Clinical Impact of De-escalation to Ertapenem (ETP) in Enterobacteriaceae (EB) infections in Intensive Care Units (ICUs) from Seven Hospitals in Colombia

Background: The increasing emergence and uncontrolled spread of antimicrobial resistance worldwide threatens patient outcomes and raises overall healthcare costs. Antimicrobial De-Escalation (DE) requires that initial optimal broad-spectrum therapy be narrowed within 48 to 72 hours after the pathogen and its antibiotic susceptibility is known. ETP has proven to be effective for ESBL-producing EB but lacks activity against non-fermenters; DE to this antibiotic may reduce the development of resistance to P. aeruginosa (Pa). Herein, we evaluated the clinical impact of DE to ETP in infections caused by EB in ICUs from 7 hospitals from 4 Colombian cities. 

Methods: A cohort prospective study was carried out between February 2008 and June 2012. Adult ICU patients diagnosed with an EB infection and in whom empiric antibiotic therapy against Pa was started, were included in the study. Patients were assigned to 3 different groups: DE to ETP (group A), changed to an antibiotic different from ETP (group B) or not DE and continued on the same empirically anti-pseudomonas antibiotic (group C). Overall mortality, length of ICU stay (LOS), and clinical failure defined as the persistence of signs and symptoms of active infection at day 7 of antibiotic therapy, were analyzed.

Results: From a total of 1536 patients assessed for eligibility, 316 were included. Of those, 148 were assigned to group A, 63 to group B and 105 to group C. Patients in group A had a more severe condition at the moment of ICU admission, median APACHE II score = 20 compared to score <= 15 for B and C (p=0.0001). LOS was similar for the 3 groups. The overall mortality was 9% for group A versus 32% and 24% for groups B and C, respectively (p=0.003). Kaplan-Meier curves showed higher survival rates for group A (mean = 66 days, 95% CI 58 - 74) than for B or C, mean of 41 and 56 days, respectively (p=0.000). Patients from group A had a much lower relative risk of clinical failure when compared to group B (RR 0.454; 95% CI 0.239 - 0.861; p=0.019).

Conclusion: Patients DE to ETP had a lower mortality rate, a greater survival time, and a lower proportion of clinical failures than patients who were either changed to other antibiotics or continued the same initial therapy. DE to ETP should be considered as part of antimicrobial stewardship programs at the ICUs whenever the clinical condition and culture results allow.