Massive intrasplenic arterial thrombosis in a patient with chronic ITP during the development of an Evans syndrome.

Long-term safety and efficacy of eltrombopag in adults with persitent/chronic primary immune thrombocytopenia (ITP) evaluated in EXTEND study, showed a high response rate (80%) but, in the clinical safety study, it was observed that 6% of the patients presented venous and arterial thrombotic events. In addition, in the course of the disease, autoimmune hemolytic anemia (Evans syndrome, ES) may occur and could increase the risk of thrombosis. We report an interesting case of splenic rupture due to massive intrasplenic arterial thrombosis in the course of ES in a patient with chronic ITP treated with eltrombopag. The purpose of this case report is to highlight the potential increase in thrombotic risk that may involve the use of eltrombopag in hemolysis situations in patients with ITP.

Community-acquired bacterial meningitis in cirrhotic patients.

The Hospital Universitari de Bellvitge (Barcelona, Spain) records all cases of bacterial meningitis in a 120-variable database. The characteristics of bacterial meningitis in cirrhotic patients are not well-known, and all cases of community-acquired bacterial meningitis occurring in cirrhotic patients were therefore identified. During 1977-2002, there were 602 episodes of community-acquired bacterial meningitis in adults, of which 29 (4.8%) occurred in cirrhotic patients. Compared to non-cirrhotic patients, there were significant differences in: duration of disease for >4 days at the time of diagnosis; absence of nuchal rigidity; certain aetiologies, e.g., Escherichia coli and Listeria monocytogenes; renal and liver function impairment; relapse of fever; and incidence of relapse and mortality. Overall, bacterial meningitis in cirrhotic patients was associated with a high mortality rate and a large number of complications. A high index of suspicion is necessary because of the frequent absence of meningeal signs. In addition to the classic meningeal pathogens, other aetiologies, including E. coli and L. monocytogenes, should be considered when prescribing empirical therapy.

Experimental study of teicoplanin, alone and in combination, in the therapy of cephalosporin-resistant pneumococcal meningitis.

OBJECTIVES: The aim of the study was to determine the efficacy of teicoplanin, alone and in combination with ceftriaxone, in a rabbit model of cephalosporin-resistant pneumococcal meningitis, and to assess the effect of concomitant therapy with dexamethasone. METHODS: In vitro killing curves of teicoplanin, with and without ceftriaxone, were performed. Groups of eight animals per treatment were inoculated with a cephalosporin-resistant pneumococcal strain (penicillin MIC, 4 mg/L; ceftriaxone MIC, 2 mg/L; teicoplanin MIC, 0.03 mg/L) and treated over a 26 h period. Teicoplanin was administered at a dose of 15 mg/kg, alone and in combination with ceftriaxone at 100 mg/kg with or without dexamethasone at 0.25 mg/kg. CSF samples were collected at different time-points, and bacterial titres, white blood cell counts, lactate and protein concentrations and bacteriostatic/bactericidal titres were determined. Blood and CSF teicoplanin pharmacokinetic and pharmacodynamic parameters were determined. RESULTS: Teicoplanin alone promoted a decrease in bacterial counts at 6 h of -2.66 log cfu/mL and was bactericidal at 24 h, without therapeutic failures. Similar good results were obtained when dexamethasone was used simultaneously, in spite of the penetration of teicoplanin into the CSF being significantly reduced, from 2.31% to 0.71%. Teicoplanin and ceftriaxone combinations were synergic in vitro, but not in the meningitis model. CONCLUSIONS: Teicoplanin alone was very effective in this model of cephalosporin-resistant pneumococcal meningitis. The use of concomitant dexamethasone resulted in lower CSF teicoplanin levels, but not in therapeutic failures. The combination of teicoplanin plus ceftriaxone and dexamethasone might be a good alternative for the empirical therapy of pneumococcal meningitis. Additional data should confirm our experiments, in advance of clinical trials to assess efficacy in humans.