Renal hemodynamic effect of tacrolimus in renal transplanted children.

Like cyclosporine (CsA), tacrolimus acts through the inhibition of renal phosphatase calcineurin. CsA induces reversible vasoconstriction, causing a transient reduction of renal plasma flow in patients with renal transplantation. The aim of this study was to determine the effect of tacrolimus on renal plasma flow in renal transplanted children. Eight children were studied with a median age of 10.6 years, a mean glomerular filtration rate (inulin clearance) of 55 ml/min per 1.73 m2 (range 29-95), and a mean follow-up after transplantation of 5.6 months. Effective renal plasma flow (ERPF) was studied in each patient for 12 h after tacrolimus administration. Clearances were obtained every 2 h for 12 h after drug administration. Tacrolimus pharmacokinetics was also studied. Average ERPF at the start of the test was 289 ml/min per 1.73 m2 (range 177-404, SD +/- 106). Variation in each of the 2-h periods was not significant, although a mild reduction of plasma flow was observed in three of the eight children. No correlation was found between tacrolimus AUC, peak, or trough levels and renal blood flow variations. Despite the relatively small number of patients studied, these data suggest that, in vivo, a therapeutic oral dose of tacrolimus is not necessarily followed by a significant reduction of ERPF in renal transplanted children.

Cyclosporine A monitoring in children: abbreviated area under curve formulas and C2 level.

Cyclosporine A (CsA) is the most commonly used drug in organ transplantation. To evaluate exposure the gold standard is area under curve (AUC), but this is expensive and requires many blood samples. For this reason, abbreviated formulae have been developed in adults. Data in children are scanty. Formulae cannot be applied in patients taking CsA every 8 h. We tested the abbreviated AUC formula published for adults in renal transplant children on twice daily therapy and we propose a method, requiring three blood samples, for those taking CsA every 8 h. A very good correlation was obtained for both groups. Furthermore, we studied the correlation between CsA concentration 2 h after administration and AUC. A good correlation was found supporting the possible use of this parameter for monitoring CsA therapy.

Potential of clindamycin in addition to vancomycin for the treatment of oxacillin-resistant Staphylococcus aureus septicemia persisting under vancomycin therapy.

We observed seven patients with persistent fever and staphylococcemia under vancomycin-containing antimicrobial regimens who promptly improved as clindamycin was added to the initial antibiotics. Moreover, in all these patients a striking increase in peak and trough serum inhibitory activity (SIR) and serum bactericidal activity (SBA) levels was observed after addition of clindamycin. SIA and SBA levels after administration of a single dose of vancomycin (500 mg), clindamycin (600 mg) or vancomycin + clindamycin were also measured in three healthy volunteers against six ORSA isolates. Unsatisfactory peak SBA levels (0% of cases 1:8) were obtained after vancomycin administration. Vice versa, peak SBA levels 1:8 were obtained in 94% of the cases after clindamycin and in 100% of cases after vancomycin + clindamycin. Time-kill studies showed a borderline or incomplete bactericidal activity of vancomycin against three ORSA isolates from infections that manifested poor or slow response to vancomycin therapy. The combination with clindamycin did not result in a synergistic interaction between the two drugs. It is concluded that addition of clindamycin may be useful in some cases of ORSA septicemia that show poor or slow response to vancomycin therapy. The recommendation for a wider use of this combination of antibiotics requires further documentation of efficacy.

[Blocking antibodies during specific hyposensitization immunotherapy in respiratory allergies in children]. / Gli anticorpi bloccanti in corso di ITS nelle allergie respiratorie del bambino.

A group of 35 children affected by bronchial asthma, rhinitis and/or allergic conjunctivitis was examined; the children selected for the study had never undergone ITS before; all patients had received preventive drug and nondrug therapy for several months but none had succeeded in significantly reducing allergic clinical symptoms. Subcutaneous ITS Lofarma was prescribed for all patients (for various allergens) and blocking antibodies (IgG1 + IgG4) were assayed using a RAST system (Kit-Pharmacia) before the start of the study, and after 3, 9 and 12 months of therapy; 25 nonatopic children represented the control group. Although a certain number of allergen-specific blocking antibodies were present in all patients before the start of ITS, a significant increase in IgG1 + IgG4 specific allergens was observed after 9 months (especially for pollenosis). Compatible results were also obtained for blocking antibodies for children affected by dermatophagoides following 12 months of ITS. The aim of the present study was to evaluate the extent of the appearance of blocking antibodies in the circulation following ITS and to discover whether or not there was a correlation between their increased titre and improvement of the disease assessed by the use of clinical scores.