The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.

These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

One strategy to minimize nephrotoxicity in maintenance immunosuppression in renal transplantation is reduction of cyclosporine (CsA) with addition of mycophenolate mofetil (MMF). This approach seems safe, but concern exists about whether it yields adequate immunosuppression in the long term. Thus, we investigated the pharmacodynamic response to CsA in stable renal allografts treated with standard CsA (n = 17, CsA-C0h> or = 125 ng/mL) and low CsA plus MMF (n = 18 CsA-C0h <100 ng/mL). Patients treated with MMF without CsA (n = 13) and healthy subjects (n = 7) were used as controls. We observed that inhibition of calcineurin (CN) activity in peripheral blood mononuclear cells (PBMC), as well as interleukin (IL)-2 and interferon (IFN)-gamma production were similar in Standard-CsA and Low-CsA+MMF groups. Moreover, addition of MMF to a low CsA dose regime improved the correlation between CsA-C2h and both CN activity and IL-2 production. Thus, our results suggest that MMF could be synergistic with the pharmacodynamic effect of low CsA in maintenance immunosuppression.

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