Inpatient Insights
Patients with pneumocystis pneumonia may see delay in care in ICU
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection affecting immunocompromised patients. The disease is prevalent in patients with HIV, but its incidence has risen in recent decades, and it now affects more patients not infected by HIV than those infected with it. Despite the increasing occurrence of PJP, it is unclear whether delayed antibiotic therapy affects survival or if corticosteroid therapy combined with antibiotics is effective in infected patients, particularly those admitted to the ICU. Members of the PCP-MULTI study group conducted a multicenter, prospective observational study involving 49 adult ICUs in France to evaluate the severity, clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality.
Results of the study, which included 149 patients from September 2020 to August 2022, were published on June 4, 2024, in Intensive Care Medicine, and showed that hospital and 6-month mortality of patients with PJP admitted to the ICU is high, especially among patients not infected by HIV, with delays in treatment linked to poorer survival. The main reason for admission was acute respiratory failure. Only 12% of patients received antibiotic prophylaxis for PJP before ICU admission. Using time-to-event analysis with a propensity score–based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 hours of ICU admission was associated with faster occurrence of death. The use of corticosteroids for PJP was also associated with faster occurrence of death. ■
Can PPIs prevent GI bleeding in critically ill patients?
Critically ill patients are at risk for stress-induced GI ulceration, which might cause clinically important upper GI bleeding.
Researchers have postulated that PPIs can help prevent upper GI bleeding and its consequences, leading to a meta-analysis comparing the effectiveness of PPIs versus placebo or no prophylaxis in critically ill adults.
The study, published on June 14, 2024, in NEJM Evidence, included 12 trials that enrolled over 9,500 patients at risk for upper GI bleeding.
Analysis of the study data showed that PPIs were associated with a reduced incidence of clinically important upper GI bleeding but may have little or no effect on mortality.
Within-trial subgroup analysis with intermediate credibility suggested that PPIs may decrease 90-day mortality in less severely ill patients and may increase mortality in more severely ill patients. In addition, the authors suggest that PPIs may have no effect on pneumonia and little or no effect on Clostridioides difficile infection. ■
Are continuous or intermittent b-lactam antibiotic infusions more effective in critically ill patients with sepsis?
Critically ill patients with sepsis are often treated with b-lactam antibiotics (meropenem and piperacillin-tazobactam), which are primarily administered as multiple, short (e.g., 30-minute) intermittent infusions.
According to a recent study in JAMA, published on June 12, 2024, it has been suggested that continuous infusion may be more effective than intermittent administration due to time-dependent killing characteristics. The BLING III study investigators conducted an open-label, randomized clinical trial in 104 ICUs spread out between Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom.
Over 7,000 eligible patients were randomized to receive an equivalent 24-hour dose of a b-lactam antibiotic by either continuous or intermittent infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality.
Within 90 days, 24.9% of the patients assigned to receive continuous infusion had died compared with 26.8% of patients assigned intermittent infusion. Clinical cure was higher in the continuous group (55.7%) compared with the intermittent infusion group (50%). Other secondary outcomes were not statistically different. The authors suggest that although the observed difference in 90-day mortality between continuous and intermittent infusions of b-lactam antibiotics did not meet statistical significance in the primary analysis, the confidence interval around the effect estimate includes the possibility of a clinically important benefit in the use of continuous infusions in this group of patients. ■
Long-term colchicine has potential for prevention of vascular recurrent events in non-cardioembolic stroke
Anti-inflammatory therapy with long-term colchicine has been shown to prevent vascular recurrence in coronary disease. In a study published in The Lancet on June 7, 2024, members of the CONVINCE research group investigated whether long-term colchicine would reduce recurrent events after ischemic stroke. The researchers conducted a randomized, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0.5 mg orally per day) plus guideline-based usual care with usual care only.
Hospital-based patients with non-severe, non-cardioembolic ischemic stroke or high-risk transient ischemic attack were eligible for the study. The primary endpoint was a composite of first fatal or non-fatal recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24-hour stay) for unstable angina. Over 3,100 patients finished the trial, with a primary endpoint occurring in 9.8% of patients receiving colchicine and usual care and in 11.7% of patients receiving usual care alone. The rates of serious adverse events were similar in both groups.
The authors suggested that although no statistically significant benefit was observed on the primary intention-to-treat analysis, their findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomized trials. ■