[Palivizumab immunoprophylaxis: use in clinical practice, safety and beneficial effects in France]. / Modalités d'utilisation, tolérance et bénéfice du palivizumab dans la prévention des infections à VRS en France : saison 2005-2006.

BACKGROUND: Infants treated have been followed for one year in order to assess conditions of use of palivizumab, safety, tolerability, and its impact on respiratory syncytial virus (RSV) hospitalisation rate. PATIENTS AND METHODS: Patients who received palivizumab during the epidemic season 2005-2006 were eligible. Follow-up was carried out 12 months after initiation of prophylaxis. RESULTS: Sixty-four neonatal level II and III centers, pulmonary and cardiology units enrolled 1420 children. Mean follow-up was 10.9+/-0.2 months, mean gestational age (GA) 30+/-4 weeks and mean age at the start of prophylaxis was 5 months. Median number of injections was 5 and mean time interval between 2 consecutive injections was 30+/-6 days. Treatment was prescribed in accordance with the marketing authorisation indications (MA) for 84% of patients. For preterm infants born before 35 SA and less than 6 months of age, 60% was born before 33 SA and without BDP. The global readmission rate (for more than 24h) for documented RSV infection during the period of protection by palivizumab was 2.7% (37 in 1371) for all treated children: respectively 2% [IC(95%)=1.3-3.2], 2.7% [IC(95%)=0.7-4.7] and 3.7% [IC(95%)=0.8-6.6] for preterm infants less than 6 months of age, preterm from 6 to 24 months of age and for children with congenital cardiopathy. Palivizumab safety and tolerability were good. CONCLUSION: Evaluation of palivizumab prophylaxis in clinical practice confirms the clinical characteristics of treated infants, outlines their evolution and confirms safety of treatment. MA were generally well observed and a registry could be usefull to track the impact of the treatment out of MA.

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily]. / Pénétration sinusienne de l'amoxicilline-acide clavulanique. Formulation 1 g/125 mg, 2 fois/jour, versus formulation 500 mg/125 mg, 3 fois/jour.

INTRODUCTION: In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. OBJECTIVES: Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. METHODS: Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). RESULTS: As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. DISCUSSION-CONCLUSION: A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.

[Evaluation of tixocortol pivalate-neomycin combination versus ++a placebo excipient in acute rhinopharyngitis in children]. / Evaluation de l'association pivalate de tixocortol-néomycine versus placebo (excipient) dans la rhinopharyngite aiguë de l'enfant.

Effectiveness and clinical tolerance of the tixocortol-neomycin combination (Pivalone-Neomycin nasal suspension) used as monotherapy were evaluated in a double-blind placebo-controlled study (placebo: vehicle i.e., N-cetylpyridinium chloride, sodium chloride, sodium hydroxide solution, benzyl alcohol, purified water, monosodium phosphate) in 211 pediatric patients (aged 6 months to 8 years) with uncomplicated acute rhinopharyngitis. After seven days therapy, improvement in symptoms of acute rhinopharyngitis, especially rhinorrhea and nocturnal cough, was greater in the tixocortol-neomycin group. Physical evaluation documented significant improvements in local superinfection with disappearance of mucopurulent nasal secretions and posterior drip. Locoregional outcome, evaluated on severity of infectious complications and antibiotic use, was also more favorable in the tixocortol-neomycin group. These results, together with the good clinical tolerance of the study drug, demonstrate the value of single-drug therapy with this local corticosteroid-neomycin combination in children with uncomplicated acute rhinopharyngitis. They confirm that local administration of corticosteroids to combat inflammatory phenomena is useful not only in the well-recognized lower respiratory tract indications (asthma, respiratory syncitial virus infections) but also in nasal diseases (rhinitis).