Dosing of Enteric-Coated Mycophenolate Sodium Under Routine Conditions: An Observational, Multicenter Study in Kidney Transplantation.

BACKGROUND Dosing of enteric-coated mycophenolate sodium (EC-MPS) should be adjusted to reflect concomitant immunosuppression, but it is largely undocumented whether such modifications are carried out during routine clinical practice. MATERIAL AND METHODS MyLIFE was an observational study of adult kidney-only or kidney-pancreas transplant patients starting -EC-MPS at 33 French transplant centers. Data were collected at first EC-MPS dose and 6 months later. The primary objective was to describe initial EC-MPS dosing according to concomitant immunosuppression. RESULTS There were 461 patients analyzed (174 started EC-MPS by month 1 post-transplant ['de novo'] and 287 started EC-MPS >1 month post-transplant ['maintenance']), receiving cyclosporine (CsA) (n=76), tacrolimus (n=363), or a mammalian target of rapamycin (mTOR) inhibitor (n=22). Mean (SD) starting dose was 1130 (511) mg/day, 1006 (441) mg/day, and 769 (300) mg/day in the CsA, tacrolimus, and mTOR inhibitor groups, respectively (p=0.003). In the de novo subpopulation, the starting dose was 1440 mg/day in 66.7% (14/21) of CsA-treated patients and 71.9% (110/153) of tacrolimus-treated patients, with an intensified dose of 2160 mg/day in 28.6% (6/21) and 8.5% (13/153), respectively. There was a non-significant trend to a higher rate of biopsy-proven acute rejection in patients receiving CsA versus tacrolimus or an mTOR inhibitor (p=0.082). Adverse events with a suspected relation to EC-MPS occurred in 21.0%, 23.1%, and 9.1% of the CsA, tacrolimus, and mTOR inhibitor subpopulations, respectively. CONCLUSIONS EC-MPS is usually initiated at the dose recommended for de novo CsA-treated kidney transplant patients, then titrated downwards as required. An early intensified regimen is not used frequently. The EC-MPS dose is modified in <20% of de novo patients to account for concomitant tacrolimus therapy instead of CsA administration.

Inverse correlation between varicella severity and level of anti-Varicella Zoster Virus maternal antibodies in infants below one year of age.

Varicella, a widespread disease of childhood, is usually benign but may in some instances lead to complications and eventually death. The aim of this study was to assess whether varicella severity in infants below one year of age was associated with the level of anti-varicella zoster virus (VZV) maternal antibodies. Two different data sets were used. Data on varicella-associated complications were collected through a national surveillance network involving 175 hospital-based pediatric wards. Data on levels of maternal acquired antibodies according to infants' age were extracted from a cohort of 345 full term infants enrolled in a prospective multicenter study in seven pediatric wards and/or pediatric emergency units. Among infants hospitalized for varicella complications, the overall prevalence of complications increased regularly from 10.4% in infants below 1 month of age to over 72.4% at 5 months of age. Conversely, the mean antibody titre decreased from 536 mIU/mL in the [0-1 [month group to below the 150 mIU/mL threshold at 3-4 months [Pearson coefficient = -0.956 (p < 0.001)]. Based on large numbers of infants, our results show for the first time, a strong inverse correlation between the levels of circulating anti-VZV maternal antibodies in full term infants and occurrence of varicella complications below one year of age. Infant protection could be optimized by increasing herd immunity, reducing the susceptibility of women in childbearing age and lowering the age of routine vaccination to 9 months. Additional vaccination for unprotected persons in close contact with infants below 12 months of age could be promoted.

PneumococcaL meningitis in french children before and after the introduction of pneumococcal conjugate vaccine.

In France, despite a high rate of pneumococcal conjugate vaccine coverage, the number of cases of pneumococcal meningitis in children did not decline significantly between 2001­2002 (n = 264) and 2007­2008 (n = 244). A decline was observed among children < 2 years old (185 [70.1%] to 134 [54.9%] cases; P = 0.0004), but was counterbalanced by an increase among children ≥ 2 years old (79 [29.9%] to 110 [45.1%] cases). Mean age increased significantly, from 2.3 (median 0.8) to 3.8 (median 1.5) years. After pneumococcal conjugate vaccine 7 implementation, a wide diversity of serotypes implicated in pneumococcalmeningitis was observed; serotypes 19A and 7F were the most frequent.

Hospitalization of newborns and young infants for chickenpox in France.

Chickenpox is often considered more severe during the first year of life, but its course is usually mild during the first 3 months of life, presumably owing to the persistence of maternal antibodies. Hospitalization and intravenous acyclovir therapy are generally restricted to severe cases but also systematically recommended in newborns in France, irrespective of the clinical severity of the infection. This recommendation was launched in 1998 when Varicella zoster virus (VZV)-specific immunoglobulins were not available in the country and has remained unchanged since. The aim of this prospective observational study was to describe complications of varicella infection in a population of 745 children hospitalized for varicella before 1 year of age, with a specific focus on newborns. Complications occurred in 65% of cases. They were very rare before the age of 1 month (10%) but their incidence then increased progressively with age and probably the disappearance of maternal antibodies: 42% (1-2 months), 66% (3-5 months), 70% (6-8 months), and 79% (9-12 months). Conclusion Chickenpox is usually mild in newborns because most of them are protected by VZV maternal antibodies. Unless the absence of maternal VZV immunity is demonstrated, newborns with mild chickenpox should not require antiviral therapy.

Association of meningococcal phenotypes and genotypes with clinical characteristics and mortality of meningitis in children.

BACKGROUND: Neisseria meningitidis meningitis represents approximately one-half of the meningococcal cases in French children. To explore the contribution of bacterial typing in improving the management of cases, we aimed to describe clinical characteristics and mortality of meningococcal meningitis in children reported to the multicenter survey system, GPIP/ACTIV, in association with phenotypes/genotypes of bacterial isolates. METHODS: From 2001 to 2005, 259 pediatric wards and 168 microbiology laboratories enrolled all children with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. RESULTS: A total of 962 cases of Neisseria meningitidis meningitis among a total of 2131 bacterial meningitis (45%) were recorded (mean age, 4.5 +/- 4.7 years). Serogroup distribution of the isolates was 62.3%, 33.7%, 2.9%, 0.6%, and 0.6% for serogroups B, C, W135, A and Y, respectively. The major clonal complexes were ST-41/44 (32.2%), ST-11 (21.9%), ST-32 (20.8%), ST-8 (8.2%), and ST-269 (4.9%). Despite global heterogeneity of the isolates, 2 phenotypes/genotypes were of interest. Isolates of the phenotype/genotype B:14:P1.7,16/ST-32 (56% clustered in the region of Haute Normandie) were observed in older children (8.6 years) and were associated with a higher case fatality rate (12%) than were other phenotypes of serogroup B. The phenotype/genotype C:2a:P1.5/ST-11 was found in 26.3% of serogroup C cases and was possibly associated with a higher mortality among serogroup C (9.9% for C and 5.9% for B, P = 0.04). CONCLUSIONS: This large survey provides data that could be important for implementation of future vaccines. Typing of meningococcal isolates could contribute to an understanding of prognosis in meningococcal meningitis.

Study of the acceptability of antibiotic syrups, suspensions, and oral solutions prescribed to pediatric outpatients.

This observational study was designed to evaluate the acceptability of oral antibiotics (including generics) commonly prescribed to children by community practitioners in France. Between February and July 2006, the parents of 953 children enrolled by 46 pediatricians completed a questionnaire, including a taste assessment based on representations of five facial expressions. The proportions of "satisfactory" taste judgments showed a significant difference between amoxicillin-clavulanate reference product and its generics (77.9% vs. 65%, p = 0.01). The amoxicillin-clavulanate generics were more likely than the reference product to be spat out at least once (28.7% vs. 19%, p = 0.05). The full treatment course was taken by 91.7% and 82.3% of children prescribed the amoxicillin-clavulanate reference product and its generics, respectively (p = 0.02). The proportions of "satisfactory" taste judgments showed no significant difference between amoxicillin reference product and generics (64.3% vs. 72.5%, p = 0.3). The amoxicillin generics were not different from the reference product to be spat out at least once (8.6% vs. 14.3%, p = 0.2). The full treatment course was taken by 90.7% and 94.6% of children prescribed the amoxicillin reference product and its generics, respectively (p = 0.3). This study suggests the role of the active substance in the taste, and calls for the evaluation of palatability of future drugs (generics and references) before granting of the marketing authorization, particularly for active substances of poor taste; this palatability plays a significant role in the compliance of the treatment, notably in children. Poor compliance increases the risk of therapeutic failures and the emergence of resistance.

Evaluation of a model for efficient screening of tuberculosis contact subjects.

RATIONALE: Contact tracing is an important component of tuberculosis (TB) control programs. Standardization of contact investigation protocols can make them more efficient. OBJECTIVES: To develop a model to select contact subjects for screening. METHODS: We prospectively collected standardized data on 325 TB index cases and their 2,009 contacts. Factors that independently influenced the risk of TB infection were included in the model, which was then validated in a second prospective cohort of 88 cases of TB and their 618 contacts. MEASUREMENTS AND MAIN RESULTS: A total of eight independent risk factors were identified (odds ratio; 95% confidence interval): age, with three subgroups: 6-14 years (3.6; 1.6-8.0); 15-29 years (3.7; 1.8-7.7); > or =30 years (4.1; 2.0-8.5); cavitation on the index case's chest radiograph (1.6; 1.1-2.2); an index case sputum smear with 100 or more acid-fast bacilli per field (1.8; 1.2-2.8); household contact at night (2.1; 1.3-3.2); first-degree family relationship with the index case (2.1; 1.3-3.3); active smoking by the contact (1.6; 1.1-2.4); free health care (2.0; 1.2-3.2); and birth in a country with TB incidence rate higher than 25 of 100,000 (2.2; 1.5-3.2). Predictive probabilities were chosen to ensure false-negative rates lower than estimated TB infection background. The number of contacts to be investigated was reduced by 26% while maintaining a false-negative rate of 8%. CONCLUSIONS: This study provides a standardized contact screening model which reduces resources required without negatively affecting disease control.