麻豆传媒

PHOENIX -- Individualized short-course antibiotic treatment proved noninferior to usual long-course treatment for 60-day mortality and pneumonia recurrence in patients with ventilator-associated pneumonia, the randomized REGARD-VAP trial showed.

In both the intention-to-treat and per-protocol populations, 41% of patients who received short-course antibiotics based on clinical response and 44% of those in the usual-care group met the primary outcome of the composite endpoint of death or pneumonia recurrence within 60 days of enrollment (absolute risk difference -3%, one-sided 95% CI -∞ to 5%), reported Gyan Kayastha, MD, MPH, of Patan Academy of Health Sciences in Lalitpur, Nepal, during the Society of Critical Care Medicine Critical Care Congress.

In the per-protocol population, antibiotic side effects occurred in 8% of the short-course group and 38% of the usual-care group (risk difference -31%, 95% CI -37 to -25, P<0.0001). The main antibiotic side effect avoided was acute kidney injury, which occurred in 5% versus 35%, respectively, according to the study results, which were simultaneously published in the .

"To our knowledge, this is the first [trial] to use clinical response to determine antibiotic duration in 'high-stakes' patient populations, predominantly from low- to middle-income settings," said Kayastha, who noted that ventilator-associated pneumonia is a top driver of antibiotic prescription in the intensive care unit (ICU).

The authors noted that the usual-care antibiotic treatment duration -- median 14 days -- was longer than most current guideline recommendations of 7 to 8 days. "This observation reflects real-world practice, in which antibiotic treatment tends to be prolonged for ventilator-associated pneumonia, especially those associated with Gram-negative non-fermenting and carbapenem-resistant Gram-negative bacilli," they wrote.

Co-author Yin Mo, DPhil, of the University of Oxford in England, told 麻豆传媒 via email that patients experiencing ventilator-associated pneumonia who respond early to the culture-directed antibiotics may have stronger immunity or more mild infections.

"These results probably confirmed many physicians' clinical experience -- that ventilator-associated pneumonias can be treated with individualized antibiotic durations rather than arbitrarily determined durations," she said. "This is because these infections are highly varied in terms of patient immunity, bacterial pathogen virulence, and antibiotic efficacy. The most reassuring aspect of these results is that similar effects were found across the different resource settings, some with limited infection prevention and control, and antibiotic stewardship policies."

In an , Emma D. Johnson, a clinical research fellow, and James D. Chalmers, MBChB, PhD, of the University of Dundee in Scotland, pointed out that there is still more to understand about the optimal duration of antibiotic therapy, as well as the different roles clinical and biomarker criteria play in discontinuing therapy for patients with ventilator-associated pneumonia.

"Antibiotic stewardship is crucial in the ongoing battle against multidrug-resistant pathogens," they wrote. "Reducing overall antibiotic use includes reducing unnecessary use of antibiotics and antibiotic duration. Demonstrating that short-course antibiotic treatment is noninferior to prolonged treatment in patients with ventilator-associated pneumonia, on the basis of clinical response, is a valuable contribution to reduce the burden of antibiotics in the ICU."

For this , a total of 461 patients from 39 ICUs in six hospitals across Nepal, Singapore, and Thailand were enrolled in the study from May 2018 to December 2022. Those enrolled met CDC National Healthcare Safety Network criteria for ventilator-associated pneumonia, had been mechanically ventilated for 48 hours or longer, and were administered culture-directed antibiotics.

Patients were assessed until fever resolution for 48 hours and hemodynamic stability, then randomly assigned 1:1 to individualized short-course treatment (≤7 days and as short as 3-5 days) or usual care (≥8 days, with durations determined by the primary clinicians).

Median patient age was 64, and 39% were women. Common comorbidities included diabetes, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, coronary heart disease, cancer, and liver cirrhosis.

The median duration of antibiotic treatment during index episodes of ventilator-associated pneumonia was 6 days in the short-course group and 14 days in the usual-care group.

The short-course strategy reduced the overall mean antibiotic treatment days during hospitalization by 5.2 days (P=0.0003).

During the 60-day follow-up period, 169 of 460 patients died: 35% in the short-course group and 38% in the usual-care group. In a post-hoc analysis in the intention-to-treat population, mortality was attributed to pneumonia for 12% of patients in each group.

Among the 63 patients who had pneumonia recurrence, 16 of 33 in the short-course group and 17 of 30 in the usual-care group had a multidrug-resistant bacteria grown in the sputum culture during the recurrent ventilator-associated pneumonia episode.

Limitations to the study included that 81% of the patients enrolled were from Thailand, potentially reducing the generalizability of the trial's findings.

However, Kayastha and team noted that the trial's findings should be applicable to different healthcare environments globally.

"Very few trials have been done in these settings, where rates of ventilator-associated pneumonia are higher than in high-income countries," they wrote. "The high rates of ventilator-associated pneumonia are a major driver for antibiotic prescription and are likely to contribute to the high prevalence of multidrug-resistant organisms, which suggests that the benefits of an intervention to reduce antibiotic use in such a setting are likely to have an even greater impact than in higher-income environments."

Mo echoed these sentiments, describing the study as "key" in its ability to potentially inform international antibiotic stewardship guidelines.

"The study used a set of easily reproducible and simple clinical criteria to reduce antibiotic duration -- absence of fever and stable blood pressure," she said. "These can be adopted in all resource settings, with no need for sophisticated blood tests. This individualized approach for tailoring antibiotic treatment duration shifts our common mindset that infections need to be treated with arbitrarily defined durations."

"We hope that this study will encourage others to rethink antibiotic treatment duration," she added. "That duration should be tailored to patient responses rather than a one-size-fits-all approach."