Routine prophylaxis lowers ICU respiratory infections

But practice could spur antibiotic-resistant bugs

Source: D'Amico R, et al. Effectiveness of antibiotic prophylaxis in critically ill adult patients: Systematic review of randomized controlled trials. BMJ 1998; 316:1,275-1,285.

The potential role of antimicrobial prophylaxis in the reduction of morbidity and mortality due to respiratory tract infection in critically ill patients is unclear. D'Amico and colleagues performed a meta-analysis of randomized, controlled trials of antimicrobial prophylaxis among ICU patients. They analyzed 30 clinical trials involving 4,898 patients; the endpoints were occurrence of respiratory tract infection and mortality. The authors grouped the trials into two categories: those comparing a combination of both systemic and topical antimicrobials, and those testing topical agents. The latter category included trials in which topical agents were compared with no treatment, and those in which topical agents combined with systemic agents were compared with systemic agents alone. The regimens used in the trials varied, but the most common topical regimen included polymyxin, aminoglycoside, and amphotericin B. The most frequently used systemic agents were third-generation cephalosporins. The combination of topical and systemic antimicrobials was associated with significant reduction in the occurrence of respiratory tract infection (odds ratio 0.35; > 95% confidence interval 0.29-0.41). There was also a significant reduction in mortality (OR 0.80; 95% CI 0.69-0.93). Topical agents led to a reduction in infection (OR 0.56; 95% CI 0.46-0.68) without a reduction in mortality.

D'Amico et al. carried their analysis one step further. From the authors of 25 of the studies included in the aggregate analysis, they obtained individual patient data on more than 4,000 patients for entry into a separate analysis. The results were similar. The combination of topical and systemic therapy led to a reduction in both respiratory infection (OR 0.40; 95% CI 0.33-0.49) and mortality (OR 0.79; 95% CI 0.65-0.97). Topical antimicrobials led to a significant decrease in infection, but not in mortality.

Comment by Robert Muder, MD, hospital epidemiologist at the Pittsburgh VA Medical Center:

Admission to a critical care area is associated with a 10-fold to 20-fold increase in the occurrence of nosocomial pneumonia; attributable mortality associated with pneumonia is approximately 30%. Effective strategies to reduce the incidence of respiratory infection in this highly susceptible population are clearly needed. At present, neither the Centers for Disease Control and Prevention nor the American Thoracic Society (ATS) recommend the routine use of prophylactic antimicrobials for the prevention of respiratory infection in ICU patients.

The meta-analysis performed by D'Amico and colleagues included a large number of trials and patients. Criteria for selection of studies for inclusion was fairly rigorous, and the data analysis appears to have been appropriate. In a remarkable display of collaboration among investigators, D'Amico and associates were able to obtain the original patient data used in the majority of trials for an independent analysis. The results were similar; the combination of topical and systemic antimicrobials led to a significant reduction in both respiratory infection and mortality.

Should the current CDC and ATS criteria be revised to recommend antimicrobial prophylaxis for the prevention of pneumonia in ICU patients? I believe that it would be premature to do so at this point. The various studies included different patient populations, different prophylactic regimens, and different criteria for the diagnosis of respiratory infection. The upper bound of the confidence interval for the odds ratio for mortality is quite close to 1.0 (> 0.93-0.97). There was little systemic surveillance for the occurrence of resistant organisms. The long-term effects of universal prophylaxis on the resistance patterns of organisms acquired in the ICU remains to be determined.

Administration of systemic cephalosporins to all ICU patients could easily lead to major increases in the prevalence of methicillin-resistant Staphylococcus aureus, enterococci, and multidrug-resistant gram-negative bacilli. The issue would best be resolved by multicenter randomized trials designed to examine the efficacy of prophylaxis regimens. Careful monitoring of the occurrence of antimicrobial resistance would be essential. This would be a large undertaking, but given the number of investigators (primarily in Europe) who have performed these trials and the degree of collegiality shown by these same investigators in providing their patient data to D'Amico and colleagues, such trials should be feasible.