CHICAGO – Antibiotic de-escalation in ICU patients with nosocomial pneumonia in the intensive care unit produced the same clinical outcome – or better – as maintaining broad-spectrum coverage through the treatment course, a study has shown.
Modifying empiric therapy by continuing with narrower-spectrum antibiotics based on culture and antibiotic susceptibility reports not only limits the emergence of multidrug-resistant pathogens, but also reduces resource utilization for the treatment of hospital-acquired pneumonia, ventilator-assisted pneumonia, and health care–associated pneumonia, Chris Destache, Pharm.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The Infectious Diseases Society of America and the American Thoracic Society both advocate early broad-spectrum empiric antibiotics with subsequent streamlining based on the organisms identified and susceptibility patterns in nosocomial pneumonia, but the effect of antibiotic de-escalation on resource utilization, particularly hospital length of stay and cost of hospitalization, has not been examined, Dr. Destache said.
To evaluate the impact of antibiotic de-escalation in the intensive care unit on these resource utilization factors, Dr. Destache of Creighton University in Omaha, Neb., and his colleagues retrospectively studied the charts of patients older than 18 years admitted to the Creighton University Medical Center ICU in 2009 with a presumptive diagnosis of hospital-acquired pneumonia, ventilator-assisted pneumonia, or health care–associated pneumonia, who also had blood or respiratory cultures collected prior to the initiation of antibiotic treatment.
Antibiotic de-escalation was defined as the discontinuation of at least one empiric agent or the change to a narrower-spectrum antibiotic, he said. Patients who received systemic antibacterial, antifungal, or antiviral treatment within 72 hours of their pneumonia diagnosis were excluded from the analysis. The primary study end point was ICU length of stay; secondary end points included total hospital length of stay, in-hospital mortality, and hospitalization costs.
"Culture-negative pneumonias derived the greatest benefit from de-escalation."
Of 378 records identified, 95 patients representing 99 cases of nosocomial pneumonia met the eligibility requirements. "All of the patients had presumptive pneumonia based on [Centers for Disease Control and Prevention] criteria and received broad-spectrum antibiotic therapy based on universal guidelines, and de-escalation was performed in 60 cases," Dr. Destache reported. Universal guidelines call for patients to receive piperacillin-tazobactam, levofloxacin, and vancomycin for at least 24 hours.
Patients in whom the streamlined antibiotic approach was utilized were more likely to be older than those in whom empiric treatment was maintained, with a mean age of 66 years compared with 55.5 years, he said, noting that patients in the de-escalation group were also more likely to have diabetes (38% vs. 18%) and to have cardiovascular disease (38% vs. 15%).
No differences in sequential organ failure assessment scores were observed between the two groups at baseline, although these scores at culture finalization were significantly lower in the de-escalation group, which may have been a factor in the decision to de-escalate, Dr. Destache said.
The ICU length of stay was shorter in the de-escalation group at 9.4 days, compared with 12.8 days in the empiric treatment group, although the difference was not significant. Total length of stay was also shorter, at 15.3 vs. 16.9 days, and hospitalization costs were lower, at $45,640 vs. $60,640, Dr. Destache said at the meeting, sponsored by the American Society for Microbiology. In-hospital mortality was significantly lower in the de-escalation group, at 17% compared with 41%.
Culture was negative in 39 of the de-escalation cases and 18 of the controls, and was positive in 21 of each group, Dr. Destache said. The most common causative pathogens identified in the de-escalation group were methicillin-resistant Staphylococcus aureus (MRSA), followed by methicillin-susceptible S. aureus (MSSA), Pseudomonas aeruginosa, and Streptococcus pneumoniae, he said. In the control group, the most common was MSSA, followed by P. aeruginosa and S. pneumoniae, he said.
In comparing the benefits of antibiotic de-escalation based on culture status, the investigators found that "culture-negative pneumonias derived the greatest benefit from de-escalation," Dr. Destache said. In culture-negative pneumonias, the de-escalation group had an ICU stay of 7.2 days, a total length of stay of 10.4 days, and a mortality of 10%; in the culture-negative control group, ICU stay was 11.9 days, total length of stay was 15.1 days, and mortality was 50%, he said. Culture-positive patients in the de-escalation group stayed in the ICU for 13.6 days and in the hospital for 24.5 days, both of which were statistically similar to the 13.6 days and 18.5 days in the control group; the respective mortality rates were 29% and 33%.
The findings confirm the feasibility and clinical benefit of antimicrobial de-escalation and indicate that the strategy reduces resource utilization, compared with maintaining broad-spectrum coverage, Dr. Destache said. As such, he said, the treatment strategy should be utilized when appropriate as a way to improve antimicrobial stewardship.