1: J Antimicrob Chemother. 2008 Feb;61(2):382-8. Epub 2007 Dec 10.

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.

De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S.

Dienst Voor Intensieve Zorgen, Ziekenhuis Oost-Limburg, B-3600 Genk, Belgium.

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.

PMID: 18070831 [PubMed - in process]

Related Links

    Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in
intensive care units. [J Antimicrob Chemother. 2006] PMID:16943209

    Lopinavir/ritonavir: a review of its use in the management of HIV infection.
[Drugs. 2003] PMID:12662125

    Population pharmacokinetics and pharmacodynamics of continuous versus short-term 
infusion of imipenem-cilastatin in critically ill patients in a randomized,
controlled trial. [Antimicrob Agents Chemother. 2007] PMID:17620371

    Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic
patients: intermittent versus continuous infusion. [Int J Antimicrob Agents.
2008] PMID:18055183

    Population pharmacokinetic modeling and Monte Carlo simulation of varying doses
of intravenous metronidazole. [Diagn Microbiol Infect Dis. 2006] PMID:16887471