[Arthritis and infections]. / Artriti e infezioni.

Arthritis caused by infectious agents can be secondary to direct invasion of the joint space or to immune mechanisms (subsequent to or concomitant to an infection). Septic arthritis refers to a situation when bacteria can be cultured in synovial fluid. Arthritis can complicate for example meningococcemia or infection by Neisseria gonorrhoeae or Haemophilus influenzae. Reactive (postinfectious) arthritides are an important diagnostic category within a pediatric rheumatology practice. Yersinia and, less frequently, Salmonella, play an important role in postdiarrheal disorders. The arthritis that can ensue is usually oligoarticular and occurs 1-2 weeks after the enteric infection. Reiter's syndrome, rare in the pediatric age, is characterized by the triad urethritis-conjunctivitis-arthritis. Postviral arthritides can occur after a variety of viral infections, including Parvovirus B19, rubella, and others (e.g. hepatitis B, Epstein-Barr virus, chickenpox, mumps). Especially in patients with acute arthritis, the presence of preceding infections should always be investigated. Although the majority of postinfectious arthritides are self-limiting in nature and do not require specific treatment, conditions such as Lyme borreliosis and rheumatic fever can be associated with significant morbidity, and sometimes can be even lethal.

Unexpected healing of cutaneous ulcers in a short child.

A boy aged 10 years was referred to the Paediatric Department of Milan University Hospital, Milan, Italy, with a long history of pain in the lower limbs, alleviated only by exposure to cold. His legs were swollen, with multiple cutaneous ulcers. He had severe painful crises, and was totally incapacitated. After the diagnosis of erythermalgia was made, numerous treatments were tried, but none were successful. After finding growth hormone (GH) deficiency, we started treatment with recombinant GH. He had immediate relief of pain and complete healing of ulcers. We postulate that the healing of the ulcers can be attributed to the GH-promoting effect on dermal connective tissue.

Short course therapy with cefitbuten versus azithromycin in pediatric streptococcal pharyngitis.

OBJECTIVE: To compare the safety and efficacy of a short course (5 days) of ceftibuten vs. azithromycin for 3 days for treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children. METHODS: A multicenter, open label, prospective, randomized trial in which patients > or =3 to < or =16 years of age with proven GABHS pharyngitis were randomized to receive either once daily ceftibuten for 5 days or azithromycin for 3 days. Patients were evaluated for clinical outcomes and/or for adverse events at days 6 to 8, 13 to 15 and 33 to 35 posttherapy. Microbiologic assessments (pharyngeal cultures) were conducted at baseline and at each follow-up visit. RESULTS: A total of 132 patients in the ceftibuten arm and 116 in the azithromycin arm were enrolled in the safety analysis, whereas 126 and 101, respectively, were enrolled for ceftibuten and azithromycin efficacy evaluation. Clinical success (cure or marked amelioration) at days 6 to 8 was recorded in 98 and 94% in the 2 groups, respectively. In the bacteriologic efficacy analysis at 6 to 8 days, the GABHS strain was eradicated in 76% of the patients treated with ceftibuten and in 76% of those receiving azithromycin. At 33 to 35 days, 84% of the patients in the ceftibuten arm and 71% in the azithromycin arm were GABHS-negative, and bacteriologic relapse was observed in 4 and 7% of the ceftibuten and azithromycin cases, respectively. Both treatments were well-tolerated by all patients. CONCLUSIONS: Ceftibuten and azithromycin allow simple treatment schedules (i.e. once daily administration, short duration of treatment). The somewhat higher eradication rate recorded after ceftibuten administration is consistent with the overall superior bactericidal activity of beta-lactams compared with macrolides vs. GABHS in vitro.

Clinical and pharmacological evaluation of a modified cefotaxime bid regimen versus traditional tid in pediatric lower respiratory tract infections.

It is generally accepted that the treatment of community-acquired pneumonia, either in adults or in pediatric patients, is mainly empirical. Thus, the treatment selection must fulfill both the epidemiological requirements, according to the most frequently described pathogens, and the pharmacological criteria to ensure adequate and prolonged drug concentrations at the infection site, to reach clinical efficacy. Cefotaxime has proven to be effective in this indication when traditionally administered three times daily and, more recently, twice daily, as a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To gain further evidence using this updated dosing schedule, 258 pediatric patients with lower respiratory tract infections were treated with cefotaxime 100 mg/kg/day, administered as a twice daily or three times daily regimen. In the cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete resolution of clinical signs and symptoms. Both drug schedules were well tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing schedules showed comparability. The serum half-life of desacetylcefotaxime was marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3 mg/kg doses, respectively). Results from this study support the use of twice-daily cefotaxime administration for the treatment of lower respiratory tract infections in pediatric patients.

Acute otitis media in pediatrics: are there rational issues for empiric therapy?

BACKGROUND: Acute otitis media in children is a significant clinical problem that requires a rational approach to treatment. The condition is extremely common and has important economic implications. At present there is considerable controversy over the most appropriate strategy and over the use and choice of antibiotics. OBJECTIVES: To analyze the various factors that influence therapeutic decisions and consider how these may assist in the formulation of a rational approach to therapy. DISCUSSION: Otitis media has a multifactorial etiology but it is extremely difficult to differentiate between bacterial and viral causes on clinical grounds. Culture of the middle ear fluid is rarely practicable; however, nasal swabs are relatively noninvasive and can provide useful microbiologic information, especially in excluding a bacterial cause. Published information provides little guidance on the most appropriate therapy; a rational approach to treatment is based on many considerations including the local epidemiology. The minimum criteria for the empiric choice of an antibiotic for acute otitis media are that it should be rapidly bactericidal and reach adequate concentrations in the middle ear fluid. In areas where beta-lactamase-producing strains are prevalent, a beta-lactamase-stable antibiotic should be chosen; good absorption from the gastrointestinal tract and high and consistent penetration into the middle ear are important characteristics. Compliance-enhancing factors such as fewer doses per day and good palatability are also important.

[Treatment of iron deficiency in infancy with iron-acetyl transferrin]. / II trattamento della carenza marziale delle prime epoche di vita con ferro-acetil-transferrina.

In twenty eight patients with iron deficiency the efficacy of iron-acetil-transferrin treatment (2-3 mg/kg/die) has been evaluated from the changes of the following variables: RBC and reticulocyte count, Hb concentration, MCV, MCH, serum ferritin, serum iron, TIBC, and ZnPP. These variables were assessed before and after three months of treatment in all patients, and after three months from the end of the treatment in thirteen patients. At the end of the treatment there was a significant increase of RBC count, Hb concentration, MCV, MCH, serum ferritin, serum iron, and TIBC, a significant decrease of ZnPP, while reticulocyte count remained essentially unchanged. After three months from the end of the treatment only serum ferritin and ZnPP underwent an additional significant increase and decrease, respectively. In twenty-six patients serum ferritin values returned to normal. The changes of RBC and reticulocyte count, Hb concentration, MCV, serum iron, and TIBC were larger the lower the initial values, suggesting that the efficacy of the treatment is greater the more serious the iron deficiency.

[Moraxella catarrhalis: an emerging respiratory pathogen]. / Moraxella (Branhamella) catarrhalis: un patogeno respiratorio emergente.

In the past years Moraxella (Branhamella) catarrhalis has finally gained respect as a pathogen thanks to the many reports of its causal role. The intent of this review is to provide a critical evaluation of the intent of this review is to provide a critical evaluation of the microbiological features (taxonomy, diagnosis, virulence, epidemiology and drug resistance), clinical diseases and therapy of this microorganism

Pidotimod in the treatment of recurrent respiratory infections in paediatric patients.

50 young patients suffering from recurrent respiratory infections (RRI) were treated with pidotimod ((R)-3-[(S)-(5-oxo-2- pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) (one 400 mg ampoule twice a day) or placebo, according to a double-blind experimental design. The treatment period was 20 days and there was then a 60-day follow-up period. Evaluation was both clinical (number and severity of the respiratory infectious episodes) and immunological, investigating the OKT 4 and OKT 8 lymphocyte sub-populations and OKT 4/OKT 8 ratio. The group of children treated with pidotimod showed a decrease in the number of infections. Patients free from RRI episodes, after 20 days of therapy, were 68% of the group treated with pidotimod compared with 8% of the placebo group. In addition, the mean duration of the episodes was lower in treated patients than in patients of the control group. Such differences were statistically significant. It was also observed that administration of the drug potentiated the immune response such that the clinical picture remained improved for a further 60 days after treatment cessation. Furthermore, only in the pidotimod group there were improving changes of OKT 4 and OKT 8 percentages which affected the OKT 4/OKT 8 ratio.

Role of immunoactivation with pidotimod in recurrent respiratory infections in childhood.

The efficacy and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) were rated in a child population with a remote history of recurrent respiratory infections (RRI). This randomized double-blind multicenter clinical trial versus placebo, stratified by age groups, involved 748 children recruited in 69 Medical Centres. The trial consisted of a 60-day treatment period and a 90-day follow-up. At the end of the treatment period the pidotimod group showed a significant decrease in the number of RRI episodes and associated symptoms vs control group. As a consequence, there was a significant decrease in the number of days of absence from kindergarten or school and in the consumption of antibiotics and symptomatic drugs. Safety was good. The effect of the drug persisted after its withdrawal throughout the whole 90-day follow-up period. During this period there was a significantly lower RRI incidence rate in the pidotimod group than in the placebo group (p < 0.01). Because of its efficacy and safety, pidotimod may be rated as an excellent drug in the RRI management in children.

Efficacy and tolerability of brodimoprim in pediatric infections.

Brodimoprim is a long acting broad spectrum antibacterial agent. It is a new selective inhibitor of bacterial dihydrofolate reductase, structurally related to trimethoprim. The aim of the present study was to investigate the efficacy and tolerability of brodimoprim (10 mg/kg on the first day, 5 mg/kg/die onward) in the treatment of upper respiratory tract infections in children (age range: 2-14 years). This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis (37 treated with brodimoprim, 31 with erythromycin 560 mg/kg/8 hours) or in 50 patients affected by otitis media (25 treated with brodimoprim, 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours) or in 52 patients affected by acute sinusitis (25 treated with brodimoprim, 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours). All patients were clinically evaluated before admission, during the trial and 48 hours after the last dose of antibiotic. At the same time blood and secretion samples were collected for hematology/biochemistry and microbiological assays. A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period, with approximately the same recovery rate (83%) among the groups. The bacteriological response was evaluated in 169 subjects. Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group, in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group. The overall eradication in brodimoprim treated patients was 77% in comparison with 76% of eradication obtained in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled, double-blind, multicenter clinical trial of iron protein succinylate in the treatment of iron deficiency in children.

A total of 502 children up to the age of 14 years were treated for iron deficiency or overt anemia. ITF 282 was prescribed to 256 children, and a commercially available ferrous polystyrene sulphonate preparation to 246, in a randomized double-blind, double-dummy, ten-center trial. One oral vial of ITF 282 (60 mg iron) was administered once a day to children weighing up to 40 kg; and twice a day to children with body weight equal or superior to 40 kg. In the reference group, oral vials of polystyrene sulphonate (52.5 mg iron) were administered once a day to children weighing up to 40 kg, and twice a day to children weighing 40 kg or more. Treatments lasted 60 days. The treatments' efficacy and tolerability were evaluated taking into consideration: special hematology, symptomatology, safety hematology and hematochemistry, urinalysis. At the end of treatment, the trend was detected to the normalization of the main hematologic parameters in both groups (hemoglobin, hematocrit, ferritin, blood iron, transferrin saturation, MCHC). Although in the first month the reference treatment appears to provide somewhat faster results, significantly greater values of blood iron are observed at the end of the observation in the ITF 282 group, indicating a more progressive and steady therapeutic effect. The overall clinical rating was, although not significant, in favor of ITF 282, with a failure rate of 18.0 vs 24.0%. The general tolerance, although favorable with both treatments, was significantly more favorable with ITF 282. With this medication, 13 patients complained of 13 events (1 heartburn, 6 constipation, 6 abdominal pain) vs 48 events reported by 43 patients with the reference medication (1 heartburn, 2 epigastric pain, 14 constipation, 14 abdominal pain, 3 skin rash, 14 vomiting). These observations confirm that, although the most modern preparations of ferrous ions exhibit a relatively low frequency of adverse events of limited clinical concern, it is nevertheless possible to decrease (with the use of more "physiologic" preparations in which the iron is reversibly bound to a protein carrier) the prevalence and, tendentially, duration and intensity of such events without prejudice for the clinical efficacy. Therefore, the good clinical tolerability of ITF 282 effectively removed one of the main obstacles to the correct compliance with iron treatments (necessarily to be taken long-term), as reduced the risks of undesired events in a particularly susceptible population subgroup, such as children.

The pharmacokinetics of cefodizime in children.

The single-dose pharmacokinetics of cefodizime were studied in ten hospitalized children aged between two and 15 years and weighing 12.5-26.2 kg. Six subjects received the drug (25 mg/kg) im and four received it iv. Cefodizime concentrations in blood and urine (iv dosage only) sampled up to 12h post dose were measured by microbiological assay and pharmacokinetic parameters were derived on the basis of a two-compartment open model. Peak serum concentrations were 131 +/- 22.7 mg/l (15 min post iv dose) and 54.8 +/- 17.8 mg/l (60 min post im dose). Mean T1/2 beta were 1.9 +/- 0.13 h (iv) and 1.88 +/- 0.25 h (im). Mean AUCs were 217.2 +/- 37.9 mg.h/l (iv) and 150.85 +/- 22.98 mg.h/l (im). Mean volumes of distribution were 7.6 +/- 2.5 l (iv) and 7.9 +/- 1.41 (im). Twelve hours after the iv administration the cumulative urinary excretion was 78-87% of the dose. The pharmacokinetic behaviour of cefodizime in children is thus similar to that of other compounds in this class.

[Treatment of hemophilia in children]. / Il trattamento dell'emofilia in età pediatrica.

Thanks to recent developments and evolution in prenatal diagnosis and early onset within the first year of life, hemophilia may now be considered a pathology of primarily pediatric interest. The treatment of hemophilia in children has furthermore undergone a number of changes that include 2 main events in therapy that have served to modify the quality of life of the hemophiliac. The first of these events regards blood products and the prevention of viral infections, hepatitis and HIV transmission. Prevention is based on various factors which include: donor selection, immunization, product testing and heat treatment of blood products. The second extremely important aspect of treatment in hemophilia is the concept of global assistance, which includes: the treatment of the bleeding episode itself, and an ongoing psycho-social support system. In this paper we suggest some practical treatment schedules for the therapy of bleeding episodes in addition to examining the severe side effects of HIV and Hepatitis viruses. The message which our paper attempts to transmit is that the hemophilic child must be ideally assisted in an exclusively pediatric environment.

Extent of lactose absorption in children with active celiac disease.

We have estimated lactose absorption indirectly by the breath H test to see if disaccharide exclusion is necessary for untreated celiac children. Lactose at 2 g/kg body weight (maximum 50 g) was administered to 42 infants and children (ranging in age from 9 months to 12 years) with flat small intestinal mucosa. Later, different amounts of lactose were given to determine the quantities tolerated and absorbed. One hundred percent of patients expired hydrogen more than 20 ppm over the baseline after an oral lactose load of 2 g/kg (maximum 50 g). Thirty-eight percent of them did not tolerate this quantity. Thirty-seven subjects aged 0-6 years absorbed and tolerated 0.5-1.5 g/kg (5-12.5 g total), and five patients aged 6-12 years absorbed and tolerated 0.5-0.6 g/kg (12-16.2 g total). We conclude that in many subjects with untreated celiac disease, lactase activity is sufficient for absorption and tolerance of the amount of lactose present in 250-300 ml cow's milk. Because of lactose's nutritional value, it should not be excluded unless necessary.