Human botulism immune globulin for the treatment of infant botulism. Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics. Oral bacterial therapy promotes recovery from acute diarrhea in children. Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. Is pertussis immune globulin efficacious for the treatment of hospitalized infants with pertussis? No answer yet. Randomized control trial of live Lactobacillus acidophilus plus Bifidobacterium infantis in treatment of infantile acute watery diarrhea. Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates.
We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.
                We performed a five-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within three days after hospital admission. We subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.
                As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (P<0.001), the mean duration of mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (P<0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; P<0.001). There were no serious adverse events attributable to BIG-IV. In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.
                Prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.
                Copyright 2006 Massachusetts Medical Society. The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants. We assessed the safety and tolerability of an experimental formula containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo-oligosaccharides.
                A 7-mo prospective, randomized, reference-controlled, double-blinded trial was performed in infants who were not breast fed after the 14th day of birth. One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old. Mean weight gain (primary outcome) and recumbent length, head circumference, tolerability (gastrointestinal symptoms), and overall morbidity (secondary outcomes) were measured at 14, 28, 56, 84, and 112 d of age.
                Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d. No statistically significant difference in recumbent length, head circumference, or incidence of adverse events was found between the two groups. Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well. Furthermore, these infants showed a trend toward fewer respiratory tract infections.
                The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated. Lactobacilli in the intestines play an important role in developing natural defenses against both intestinal bacterial and viral infections. So a prospective clinical study was carried out at Cathay General Hospital to determine the effect of Lactobacillus acidophilus and Bifidobacterium infantis on the course of acute diarrhea in hospitalized children. Altogether 100 children between 6 and 60 months of age were collected and randomly allocated into 2 groups. Study group (n = 50) was given Infloran Berna, which contains 10(9) viable Lactobacillus acidophilus and 10(9) Bifidobacterium infantis, one capsule tid for 4 days and control group (n = 50) received parenteral rehydration only without any medication. Only 20 stool cultures in study group had positive culture results for Lactobacillus or Bifidobacterium. All children were evaluated for the degree of dehydration before rehydration. The clinical course of diarrhea was followed during the treatment period. Features on admission were similar between the study group and control group in age, duration of diarrhea at home, serum sodium & potassium and dehydration degree. The duration of diarrhea was defined as the time until the last appearance of watery stool. There was no difference between the study group and control group in the frequency of diarrhea stools on the day before admission (p > 0.05). However, the frequency of diarrhea for study group improved on the first and second day of hospitalization with statistical difference (p < 0.01). The duration of diarrhea during hospitalization in study group also decreased (3.1 vs. 3.6 days, p < 0.01). Oral bacterial therapy is an effective adjuvant therapy in rotavirus positive and negative children with diarrhea and can safely be administered during an episode of acute diarrhea. Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation.
                We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed.
                The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02).
                For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection. Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections.
                In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital.
                Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group.
                Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants. Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.
                We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies.
                The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens.
                High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis. In a multicenter, randomized, placebo-controlled clinical trial of pertussis immune globulin, intravenous (P-IGIV), 25 infants hospitalized with pertussis were enrolled in 24 months (15% of the target sample size) before the study was prematurely terminated because of expiration of the P-IGIV lots and unavailability of additional study product. Although well tolerated, there was no difference in the number or rate of improvement of symptoms (paroxysmal cough, whoop, apnea, bradycardia, oxygen desaturations) in P-IGIV recipients compared with placebo. To evaluate the effectiveness of live Lactobacillus acidophilus plus Bifidobacterium infantis in the treatment of acute watery diarrhea.
                Open, randomized control trial.
                King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
                Seventy-one infants (aged 1-24 months) with acute watery diarrhea that presented at Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok were enrolled after parental signed informed consent. They were randomized into 2 groups. The Study group (n = 35) received live Lactobacillus plus Bifidobacterium (3 x 10(9) CFU) bid and ORS and the Control group (n = 36) received ORS only. All infants received lactose free milk. Case record forms were completed daily for 5 days by the parents.
                All 71 infants completed the present study. There was no difference of the patients'characteristics and baseline clinical symptoms between the study group and the control group. Live Lactobacillus plus Bifidobacterium shortened the diarrhea duration (1.6 +/- 0.7 days vs 2.9 +/- 1.7 days, p < 0.01) compared to controls. However the stool frequency and duration of hospitalization were not significantly different (p > 0.05, study group vs control group).
                Live Lactobacillus acidophilus plus Bifidobacterium infantis may be an effective treatment for acute watery diarrhea in infants. The 2-day course treatment can significantly shorten the duration of diarrhea. This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone.
                Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures.
                Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent).
                There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry.
There is good evidence supporting the use of human-derived botulinum immune globulin in infant intestinal botulism. A single randomized controlled trial demonstrated significant decreases in the duration of hospitalization, mechanical ventilation and tube or parenteral feeding among treated patients. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.