David Brill
Adopting a widespread preemptive approach with antibiotics could save lives in the Intensive Care Unit (ICU), Dutch researchers have recently reported.
Absolute mortality at 28 days was reduced by 3.5 percent in patients who received intravenous cefotaxime along with a cocktail of antibiotics applied topically to the stomach and orophyarynx. A simpler regimen – applying antibiotics only to the oropharynx – reduced mortality by 2.9 percent, as compared with standard care.
The findings are likely to prove contentious in the era of rising antibiotic resistance rates and hospital-associated infections. A Singapore infectious disease expert, who recently called for tighter regulation of the nation’s antibiotic usage, said that a similar approach could be adopted here but expressed his concern that resistance levels would increase in the long term.
The study, conducted across 13 ICUs in the Netherlands, randomized 5,939 patients to standard care or one of the two antibiotic regimens. Patients were only eligible if they were expected to be intubated for more than 48 hours or to remain in the ICU for more than 72 hours. [N Engl J Med 2009 Jan 1;360(1):20-31]
Lead researcher Dr. Anne Marie de Smet, of the University Medical Center Utrecht, said that the trial demonstrates that the benefits of preventive antibiotics outweigh the disadvantages.
“There are very few interventions in the ICU which can lower mortality on their own. These are not patients who come in for surgery and leave the next day – these people are really ill,” she said.
Antibiotic resistance rates did not rise significantly over the course of the 6-month study but longer follow-up data are needed, said de Smet. She added that The Netherlands has unusually low rates of resistance due to its strict regulations on antibiotic usage.
Dr. Hsu Li Yang, an infectious disease consultant at National University Hospital, Singapore, said that he would be “very concerned that resistance rates would increase” were the strategy to be adopted here, but added that is “for society as a whole to decide” whether such a move would be beneficial given the obvious short-term advantages.
“Doctors should not ‘allow’ patients to die so that future patients may be better or more easily treated. What we try to do is to retard the rise of resistance while preventing any increased mortality that may arise from inadequate use of antibiotics … minimize the use of antibiotics for those who do not need them and prescribe appropriate but not excessive antibiotics for those patients who do,” he said.
“Similar strategies might be adopted [here] in the future following the results of this study,” said Hsu, adding that the trial was very well conducted and one of the few in this field with adequate statistical power to demonstrate a significant mortality reduction.
The researchers used an antibiotic paste containing colistin, tobramycin and amphotericin B for both strategies. In the more comprehensive approach – selective digestive tract decontamination – the paste was applied topically to the stomach and oropharynx, and intravenous cefotaxime was given for the first 4 days. In the simpler strategy – selective orophyarygeal decontamination – the paste was just applied to the oropharynx.
Hsu added that that a different combination of antimicrobial agents would probably be necessary were the approach to be adopted in Singapore hospitals, where resistance rates are considerably higher than in the Netherlands.
Hsu recently co-authored a position paper calling for more data to be gathered on the use of antibiotics in Singapore and for the Ministry of Health to take a greater role in regulating usage. [Singapore Med J 2008 Oct;49(10):749-55]
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