Selective decontamination of the digestive tract in neurosurgical intensive care unit patients: a double-blind, randomized, placebo-controlled study. Selective intestinal decontamination in multiple trauma patients: prospective, controlled trial. Prevention of infection in critically ill patients by selective decontamination of the digestive tract. Utility of selective digestive decontamination in mechanically ventilated patients. Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Selective decontamination of the digestive tract in multiple trauma patients. A prospective double-blind, randomized, placebo-controlled study. Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study. Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomized study. Oropharyngeal decontamination with gentamicin for long-term ventilated patients on stress ulcer prophylaxis with sucralfate? Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli. Study of an outbreak in an intensive care unit. Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis. Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen. The effect of selective decontamination of the digestive tract on colonisation and infection rate in multiple trauma patients. Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract. A randomized, double blind, placebo-controlled study. Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma. The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial. Prevention of acquired infections in intubated patients with the combination of two decontamination regimens. Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD). Prevention of colonization and infection in critically ill patients: a prospective randomized study. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract. Selective gut decontamination reduces nosocomial infections and length of stay but not mortality or organ failure in surgical intensive care unit patients. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trial.
The aim of this study was to assess, in a selected population, the effects of selective decontamination of the digestive tract on colonization of the oropharynx, trachea, stomach and rectum, and on the infection rate. An economical assessment was also performed.
                A prospective, double-blind, randomized, placebo-controlled, dual-center trial.
                Two neurosurgical intensive care units.
                A total of 191 comatose patients admitted emergently and intubated within < 24 hrs were enrolled. Of these patients, 68 were excluded because they either died, got an early infection, or were extubated within the first 5 days. A total of 123 patients were analyzed: 63 treated and 60 placebo patients.
                Topical antibiotics (tobramycin, polymyxin E, amphotericin B) were applied in the oropharynx and in the stomach. Vancomycin was added in the oropharyngeal paste. Placebo patients received the same regimen (i.e., a suspension of fluid and a paste) but without antibiotics. No parenteral antibiotics were given during the study period.
                Bronchopneumonia episodes were diagnosed with protected specimen brush or plugged telescoping catheter and other infections were diagnosed according to the Center for Disease Control of Atlanta criteria. Antibiotic costs and cost per survivor were calculated. Selective decontamination of the digestive tract significantly reduced Gram-negative bacilli colonization as well as the number of episodes of bronchopneumonia, urinary tract infections, and sinusitis. Despite the addition of vancomycin, Staphylococcus aureus remained the main potential pathogen causing tracheal colonization and subsequent bronchopneumonia. The reduction in bronchopneumonia rate was observed in head-trauma patients only. We were able to show that: a) the trachea was the main reservoir of microorganisms responsible for pneumonia; b) pneumonia developed after tracheal colonization. Total charges for antibiotics were 2.8 times higher in the treated group than in the placebo group; in calculating the cost per survivor, selective decontamination of the digestive tract might be beneficial due to the reduced length of stay.
                Selective decontamination of the digestive tract is an effective technique in reducing infectious morbidity in comatose neurosurgical patients. Because of its cost, this technique should be used only in selected populations. Reduction of potential pathogens by selective intestinal decontamination has been proposed to improve intensive care. Despite large scientific interest in this method, little is known about its benefit in homogeneous trauma populations.
                In a prospective, controlled study, we enrolled non-infected trauma patients (age over 18 years, mechanical ventilation > or = 48 hours, intensive care for more than 3 days) who primarily were admitted to our university medical center. We randomized patients to be treated with two different topical regimens (polymyxin, tobramycin, and amphotericin (PTA) or polymyxin, ciprofloxin, amphotericin (PCA)) or the carrier only (placebo), administered four times daily both to the oropharynx and to the gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg, bd) for 4 days.
                Of 357 enrolled patients, 310 (age 38.0 +/- 16.5 years, Injury Severity Score 35.2 +/- 12.7) met all inclusion criteria. Selective decontamination successfully reduced intestinal bacterial colonization. However, we did not identify significant differences between groups regarding pneumonia (PTA 47.5%, PCA 39.0%, placebo 45.3%), sepsis (PTA 47.5%, PCA 37.8%, placebo 42.6%), multiple organ failure (PTA 56.3%; PCA 52.4%, placebo 58.1%), and death (PTA 11.3%, PCA 12.2%, placebo 10.8%). Total costs per patient were highest with the PTA regimen.
                We found no benefit of selective decontamination in trauma patients. Apparently, bacterial overgrowth in the intestinal tract is not the sole link between trauma, sepsis, and organ failure. To determine whether selective decontamination of the digestive tract using oral and nonabsorbable antimicrobial agents and parenteral cefotaxime prevents infection in critically ill patients.
                Randomized, controlled trial without blinding.
                Surgical trauma and medical intensive care units in a tertiary referral hospital.
                One hundred fifty patients admitted to surgical trauma and medical intensive care units during a 3-year interval, whose condition suggested a prolonged stay (greater than 3 days).
                Patients were randomly allocated to an experimental group (n = 75) that received cefotaxime, 1 g intravenously every 8 hours for the first 3 days only, and oral, nonabsorbable antibiotics (gentamicin, polymyxin, and nystatin by oral paste and oral liquid) for the entire stay in the intensive care unit. Control patients (n = 75) received usual care.
                The number of infections, total hospital days, and deaths, as well as the number of days in intensive care unit, were recorded.
                Control patients experienced more infections (36 compared with 12, P = 0.04), including bacteremias (14 compared with 4, P = 0.05) and pulmonary infections (14 compared with 4, P = 0.03). Although total hospital days, days in intensive care, and the overall death rate all were lower in the treatment group, these differences were not statistically significant. Clinically important complications of selective decontamination of the digestive tract were not encountered.
                Selective decontamination of the digestive tract decreases subsequent infection rates, especially by gram-negative bacilli, in selected patients during long-term stays in the intensive care unit. To assess selective digestive decontamination for preventing nosocomial pneumonia and mortality in mechanically ventilated patients.
                Prospective, randomized, placebo-controlled, double-blind study.
                Respiratory intensive care unit of a 1000-bed teaching hospital.
                80 patients receiving mechanical ventilation for more than 72 hours.
                Patients received selective digestive decontamination using polymyxin E, tobramycin, and amphotericin B through a nasogastric tube and also topically in the oropharynx; control patients received placebo. All patients received intravenous cefotaxime for 4 days or other systemic antibiotics if required.
                Bacteriologic surveillance (three times a week) was done by quantitatively culturing tracheal aspirates, pharyngeal swabs, and gastric juice. The diagnosis of pneumonia was based on quantitative cultures of protected specimen brush samples (> or = 10(3) CFU/mL [colony forming units/mL]) or bronchoalveolar lavage fluid (> or = 10(4) CFU/mL) and autopsy findings.
                Bronchial, oropharyngeal, and gastric colonization by gram-negative bacilli and Candida species was lower in the selective digestive decontamination group compared with the placebo group. Nonsignificant differences were found in the incidence of nosocomial infections (28% compared with 37%; odds ratio, 0.66; 95% CI, 0.35 to 1.25) and nosocomial pneumonia (18% compared with 24%; odds ratio, 0.7; CI, 0.33 to 1.46) and in the crude mortality rate (31% compared with 27%; odds ratio, 1.21; CI, 0.63 to 2.34) when comparing digestive decontamination with placebo, respectively.
                Selective digestive decontamination in our mechanically ventilated patients significantly decreased the colonization rate of gram-negative bacilli and of Candida species but not of Staphylococcus aureus. It did not decrease the incidence of nosocomial pneumonia, mortality, length of stay, or the duration of mechanical ventilation. To evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients.
                Prospective, randomized, concurrent trial.
                Multidisciplinary intensive care unit (ICU) in a 1,800-bed university hospital.
                Consecutive patients (n = 660) who were likely to require mechanical ventilation for at least 48 hrs were randomized to one of three groups: conventional antibiotic regimen (control group A); oral and enteral ofloxacin-amphotericin B (group B); and oral and enteral polymyxin E-tobramycin-amphotericin B (group C). Both treatment groups received systemic antibiotics for 4 days (ofloxacin in group B and cefotaxime in group C).
                Patients were randomized to receive standard treatment (control group A, n = 220), selective decontamination regimen B (group B, n = 220), and selective decontamination regimen C (group C, n = 220). After early deaths and exclusions from the study, 185 controls (group A) and 193 (group B)/200 (group C) selective decontamination regimen patients were available for analysis.
                Measurements included colonization and primary/secondary infection rate, ICU mortality rate, emergence of antibiotic resistance, length of ICU stay, and antimicrobial agent costs. The study duration was 19 months. The patient groups were fully comparable for age, diagnostic category, and severity of illness. One third of patients in each group suffered a nosocomial infection at the time of admission. There was a significant difference between treatment group B and control 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% confidence interval of 0.27 to 0.81). Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A (odds ratio of 1.22, 95% confidence interval 0.72 to 2.08). Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups. ICU mortality rate was almost identical (group A 16.8%, group B 17.6%, and group C 15.5%) and was not significantly related to primary or secondary infection. Increased antimicrobial resistance was recorded in both treatment groups: tobramycin-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 comparable in control and group C patients; one third less was spent for group B patients.
                In cases of high colonization and infection rates at the time of ICU admission, the preventive benefit of selective decontamination is highly debatable. Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental, colonizing, and infecting bacteria. The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous. No beneficial effect on survival is observed. Moreover, selective decontamination adds substantially to the cost of ICU care. Study objective: The aims of the study were to evaluate the technique of selective digestion decontamination (SDD) in preventing the development of nosocomial infections in a selected population and to assess the effects on colonization of the oropharynx, nares, and bronchi. A financial assessment was also performed. Design: Prospective, double-blind, randomized placebo-controlled trial using amphotericin B, colistin sulfate (polymixin E), and gentamicin applied to the nares, the oropharynx, and enterally; no parenteral antibiotics were given during the study period. The SDD was applied every 6 h during the study period. Setting: Multidisciplinary ICU in a university hospital. Patients: A total of 148 trauma patients admitted emergently and intubated within less than 24 h were enrolled. Seventy-two patients who received placebo and 76 treated patients were analyzed on an "intention-to-treat" basis. Interventions: Microbiologic surveillance samples of oropharyngeal and bronchial secretions, urine, and any other potentially infected sites were taken at the time of ICU admission and twice weekly thereafter until discharge from the unit. Measurements and results: With the use of SDD, colonization was significantly reduced in the oropharynx and nares (<0.05) but not in bronchi. However, episodes of bronchopneumonia were significantly reduced (19 in the active group vs 37 in the placebo group; p,0.01). Staphylococcus aureus remained the main potential pathogen causing bronchial colonization and subsequent bronchopneumonia. There was no reduction in the incidence of other infections. Days in the ICU, duration of mechanical ventilation, and mortality rate were unchanged. After the use of SDD, Gram-positive colonization tended to increase and this was mainly due to methicillin-resistant coagulase-negative staphylococci. The total cost of antibiotic therapy ($62,117 [US] in the placebo group and $36,008 in the SDD group) was decreased by 42% with the use of SDD. Clinically important complications of SDD were not encountered. Conclusions: The use of SDD in this population of trauma patients reduced the incidence of bronchopneumonia and the total charge for antibiotics. Stay in the ICU, mechanical ventilation, and mortality rate were unchanged. Methicillin-resistant coagulase-negative staphylococci were selected by SDD in some patients and the clinical relevance of this colonization needs further evaluation. Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. Keywords: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects The efficacy of a relatively cheap regimen of selective decontamination (SDD) was evaluated in a diverse population of ICU patients. Patients requiring prolonged ICU stay (greater than 5 days) were randomly allocated to a treatment group or control group. Control patients (n = 52) received perioperative antimicrobial prophylaxis and antibiotic treatment was instituted only on sound clinical and bacteriological criteria. Treated patients (n = 48) received gastro-intestinal and oro-pharyngeal decontamination with polymyxin E, norfloxacin, amphotericin B and systemic antibiotic prophylaxis with trimethoprim until decontamination was achieved. The rate of gram-positive infections was not altered by SDD. The incidence of gram-negative respiratory tract, urinary tract and line infections was significantly reduced from 44%, 27% and 15% respectively in the control group to 6%, 4% and 0% in the treatment group. Mortality from nosocomial sepsis and overall mortality were also significantly reduced from 15% and 54% to 0% and 31% respectively. The ICU stay was not reduced by SDD, nor was time on the ventilator or use of therapeutic antibiotics. The reduction in morbidity and mortality was achieved at a relatively low cost. The incidence of nosocomial pneumonia in long-term ventilated patients has been reduced by stress ulcer prophylaxis with sucralfate. In a double-blind trial we studied whether gentamicin administered topically to the oropharynx (OPG) had additional clinical benefits in these patients. 67 critically ill adult patients fulfilled entry criteria for > or = 5 days on ventilation. The OPG group received 40 mg gentamicin, the control group received 5% dextrose topically administered to the oropharynx 4 times a day. During OPG, pharyngeal colonization rate (21 vs 44%) and tracheal secretion colonization rate (12 vs 41%) were significantly lower than during placebo (p < 0.05). Despite these differences nosocomial pneumonia rate (3 vs 12%), duration of mechanical ventilation [15.8 +/- 11.1 vs 19.9 +/- 37.5 days (means +/- SD)] and mortality (27 vs 41%) were not significantly affected by OPG. Moreover, 13 of 15 bacteria (87%) that occurred during OPG were resistant to gentamicin. Despite its reduction of bacterial colonization rates of pharyngeal and tracheal secretions, OPG did not seem to offer additional clinical benefits in long-term mechanically ventilated patients on stress ulcer prophylaxis with sucralfate. To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates.
                A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3).
                A medical intensive care unit of a tertiary care university hospital.
                Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination).
                Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit.
                Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3).
                Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections. In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of greater than 6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p less than 0.001); trachea 19 vs 11 (p less than 0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p less than 0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients, but in the present study the host setting appeared to be the major determinant of outcome. 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. 122 multiple trauma patients staying in the ICU for 5 or more days and needing mechanical ventilation were investigated to determine the effect of selective decontamination of the digestive tract on prevention of infection. The (retrospectively studied) control group of 59 patients received no antibiotic prophylaxis. The infection rate during ICU-stay was 81%. Most infections were caused by potentially pathogenic microorganisms (PPM) from the oral cavity or the intestines (i.e. endogenous infections). The oropharynx and the intestines were rapidly colonised with ICU-associated gram-negative bacilli. After 2 weeks more than 80% of patients were found colonised. This secondary colonisation of the digestive tract is a very important stage in the pathogenesis of infections. Sixty-three patients were selectively decontaminated with nonabsorbable antibiotics, administered through the gastric tube even if peristalsis was absent. Emphasis was laid on the selective decontamination of the oral cavity, using topical application of an antibiotic paste. With this technique the oral cavity was free of PPM within 3 days in most patients. No secondary colonisation was found. Rectal colonisation decreased significantly after 5 days. Secondary colonisation occurred in 9 patients with PPM sensitive to the antibiotics used. The prophylactic regimen included systemic cefotaxim, directed against early endogenous infection. The suppression and after some time the absence of the endogenous source of PPM resulted in a significant reduction of colonisation and infection. The total infection rate decreased to 16%. A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx. We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis. We evaluated the effect of selective decontamination of the digestive tract (SDD) on the incidence of ventilator-associated pneumonia (VAP) and its associated morbidity and cost in a mixed population of intubated patients. Two hundred seventy-one consecutive patients admitted to the intensive care units (ICUs) of five teaching hospitals and who had an expected need for intubation exceeding 48 h were enrolled and received topical antibiotics or placebo. Uninfected patients additionally received ceftriaxone or placebo for 3 d. VAP occurred in 11.4% of SDD-treated and 29.3% of control-group patients (p < 0.001; 95% confidence interval [CI]: 7.8 to 27.9). The incidence of nonrespiratory infections in the two groups was 19.1% and 30.7%, respectively (p = 0.04; 95% CI: 0.7 to 22.7). Among survivors, the median length of ICU stay was 11 d (interquartile range: 7 to 21.5 d) for the SDD-treated group and 16. 5 d (10 to 30 d) for the control group (p = 0.006). Mean cost per survivor was $11,926 for treated and $16,296 for control-group patients. Mortality was 38.9% and 47.1%, respectively (p = 0.57). In decontaminated patients, the prevalence of gram-negative bacilli fell within 7 d from 47.4% to 13.0% (p < 0.001), whereas colonization with resistant gram-positive strains was higher (p < 0. 05) than in the placebo group. In a mixed population of intubated patients, SDD was associated with a significant reduction of morbidity at a reduced cost. Our findings support the use of SDD in this high-risk group. To evaluate the effect of a method of Selective Decontamination of the Digestive Tract (SDD) on colonization, nosocomial infection (NI), bacterial resistance, mortality and economic costs.
                Randomized, double blind, placebo controlled study.
                Polyvalent intensive care unit (ICU) of a tertiary care hospital with 27 beds.
                101 patients with > 3 days of mechanical ventilation and > 5 days of stay, without infection at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG).
                The TG was given Cefotaxime i.v. (6 g/day) for the first four days and an association of Polymyxin E, Tobramycin and Amphotericin B at the oropharyngeal and gastrointestinal level throughout the whole stay.
                In the TG, colonization by gram-negative agents at oropharyngeal, tracheal and gastrointestinal level fell significantly. There was a significant drop in the overall, respiratory and urinary NI (26% vs 63%, p < 0.001; 15% vs 46%, p < 0.001; 9% vs 31%, p < 0.01). The overall mortality and NI related mortality was less in the TG (21% vs 44%, p < 0.05; 2% vs 20%, p < 0.01). The economic costs, mechanical ventilation time and length of stay were similar. The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG (38% vs 15% and 38% vs 9%, p < 0.001).
                colonization by gram-negative bacilli, NI and the mortality related to it can be modified by SDD. Continuous bacteriological surveillance is necessary. To determine whether selective decontamination locally in the subglottic area (SDSA) reduces tracheal colonization and prevents ventilator-associated pneumonia (VAP) in patients with multiple trauma.
                A prospective randomized, controlled, clinical study in a 14-bed general intensive care unit of a university hospital.
                79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 5 days; 61 patients completed the protocol.
                Patients were randomly assigned to receive SDSA using a continuous infusion of a suspension containing three nonabsorbable antibiotics (polymyxin, tombramycin, and amphotericin B; n=30) or placebo ( n=31).
                The incidence of bronchial and gastric colonization and the number of cases of VAP were recorded. Gastric fluid and tracheal secretion cultures were obtained soon after intubation and thereafter every 4 days. Etiological diagnosis of VAP was based on samples taken by a specific protected double catheter set.
                VAP developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%) patients receiving placebo. Negative bronchial secretion cultures were found in 14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients in the control group. No patient with negative bronchial secretion culture developed VAP. No significant differences in outcome were found.
                The SDSA is an effective and safe type of chemoprophylaxis against tracheal colonization and can significantly reduce the incidence of VAP in mechanically ventilated patients with multiple trauma. Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU).
                A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n=200) or SDD (n=201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction.
                Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found.
                This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit. The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined.
                The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design.
                The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France.
                Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs.
                Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs.
                The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001).
                Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation. To determine the influence of selective oropharyngeal decontamination (SOD) on the rate of colonization and infection of the respiratory tract in intensive care patients requiring mechanical ventilation for more than 4 days. A financial assessment was also performed.
                Randomized, prospective, controlled study using amphotericin B, colistin sulfate (polymyxin E), and tobramycin applied to the oropharynx and systemic cefotaxime prophylaxis.
                Anesthesiology intensive care unit (ICU) of a 1500-bed hospital.
                A total of 88 patients admitted as emergencies and intubated within less than 24 h were enrolled. Fifty-eight patients received SOD and 30 patients served as controls. Randomization was in the proportion of 2 : 1 study patients to controls.
                Microbiological samples from the oropharynx and other infected sites were taken at the time of admission, then twice a week and after extubation.
                With the use of SOD, colonization was significantly reduced. Furthermore, the infection rate decreased from 77% in the controls to 22% in the study patients. Staphylococcus aureus was the main potential pathogen causing colonization and pneumonia. Number of days in the ICU, duration of ventilation, and mortality were not significantly decreased. The total cost of antibiotics was reduced. Development of resistance was not observed.
                The use of SOD significantly reduced the colonization and pneumonia and the total charge for antibiotics. The length of stay in the ICU, duration of ventilation, and mortality were similar. No resistance was observed. Staphylococcus aureus was selected by SOD in some patients and the clinical relevance needs further observation. In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics. Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care.
                We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria.
                In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus.
                In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria. Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival.
                We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization.
                A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group.
                Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care. Suppression of the gut luminal aerobic flora to reduce nosocomial infections was tested in a prospective, randomized, double-blind, placebo-controlled clinical trial in patients in a surgical intensive care unit who had persistent hypermetabolism. Forty-six patients were randomized to receive either norfloxacin, 500-mg suspension every 8 hours, together with nystatin, 1 million units every 6 hours, or matching placebo solutions administered through a nasogastric tube within 48 hours of surgical intensive care unit admission. Selective gut decontamination with the experimental therapy or placebo solutions continued for at least 5 days or until the time of surgical intensive care unit discharge. Patients were monitored with routine surveillance cultures for the development of nosocomial infections, as defined by criteria from the Centers for Disease Control. All other therapy was given as clinically indicated, including systemic antibiotics. The selective gut decontamination group experienced a significant reduction in the incidence of nosocomial infections and a reduced length of stay. However, these results were not associated with a concomitant decrease in progressive multiple organ failure syndrome, adult respiratory distress syndrome, or mortality. Secondary pneumonia in patients requiring mechanical ventilation has a high morbidity and mortality. Diagnosis is difficult and treatment failure common; therefore, preventive measures are important. In a double-blind, placebo-controlled trial, we evaluated selective decontamination of the oropharynx with polymyxin B sulfate, neomycin sulfate, and vancomycin hydrochloride (PNV) in 52 patients requiring mechanical ventilation during a 3- to 34-day period (mean, 10 days). Either PNV or placebo was administered six times daily in the oropharynx. During the first 12 days of intubation, tracheobronchial colonization by gram-negative bacteria and Staphylococcus aureus, as well as pneumonia, occurred less frequently in the PNV than in the placebo group (16% vs 78%; P less than .0001). Hospital mortality was not different, but systemic antibiotics were prescribed less often in the PNV group and no resistant microorganism emerged. In these critically ill patients, topical oropharyngeal antibiotic application lowered the rate of ventilator-associated pneumonia by a factor of 5, probably by interrupting the stomach-to-trachea route of infection, and decreased the requirement for intravenous antibiotics.
A combination of topical and systemic prophylactic antibiotics reduces RTIs and overall mortality in adult patients receiving intensive care. Treatment based on the use of topical prophylaxis alone reduces respiratory infections but not mortality. The risk of resistance occurring as a negative consequence of antibiotic use was appropriately explored only in one trial which did not show any such effect.