Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen. Randomized, controlled trial on tracheal colonization of ventilated infants: can gravity prevent ventilator-associated pneumonia?
The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation. The goal was to test the hypothesis that intubated infants positioned on their sides would be less likely to contract bacterial colonization in their tracheae, compared with those positioned supine.
                We conducted a prospective, randomized, controlled trial with 60 intubated infants; 30 infants were positioned supine (supine group), and 30 infants were maintained in the lateral position (lateral group). Tracheal aspirates were cultured and bacterial colony counts were recorded after 48 hours and after 5 days of mechanical ventilation.
                After 2 days, the numbers of positive tracheal cultures in the supine group (67%) and in the lateral group (47%) showed no statistical difference. After 5 days of mechanical ventilation, tracheal cultures differed significantly between groups. Cultures were positive for 26 infants (87%) in the supine group and 9 infants (30%) in the lateral group. Compared with the lateral group, more infants in the supine group experienced increased colony counts or had new organisms in their tracheal aspirates over time (21 vs 8 infants). The most common organisms isolated from tracheal aspirates in both groups were Gram-negative rods.
                Respiratory contamination is very common among ventilated infants. Therefore, judicious use of mechanical ventilation cannot be overemphasized. Gravitational force can ameliorate the onset of respiratory colonization. The mechanism and clinical applicability of such observations need to be explored further.
There is insufficient evidence from randomised trials to support or refute the use of prophylactic antibiotics when starting mechanical ventilation in newborn infants, or to support or refute continuing antibiotics once initial cultures have ruled out infection in mechanically ventilated newborn infants.