Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit

Abstract

Background: The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU).

Methods: Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission.

Results: Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile. The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes.

Conclusions: The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

Keywords: antibiotic stewardship; antimicrobials; broad-spectrum; intensive care unit; nosocomial.

Figure 1.

The number of patients among the study population who received ≥1 antimicrobials in 1, 2, 3, 4, or 5 categories of broad-spectrum antimicrobial.

Figure 2.

Distribution of antimicrobials by spectrum of activity category over time. The plot indicates the fraction of the study population receiving at least 1 antimicrobial with the defined spectrum of coverage at anytime during the first 4 days after enrollment. In the case of Gram-negative agents, data represented are for the fraction of patients receiving 1 or more antimicrobials with activity against Gram-negative bacteria. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.