De Jongh, Raf
Hens, Ria
Basma, Violetta
[UCL]
Mouton, Johan W.
Tulkens, Paul M.
[UCL]
Carryn, Stéphane
[UCL]
Background and aims: Temocillin, a 6 alpha-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 >= 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, C-max (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 <= 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.
Bibliographic reference |
De Jongh, Raf ; Hens, Ria ; Basma, Violetta ; Mouton, Johan W. ; Tulkens, Paul M. ; et. al. 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. In: Journal of Antimicrobial Chemotherapy, Vol. 61, no. 2, p. 382-8 (2008) |
Permanent URL |
http://hdl.handle.net/2078.1/36857 |