A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children

Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children.     

Seven days vs. 10 days ceftriaxone therapy in bacterial meningitis

Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days. However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization. The aim of this study was to compare the outcome of 7 days vs. 10 days' ceftriaxone therapy in children with ABM. Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled. Ceftriaxone was given for 7 days to all. Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day. At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system. Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone. If a score was less than 10, the antibiotic was stopped. Complications were appropriately evaluated and managed. All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done. After excluding four patients, there were 35 children in group I and 34 in group II. The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters. Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent). Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1). Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05). Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05). It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge. Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.     

Prospective study of computed tomography in acute bacterial meningitis

We performed serial CT scans at the time of admission and discharge, and again after 6 to 18 months, in children older than 2 months of age with bacterial meningitis. During the 2-year study period, 60 patients with bacterial meningitis were admitted to British Columbia's Children's Hospital. Forty-one were included in the study, two of whom died soon after admission. The infecting organism was Haemophilus influenzae in 29, Neisseria meningitidis in six, and Streptococcus pneumoniae in six. Abnormalities on the first two CT scans included subdural effusion in eight patients, focal infarction in five, and pus in the basal cisterns in one. All patients with focal infarction or cisternal pus had hemiparesis. Marked cerebral edema was seen in the two patients who died. Transient mild dilation of the subarachnoid space was a common finding; the size of the ventricles or subarachnoid space was increased on the second scan in 29 of 36 patients, and decreased to normal on the third scan in 30 of 33 patients. Clinical management was not influenced by the CT findings, which failed to reveal any clinically significant abnormalities that were not suspected on neurologic examination.     

Benefit of glucocorticosteroid in the routine therapy of bacterial meningitis in children.

Based on the most recent randomised-controlled studies, meta-analysis, and observational studies, the use of corticosteroids is recommended in most cases of acquired community purulent meningitis in children from industrialised countries, in order to reduce the incidence of severe deafness and likely of other neurological morbidities.     

Claims of equivalence in randomized controlled trials of the treatment of bacterial meningitis in children

OBJECTIVE: To evaluate claims of therapeutic equivalence in studies of the treatment of bacterial meningitis in children. METHODS: We performed a systematic review of randomized controlled trials of antimicrobial therapy for bacterial meningitis in children indexed in MEDLINE and published after 1980 and that claimed equivalency. The sample size of each trial was compared with the minimum sample size needed to rigorously claim equivalence. The primary endpoint was case fatality. RESULTS: Twenty-five studies were identified that met the inclusion criteria. Two of these were specifically designed to test equivalence, and the remaining based claims of equivalence on failed tests of superiority. The majority of these trials (24 of 25) that claimed equivalence had sufficient sample size to exclude a 20% difference in mortality between the tested therapies. Only 3 of the 25 trials could exclude a 10% difference in mortality. CONCLUSION: Few of the trials in this study had sufficient sample size to claim equivalence within 10% of the expected mortality. Proving equivalency is challenging because large sample sizes are often needed to ensure adequate statistical power to rule out clinically important differences between the standard of care and new therapies.     

Double-blind, randomized clinical trial for safety and efficacy of norfloxacin for shigellosis in children

In a randomized, double-blind clinical trial, the efficacy and safety of norfloxacin were compared with nalidixic acid in the treatment of shigellosis in children. Out of 59 cases, Shigella spp. were isolated from 8 cases in the nalidixic acid group and 14 cases in the norfloxacin group. The norfloxacin group had significantly less duration of diarrhoea and presence of blood in stool as compared to the nalidixic acid group. No joint problem was encountered in this study at up to 4 months follow-up. Norfloxacin is safe and effective and showed no cartilage toxicity on short-term follow-up.     

Fc gamma receptor allotypes in children with bacterial meningitis. A preliminary study

IgG2 antibody is the essential subclass to protect against encapsulated bacteria Fc gamma RIIa is the only Fc gamma receptor that interacts with human IgG2. The two genetically determined allotypes of human Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131 alleles have functionally different reactivities with IgG2 in vitro, and H/H-131 cells have markedly higher binding affinity for human IgG2. Homozygous Fc gamma RIIIb-NA1/NA1 PMNLs show higher phagocytic capacity than Fc gamma RIIIb-NA2/NA2 PMNLs. To evaluate in vivo significance of Fc gamma RIIa and Fc gamma RIIIb allotypes, we analyzed Fc gamma R allotypes in children with bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Fc gamma RII and Fc gamma RIIIb polymorphisms were determined by using quantitative flow cytometry. Fc gamma RIIa were studied in 23 children with bacterial meningitis and 50 healthy Turkish controls, and Fc gamma IIIb in 18 and 43 such individuals, respectively. The distribution of Fc gamma RIIa in the healthy Turkish control group was found to be significantly different from that in the Chinese and Japanese population (p < 0.05), but similar to that of the white population in the USA and the Netherlands. No case (0%) had the Fc gamma RII-H/H-131 Fc gamma RIIIb-NA1/NA1 the corresponding figure in the controls was 4 (9.3%). Homozygous Fc gamma RIIa-H/H-131 phenotype was underrepresented with borderline significance (p: 0.057) in patients below two years of age in comparison with the healthy subjects and with patients with meningitis over two years of age (p: 0.059). Although the study needs to be conducted in a large series of patients in order to draw a firm conclusion, Fc gamma RIIa polymorphism may be a contributing factor to the increased susceptibility to meningitis with encapsulated bacteria in children below two years of age.     

Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group

OBJECTIVES: To determine the efficacy, safety, and tolerability of omeprazole in children and to determine the doses required to heal chronic, severe esophagitis. STUDY DESIGN: Open multicenter study in children aged 1 to 16 years with erosive reflux esophagitis. The healing dose of omeprazole used was that with which the duration of acid reflux was <6% of a 24-hour intraesophageal pH study. Follow-up endoscopy was performed after 3 months of treatment with the healing dose. RESULTS: At entry, two thirds of 57 patients who completed the study had esophagitis grade 3 or 4 (scale 0-4); some 50% had neurologic impairment or repaired esophageal atresia. Of the 57 patients, 54 healed; 3 did not heal and left the study, and 3 healed with a second course. Doses required for healing were 0.7 to 3.5 mg/kg/d: 0.7 mg/kg/d in 44% of patients and 1.4 mg/kg/d in another 28%. Healing dose correlated with grade of esophagitis but not with age or underlying disease. Reflux symptoms improved dramatically in almost all of the 57 patients, including the unhealed patients. CONCLUSIONS: Omeprazole is well tolerated, highly effective, and safe for treatment of erosive esophagitis and symptoms of gastroesophageal reflux in children, including children in whom antireflux surgery or other medical therapy has failed. On a per-kilogram basis, the doses of omeprazole required to heal erosive esophagitis are much greater than those required for adults.     

The outcome of bacterial meningitis in children is related to the initial antimicrobial therapy

Even when highly effective antibiotic therapy is provided to patients, death and long-term disabilities are common outcomes of acute bacterial meningitis (BM) in developing countries. The aim of this study was to analyze how the outcome of disease was related to the initial antimicrobial therapy used to treat the patients. We analyzed 277 children younger than 16 years of age who were treated for BM in the Hospital of Infectious Diseases in Prishtina, Kosova, over a six-year period. Of the 277 children treated for BM, 36.1% of cases were given initial antimicrobial therapy with one antibiotic, 63.2% of cases received two antibiotics and 0.7% of the cases received three antibiotics. Of the 60 patients who had neurologic complications (NC), 50 (28.6%) were treated with two antibiotics, 9 (9%) received one antibiotic and 1 patient was treated with three antibiotics. The antibiotics used most often as monotherapy were penicillin G (63 cases) and ceftriaxone (33 cases). The incidence of NC was higher in children treated with ceftriaxone (NC=22%, mortality [M]=3%) compared with patients treated with penicillin G (NC=3%, M=0). The most commonly used combination of antibiotics was ceftriaxone with chloramphenicol (82 cases) followed by penicillin G with chloramphenicol (63 cases). The incidences of NC and M were higher in children treated with ceftriaxone and chloramphenicol (NC=43%, M=8%) compared to children treated with penicillin G and chloramphenicol (NC=13%, M=3%). The initial treatment of BM with penicillin G did not result in death and was associated with a lower incidence of NC compared with the use of ceftriaxone. The combination of penicillin G and chloramphenicol resulted in a lower incidence of NC and M compared with the combination of ceftriaxone and chloramphenicol.     

Prospective follow-up and pulmonary functions from a placebo-controlled randomized trial of ribavirin therapy in respiratory syncytial virus bronchiolitis. Ribavirin Study Group.

OBJECTIVE: To determine any long-term differences in adverse effects and pulmonary function between infants with respiratory syncytial virus and lower respiratory tract infection who were treated with ribavirin and a control group. STUDY DESIGN: Long-term follow-up included enumeration of episodes of respiratory illness, wheezing, and pneumonia and, ultimately, administration of pulmonary function tests (PFTs). Pulse oximetry was done at each visit. During the first 3 years we conducted follow-up in the fall and spring. In years 4 and 5 we conducted 1 visit per year. During years 5 through 7 we conducted PFTs, and starting with year 7 a methacholine chloride challenge was done if forced expiratory volume in 1 second (FEV1) was greater than 70% of predicted value. RESULTS: We prospectively enrolled (December 1983 to February 1985) in a randomized trial of ribavirin vs placebo children who were previously healthy, were premature, or had chronic pulmonary disease. One pulmonologist (R.F.; blinded) scored and interpreted the results of the PFTs. We studied 42 patients aged 1 to 33 months; 2 patients died (1 receiving ribavirin and 1 receiving placebo) and 5 patients receiving placebo were lost to follow-up; 35 patients (24 taking ribavirin and 11 taking placebo) attended 212 visits. Four patients were premature (3 in the ribavirin and 1 in the placebo group), and 3 of these had bronchopulmonary dysplasia (2 in the ribavirin and 1 in the placebo group). From years 1 to 3, there was more reactive airway disease, wheezing, and pneumonia in the placebo than in the ribavirin group (mean score, 22.3 for 12 placebo-treated patients vs. 15.8 for 23 ribavirin-treated patients; P = .07 by Kruskal-Wallis test); for all years, it was 22.0 for 11 placebo-treated patients vs. 16.0 for 22 ribavirin-treated patients (P = .10). After informed consent was given, 19 patients completed PFTs (13 receiving ribavirin and 6 receiving placebo); 7 of 13 ribavirin-treated patients (53%) had normal or mild PFT results vs. 0 of 6 placebo-treated patients (P = .04 by Fisher exact test). On methacholine challenge (7 ribavirin-treated patients and 5 placebo-treated patients), there was more reactivity in the placebo vs. the ribavirin group (exact P = .07). Scoring done by weighting for severity for 19 patients (13 ribavirin-treated patients and 6 placebo-treated patients) (even after correcting for asthma) showed a significant difference in favor of previously ribavirin-treated patients (exact P = .02). CONCLUSIONS: No outward effects were identified from ribavirin exposure. We observed no increase in reactive airway disease, wheezing, and pneumonia in the ribavirin compared with the placebo group. Weighted severity scores suggest long-term beneficial effect of ribavirin therapy; however, larger numbers should be evaluated.     

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??ObjectiveTo assess the efficacy of pharmacological prophylactic treatments for migraine in children,and to study an appropriate and safe therapy benefitial to pediatric migrainuer.MethodsPedsQl 4.0 and headache index were used to assess the effect of Sibelium (Flunarizine) and valproate (VPA) after provided to the children with migraine.The two groups of 200 moderate migrainuers were compared in a prospective,randomized,controlled and open-label trial.ResultsWith the aspect of comparision between sibelium and VPA,both showed effects on increasing the quality of life of children with migraine.Total score of with Sibelium increased from 68.27??11.06 to 82.07??5.36,while the group with VPA increased from (71.82??9.03) to (82.74??5.36).Each group P<0.05,within group P>0.05.The two pharmacological ways were also effective to decrease the index of headache.The group with Sibelium decrease from (10.45??7.25) to (2.20??2.75); the group with VPA decreased from (9.81??7.58) to (2.03??2.50)??Each group P<0.05,within group P>0.05.Comparing the two groups,there were no significance about quality of life and headache index.ConclusionChildren with migraine benefit from appropriate prophylactic therapy.Sibelium and VPA could also be used for children with migraine.     

Prospective study of 59 cases of viral meningitis in children. Clinical and virologic diagnosis. Epidemiology and physiopathology

In a prospective 2 year study of 59 cases of childhood meningitis, mumps was the most common etiological virus (39%), followed by enterovirus (27%). The analysis of the cases suggested that a diagnosis of the infectious agent may be arrived at using clinical data such as the degree of nuchal rigidity, the age of the patients, and the presence of associated parotiditis or macular rash. Pleiocytosis in the CSF was higher and included a larger percentage of lymphocytes during mumps meningitis than during enterovirus meningitis. Mumps or enterovirus were isolated in the CSF of 23% (mumps) and 27% (enterovirus) of the patients. Alpha interferon which was acid labile was detected in the CSF of 89% and 63% respectively of patients with mumps and enterovirus meningitis.