Pharmacokinetics and safety of caspofungin in neonates and infants less than 3 months of age.

Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C(1 h)) and trough (C(24 h)) caspofungin levels were 8.2 and 1.8 microg/ml, respectively, on day 1, and 11.1 and 2.4 microg/ml, respectively, on day 4. GM ratios for C(1 h) and C(24 h) for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m(2) once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.

In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends).

OBJECTIVES: SMART (Study for Monitoring Antimicrobial Resistance Trends) is an ongoing study to monitor worldwide antimicrobial resistance trends among aerobic and facultatively anaerobic Gram-negative bacilli (GNB) isolated from intra-abdominal infections. This 2004 report summarizes the most recently completed annual data from SMART. METHODS: During 2004, 81 medical centres from 28 countries in five global regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 6156 unique aerobic and facultatively anaerobic GNB were isolated from intra-abdominal infections. Enterobacteriaceae composed 86% of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most consistently active against the Enterobacteriaceae. Escherichia coli was the most commonly isolated species (48%), and the susceptibility rate to the quinolones was lowest in Asia/Pacific and Latin America. Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 10% of E. coli, 17% of Klebsiella spp. and 22% of Enterobacter spp. worldwide, representing a slight increase over the two previous years. ESBL producers typically had a more antibiotic-resistant profile than non-ESBL producers but were usually susceptible to the carbapenems. CONCLUSIONS: Antimicrobial resistance among GNB isolated from intra-abdominal infections continued to be a problem worldwide in 2004, with the highest rates of resistance overall in the Asia/Pacific region. The carbapenems and amikacin were the most consistently active agents in vitro against Enterobacteriaceae isolated from intra-abdominal infections worldwide.