Isoniazid dose adjustment in a pediatric population.

This retrospective analysis was designed to evaluate the inactivation index (I3) method used to adjust the isoniazid dose during long-term administration in a pediatric population. Before starting on antituberculosis therapy, sixty-one children received one 10 mg.kg-1 isoniazid test-dose (D). The isoniazid and acetyl isoniazid concentrations were measured by high-performance liquid chromatography on a plasma sample collected 3 hours (C3h) after administration. The patients were separated into slow and fast acetylator groups according to the metabolic ratio. The dose adjustment method using the I3 is based on the assumption that there is a linear correlation between C3h and D [C3h = (I3 x D) - 0.6] in which the slope is I3 and the Y intercept is equal to -0.6 mg.l-1. I3 was determined from a single plasma concentration determination and used to calculate the dose recommended to obtain a desired C3h equal to 1.5 micrograms.ml-1: recommended dose (mg.kg-1) = (1.5 + 0.6)/I3.I3 was significantly higher in the slow acetylator group (0.55 +/- 0.16) than in the fast one (0.26 +/- 0.13), which leads us to recommend a significantly lower dose in the slow acetylator group (4.2 +/- 1.5 mg.kg-1) than in the fast one (10.3 +/- 4.6 mg.kg-1). The data obtained in a subgroup of 21 patients who had at least three consecutive determinations of C3h after different dosages allowed us to verify that there was a linear correlation between C3h and the dose. The mean slope of the correlation lines in that subgroup was 0.61 +/- 0.25 and the 95% confidence interval of the estimated Y-intercept include the theoretical value of -0.60, which shows that our data are consistent with those previously reported in adults. The percentage of patients with a C3h plasma concentration within the expected range (1.5 +/- 0.5 micrograms.ml-1) was significantly higher (69%) in those whose dose was derived from the calculation than in the others (25%). Within each acetylator group, the range of the recommended dose varied widely, and these results emphasize the usefulness of individual dose adjustment based on the inactivation index method.

Metoclopramide plasma concentration in neonates.

During the course of a multiple-dose metoclopramide (M) oral treatment, M plasma concentrations were measured just before (Cmin) and 1 hour after the administration (C1h) at steady-state in 5 (3 premature and 2 term) neonates. Mean Cmin was equal to 91.6 +/- 45.5 ng/ml and higher than C1h (87.4 +/- 43.2 ng/ml), but not significantly. A significant negative correlation was found between Cmin plasma concentration and gestational age as well as with postconceptional age, suggesting that the lower the gestational and postconceptional age, the lower the metoclopramide dosage should be.

Isoniazid acetylation metabolic ratio during maturation in children.

Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N-acetyltransferase activity and to determine the acetylation phenotype. MR had a bimodal distribution with an antimode between 0.48 and 0.77. MR and the percentage of fast acetylators increased significantly with age. The cumulative frequency of fast acetylators increased with age, with a plateau reached around 4 years. MR value was checked during treatment in 44 children. All children but one who initially appeared as fast acetylators remained in this group after repeated testing. Among the 30 slow acetylators, 12 became fast acetylators, and 10 showed a variable phenotyping at different ages. A bimodal distribution of the isoniazid acetylation MR was shown in children, with an antimode close to that described in the literature and a maturation of isoniazid acetylation during the first 4 years.

Staphylococcal scalded skin syndrome in a neonate.

A case of staphylococcal scalded skin syndrome in a neonate caused by mother-to-child transmission through breast-feeding is reported. Staphylococcus aureus isolates from mother and child were identified using random-amplified polymorphic DNA analysis, which is a simple and rapid method for comparing strains. This study confirms the need to avoid breast-feeding in cases of breast abscess.

[Pneumococcal meningitis resistant to penicillin and nosocomial transmission in pediatric hospitals confirmed by genomic analysis]. / Méningite à la pneumocoque résistant à la pénicilline et transmission nosocomiale en milieu hospitalier pédiatrique confirmée par analyse génomique.

BACKGROUND: Careful epidemiological studies and sophisticated diagnostic procedures are necessary to prove that bacterial infection is nosocomial in origin. DNA finger printing method can be useful with this aim in view. CASE REPORTS: A 11 month-old girl suffered from a febrile pneumonia. She developed acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae, serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She died 24 hours later. Five days after this death, a 5 month-old infant hospitalized in the next bed developed an acute pulmonary infection due to the same strain with the same bacterial characteristics; this patient was cured with cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA analysis showed an identical profile of both strains. CONCLUSION: This is the first case of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRSP) associated with nosocomial spread between two children in adjacent beds. This case suggests that it is necessary to isolate patients with PRSP infection during hospitalization.

Procalcitonin as a marker for the early diagnosis of neonatal infection.

Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.

Small-bowel bacterial overgrowth in children with chronic diarrhea, abdominal pain, or both.

OBJECTIVE: To evaluate the frequency of small-bowel bacterial overgrowth (SBBO) as a cause of chronic digestive symptoms in a large cohort of children, using the glucose breath hydrogen test (BHT). DESIGN: Patients were 53 children (aged 2 months to 12 years) with chronic diarrhea, abdominal pain, or both. Diagnosis of SBBO was defined with a BHT by a change in H2 concentration of 10 ppm H2 or more in expired air after an oral glucose load. Patients with a positive BHT result were included in group 1 and treated with a combination of colistin and metronidazole for 10 days; a second BHT was performed 1 month later. Group 2 comprised patients with a negative BHT result. Group 3 (n = 15) was a control group of healthy subjects, and group 4 (n = 6) a comparison group of subjects with bacteriologically documented SBBO. RESULTS: Eighteen patients (34%) had a positive BHT result and 35 a negative result. The BHT results were comparable in groups 1 and 4 and in groups 2 and 3, respectively. Fasting H2 levels were higher in group 1 than in groups 2 (p < 0.001) and 3 (p < 0.01). In group 1, children were younger than in group 2 (1 +/- 1 year vs 3.9 +/- 3 years; p < 0.001) and diarrhea was frequent (83%), but 17% of patients had abdominal pain alone. Fetid stools (p < 0.01), mucus in stools (p < 0.01), and flatulence (p < 0.05) were more frequent in group 1 than in group 2. Antibiotic treatment of children in group 1 led to a rapid disappearance of symptoms and normalization of BHT results. CONCLUSION: SBBO appears to be a frequent cause of chronic digestive symptoms in children, especially before the age of 2 years. The BHT provides a simple and noninvasive method of detecting it. The recognition of SBBO in children leads to effective treatment.

Non invasive in vivo study of the maturation of CYP IIIA in neonates and infants.

OBJECTIVE: Cytochrome P450 III (CYP III) has previously been demonstrated in vitro in fetal liver. METHODS: A study was performed in 7 premature, 13 term neonates and 30 infants to assess whether or not maturation had any influence on CYP IIIA activity in children from birth to 1 year of age. A simple non invasive procedure was used (6 beta OHF/FF concentration ratio in a morning spot urine sample). RESULTS: The 6 beta OHF/FF ratio was 7.2, 7.9 and 5.0 in premature and term neonates and infants, respectively. CYP IIIA activity is present at birth, with a 6 beta OHF/FF ratio comparable to adults. Its activity seemed lower in infants. This might be due to the decrease in CYP IIIA7 activity during maturation after birth, which might be more rapid than the increase in CYP IIIA3/4 activity.

[Eradication of asymptomatic carrier state of non-typhoid Salmonella with two doses of pefloxacin]. / Eradication du portage asymptomatique des salmonelles non typhoïdiques par deux doses péfloxacine.

BACKGROUND: The carrier state of Salmonella may represent a source of contamination for other people. Its treatment is unsatisfactory so that a carrier may shed organisms for numerous months. POPULATION AND METHODS: From 1990 to 1993, 17 children aged 1.5 months to 8 years were seen because they were asymptomatic carriers of non-typhoid Salmonella, confirmed by three successive stool cultures. All had presented earlier acute severe infection having required treatment with amoxicillin (13 cases) and ceftriaxone or cefotaxime (four cases). They were given one dose of pefloxacin, 12 mg/kg, 4 to 8 weeks after the initial episode. This unique dose was administered again 4 days later. Stool cultures were performed before the first administration and 10, 30, 45 and 60 days after, with a last control 3 to 4 months later. RESULTS: Eradication of the Salmonella was obtained by the 10th day in 13 patients and within the 3 following weeks in 2 others. Those children who excreted a few number of organisms were early eradicated while the 2 patients who did not respond to pefloxacin shed larger number of bacteria. There was no side-effects of treatment. CONCLUSION: A short treatment with pefloxacin appears to be effective and safe in eradicating the carrier state when stool excretion of Salmonella is moderate.

[Failure of the treatment with antibiotics in severe Salmonella infections in children and use of quinolones]. / Echecs du traitement antibiotique des salmonelloses sévères de l'enfant et utilisation des quinolones.

BACKGROUND: Quinolone antibiotics are effective in the treatment of Salmonella infections in adults. Their use in children is limited by their side-effects. POPULATION AND METHODS: Forty-two patients (21 girls and 21 boys), aged 1 month to 12 years (mean 3.3 yrs) were admitted from September 1991 to June 1993 for severe Salmonella infections. Criteria of severity were persistent diarrhea and fever for more than 3 days. Thirty-one of these patients were less than 5 years of age. Blood culture was positive in 7 out of 35 patients: culture of the stools was positive in all patients. Five of the 42 patients had presented an acute episode of Salmonella infection a few weeks earlier and had remained asymptomatic carriers until the new acute and severe episode of diarrhea. All patients were given usual antibiotics, mainly ampicillin, amoxicillin, trimethoprime-sulfamethoxazole. Twenty-five of these patients were then given pefloxacin, 12 mg/kg/day, since the 5th day, for 7 days, because persistence of diarrhea and fever. RESULTS: Diarrhea and fever disappeared within less than 2 days in the group of patients given pefloxacin, even though in 6 patients the infecting Salmonella was in vitro resistant to beta-lactamins. Twenty % of patients remained asymptomatic carriers of Salmonella in the group treated by pefloxacin vs 47% in the group without it. There was no difference in species of Salmonella between both groups. None of the patients treated by pefloxacin developed side-effects during the six months following its administration. CONCLUSIONS: Short treatment by pefloxacin may be an alternative choice for treating severe Salmonella infections in children.

Allergy to nondairy proteins in mother's milk as assessed by intestinal permeability tests.

The intestinal permeability test is a noninvasive method which, when done during a food provocation procedure, can detect the deleterious effect of food on the intestinal mucosa in allergic children. We report on a 1-month-old breast-fed boy with a history of regurgitation, diarrhea, difficult feeding, and malaise suggesting food allergy. Intestinal permeability tests were done with the mother's milk and showed breast-milk-induced alterations of intestinal permeability. No improvement occurred in the child's clinical symptoms or in the results of the intestinal permeability test when the mother withdrew dairy products from her diet. Disappearance of the child's symptoms and normalization of intestinal permeability during provocation with the milk were obtained after elimination of egg and pork from the mother's diet. This observation suggests that dietary proteins different from cow's milk antigens may be transferred to breast milk and induce adverse reactions in hypersensitive infants.

[Abdominal pain in children caused by lactose intolerance. Prospective use of the hydrogen breath test]. / Douleurs abdominales de l'enfant par intolérance au lactose. Utilisation prospective du test respiratoire à l'hydrogène.

OBJECTIVES: We performed the breath hydrogen test in children consulting for abdominal pain in order to determine the minimal quantity of lactose required to prove malabsorption with least patient incomfort and to evaluate the effect of an adapted diet in children with a positive test. METHODS: The breath hydrogen test after lactose intake was performed in 109 children (51 boys, 58 girls, mean age 8.2 + 3.2 years, range 3 to 15) seen for unexplained abdominal pain. All these children had complained of abdominal pain daily for at least 6 months and no other cause could be identified. Children with acute or chronic diarrhoea or constipation were excluded. Nineteen children had been transferred from the surgery unit and 6 had been followed by the psychiatry unit. All these children drank milk regularly. RESULTS: The diagnosis of lactose intolerance was established in 83 children (76.1%) on the basis of a hydrogen peak in the breath after lactose ingestion. One-fourth of the children were of French origin and the others had at least one grandparent who was of Mediterranean or African origin. A lactose-free diet was proposed and led to the disappearance of abdominal pain in 24% and a clear improvement in 32%. CONCLUSION: The breath hydrogen test is a simple non-invasive test which allows a selection of children who could benefit from a lactose-free diet although it cannot be used to predict the effect of diet.

Distinct features of upper gastrointestinal endoscopy in the newborn.

Between January 1987 and December 1990, 293 upper GI endoscopic procedures were performed in 219 neonates < 1 month of age. No lesion was found in 57 cases (26%; group 1), whereas esophagitis was present in 158 cases, alone in 45 cases (20.6%; group 2) and associated with gastritis in 113 cases (51.8%; group 3). The association of esophagitis with gastritis seems to be a specific feature of neonates and not older children. The presence of gastritis with esophagitis suggests that a primary peptic mechanism is unlikely to explain all endoscopic findings, although the presence of such a mechanism secondary to esophagitis could contribute to the esophageal lesions. Acute fetal distress was more frequent in group 3 than in the other groups. Symptoms associated with endoscopic lesions in groups 2 and 3 were, respectively, malaise (38 and 42%), hematemesis (4 and 35%), frequent regurgitation (45 and 26%), and difficult feeding and/or failure to thrive (26 and 24%). In Group 3, minor symptoms often led to the diagnosis of severe mucosal lesions, and antireflux therapy elicited prompt relief of clinical symptoms. The causes of neonatal esophagogastritis remain unknown. Wide use of endoscopy in the presence of discrete clinical abnormalities is likely to considerably improve the clinical condition of some children in their first days of life.

Eradication of convalescent-phase Salmonella carriage in children with two oral doses of pefloxacin.

Fifteen children (age range 1.5 months to 7.2 years), who were excluded from schools or nurseries due to asymptomatic convalescent-phase non-typhoidal Salmonella carriage, received two oral doses of pefloxacin (12 mg/kg on days 1 and 4) and were examined on days 10, 30, 45 and 60. Definitive eradication was observed in 13 patients, all of whom had initial low Salmonella counts in stools and were culture-negative by day 10. In the two patients who failed to respond, the same treatment was effective when repeated 4 and 6 months later respectively. No side-effects were observed. In six other children, considered as controls, eradication by day 10 was observed in only one case after administration of amoxicillin for eight days. Two oral doses of pefloxacin could be a useful and safe means for eliminating Salmonella carriage in young children.