RANDOMIZED, CONTROLLED TRIAL OF SELECTIVE DIGESTIVE DECONTAMINATION IN 600 MECHANICALLY VENTILATED PATIENTS IN A MULTIDISCIPLINARY INTENSIVE-CARE UNIT

Objective: To evaluate the efficacy of two regimens of selective decon tamination of the digestive tract in mechanically ventilated patients. Design: Prospective, randomized, concurrent trial. Setting: Multidisc iplinary intensive care unit (ICU) in a 1,800-bed university hospital. Patients: Consecutive patients (n = 660) who were likely to require m echanical ventilation for at least 48 hrs were randomized to one of th ree groups: conventional antibiotic regimen (control group A); oral an d enteral ofloxacin-amphotericin B (group B); and oral and enteral pol ymyxin E-tobramycin-amphotericin B (group C). Both treatment groups re ceived systemic antibiotics for 4 days (ofloxacin in group B and cefot axime in group C). Interventions: Patients were randomized to receive standard treatment (control group A, n = 220), selective decontaminati on regimen B (group B, n = 220), and selective decontamination regimen C (group C, n = 220). After early deaths and exclusions from the stud y, 185 controls (group A) and 193 (group B)/200 (group C) selective de contamination regimen patients were available for analysis.Measurement s and Main Results: Measurements included colonization and primary/sec ondary infection rate, ICU mortality rate, emergence of antibiotic res istance, length of ICU stay, and antimicrobial agent costs. The study duration was 19 months. The patient groups were fully comparable for a ge, diagnostic category, and severity of illness. One third of patient s in each group suffered a nosocomial infection at the time of admissi on. There was a significant difference between treatment group B and c ontrol group A in the number of infected patients (odds ratio of 0.42, 95% confidence interval of 0.27 to 0.64), secondary lower respiratory tract infection (odds ratio of 0.47, 95% confidence interval of 0.26 to 0.82), and urinary tract infection (odds ratio of 0.47, 95% confide nce interval of 0.27 to 0.81). Significantly more Gram-positive bacter emias occurred in treatment group C vs. group A (odds ratio of 1.22, 9 5% confidence interval 0.72 to 2.08). Infection at the time of admissi on proved to be the most significant risk factor for subsequent infect ion in control and both treatment groups. ICU mortality rate was almos t identical (group A 16.8%, group B 17.6%, and group C15.5%) and was n ot significantly related to primary or secondary infection. Increased antimicrobial resistance was recorded in both treatment groups: tobram ycin-resistant enterobacteriaceae (group C 48% vs. group A 14%, p <.01 ), ofloxacin-resistant enterobacteriaceae (group B 50% vs. group A 11% , p <.02), ofloxacin-resistant nonfermenters (group B 81% vs. group A 52%, p <.02), and methicillin-resistant Staphylococcus aureus (group C 83% vs. group A 55%, p <.05). Antimicrobial agent costs were comparab le in control and group C patients; one third less was spent for group B patients. Conclusions: In cases of high colonization and infection rates at the time of ICU admission, the preventive benefit of selectiv e decontamination is highly debatable. Emergence of multiple antibioti c-resistant microorganisms creates a clinical problem and a definite c hange in the ecology of environmental, colonizing, and infecting bacte ria. The selection of multiple antibiotic-resistant Gram-positive cocc i is particularly hazardous. No beneficial effect on survival is obser ved. Moreover, selective decontamination adds substantially to the cos t of ICU care.