November 06, 2019
By Gene Emery
NEW YORK (Reuters Health) - Just two days of injected antibiotic therapy can prevent nearly half the cases of ventilator-associated pneumonia (VAP) in people who are getting targeted temperature management after an out-of-hospital cardiac arrest with an initial shockable rhythm, a new clinical trial from France shows.
"In this high-risk population, I think the results are so significant, it's such a simple intervention, and it's really cost-effective because the cost of the drug is very low, I'm pretty sure it will be widely used by physicians," chief author Dr. Bruno Francois told Reuters Health by phone.
The therapy had no impact on the odds of late VAP or the number of ventilator-free days in the intensive-care unit (ICU). In addition, mortality was not affected, according to the findings of the study, known as ANTHARTIC and published in Thursday's New England Journal of Medicine.
But reduction in the secondary endpoints was not surprising, said Dr. Francois, of CHU de Limoges. "The evolution of the cardiac arrest and the sequelae are much more the driver for the length of stay in the ICU than VAP."
He also speculated that the short preventive regimen, if given routinely, might actually cut down on the risk of antibiotic resistance by reducing longer-term antibiotic consumption when VAP does arise, which gives bacteria more time to develop resistance.
Keeping the patient's body between 32 and 34 C. has been associated with a higher risk of secondary infections, so the ANTHARTIC team wanted to see if a brief course of antibiotics might lower that risk.
The team gave a combination of 1 g of amoxicillin and 200 mg of clavulanate three times per day because of their history of countering the most frequently isolated bacteria responsible for early VAP. Of the 194 randomized patients included in the analysis, 95 received saline injections instead.
Sixteen ICUs in France were involved in the test. Early VAP was classified as occurring during the first seven days of hospitalization. Pneumonia was classified as late if it manifested after day 7 until death or ICU discharge. Patients with overt aspiration were excluded from the test.
The rate of early ventilator-associated pneumonia by day 7 was 19% with antibiotics and 34% with placebo, for a hazard ratio of 0.53 (P=0.03).
Antibiotics also showed a benefit when the cutoff time for early pneumonia was adjusted to the first five days - with rates of 17% and 31% respectively (P=0.03).
There were four cases of late pneumonia in the antibiotic group and five in the control group.
"Nonpulmonary secondary infectious complications were equally distributed between the two groups," the researchers reported.
The rates of mortality at day 28 were 41% with the two-day antibiotic therapy and 37% with placebo. However, VAP was not blamed for any of the deaths.
Serious adverse events were comparable between the two groups.
"Whether the present results apply to patients with out-of-hospital cardiac arrest whose condition is managed with a different targeted temperature remains to be determined," the researchers said.
Dr. Francois said because the findings were presented at a medical meeting, "Now I've got a lot of colleagues using this as the standard of care."
He also said there are plans to test an even shorter course of antibiotic prophylaxis.
"We are convinced that even one day should be enough," he said. "We are setting up a new trial to show that one day is just as effective as a 2-day course."
N Engl J Med 2019.(c) Copyright Thomson Reuters 2019. Click For Restrictions - https://agency.reuters.com/en/copyright.html