Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

[A 41 year-old male patient with fever of unknown origin and bacteremia with actinobacillus actinomycetemcomitans]. / 41-jähriger Patient mit unklarem Fieber und Bakteriämie mit Actinobacillus actinomycetemcomitans.

A 41-year-old male patient presented with fever of unknown origin which had been present for 5 months. The primary diagnostic procedures did not identify an infectious focus. After a lag phase of 13 days, blood cultures became positive for Actinobacillus actinomycetemcomitans, which belongs to the HACEK group of microorganisms. According to the DUKE criteria, infective endocarditis was diagnosed despite negative transesophageal echocardiography (TEE). The sensitivity of TEE is estimated between 86 and 94%. An infected tooth was extracted as a possible focus, and the patient was treated with i.v. antibiotics for 5 weeks according to the guidelines of the AHA and ACC. The fever was permanently terminated, and the further course of the patient was uneventful. Despite negative TEE, the diagnosis "infective endocarditis" should not be rejected, and blood cultures should be grown for up to 30 days.