Trial Information

Randomized, Multi-Center, Comparative Trial of Short-Course Empiric Antibiotic Therapy Versus Standard Antibiotic Therapy for Subjects With Pulmonary Infiltrates in the Intensive Care Unit (ICU): Impact on Antimicrobial Resistance, Superinfections, Length of ICU Stay and Hospitalization, and Mortality

Intensive care units (ICUs) are the most frequently identified source of nosocomial
infections within the hospital, with infection rates and antimicrobial resistance rates
significantly higher than in the general ward. In one study, antimicrobial use was reported
to be 10 times higher in the ICU compared to antimicrobial use in the general ward. Although
antibiotics are given for a variety of conditions, antibiotics prescribed for respiratory
infections, suspected or proven, account for almost one-half of all antibiotic consumption
in the ICU. Importantly, the use of antimicrobial agents has been identified as a critical
risk factor in the emergence of resistant bacterial infections. By identifying and focusing
on subsets of subjects who are unlikely to have infection and therefore unlikely to benefit
from antibiotics, antibiotic use and the subsequent emergence of antimicrobial-resistant
organisms could be limited. This is a Phase III, multi-center, randomized, open-label study
designed to determine whether 3 days of antibiotic treatment with meropenem (with or without
coverage for MRSA) for ICU subjects diagnosed with new pulmonary infiltrates can reduce the
emergence of antimicrobial-resistant organisms and the isolation of a potential pathogen
compared to a standard course of antibiotic therapy (minimum of 8 days of therapy with
antibiotics of the primary care team's choosing). The primary objective of this study is to
compare risk of resistant infection in the ICU by evaluating the difference in the incidence
of either the emergence of antimicrobial-resistant bacteria or the isolation of a potential
pathogen in ICU subjects who receive short-course empiric antibiotic therapy to ICU subjects
who receive standard antibiotic therapy for the treatment of pulmonary infiltrates (with low
likelihood of having pneumonia). Secondary objectives are to: 1) assess the mortality of
subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic
therapy; 2) assess the ICU length of stay (LOS) in subjects receiving short-course empiric
antibiotic therapy compared to standard antibiotic therapy; 3) assess the hospital LOS in
subjects receiving short-course empiric antibiotic therapy compared to standard antibiotic
therapy; 4) assess the costs of antibiotic therapy in subjects receiving short-course
empiric antibiotic therapy compared to standard antibiotic therapy. The costs will be based
on ICU LOS, hospital LOS, antibiotic treatment, and standard costs related to the treatment
of infection-related adverse experiences; 5) assess the risk of clinically significant
infection in subjects receiving short-course empiric antibiotic therapy compared to standard
antibiotic therapy. This study will enroll 460 subjects who have new pulmonary infiltrates
during their ICU stay and who are at low risk of having pneumonia, as determined using the
Clinical Pulmonary Infection Score (CPIS).