A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.

This open-label, dose-escalation study assessed the maximum tolerated dose (MTD) of the new antifungal micafungin in patients undergoing haematopoietic stem cell transplantation (HSCT). Participants received 3, 4, 6 or 8 mg/kg/day micafungin intravenously from 7 days to a maximum of 28 days or until neutropaenia resolved. The MTD was defined as the highest dose not causing the same Grade 3 or 4 adverse event in three or more patients. All 36 participants received >/=8 days treatment for a median of 18 days (range: 8-28); 1 patient withdrew consent and a further 11 discontinued to receive another systemic antifungal agent for a suspected infection. No case of confirmed invasive fungal infection occurred. Adverse events were those expected for patients undergoing HSCT and showed no evidence of dose-related toxicity. Criteria for MTD were not met; no patient had a Grade 3 or 4 adverse event considered causally related to micafungin. Thus, the MTD of micafungin can be inferred to be 8 mg/kg/day or higher.

[Transperitoneal resorption of cefotiam in CAPD patients with and without peritonitis]. / Transperitoneale Resorption von Cefotiam bei CAPD-Patienten mit und ohne Peritonitis.

BACKGROUND: Cephalosporins of the second generation have been repeatedly recommended for the treatment of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), because they are effective against most of the clinically relevant bacteria. In this study, we tested cefotiam, a member of this group of antibiotics, for its suitability in this indication, and determined the intraperitoneal dosage needed to achieve effective serum levels. PATIENTS AND METHODS: IN 10 CAPD-patients with and 10 without peritonitis, cefotiam was added to the dialysis bags (2 l) over a period of seven days. Prior to initiating antibiotic treatment, a sample of dialysis fluid was submitted to bacteriological and cytological examination. During the treatment period, the bags were changed four times a day. In the first three patients 0.5 g cefotiam/bag was administered. Two to four days after initiating treatment, these patients developed nausea and occasional vomiting. Thereupon, all the other patients were given a dose of 0.5 cefotiam/bag only on the first day--a loading dose--followed by 0.25 g/bag for the next six days. Samples of blood and dialysate were obtained after 24, 48, 72, 96, 120, 144 and 168 hours. The cefotiam concentration was determined by the agar diffusion technique. Side effects were checked by clinical observation and measurement of GOT, GOP, alkaline phosphatase, gamma GT, Na, K, and creatinine together with a blood count at the beginning and end of the trial. RESULTS: Among the peritonitis patients, Staphylococcus epidermidis and Staphylococcus pyogenes aureus were each found in four, and Pseudomonas aeruginosa in two patients. In all patients effective serum levels were reached after one day of treatment. In the following period, these levels were maintained. Serum concentrations were higher in patients with than in those without peritonitis (18 to 21 micrograms/ml and 11 to 16 micrograms/ml, respectively). The first three patients had toxic cefotiam levels of about 30 micrograms/ml. All the cases of staphylococcus-induced peritonitis were cured with this therapeutic regimen, while those with Pseudomonas aeruginosa peritonitis required additional treatment with tobramycin. Neither clinical nor chemical side effects were observed. CONCLUSION: Using the regimen described, cefotiam is an effective and safe first-line antibiotic for the treatment of CAPD-related peritonitis.