 minutes, in contrast to the 5-to-20-minute duration of induction agents, suggesting a potential period of time without sedation. The authors concluded that a large proportion of patients intubated in ICUs with rocuronium were exposed to risk of awareness while paralyzed. They note that future work describing appropriateness of sedation provided in both EDs and ICUs is needed to prevent awareness while paralyzed. ■