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? Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial. A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section. Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture. Prophylactic antibiotics in neonates with umbilical artery catheter placement: a prospective study of 137 patients. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis. [Antibiotic prophylaxis in a priori cesarean sections without a high risk of infection. Experiences of a Tunisian maternity department].
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 Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons.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. To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.
                Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.
                Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.
                Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies. In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo. Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.
                Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.
                From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).
                The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes. To analyze the risk of cannula sepsis from indwelling umbilical arterial catheters and the indication for prophylactic antibiotics, 137 catheterized neonates with respiratory distress were prospectively placed into either antibiotic-treated (penicillin 50,000U/kg/day and kanamycin 15 mg./kg./day) or non-treated groups. Although bacteria were frequently isolated from blood and catheter tip cultures obtained upon removal of the catheter, especially among non-antibiotic treated infants, these isolates were predominantly non-pathogens and probably skin flora. Corresponding peripheral blood cultures were usually sterile. No cases of cannula-associated sepsis occurred among treated and non-treated newborns. The risk of bacteriologically proven sepsis resulting from an indwelling umbilical artery catheter appears insufficient to justify prophylactic antibiotics. Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.
                A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.
                Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.
                The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes. 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. This study was conducted to evaluate the effect of antibiotic prophylaxy on decreasing the frequency of postoperative infections after cesarean sections performed in cases with no prior indication of a high risk of infection.
                A prospective randomized study included 269 cesarean sections without a high risk of infection performed in the Maternity and Neonatology Ward of the Sousse Hospital from February 1991 to July 1991. The patients were randomly divided into two groups. One group received an antibiotic prophylactic treatment including cephapirine, gentamicin and metronidazole) and the second group was given no treatment.
                Antibiotic prophylactic therapy led to a reduction of infectious morbidity after cesarean section in patients without high risk o infection from 33% to 11%. A 66% rate of efficacy was observed. In addition, antibiotics given in this context led to substantial cost reduction both by reducing the cost of antibiotics prescribed in the postoperative period and by reducing the number of days of hospitalization, and thus total cost.
                This study demonstrated the effectiveness of antibiotic prophylaxy for cesarean sections in patients without a high risk of infection. Nevertheless, a reevaluation of the antibiotic protocols and a rigorous operative procedure are essential.
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.