The Journal of antimicrobial chemotherapy · 2007
Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection.
Сравнительное исследованиеСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
De Jongh Raf, Hens Ria, Basma Violetta, Mouton Johan W, Tulkens Paul M, Carryn Stéphane
Аннотация
BACKGROUND AND AIMS: Temocillin, a 6alpha-methoxy-penicillin stable towards most beta-lactamases (including extended-spectrum beta-lactamase), is presented as an alternative to carbapenems for susceptible Enterobacteriaceae in microbiological surveys. We aimed at documenting its potential clinical usefulness in intensive care (IC) patients using pharmacokinetic/pharmacodynamic approaches applied to conventional (twice daily) and continuous infusion (CI) modes of administration.
METHODS: (i) In vitro evaluation of temocillin stability and compatibility with other drugs under conditions pertinent of CI in IC patients; (ii) pharmacokinetic study in patients treated by CI (4 g/day; n = 6) versus [twice daily (2 g every 12 h); n = 6]; (iii) population pharmacokinetic analysis of twice daily with Monte Carlo simulations to determine 95% probability of target attainment (PTA(95)) versus MIC (based on time above MIC > or = 40% for measured free drug).
RESULTS: Temocillin was stable at 37 degrees C in 8.34% solutions for 24 h and compatible with flucloxacillin and aminoglycosides, but not with several other antibiotic and non-antibiotic drugs. With CI, stable total serum concentrations were 73.5 +/- 3.0 mg/L (SEM) and free concentration 29.3 +/- 2.8 mg/L. With twice daily, Cmax (total drug) was 147 +/- 12.3 mg/L (SEM; free drug: 50.3 +/- 15.8 mg/L), lowest trough (total drug) 12.3 mg/L, and PTA(95) (free drug) obtained for MIC < or = 8 mg/L.
CONCLUSIONS: Temocillin (4 g/day) by CI yields stable free serum concentrations above the current breakpoint (16 mg/L), although individual variations may suggest lowering the breakpoint to 8 mg/L (as for twice daily) unless the daily dose or the frequency of administration is increased.
METHODS: (i) In vitro evaluation of temocillin stability and compatibility with other drugs under conditions pertinent of CI in IC patients; (ii) pharmacokinetic study in patients treated by CI (4 g/day; n = 6) versus [twice daily (2 g every 12 h); n = 6]; (iii) population pharmacokinetic analysis of twice daily with Monte Carlo simulations to determine 95% probability of target attainment (PTA(95)) versus MIC (based on time above MIC > or = 40% for measured free drug).
RESULTS: Temocillin was stable at 37 degrees C in 8.34% solutions for 24 h and compatible with flucloxacillin and aminoglycosides, but not with several other antibiotic and non-antibiotic drugs. With CI, stable total serum concentrations were 73.5 +/- 3.0 mg/L (SEM) and free concentration 29.3 +/- 2.8 mg/L. With twice daily, Cmax (total drug) was 147 +/- 12.3 mg/L (SEM; free drug: 50.3 +/- 15.8 mg/L), lowest trough (total drug) 12.3 mg/L, and PTA(95) (free drug) obtained for MIC < or = 8 mg/L.
CONCLUSIONS: Temocillin (4 g/day) by CI yields stable free serum concentrations above the current breakpoint (16 mg/L), although individual variations may suggest lowering the breakpoint to 8 mg/L (as for twice daily) unless the daily dose or the frequency of administration is increased.