Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care

BACKGROUND: Pneumonia is an important cause of mortality in intensive care units. The incidence of pneumonia in such patients ranges between 7% and 40%, and the crude mortality from ventilator associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in intensive care units independently of other factors that are also strongly associated with such deaths. OBJECTIVES: The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2003), which contains the Acute Respiratory Infections (ARI) Group specialised trials register; MEDLINE (January 1966 to September 2003); EMBASE (January 1990 to September 2003); proceedings of scientific meetings and reference lists of articles from January 1984 to December 2002. We also contacted investigators in the field. SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Overall 36 trials involving 6922 people were included. There was variation in the antibiotics used, patient characteristics and risk of respiratory tract infections and mortality in the control groups. In 17 trials (involving 4295 patients) that tested a combination of topical and systemic antibiotic, the average rates of respiratory tract infections and deaths in the control group were 36% and 29% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.35, 95% confidence interval 0.29 to 0.41) and total mortality (odds ratio 0.78, 95% confidence interval 0.68 to 0.89) in the treated group. On average 5 patients needed to be treated to prevent one infection and 21 patients to prevent one death. In 17 trials (involving 2664 patients) that tested topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) the rates of respiratory tract infections and deaths in the control groups were 30% and 26% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.52, 95% confidence interval 0.43 to 0.63) but not in total mortality (odds ratio 0.97, 95% confidence interval 0.81 to 1.16) in the treated group. REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics reduces respiratory tract infections and overall mortality in adult patients receiving intensive care. A treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of occurrence of resistance as a negative consequence of antibiotic use was appropriately explored only in the most recent trial by de Jonge which did not show any such effect.