Nationwide survey in Italy of treatment of Streptococcus pyogenes pharyngitis in children: influence of macrolide resistance on clinical and microbiological outcomes. Artemis-Italy Study Group.

Throat swab specimens were obtained from 3,227 children with symptoms of acute pharyngotonsillitis. After 14 to 21 days, a second throat swab specimen was obtained at a follow-up visit. Over 42% of the 934 strains of Streptococcus pyogenes isolated in the primary study were resistant to erythromycin, azithromycin, and clarithromycin. Eradication rates among the 668 patients who entered the follow-up study were as follows: 84.1%, penicillin recipients; 82.7%, cephalosporin recipients; and 71.7%, macrolide recipients. Among patients treated with macrolides, the eradication rate was approximately 80% when the infecting organisms were erythromycin-susceptible and approximately 60% when they were erythromycin-resistant. These results indicate substantial in vitro macrolide resistance among Italian isolates of S. pyogenes. However, at least for a minor self-limiting condition such as acute S. pyogenes pharyngitis, our findings point to a limited overall correlation between in vitro susceptibility (to penicillins, cephalosporins, or macrolides) and eradication in patients treated with these drugs and an even weaker correlation between in vitro resistance (to macrolides) and noneradication in patients receiving macrolide therapy.

Evaluation of the efficacy of oral cromolyn sodium or an oligoantigenic diet in children with atopic dermatitis: a multicenter study of 1085 patients.

One thousand eighty-five children with atopic dermatitis were enrolled in a multicenter study to evaluate the efficacy of 4 weeks of oral sodium cromoglycate or 4 weeks of a restricted diet. One thousand-eleven children (93%) concluded the study. At the end of the trial there was a significant improvement in skin lesions in the two groups: 61% of the patients in the sodium cromoglycate group and 69% in the restricted diet showed a significant improvement in atopic dermatitis. We concluded that, at least in our experimental design, both sodium cromoglycate and a restricted diet are equally effective in atopic dermatitis.

Retrospective survey on the epidemiology of H. influenzae type B meningitis in Italy (1987-91).

A retrospective survey on the epidemiology of H. Influenzae type b (Hib) meningitis was carried out in seven Italian hospitals. During the period 1987-1991, 95 (16.3%) Hib meningitis cases out of 581 bacterial meningitis cases were observed. The proportion of Hib meningitis was lowest in 1987 (11.3%); elevated in 1988 (17.9%); thereafter it did not change. A male preponderance was observed (Sex ratio 1.6). The age distribution showed that 93.7% of cases occurred in subjects < 5 years, 53.7% of cases in those < 1 year. Although Hib meningitis accounts for a small proportion of all bacterial meningitis, it is also a major problem in Italy in early childhood, because nearly all cases occur in children < 5 years.

Pharmacokinetics of brodimoprim in special populations.

The pharmacokinetics of brodimoprim have been investigated after single oral dose administration in children, in healthy adults, and elderly subjects, as well as in patients with mild renal failure (creatinine clearance 40-70 mL/min) or liver insufficiency (Child-Pugh grade A or B). The plasma half-life increased moderately with age. The percent brodimoprim bound to plasma proteins, 93%, was identical in renally impaired patients and in healthy controls but decreased to 90% or less in liver insufficiency. The apparent distribution volume and clearance were much higher in children than in adults. Urinary excretion of unchanged brodimoprim amounted to 5-10% of the administered dose. The steady-state pharmacokinetics of brodimoprim has also been investigated in elderly subjects (400 mg loading dose followed by 7 days 200 mg once daily). There was no significant modification of elimination half-life and of clearance upon repeated dosing. Renal excretion of brodimoprim and hydroxy metabolite at steady-state reached 9% and 14% per 24 hours in the elderly, compared to 9% and 24% in young adults. The accumulation factor reached 3.3 +/- 0.4 and 2.7 +/- 0.3 respectively.

Clinical comparative study of azithromycin versus erythromycin in the treatment of acute respiratory tract infections in children.

The efficacy and tolerability of azithromycin and erythromycin in the treatment of acute respiratory tract infections in children were compared in an open, multicenter, randomized trial. A total of 151 children, aged from 2 months to 14 years, suffering from upper airways infections (60), or lower respiratory tract infections (91), were randomized to be treated either with azithromycin, 10 mg/Kg/day per os once daily for 3 or 10 mg/Kg/day 1 and 5 mg/Kg/days 2-5 (77 patients) or with erythromycin, 50 mg/Kg/day thrice daily for at least 7 days (74 patients). The two treatment groups did not significantly differ as to sex, age, weight, type and severity of infection, and infecting pathogens. Clinical evaluation was performed prior to therapy, on treatment days 1, 3, 5 and 7, and on day 10. Microbiological and laboratory assessment were carried out at baseline and after the end of therapeutic course. Chest X-ray and serologic assays for Mycoplasma pneumoniae infection were obtained in patients suspected to have lower respiratory tract infections. At the end of therapy, clinical cure was achieved in 73 out of 77 patients (94.8%) in the azithromycin group, and in 60/72 evaluable subjects (83.3%) in the erythromycin group. A significantly more rapid remission of several illness-related signs and symptoms was observed in patients treated with azithromycin. A total of 75 bacterial pathogens were isolated at baseline microbiological examination; at the end of the therapeutic course bacteriological eradication was obtained in 34/34 cases (100%) treated with azithromycin, and in 40/41 children (97.5%) treated with erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rational bases of current etiopathogenetic therapy of bacterial meningitis. Review of the literature and personal experience in 122 pediatric cases]. / Basi razionali della moderna terapia eziopatogenetica della meningite batterica. Revisione della letteratura ed esperienza personale su 122 casi pediatrici.

Bacterial meningitis is a serious infectious disease, the course of which depends on the correct use of antibiotics and an intensive symptomatic and support therapy. The presence of microbes and their fractions in the CNS determines inflammatory phenomena that lead, through complex mechanisms, to the supportive treatment has the purpose of curbing the inflammatory phenomena, reducing cerebral oedema and avoiding ischaemia. This therapy makes use of cortisone and mannitol. The effectiveness of cortisone in reducing cerebral damage and, consequently, the neurological sequelae of the disease has been documented in experimental models and in man. After analysing the pathogenetic events of cerebral damage and the rationale of the treatment, reference is made to a personal therapeutic protocol that includes an aetiological treatment (Ceftriaxone 100 mg/kg/die), a support therapy (dexamethasone 0.2-0.3 mg/kg/die, mannitol, water restriction) and a symptomatic therapy (for convulsions, high temperature and shock). Both the antibiotic and cortisone are also introduced into the spine on the occasion of lumbar injection. 122 children suffering from non-tubercular bacterial meningitis, admitted to the Emergency Department of the Regina Margherita Infant Hospital of Turin in the period 1984-89, were treated. A further 7 patients, admitted for the same pathology, died within a few hours. In 88% of cases, aetiological agents were found by bacterioscopic and/or cultural and/or co-agglutinin on liquor examination (Neisseria meningitidis 47.5%, Haemophilus influenzae 20.5%, Streptococcus pneumoniae 15.6%, others 4.1%). The patients were treated with support therapy for as long as clinical conditions required it and with Ceftriaxone until clinical cure, end of fever and normalisation of PRC. In the reported series, 90% of patients were treated for from 3 to 6 days. This duration of antibiotic therapy is shorter than that reported and recommended in the literature. Therapeutic results were very good with 95% cure without neurological sequelae even at 6 month/1 year follow-up. Only 6 patients reported sequelae (2 irritative anomalies at EEG, 3 hypoacusis, 12 psychomotor retardation). The results were also better than those reported in the Italian and foreign literature. The Authors are convinced that, in the hands of experienced physicians, timely antibiotic, anti-inflammatory, cerebral anti-oedema and symptomatic treatment will improve the prognosis for bacterial meningitis in infancy.

Rational basis of modern therapy of bacterial meningitis. Review of the literature and our clinical experience of 122 pediatric cases.

In recent years the treatment of bacterial meningitis has been modified on the basis of a better understanding of its physiopathological mechanisms. It has been shown, for example, that the inflammatory reaction is the primary cause of brain damage in bacterial meningitis. Inflammation and consequent brain damage are greatest in the first hours of antibiotic treatment when rapid and massive bacteriolysis takes place. In effect, the bacterial components activate metabolic pathways and cellular elements leading to the release of inflammation mediators: cytokines (TNF, IL-I) neutrophil degranulation products, complement components and clotting factors. Initially these substances make the blood-fluid and blood-brain barriers permeable. The result is cerebral oedema, excessive fluid pressure, congestion of the cerebral blood vessels and finally endocranial hypertension, reduced cerebral flow, cerebral hypoxia and brain damage. This sequence of events can be stopped by a multifactorial therapy that is not only aetiological (antibiotic) but also treats the inflammation, oedema (Dexamethasone, Mannitol) and symptoms. In this study 129 patients with non-tubercular bacterial meningitis were treated as described. All patients were administered Ceftriaxone (100 mg/kg per diem) Dexamethasone (0.2-0.3 mg/kg/per diem), Mannitol, fluid restriction and--where necessary--intensive symptomatic therapy (against shock, convulsions, fever). Both the antibiotic and the corticosteroid were also administered intrathecally at the time of the first lumbar puncture at intake. Of these 129 patients, 7 died very soon after admission as they had arrived in a moribund condition. Duration of therapy was 3-6 days in 90% of these cases. There were no recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

Imipenem use in serious childhood infections.

Imipenem plus cilastatin is a beta-lactam antibiotic with a broad spectrum and good tolerance. For this its use is indicated in serious infections even in children. The authors carried out a preliminary bacteriological study in patients affected by serious infection, cystic fibrosis, tumors, neutropenia, subjects undergoing intensive therapy and those with abdominal surgical infection. Isolated microorganism sensitivity in these patients, towards imipenem was very high (89%-100%). With these premises, 35 patients with serious infections in various locations were treated only with imipenem. Of these, 15 were oncologic neutropenic and 20 normal. In the first group therapeutic success was 66.6% and in the second one 80%. Local and systemic tolerance always showed good results.

[Macrolide-theophylline interaction. Experiences in pediatrics]. / Interazione macrolidi-teofillina. Esperienze in pediatria.

Subjects suffering from bronchial asthma being treated with theophylline often have to be treated with an antibiotic during acute stages. The purpose of the present study is to assess to clearance variation in theophylline when a macrolide antibiotic is associated after theophyllinemia steady-state has been attained. It has been seen that macrolides interfere differently on the blood levels of theophylline. Whereas erythromycin and josamycin determine a significant reduction in theophylline clearance, Miocamycin seems not to modify this parameter significantly.

[Amoxicillin and clavulanic acid suspension for children in the treatment of bronchopulmonary infections]. / Amoxicillina ed acido clavulanico sospensione pediatrica nel trattamento di infezioni broncopolmonari.

The present study has been tested on 30 children, 14 males and 16 females, average age 4.11 +/- 0.44 (range 9 months to 10 years), weight of 17.08 +/- 1.25 Kg, with infections concerning low respiratory tract (8 cases of broncho-pneumonia, 9 cases of acute bronchitis and 13 cases of lobar pneumonia). It has been used a chemotherapy composed of amoxycillin and clavulanic acid in pediatric suspension of 312.5 mg/5 ml (in the ratio of 4 to 1); the daily dosage, related to the children's weight has been of 43.91 +/- 1.21 mg/Kg in two daily doses. On the average the therapy has lasted for 6.43 +/- 0.19 days from a minimum of 4 to a maximum of 8 days. During the treatment the symptomatologic parameters (dyspnoea, cough), and the objective ones (pathological lung signs, rales, hypophonesis, bronchial breath...) have progressively improved till they have disappeared; morning and evening body temperature has promptly returned to normal. Both the physical and radiological exams of the chest confirm either the improvement or the regression of the infection in most of the cases. Side effects due to the antibiotic have not been registered and local and general tolerability was excellent. Considering the more or less fast and complete symptomatological regression, the evolution of the infective clinical picture and the tolerability, the final evaluations have been: excellent efficacy in 13 cases, good efficacy in 9 cases, fairly good in 5 cases and poor in 3 cases.

Short-term treatment of streptococcal tonsillitis with ceftriaxone.

The short-term therapy of streptococcal pharyngotonsillitis and scarlet fever with ceftriaxone (Rocephin) is reported. Sixty children, in whom the clinical diagnosis was confirmed by rapid enzyme immunoassay and smear test, were divided into two randomized groups and treated with a single dose of 50 mg/kg ceftriaxone or 50 mg/kg ceftriaxone on 3 consecutive days. Clinical cure was obtained in 100% of the patients and pharyngeal sterilization in 95%, with no significant differences between the two groups.

[Cefotiam, a new cephalosporin. Microbiological research, preliminary evaluation of its effect on phagocytosis and clinical multicenter research]. / Cefotiam, nuova cefalosporina. Ricerca microbiologica, valutazione preliminare dell'interferenza sulla fagocitosi e ricerca clinica policentrica.

After a brief review of the data on cefotiam in the literature the report presents the results of microbiological research, a preliminary study into the drug's possible actions on phagocytosis and a polycentric clinical study of 93 cases of broncho-pleuro-pulmonary pathology and one sinusitis of the jaw. In vitro cefotiam was found to have an excellent inhibitory effect on gram positive and gram negative bacteria with MICs50 and 90 respectively 0.2 and 0.8 mcg/ml V. Staph. aureus, Str. pyogenes. E. Coli, K. pneumoniae and Pr. mirabilis. A dose-dependent increase in phagocytosis was noted. The clinical response was excellent with 90.43% (88/94) of the cases achieving clinical and radiological cure or very much improved. Cefotiam was very well tolerated with the appearance of 2/94 skin rashes (2.12%). The liver and kidney parameters showed no change at the end of treatment. No increase in enzymuria was noted during treatment with cefotiam.