Study: In ICU prophylactic antibiotics save lives

Study: In ICU prophylactic antibiotics save lives

Could practice contribute to drug resistance?

A recent study conducted in the Netherlands shows some positive results in the ICU when antibiotics are given to patients before any infection develops,¹ but it also raises a question that the researchers are not prepared to answer: whether the strategy could have unintended consequences in the form of increased drug resistance. However, the researchers did assert that, at least in the case of the facilities they studied, the benefits outweighed the risks that people will develop resistance to the drugs.

In the study, published in the New England Journal of Medicine, Anne Marie de Smet, MD, and her colleagues at University Medical Center Utrecht compared the effects of different antibiotic treatments in 5,939 men and women who were cared for in intensive care units for at least two days at 13 hospitals in the Netherlands.

The patients were divided into three groups: One group (2,045 patients) received infection prevention measures called selective digestive tract decontamination (SDD); another (1,904) received selective oropharyngeal decontamination (SOD); while a third group (1,990) received standard care. SOD involves the application of topical antibiotics in the oropharynx only, while SDD aims to prevent secondary infections through the additional use of IV antibiotics. "In the standard care protocol, you don't use antibiotics in a preventive way at all, but only when there is a proven infection or the clinical suspicion of an infection," Smet explains.

After 28 days, the mortality rate associated with standard care was 27.5%. This was reduced by an estimated 3.5 percentage points with SDD, or a 13% reduction, and by 2.9 percentage points with SOD, or an 11% drop. For this time period, say the researchers, the number of antibiotic-resistant bacterial infections did not increase among the people on the drugs. They acknowledged, however, that this issue should be studied on a longer-term basis.

Closer look at protocols

The rationale for the study, says Smet, was to take a closer look at these protocols, which have been the subject of much discussion in the Netherlands. "We started using this system in Holland almost three years ago for leukemia patients; it has been a hot topic among both believers and non-believers," she shares. "We wanted to see if we needed all parts of SDD, which had shown much lower rates of bacteremia [bacteria in the blood] than SOD, so we brought it to the ICU."

The rationale for combining oral and IV antibiotics was derived from the literature, she continues. "If you look at other publications, such as The Lancet, you will see much more discussion," says Smet. "You can kill gram-negative bacteria in the gut with antibiotics so they will not be resorbed into the blood, so you usually have to give them intravenously. These antibiotics we use are antibiotics that stay in the gut and are not resorbed into the blood."

Would it stand to reason that if the patients only receive IV antibiotics that the mortality rates would be lower? "We didn't look at only IV, so we don't know," says Smet. "However, we do know that one of the hospitals in Holland tried it a long time ago and saw a lot of [drug] resistance, although the study was not published. But that's not the next question we're going to ask."

Looking at resistance

What Smet and her colleagues plan next is a new trial comparing SOD and SDD to look at resistance, she shares. "You need to do it at least for a year," she explains. "In general, the more antibiotics you use, the higher the resistance you will see, so if you consider it from that point of view, it might be better to use SOD. But on the other hand, [in this trial] it seemed even lower in SDD, so we'd like to do a new trial."

She adds, however, that it is very important for a similar trial to be conducted in the United States. "The Netherlands is a country where there is a very low antibiotic resistance level — it's not like southern Europe and the U.S., and it might be different for other countries," she explains. "We have hardly any MRSA [methicillin-resistant Staphylococcus aureus] here, so I suggest you should have a separate look at a trial yourselves."

Because of these differences between the United States and the Netherlands, Smet does not suggest that quality managers in the United States begin advocating for prophylactic antibiotics in the ICU. "In the Dutch situation we said we were OK, but in the United States you still have to look at your own level of resistance; do a trial and have a very proper look to see if you have an emergence [of cases]. We do know that this approach is positive in terms of reducing mortality."

Reference

1. Smet AMGA de, Kluytmans JAJW, Cooper BS, Mascini EM, et al. Decontamination of the Digestive Tract and Oropharynx in ICU patients. N Engl J Med January 2009, 360;1:20-31.

[For additional information, contact:

Anne Marie de Smet, MD, University Medical Center Utrecht. Phone: +31-88-7555555; ask for beeper 1368. E-mail: asmet@umcutrecht.nl]