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Study shows similar risk of empiric broad-spectrum antimicrobials in ICUs
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Empiric broad-spectrum antibiotic treatment of ICU patients for whom an infection was eventually ruled out was not associated with adverse effects, according to recent study findings.
“Given the prior data supporting empiric broad-spectrum use as part of a bundle of interventions for the management of sepsis, it remains important to ensure that adequate spectrum of activity is given for the suspected infection,” Graham M. Snyder, MD, an infectious diseases specialist at Beth Israel Deaconess Medical Center in Boston (BIDMC), told Infectious Disease News. “Our study suggests the risks of any of the broad-spectrum choices are similar (for the risks we quantified), and therefore choice should be made on best clinical judgement with the information available.”
Studies have shown that antimicrobial therapy is associated with adverse clinical effects, including colonization and infection with multidrug-resistant bacteria and Clostridium difficile, as well as end-organ dysfunction. These consequences can be deadly, researchers noted.
Snyder and colleagues sought to quantify the risk of adverse effects of prompt and brief empiric use of broad-spectrum antimicrobials in approximately 2,000 adult ICU patients at BIDMC for whom infection was initially suspected but subsequently excluded.
The researchers hypothesized that there may be a correlation between the spectrum of activity of certain antimicrobials that were selected for empiric coverage — including agents with activity against gram-negative bacilli, Pseudomonas aeruginosa, anaerobic bacteria, MRSA and atypical bacteria like Mycoplasma pneumoniae — and patient outcomes, such as 30-day mortality, increased length of stay in the hospital or ICU and the acquisition of nosocomial drug-resistant bacteria or C. difficile.
“With this work we sought to understand the relative sources of antimicrobial-associated risk in this critical scenario of suspected systemic infection,” Snyder said. “Since a provider has multiple choices of empiric antimicrobial regimens, can this choice be informed by risks that differ among broad-spectrum categories?”
Among the 1,918 patients who were included in the study, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay that exceeded 7 days or a length of ICU stay that lasted more than 3 days and 106 (5.5%) acquired nosocomial drug-resistant bacteria or C. difficile within 30 days of admission. In their analysis, however, Snyder and colleagues found that the short-term use of broad-spectrum antimicrobials — no matter their category — was not significantly associated with any of these outcomes.
Snyder noted that the study focused on a population for which antibiotic treatment was quickly de-escalated in the absence of infection — an important antimicrobial stewardship intervention that could mitigate any potential harm.
“Given the relatively short duration of antimicrobial exposure, it may not be entirely surprising to readers that there was no significant difference in our mortality, length-of-stay, or resistant pathogens and C. difficile outcomes,” Snyder said. “However, it is intriguing that there was not an observed difference in outcomes even when we characterized the risk of receiving multiple broad-spectrum categories of antimicrobials.”
Snyder and colleagues said there were two other potential explanations for their findings — either the study was underpowered to detect any harm caused by unnecessary short-term exposure to broad-spectrum antimicrobials, or the risk for harm was not the same for all ICU patients and that those who were adversely affected may have gone unnoticed. A larger database would be required to rule out these possibilities, they said.
“Future studies may parse out differences in the adverse risk of different empiric antimicrobial regimens, but our study supports making a prudent empiric choice with a lessened concern for the relative risks to the individual patient of different broad-spectrum categories,” Snyder said. “Antimicrobial stewardship teams will still find it important for the community of patients to guide antimicrobial choices based on local susceptibility and transmission patterns.”
Snyder said their findings also suggested that clinicians are using criteria to select antimicrobials beyond the information that was used in their “very robust” database.
“That is to say, clinical judgment may have been more complex, based on unmeasured factors, or based on subjective reasons,” he said. “For antimicrobial stewards, this suggests an important area of future study may be to better identify the information clinicians are using to select an empiric regimen, and how informatics tools may be used to aid the clinician in making best choices in empiric antimicrobial therapy.” – by John Schoen
Disclosures: The authors report no relevant financial disclosures.
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